ORCID Profile
0000-0001-8337-550X
Current Organisations
Monash University
,
University of Aberdeen
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Publisher: BMJ
Date: 12-2020
DOI: 10.1136/BMJOPEN-2020-041409
Abstract: Polycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women with PCOS and is associated with lower live birth rates. However, evidence regarding the effectiveness of vitamin D supplementation in women with PCOS is inconclusive. This multicentre randomised, double-blinded, placebo-controlled trial aims to evaluate the effectiveness of vitamin D supplementation prior to in vitro fertilisation (IVF) on the live birth rate in women with PCOS. We plan to enrol women with PCOS scheduled for IVF. After informed consent, eligible participants will be randomised in a 1:1 ratio to receive oral capsules of 4000 IU vitamin D per day or placebo for around 12 weeks until the day of triggering. All IVF procedures will be carried out routinely in each centre. The primary outcome is live birth after the first embryo transfer. The primary analysis will be by intention-to-treat analysis. To demonstrate or refute that treatment with vitamin D results in a 10% higher live birth rate than treatment with placebo, we need to recruit 860 women (48% vs 38% difference, anticipating 10% loss to follow-up and non-compliance, significance level 0.05 and power 80%). This study has been approved by the Ethics Committee in Women’s Hospital of Zhejiang University on 2 March 2020 (reference number: IRB-20200035-R). All participants will provide written informed consent before randomisation. The results of the study will be submitted to scientific conferences and a peer-reviewed journal. NCT04082650 .
Publisher: Wiley
Date: 27-12-2018
DOI: 10.1111/AOGS.13505
Abstract: The aim of this study was to explore the prevalence and predictors of cesarean scar defect (CSD) at 6 weeks postpartum in Shanghai, China. Women scheduled to receive a cesarean section (CS) were recruited from a university hospital. Surgery-related factors, pregnancy complications, routine examinations, perioperative medications, and physical signs were collected and transvaginal ultrasonography was performed to assess the presence of a CSD at 6 weeks postpartum. Multivariate logistic regression was applied to identify the predictors for CSD. A CSD was detected in 223 of 514 women (43.4%, 95% CI 39.1%-47.7%) by transvaginal ultrasonography. Of women with normal temperature (T < 37.5°C, CSD prevalence 33.9%, 95% CI 28.4%-39.5%), women with postpartum fever (T ≥ 38°C, CSD 44.1%, 95% CI 31.0%-57.1%), and women who were subfebrile in the postpartum (37.5 ≤ T ≤ 38.0°C, CSD 58.3%, 95% CI 50.9%-65.7%), the latter two had significantly increased risk for CSD (adjusted odds ratio [aOR] 2.7, 95% CI 1.3-5.2 and aOR 3.3, 95% CI 2.1-5.3, respectively). In comparison to single-dose antibiotic administration (CSD 49.0%, 95% CI 43.8%-54.3%), multi-dose antibiotic administration (CSD 31.1%, 95% CI 23.8%-38.3%) had a protective effect (aOR 0.4, 95% CI 0.3-0.7). Postpartum fever, intrapartum infection, emergency CS, and cervical dilation ≥ 3 cm were found to be the main predictors of multi-dose antibiotics management. Low platelet count postpartum (defined as ≤ 150 × 10 The prevalence of CSD in the Chinese population is high enough to be a concern. Perioperative infection and hypercoagulability should be considered CSD predictors, and multi-dose antibiotics have a protective effect.
Publisher: Oxford University Press (OUP)
Date: 09-2020
Abstract: Over a time period of 3 years, which order of expectant management (EM), IUI with ovarian stimulation (IUI-OS) and IVF is the most cost-effective for couples with unexplained subfertility with the female age below 38 years? If a live birth is considered worth €32 000 or less, 2 years of EM followed by IVF was the most cost-effective, whereas above €32 000 this was 1 year of EM, 1 year of IUI-OS and then 1 year of IVF. IUI-OS and IVF are commonly used fertility treatments for unexplained subfertility although many couples can conceive naturally, as no identifiable barrier to conception could be found by definition. Few countries have guidelines on when to proceed with medically assisted reproduction (MAR), mostly based on the expected probability of live birth after treatment, but there is a lack of evidence to support the strategies proposed by these guidelines. The increased uptake of IUI-OS and IVF over the past decades and costs related to reimbursement of these treatments are pressing concerns to health service providers. For MAR to remain affordable, sustainable and a responsible use of public funds, guidance is needed on the cost-effectiveness of treatment strategies for unexplained subfertility, including EM. We developed a decision analytic Markov model that follows couples with unexplained subfertility of which the woman is under 38 years of age for a time period of 3 years from completion of the fertility workup onwards. We ided the time axis of 3 years into three separate periods, each comprising 1 year. The model was based on contemporary evidence, most notably the dynamic prediction model for natural conception, which was combined with MAR treatment effects from a network meta-analysis on randomized controlled trials. We changed the order of options for managing unexplained subfertility for the 1 year periods to yield five different treatment policies in total: IVF-EM-EM (immediate IVF), EM-IVF-EM (delayed IVF), EM-EM-IVF (postponed IVF), IUIOS-IVF-EM (immediate IUI-OS) and EM-IUIOS-IVF (delayed IUI-OS). The main outcomes per policy over the 3-year period were the probability of live birth, the average treatment and delivery costs, the probability of multiple pregnancy, the incremental cost-effectiveness ratio (ICER) and finally, which policy yields the highest net benefit in which costs for a policy were deducted from the health effects, i.e. live births gained. We chose the Dutch societal perspective, but the model can be easily modified for other locations or other perspectives. The probability of live birth after EM was taken from the dynamic prediction model for natural conception and updated for Years 2 and 3. The relative effects of IUI-OS and IVF in terms of odds ratios, taken from the network meta-analysis, were applied to the probability of live birth after EM. We applied standard discounting procedures for economic analyses for Years 2 and 3. The uncertainty around effectiveness, costs and other parameters was assessed by probabilistic sensitivity analysis in which we drew values from distributions and repeated this procedure 20 000 times. In addition, we changed model assumptions to assess their influence on our results. From IVF-EM-EM to EM-IUIOS-IVF, the probability of live birth varied from approximately 54–64% and the average costs from approximately €4000 to €9000. The policies IVF-EM-EM and EM-IVF-EM were dominated by EM-EM-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. The policy IUIOS-IVF-EM was dominated by EM-IUIOS-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. After removal of policies that were dominated, the ICER for EM-IUIOS-IVF was approximately €31 000 compared to EM-EM-IVF. The range of ICER values between the lowest 25% and highest 75% of simulation replications was broad. The net benefit curve showed that when we assume a live birth to be worth approximately €20 000 or less, the policy EM-EM-IVF had the highest probability to achieve the highest net benefit. Between €20 000 and €50 000 monetary value per live birth, it was uncertain whether EM-EM-IVF was better than EM-IUIOS-IVF, with the turning point of €32 000. When we assume a monetary value per live birth over €50 000, the policy with the highest probability to achieve the highest net benefit was EM-IUIOS-IVF. Results for subgroups with different baseline prognoses showed the same policies dominated and the same two policies that were the most likely to achieve the highest net benefit but at different threshold values for the assumed monetary value per live birth. Our model focused on population level and was thus based on average costs for the average number of cycles conducted. We also based the model on a number of key assumptions. We changed model assumptions to assess the influence of these assumptions on our results. The change in relative effectiveness of IVF over time was found to be highly influential on results and their interpretation. EM-EM-IVF and EM-IUIOS-IVF followed by IVF were the most cost-effective policies. The choice depends on the monetary value assigned to a live birth. The results of our study can be used in discussions between clinicians, couples and policy makers to decide on a sustainable treatment protocol based on the probability of live birth, the costs and the limitations of MAR treatment. This work was supported by the ZonMw Doelmatigheidsonderzoek (80-85200-98-91072). The funder had no role in the design, conduct or reporting of this work. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research support from ObsEva, Merck and Guerbet. N/A.
Publisher: Wiley
Date: 09-10-2023
DOI: 10.1002/UOG.26282
Abstract: To assess whether coexisting fetal growth restriction (FGR) influenced pregnancy latency among women with preterm preecl sia undergoing expectant management. Secondary aims were whether FGR influenced indication for delivery and mode of birth. Secondary analysis of the Preecl sia Intervention (PIE) trial and the Preecl sia Intervention 2 (PI 2) trial. These randomized trials evaluated whether esomeprazole and metformin could prolong gestation for women diagnosed with preecl sia between 26‐ and 32‐weeks undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or no later than 34 weeks gestation. All outcomes were collected prospectively from diagnosis of preecl sia to six weeks after the due date. FGR (defined by Delphi consensus) at the time of preecl sia diagnosis was examined as a predictor of outcome. Only placebo data from PI 2 were included as metformin was associated with prolonged gestation. Of the 202 women included, 92 (45.5%) had FGR at the time of preecl sia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days adjusted 0.49‐fold change, 95% CI 0.33 to 0.74, p .001). FGR pregnancies were less likely to reach 34 weeks gestation (12.0% vs 30.9%, adjusted relative risk (aRR) 0.44, 95% CI 0.23 to 0.83) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%.0, aRR 1.84, 95% CI 1.36 to 2.47). More women with FGR underwent an emergency pre‐labor caesarean section (66.3% vs 43.6%, aRR 1.56, 95% CI 1.20 to 2.03) and fewer had a successful induction of labor (4.3% vs 14.5%, aRR 0.32, 95% CI 0.10 to 1.00). Maternal complications did not differ. FGR was associated with a higher rate of neonatal death (14.1% vs 4.5%, aRR 3.26, 95% CI 1.08 to 9.81) and need for intubation and mechanical ventilation (15.2% vs 5.5%, aRR 2.97, 95% CI 1.11 to 7.90). FGR is commonly present in women with early preterm preecl sia being managed expectantly and outcomes are poorer. FGR is associated with a shorter latency, more emergency caesarean deliveries, fewer successful inductions, and increased rates of neonatal morbidity and death. This article is protected by copyright. All rights reserved.
Publisher: Cold Spring Harbor Laboratory
Date: 06-07-2022
DOI: 10.1101/2022.07.04.22277193
Abstract: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. The aim of this study was to investigate the sociodemographic characteristics associated with vaccine uptake in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. Retrospective multicenter cohort study in Melbourne following the national recommendations for mRNA COVID-19 vaccination during pregnancy in June 2021. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births ≥ 20 weeks’ gestation from 1 st July 2021 to 31 March 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20-43 of gestation fell entirely within the 9-month data collection period. The primary outcome was the rate of congenital anomaly in singleton infants ≥ 20 weeks’ gestation among women vaccinated during pregnancy. Secondary perinatal outcomes including stillbirth, preterm birth (spontaneous and iatrogenic), birthweight ≤ 3 rd centile, and newborn intensive care unit admissions were examined for singleton infants ≥ 24 weeks’ gestation without congenital anomalies. We calculated the adjusted odds ratio of congenital anomalies and perinatal outcomes among vaccinated versus unvaccinated women using inverse propensity score weighting regression adjustment with multiple covariates p 0.05 was considered statistically significant. Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth: compared with women born in Australia, women born in South and Eastern Europe, the Middle East, Africa and Oceania had lower adjusted odds of vaccination. There was no significant increase in the rate of congenital anomalies or birth weight ≤ 3 rd centile in vaccinated women. Vaccinated women were significantly less like to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%, aOR 0.72, 95%CI 0.56-0.94, p=0.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks’ gestation. Vaccinated women had a significantly lower rate of stillbirth (0.2% vs 0.8%, aOR 0.18, 95%CI 0.09-0.37, P 0.001. Vaccination was associated with a significant reduction in total preterm births 37 weeks (5.1% vs 9.2%, aOR 0.60, 95% CI 0.51-0.71, p 0.001), spontaneous preterm birth (2.4% vs 4.0%, aOR 0.73 95% CI 0.56-0.96, p=0.02) and iatrogenic preterm birth (2.7% vs 5.2%, aOR 0.52, 95%CI 0.41-0.65, p 0.001). COVID-19 Vaccine coverage was significantly influenced by known social determinants of health, which is likely to influence the strong association between COVID-19 vaccination and lower risks of stillbirth and preterm birth. We did not observe any adverse impacts of vaccination on fetal growth or development. ⍰ COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. ⍰ Most of the published literature on COVID-19 vaccination in pregnancy have methodological limitations including fixed cohort bias and time-varying exposure. ⍰ We conducted this multicenter study to provide robust evidence on mRNA COVID-19 vaccination and perinatal outcomes including congenital anomalies, stillbirth, and preterm birth. ⍰ The adjusted odds of stillbirth, preterm birth, and neonatal intensive care admission were significantly reduced among infants born to COVID-19 vaccinated women compared with unvaccinated women. COVID-19 vaccination during pregnancy was not associated with an increase in congenital anomalies. ⍰ Our results conclusively demonstrate a significant reduction in both spontaneous and iatrogenic preterm birth for vaccinated women ⍰ Vaccinated women were significantly more likely to be older, nulliparous, non-smoking, not requiring an interpreter, residing in a higher socioeconomic postcode, and vaccinated against pertussis and influenza. There were also significant differences in vaccination rates by region of birth. ⍰ Our analysis confirmed a strong relationship between the COVID-19 mRNA vaccine and lower preterm births and stillbirths ⍰ In addition to its impact on reducing severe COVID-19 illness, vaccination may be a proxy for other biological and social determinants of health among our pregnant population.
Publisher: Informa UK Limited
Date: 31-01-2023
Publisher: Springer Science and Business Media LLC
Date: 21-03-2021
Publisher: Wiley
Date: 11-03-2023
DOI: 10.1002/UOG.26160
Abstract: Birth weight, fetal growth and placental function influence cognitive development. The gradient of these associations is understudied, especially among those with a birth weight considered appropriate‐for‐gestational age. The aim of this study was to evaluate the associations between birth‐weight centile and intellectual development in term/near‐term infants across the entire birth‐weight spectrum, in order to provide a basis for better understanding of the long‐term implications of fetal growth restriction and reduced placental function. This was a population‐based cohort study of 266 440 liveborn singletons from uncomplicated pregnancies, delivered between 36 and 42 weeks of gestation. Perinatal data were obtained from the Dutch Perinatal Registry over the period 2003–2008 and educational data for children aged approximately 12 years were obtained from Statistics Netherlands over the period 2016–2019. Regression analyses were conducted to assess the association of birth‐weight centile with school performance. The primary outcomes were mean school performance score, on a scale of 501–550, and proportion of children who reached higher secondary school level. Mean school performance score increased gradually with increasing birth‐weight centile, from 533.6 in the 1 st –5 th birth‐weight‐centile group to 536.8 in the 81 st –85 th birth‐weight‐centile group. Likewise, the proportion of children at higher secondary school level increased with birth‐weight centile, from 43% to 57%. Compared with the 81 st –85 th birth‐weight‐centile group, mean school performance score and proportion of children at higher secondary school level were significantly lower in all birth‐weight‐centile groups below the 80 th centile, after adjusting for confounding factors. Birth‐weight centile is associated positively with school performance at 12 years of age across the entire birth‐weight spectrum, well beyond the conventional and arbitrary cut‐offs for suspected fetal growth restriction. This underlines the importance of developing better tools to diagnose fetal growth restriction and reduced placental function, and to identify those at risk for associated short‐ and long‐term consequences. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Oxford University Press (OUP)
Date: 11-01-2019
Publisher: Wiley
Date: 18-10-2019
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 18-06-2019
DOI: 10.1111/AOGS.13630
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 28-08-2020
DOI: 10.1111/AOGS.13976
Publisher: Public Library of Science (PLoS)
Date: 08-12-2020
DOI: 10.1371/JOURNAL.PMED.1003436
Abstract: The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an in idual participant data meta-analysis (IPD-MA) on this subject. We searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. In idual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age ( /≥35 years), and body mass index (BMI) ( /≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available. From 89 full-text articles, we identified three eligible RCTs ( n = 5,161), and two contributed with IPD ( n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280] relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p -value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I 2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267). Perinatal deaths occurred in one ( .1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p -value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I 2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p -value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I 2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7% RR 0.98, [95% CI 0.83 to 1.16], p -value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results. Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect ( p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264] RR 0.20 [95% CI 0.07 to 0.60], p -value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I 2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264] RR 1.59 [95% CI 0.15 to 17.30], p -value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I 2 55%). A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA thus, the possibility to assess severe adverse neonatal outcomes with few events was limited. In this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks. Study Registration: PROSPERO CRD42020163174
Publisher: Wiley
Date: 03-04-2016
DOI: 10.1111/AOGS.12886
Abstract: In this prospective cohort study we aimed to investigate the hypothesis that fluctuations in anti-Müllerian hormone levels stem from fluctuations in the number of antral follicles. Repeated measurements of anti-Müllerian hormone and antral follicles (follicles 2-8 mm) were performed in 44 women with a regular cycle, during one menstrual cycle. If our hypothesis that anti-Müllerian hormone fluctuations stem from fluctuations in the antral follicles is correct, a fluctuation in the antral follicles would result in an equal and parallel shift in anti-Müllerian hormone. Hence, the difference between antral follicles and anti-Müllerian hormone would remain constant over time. A mixed model analysis, assessing the stability between anti-Müllerian hormone and antral follicles, was performed using the difference between log antral follicles and log anti-Müllerian hormone. Cohen's D was calculated for the largest of fixed effects in order to assess stability in relative distance between antral follicles and anti-Müllerian hormone. To assess if fluctuation in anti-Müllerian hormone or antral follicles originated from between-subject fluctuation, or from within subject fluctuation, the intra-class correlation coefficient was calculated. Mixed model analysis and Cohen's D (0.12) confirmed the stability of the difference between log antral follicles and log anti-Müllerian hormone and so confirmed our hypothesis. The good intra-class correlation coefficient (0.73) indicated a small contribution of within-subject variation to anti-Müllerian hormone fluctuations. Fluctuations in anti-Müllerian hormone levels parallel fluctuations in antral follicles, suggesting that anti-Müllerian hormone levels are closely linked to variation in the antral follicles. This knowledge adds to the basic understanding of the origin of anti-Müllerian hormone and could aid in interpretation of in idual anti-Müllerian hormone levels.
Publisher: BMJ
Date: 07-2022
DOI: 10.1136/BMJOPEN-2022-062578
Abstract: Existing randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and in idual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy. We will search electronic databases (Medline, Embase, PsycINFO and CENTRAL) and trial registries (ClinicalTrials.gov and the International Clinical Trials Registry Platform) from their inception to present to identify eligible RCTs. We will also check reference lists of relevant papers. The search was performed on 23 September 2020 and will be updated. We will include RCTs comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy in couples undergoing IVF. The primary outcome will be live birth resulting from the first embryo transfer. All outcomes listed in the core outcome set for infertility research will be reported. We will invite the lead investigators of eligible trials to join the In idual participant data meta-analysis of trials comparing f r o zen versus f r esh e m bryo transfer strategy (INFORM) collaboration and share the deidentified in idual participant data (IPD) of their trials. We will harmonise the IPD and perform a two-stage meta-analysis and examine treatment–covariate interactions for important baseline characteristics. The study ethics have been granted by the Monash University Human Research Ethics Committee (Project ID: 30391). The findings will be disseminated via presentations at international conferences and publication in peer-reviewed journals. CRD42021296566.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.EJOGRB.2019.12.021
Abstract: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity. For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures. We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (β) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures. Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity.
Publisher: Wiley
Date: 06-2023
DOI: 10.1111/PPE.12990
Abstract: Gestational age is positively associated with cognitive development, but socio‐demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio‐economic status (SES) at increased risk of the negative effects of prematurity. To investigate the association between gestational age in weeks, socio‐demographic characteristics, and school performance at the age of 12 years among children in regular primary education. Population‐based cohort study among liveborn singletons ( N = 860,332) born in the Netherlands in 1999–2006 at 25–42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction. School performance increased with gestational age up to 40 weeks. This pattern was evident across socio‐demographic strata. Children born at 25 weeks had −0.57 SD (95% confidence interval −0.79, −0.35) lower school performance z‐scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non‐European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25–29 years, with intermediate SES or first borns (evidence of interaction). Higher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut‐off of preterm birth and across socio‐demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow‐up.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.EJOGRB.2019.12.022
Abstract: Ectopic pregnancy is a potentially life-threatening health problem that affects fertility and generates a significant economic burden. Optimal management, including when to choose methotrexate, and whether to do salpingectomy or salpingostomy, is still unclear. This study aimed to assess the quality and utility of research on ectopic pregnancy in the last three decades. We analyzed the quantity, quality and utility of the published literature, including 6,309 articles published over a 30-year period. We searched PubMed for studies on ectopic pregnancy, with subsequent analysis utilizing bibliometric network maps. Consolidated Standards of Reporting Trials (CONSORT) guidelines and a newly adapted checklist for usefulness of research were applied to assess randomized controlled trial (RCT) quality. The initial search returned 14,727 articles, of which, after filters of publication date (1987/01/01 to 2017/12/31), species (Human) and language (English) were applied, 6,309 articles remained. The number of publications each year remained relatively stable, with a mean number of 280 articles published three decades ago versus 248 articles published on average in the last decade. The 7,733 human species articles published between 1987-2017 were written in 27 different languages, with 82 % in English. Publications in 14 selected high-impact journals accounted for 26.5 % (1,673/6,309) of all articles, with on average 54 publications per year across three decades. An increase in systematic reviews and meta-analyses (+1000 %), and case reports (+53 %) was seen between 1987-2017, while the percentage of RCTs (-25 %) decreased. The analyzed RCTs were of moderate quality, and few addressed the most important clinical questions. In the last three decades, both the number of articles on ectopic pregnancy and the number of articles in high-impact journals have remained stable. Despite these constant numbers, the quality of RCTs was suboptimal and there was a decrease in the annual number of published RCTs, while the use of meta-analysis significantly lified. This study suggests continued review of research practices and provides suggestions on how the quality of the published literature can be improved.
Publisher: Wiley
Date: 07-02-2019
DOI: 10.1111/AJO.12952
Abstract: Vaginal instrumental delivery is a common obstetrical intervention, but its effect on children's later development is not well known. To determine if vaginal instrumental delivery is associated with adverse neurodevelopment as measured by school achievement. We performed a whole‐of‐population study involving linkage of routinely collected perinatal data with school assessments among children born in South Australia from 1999 to 2008. Participants were singleton children born by forceps ( n = 5494), ventouse ( n = 6988), or normal delivery ( n = 80 803). School achievement was measured through performance on the National Assessment Program in Literacy and Numeracy (NAPLAN), at around eight years of age. This assessment involved five domains and scores were categorised according to performing at or above National Minimum Standards (NMS). Effects of instrumental versus normal vaginal delivery were analysed via augmented inverse probability weighting (AIPW), taking into account a variety of maternal, perinatal and sociodemographic characteristics. In unadjusted analyses, instrumental delivery was not associated with poor NAPLAN scores. AIPW analyses also suggested that instrumental delivery had minimal adverse effect on NAPLAN scores, with the largest difference being lower spelling scores among forceps‐delivered children (−0.022 (95% CI −0.0053–0.009)) compared with spontaneous vaginal births. The findings were consistent among exploratory subgroup analyses involving births in the absence of prolonged labour, with APGAR ≥ 9, and among normotensive and non‐diabetic mothers. In singleton children born at term, instrumental delivery does not have an adverse effect on neurodevelopment as measured by NAPLAN performance at age eight.
Publisher: Wiley
Date: 06-2021
DOI: 10.1111/AJO.13369
Abstract: To develop a core outcome set for trials investigating interventions to prevent stillbirth. Outcomes identified from a systematic literature review and semi‐structured interviews with parents in Australia and the UK were entered into a two‐round online Delphi survey and focus group/consensus meetings. A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher‐level neonatal care length of stay. Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.
Publisher: Oxford University Press (OUP)
Date: 30-05-2020
Publisher: Wiley
Date: 19-02-2023
Abstract: This article includes Author Insights, a video abstract available at: 85911255
Publisher: Elsevier BV
Date: 05-2020
Publisher: Oxford University Press (OUP)
Date: 18-05-2022
Abstract: Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for unexplained infertility. Gonadotrophins, letrozole and clomiphene citrate (CC) are commonly used agents during IUI-OS and have been compared in multiple aggregate data meta-analyses, with substantial heterogeneity and no analysis on time-to-event outcomes. In idual participant data meta-analysis (IPD-MA) is considered the gold standard for evidence synthesis as it can offset inadequate reporting of in idual studies by obtaining the IPD, and allows analyses on treatment–covariate interactions to identify couples who benefit most from a particular treatment. We performed this IPD-MA to compare the effectiveness and safety of ovarian stimulation with gonadotrophins, letrozole and CC and to explore treatment–covariate interactions for important baseline characteristics in couples undergoing IUI. We searched electronic databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO from their inception to 28 June 2021. We included randomized controlled trials (RCTs) comparing IUI-OS with gonadotrophins, letrozole and CC among couples with unexplained infertility. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA Collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Secondary outcomes were other reproductive outcomes, including time to conception leading to live birth. We performed a one-stage random effects IPD-MA. Seven of 22 (31.8%) eligible RCTs provided IPD of 2495 couples (62.4% of the 3997 couples participating in 22 RCTs), of which 2411 had unexplained infertility and were included in this IPD-MA. Six RCTs (n = 1511) compared gonadotrophins with CC, and one (n = 900) compared gonadotrophins, letrozole and CC. Moderate-certainty evidence showed that gonadotrophins increased the live birth rate compared to CC (6 RCTs, 2058 women, RR 1.30, 95% CI 1.12–1.51, I2 = 26%). Low-certainty evidence showed that gonadotrophins may also increase the multiple pregnancy rate compared to CC (6 RCTs, 2058 women, RR 2.17, 95% CI 1.33–3.54, I2 = 69%). Heterogeneity on multiple pregnancy could be explained by differences in gonadotrophin starting dose and choice of cancellation criteria. Post-hoc sensitivity analysis on RCTs with a low starting dose of gonadotrophins (≤75 IU) confirmed increased live birth rates compared to CC (5 RCTs, 1457 women, RR 1.26, 95% CI 1.05–1.51), but analysis on only RCTs with stricter cancellation criteria showed inconclusive evidence on live birth (4 RCTs, 1238 women, RR 1.15, 95% CI 0.94–1.41). For multiple pregnancy, both sensitivity analyses showed inconclusive findings between gonadotrophins and CC (RR 0.94, 95% CI 0.45–1.96 RR 0.81, 95% CI 0.32–2.03, respectively). Moderate certainty evidence showed that gonadotrophins reduced the time to conception leading to a live birth when compared to CC (6 RCTs, 2058 women, HR 1.37, 95% CI 1.15–1.63, I2 = 22%). No strong evidence on the treatment–covariate (female age, BMI or primary versus secondary infertility) interactions was found. In couples with unexplained infertility undergoing IUI-OS, gonadotrophins increased the chance of a live birth and reduced the time to conception compared to CC, at the cost of a higher multiple pregnancy rate, when not differentiating strategies on cancellation criteria or the starting dose. The treatment effects did not seem to differ in women of different age, BMI or primary versus secondary infertility. In a modern practice where a lower starting dose and stricter cancellation criteria are in place, effectiveness and safety of different agents seem both acceptable, and therefore intervention availability, cost and patients’ preferences should factor in the clinical decision-making. As the evidence for comparisons to letrozole is based on one RCT providing IPD, further RCTs comparing letrozole and other interventions for unexplained infertility are needed.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 21-06-2020
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.IJOA.2018.10.013
Abstract: During labour, remifentanil patient-controlled analgesia is used as an alternative to neuraxial analgesia. Remifentanil is associated with hypoventilation and respiratory depression but the frequency of serious maternal and neonatal adverse events is unknown. The aim of this study was to estimate the number of serious adverse events attributed to the use of remifentanil patient-controlled analgesia during labour in The Netherlands and to investigate the circumstances (e.g. monitoring, practice deviations) of these events and the subsequent management. In a nationwide survey among obstetricians, anaesthetists and clinical midwives the frequency of serious adverse events was assessed. A questionnaire was sent by email to all 61 Dutch hospitals in which remifentanil patient-controlled analgesia is, or has been, available for labour analgesia. All reported cases were assessed independently by two expert teams. We received information from all hospitals. After independent assessments, 17 cases of single maternal desaturation 10 maternal cases of apnoea, bradycardia and/or cardiac arrest and two neonatal cases of respiratory depression, over a period of more than 10 years of remifentanil patient-controlled analgesia use, were identified as a serious adverse event. All serious adverse events were resolved without irreversible damage. The risk of a potentially life-threatening serious adverse event attributed to remifentanil patient-controlled analgesia seems to be low. All patients recovered without deficit. Adherence to strict monitoring and the attendance of trained healthcare providers is required to safely use remifentanil for labour analgesia.
Publisher: Wiley
Date: 06-2022
DOI: 10.1002/UOG.24894
Abstract: Linked article: This Editorial comments on the article by Cho et al. Click here to view the article.
Publisher: Wiley
Date: 10-2023
DOI: 10.1002/UOG.26279
Abstract: To reduce emergency Cesarean section (EmCS) rates by using ST analysis of the fetal electrocardiogram (STan) as an adjunct to continuous cardiotocography (CTG). A randomized, controlled trial enrolled patients with a singleton fetus in cephalic presentation, greater than or equal to 36 weeks gestation, requiring continuous electronic fetal monitoring in labor at a tertiary maternity hospital in Adelaide, Australia, between January 2018 and July 2021. Participants were randomized to receive CTG+STan or CTG alone. Calculated s le size was 1818 participants. The primary outcome was EmCS. Secondary outcomes included metabolic acidosis, a composite perinatal outcome, and other maternal and neonatal morbidity and safety outcomes. The present study enrolled 970 women. The primary outcome of EmCS occurred in 107/482 (22.2%) of the CTG+STan arm and in 107/485 (22.1%) in the CTG alone arm (adjusted relative risk (RR), 1.02 (95% CI, 0.81–1.27), P =0.89). The addition of STan as an adjunct to continuous CTG did not reduce the EmCS rate. The smaller than anticipated s le size for this study meant that it was underpowered to detect absolute differences less than or equal to 5% and therefore this finding is possibly due to a Type 2 error, where a difference may exist but the study was underpowered to detect it. This article is protected by copyright. All rights reserved.
Publisher: Wiley
Date: 02-2021
DOI: 10.1002/UOG.23563
Abstract: To compare the effectiveness and safety of Foley catheter and oral misoprostol for induction of labor (IOL). The Cochrane Review on Mechanical Methods for Induction of Labour and Ovid MEDLINE, EMBASE via Ovid, Ovid Emcare, CINAHL Plus, ClinicalTrials.gov and Scopus, from inception to April 2019, were searched for randomized controlled trials (RCTs) comparing Foley catheter to oral misoprostol for IOL in viable singleton gestations. Eligible trials for which raw data were obtained were included and in idual participant data meta‐analysis was performed. Primary outcomes were vaginal birth, a composite of adverse perinatal outcome (including stillbirth, neonatal death, neonatal seizures, admission to the neonatal intensive care unit, severe respiratory compromise or meconium aspiration syndrome) and a composite of adverse maternal outcome (including admission to the intensive care unit, maternal infection, severe postpartum hemorrhage, maternal death or uterine rupture). The quality of the included RCTs was assessed using the Cochrane Risk of Bias 2 tool and the certainty of evidence was evaluated using the GRADE approach. A two‐stage random‐effects model was used for meta‐analysis according to the intention‐to‐treat principle and interactions between treatment and baseline characteristics were assessed. Of seven eligible trials, four provided in idual participant data for a total of 2815 participants undergoing IOL, of whom 1399 were assigned to Foley catheter and 1416 to oral misoprostol. All four trials provided data for each of the primary outcomes in all 2815 women. Compared with those receiving oral misoprostol, Foley catheter recipients had a slightly decreased chance of vaginal birth (risk ratio (RR), 0.95 (95% CI, 0.91–0.99) I 2 , 2.0% moderate‐certainty evidence). A trend towards a lower rate of composite adverse perinatal outcome was found in women undergoing IOL using a Foley catheter compared with oral misoprostol (RR, 0.71 (95% CI, 0.48–1.05) I 2 , 14.9% low‐certainty evidence). Composite adverse maternal outcome did not differ between the groups (RR, 1.00 (95% CI, 0.97–1.03) I 2 , 0% moderate‐certainty evidence). Meta‐analyses of effect modifications did not show significant interactions between intervention and parity or gestational age for any of the primary outcomes. For women undergoing IOL, Foley catheter is less effective than oral misoprostol, as it was associated with fewer vaginal births. However, while we found no significant difference in maternal safety, Foley catheter induction may reduce adverse perinatal outcomes. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Authorea, Inc.
Date: 03-01-2023
DOI: 10.22541/AU.167275806.65061511/V1
Abstract: Background: Multiple gestation has a higher incidence of preterm birth(PTB), especially in the presence of a short cervix. Objectives: To perform a systematic review and network meta-analysis(NMA) evaluating the effect of progesterone, cerclage, cervical pessary and their combination as treatments for preventing PTB weeks. Search strategy: PubMed, MEDLINE, Cochrane Library, EMBASE, Web of Science, BVS, Scopus, and grey literature were explored. Selection criteria: We included randomized controlled trials that compared an intervention with a control group or another intervention to prevent PTB in women with a twin pregnancy and a short cervix mm. Data collection and Analysis:Studies were checked for trustworthiness. We presented summary relative effect sizes(Odds Ratios) for each possible pair of interventions and we used the surface under the cumulative ranking curves(SUCRA) to rank all interventions. Main Results: A total of 20 studies participated in NMA. We found no evidence that the combined treatment of pessary and vaginal progesterone reduced the risk of spontaneous PTB weeks when compared to no intervention(OR 0.68 95%CI 0.16 to 2.9). Also, pessary(OR 0.78 95%CI 0.49 to 1.3), vaginal progesterone(OR 0.79 CI95% 0.45 to 1.4) and injectable 17-OH progesterone alone(OR 0.85 CI95% 0.26 to 2.8) did not show a statistically significant reduction in spontaneous PTB. For overall PTB weeks, findings were similar. Conclusions: We found no evidence that progesterone, cervical pessary, cerclage or their combination reduce PTB weeks. There is an urgent need for randomized trials assessing these treatments in women with a multiple pregnancy and a short cervix.
Publisher: Wiley
Date: 22-06-2023
DOI: 10.1111/AOGS.14617
Abstract: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. We performed a systematic review and in idual participant data meta‐analysis (IPD‐MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG ( IU/L). A one‐stage IPD‐MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side‐effects and hCG resolution times. Trial registration number: PROSPERO: CRD42021214093. 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95–1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23–1.14). Mean time to success was 19.7 days (95% CI 17.4–22.3) after MTX and 21.2 days (95% CI 17.8–25.2) after expectant management ( P = 0.25). MTX specific side‐effects were reported in 33 MTX compared to four in the expectant group. Our IPD‐MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side‐effects.
Publisher: Wiley
Date: 11-12-2019
DOI: 10.1111/AOGS.13767
Abstract: Midwife-led models of care have been the subject of debate for many years. We conducted a study to compare intrapartum and neonatal mortality rates in midwife-led (primary) vs obstetrician-led (secondary) care at the onset of labor in low-risk term women. We performed an unmatched and a propensity score matched cohort study using data from the national perinatal audit registry (PAN) and from the national perinatal registry (PERINED) of the Netherlands. We included women with singleton pregnancies (without congenital anomalies or antepartum fetal death) who gave birth at term between 2010 and 2012. We excluded the following major risk factors: non-vertex position of the fetus, previous cesarean birth, hypertension, diabetes mellitus, prolonged rupture of membranes (≥24 hours), vaginal bleeding in the second half of pregnancy, nonspontaneous start of labor and post-term pregnancy (≥42 weeks). The primary outcome was intrapartum or neonatal mortality up to 28 days after birth. Secondary outcome measures were mode of delivery and a 5-minute Apgar score <7. We included 259 211 women. There were 100/206 642 (0.48‰) intrapartum and neonatal deaths in the midwife group and 23/52 569 (0.44‰) in the obstetrician group (odds ratio [OR] 1.11, 95% CI 0.70-1.74). Propensity score matched analysis showed mortality rates of 0.49‰ (26/52 569) among women in midwife-led care and 0.44‰ (23/52 569) for women in obstetrician-led care (OR 1.13, 95% CI 0.65-1.98). In the midwife group there were significantly lower rates of vaginal instrumental deliveries (8.4% vs 13.0% matched OR 0.65, 95% CI 0.62-0.67) and intrapartum cesarean sections (2.6% vs 8.2% matched OR 0.32, 95% CI 0.30-0.34), and fewer neonates with low Apgar scores (<7 after 5 minutes) (0.69% vs 1.11% matched OR 0.61, 95% CI 0.53-0.69). Among low-risk term women, there were comparable intrapartum and neonatal mortality rates for women starting labor in midwife-led vs obstetrician-led care, with lower intervention rates and fewer low Apgar scores in the midwife group.
Publisher: Cold Spring Harbor Laboratory
Date: 17-04-2021
DOI: 10.1101/2021.04.14.21251044
Abstract: Infertility is a significant problem with multiple causes and a corresponding array of therapeutic options. In an era of increasing assisted reproductive treatments, few studies examine the role of conventional non-assisted reproductive treatments to address underlying behavioural, lifestyle and medical issues. To assess outcomes from a conventional or non-assisted reproductive treatment approach Retrospective case series of 162 couples that attended an Australian, hospital-based, multidisciplinary fertility clinic between 2005 and 2010. There were 58 live births for all couples giving a crude live birth rate of 35.4% over a 24-month analysis period. When adjusted by Kaplan-Meier method, a 57.4% cumulative live birth rate (CLBR) was achieved. Couples had a median 33.9 months duration of infertility and the median female age was 33.7. For the 74 couples with an unexplained infertility diagnosis, 32 achieved a live birth at a crude rate of 43.2% or 71.2% CLBR when adjusted by Kaplan-Meier method. This observational data indicates that reproductive medicine should have a personalized approach in which alternatives for immediate IVF are considered.
Publisher: Oxford University Press (OUP)
Date: 20-05-2022
Abstract: Does an increased dosing of FSH improve the live birth rate as compared to standard FSH dosing in expected poor responders who undergo IVF? In this trial, women with an expected poor response allocated to increased FSH dosing did not have a statistically significant increase in cumulative live births as compared to a standard FSH dose. Poor ovarian reserve leads to worse IVF outcomes owing to the low number and quality of oocytes. Clinicians often in idualize the FSH dose using ovarian reserve tests, including antral follicle count (AFC), and basal plasma FSH or anti-Müllerian hormone level. However, the evidence that increased FSH dosing improves fertility outcomes in women with an expected poor response is lacking. We performed a parallel, open-label randomized controlled trial between March 2019 and October 2021 in an assisted reproduction centre. Women & years of age with AFC & referred for their first IVF cycle were randomized for increased or standard FSH dosing. In participants allocated to increased FSH dosing, women with AFC 1–6 started with 300 IU/day, while women with AFC 7–9 started with 225 IU/day. In participants allocated to the standard care, women started with 150 IU/day. The primary outcome was cumulative live birth attributable to the first IVF cycle including fresh and subsequent frozen-thawed cycles within 18 months of randomization. Live birth was defined as the delivery of one or more living infants ≥24 weeks’ gestation. This trial was powered to detect an 11% difference in live birth attributable to the first IVF cycle. Outcomes were evaluated from an intention-to-treat perspective. We randomized 661 women to start FSH at increased dosing (n = 328) or standard dosing (n = 333). The primary outcome cumulative live birth occurred in 162/328 (49.4%) women in the increased group versus 141/333 (42.3%) women in the standard group [risk ratio (RR) 1.17 (95% CI, 0.99–1.38), risk difference 0.07 (95% CI, −0.005, 0.15), P = 0.070]. The live birth rate after the first embryo transfer in the increased versus standard group was 125/328 (38.1%) versus 117/333 (35.1%), respectively [RR 1.08 (95% CI, 0.83–1.33), P = 0.428]. Cumulative clinical pregnancy rates were 59.1% versus 57.1% [RR 1.04 (95% CI, 0.91–1.18), P = 0.586] with miscarriage rates of 9.8% versus 14.4% [RR 0.68 (95% CI, 0.44–1.03), P = 0.069] in the increased versus standard group, respectively. Other secondary outcomes, including biochemical pregnancy, ongoing pregnancy, multiple pregnancy and ectopic pregnancy, were not significantly different between the two groups both from the first and cumulative embryo transfer. As this study is open-label, potential selective cancelling and small dose adjustments could have influenced the results. In women with predicted poor response, we did not find evidence that increased FSH dosing improves live birth rates. A standard dose of 150 IU/day is recommended at the start of IVF in these women to reduce potential adverse effects and costs. This study was funded by the General Projects of Social Development in Shaanxi Province (No. 2022SF-565). B.W.M. is supported by NHMRC (GNT1176437). B.W.M. reports personal fees from ObsEva, and funding from Merck and Ferring outside the submitted work. Registered at Chinese clinical trial registry (www.chictr.org.cn). Registration number ChiCTR1900021944. 17 March 2019 20 March 2019
Publisher: Wiley
Date: 02-08-2022
DOI: 10.1111/AJO.13599
Abstract: Postpartum haemorrhage (PPH) remains a leading cause of maternal mortality and morbidity worldwide, and the rate is increasing. Using a reliable predictive model could identify those at risk, support management and treatment, and improve maternal outcomes. To systematically identify and appraise existing prognostic models for PPH and ascertain suitability for clinical use. MEDLINE, CINAHL, Embase, and the Cochrane Library were searched using combinations of terms and synonyms, including 'postpartum haemorrhage', 'prognostic model', and 'risk factors'. Observational or experimental studies describing a prognostic model for risk of PPH, published in English, were included. The Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist informed data extraction and the Prediction Model Risk of Bias Assessment Tool guided analysis. Sixteen studies met the inclusion criteria after screening 1612 records. All studies were hospital settings from eight different countries. Models were developed for women who experienced vaginal birth (n = 7), caesarean birth (n = 2), any type of birth (n = 2), hypertensive disorders (n = 1) and those with placental abnormalities (n = 4). All studies were at high risk of bias due to use of inappropriate analysis methods or omission of important statistical considerations or suboptimal validation. No existing prognostic models for PPH are ready for clinical application. Future research is needed to externally validate existing models and potentially develop a new model that is reliable and applicable to clinical practice.
Publisher: Oxford University Press (OUP)
Date: 04-11-2022
Abstract: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (& % in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (& % in 12 months), the effectiveness of IUI-OS is uncertain. We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (& % in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20% 90% CI: −30% to −9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59 RD −24%, 90% CI −36% to −13%) in line with inferiority of EM. Our trial did not reach the planned s le size, therefore the results are limited by the number of participants. This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. The trial was supported by a grant of the SEENEZ healthcare initiative. The subsidizing parties were The Dutch Organisation for Health Research and Development (ZonMW 837004023, www.zonmw.nl) and the umbrella organization of 10 health insurers in The Netherlands. E.R.G. receives personal fees from Titus Health care outside the submitted work. M.G. declares unrestricted research and educational grants from Guerbet, Merck and Ferring not related to the presented work, paid to their institution VU medical centre. A.B.H. reports receiving travel and speakers fees from Nordic Pharma and Merck and he is member of the Nordic Pharma ANGEL group and of the Safety Monitoring Board of Womed. C.B.L. reports speakers fee from Inmed and Yingming, and his department receives research grants from Ferring, Merck and Guerbet paid to VU medical centre. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck. M.v.W. received a grant from the Netherlands Organisation for Health Research and Development ZonMW (80-8520098-91072). F.M. received two grants from the Netherlands Organisation for Health Research and Development ZonMW (NTR 5599 and NTR 6590). The other authors report no competing interest. Dutch Trial register NL5455 (NTR5599) 18 December 2015 26 January 2017
Publisher: Oxford University Press (OUP)
Date: 06-2020
Abstract: Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles? Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles. For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. It is unclear whether EMT can be used to identify women who can continue on CC with similar live birth rates without the extra costs of gonadotropins. Between 8 December 2008 and 16 December 2015, 666 women with CC failure were randomly assigned to receive an additional six cycles with a change to gonadotropins (n = 331) or an additional six cycles continuing with CC (n = 335), both in conjunction with intercourse or IUI. The primary outcome was conception leading to live birth within 8 months after randomisation. EMT was measured mid-cycle before randomisation during their sixth ovulatory CC cycle. The EMT was available in 380 women, of whom 190 were allocated to gonadotropins and 190 were allocated to CC. EMT was determined in the sixth CC cycle prior to randomisation. We tested for interaction of EMT with the treatment effect using logistic regression. We performed a spline analysis to evaluate the association of EMT with chance to pregnancy leading to a live birth in the next cycles and to determine the best cut-off point. On the basis of the resulting cut-off point, we calculated the relative risk and 95% CI of live birth for gonadotropins versus CC at EMT values below and above this cut-off point. Finally, we calculated incremental cost-effectiveness ratios (ICER). Mid-cycle EMT in the sixth cycle interacted with treatment effect (P & 0.01). Spline analyses showed a cut-off point of 7 mm. There were 162 women (45%) who had an EMT ≤ 7 mm in the sixth ovulatory cycle and 218 women (55%) who had an EMT & 7 mm. Among the women with EMT ≤ 7 mm, gonadotropins resulted in a live birth in 44 of 79 women (56%), while CC resulted in a live birth in 28 of 83 women (34%) (RR 1.57, 95% CI 1.13–2.19). Per additional live birth with gonadotropins, the ICER was €9709 (95% CI: €5117 to €25 302). Among the women with EMT & 7 mm, gonadotropins resulted in a live birth in 53 of 111 women (48%) while CC resulted in a live birth in 52 of 107 women (49%) (RR 0.98, 95% CI 0.75–1.29). This was a post hoc analysis of a randomised controlled trial (RCT) and therefore mid-cycle EMT measurements before randomisation during their sixth ovulatory CC cycle were not available for all included women. In women with six failed ovulatory cycles on CC and an EMT ≤ 7 mm in the sixth cycle, we advise switching to gonadotropins, since it improves live birth rate over continuing treatment with CC at an extra cost of €9709 to achieve one additional live birth. If the EMT & 7 mm, we advise to continue treatment with CC, since live birth rates are similar to those with gonadotropins, without the extra costs. The original MOVIN trial received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). C.B.L.A. reports unrestricted grant support from Merck and Ferring. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva, IGENOMIX and Guerbet. All other authors have nothing to declare. Netherlands Trial Register, number NTR1449
Publisher: Wiley
Date: 26-04-2019
DOI: 10.1111/AJO.12821
Publisher: Informa UK Limited
Date: 21-03-2023
Publisher: Springer Science and Business Media LLC
Date: 23-07-2019
Publisher: JMIR Publications Inc.
Date: 22-08-2017
DOI: 10.2196/RESPROT.7224
Publisher: Wiley
Date: 02-2021
DOI: 10.1002/UOG.23117
Abstract: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins. This was a follow‐up study of two large randomized controlled trials (PROBAAT‐1 and PROBAAT‐2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30‐mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT‐1 and oral misoprostol in PROBAAT‐2). Data on subsequent ongoing pregnancies 16 weeks’ gestation were collected from hospital charts from clinics participating in this follow‐up study. The main outcome measure was preterm birth 37 weeks’ gestation in a subsequent pregnancy. Fourteen hospitals agreed to participate in this follow‐up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow‐up. In total, 251 and 258 women had a known subsequent pregnancy 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93 95% CI, 0.38–2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03 95% CI, 0.30–3.51). In women with term singleton pregnancy, induction of labor using a 30‐mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Wiley
Date: 19-01-2020
DOI: 10.1111/AOGS.13770
Publisher: Wiley
Date: 08-12-2019
DOI: 10.1111/AOGS.13771
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.PREGHY.2020.06.005
Abstract: To develop consensus definitions for the core outcome set for pre-ecl sia. Potential definitions for in idual core outcomes were identified across four formal definition development initiatives, nine national and international guidelines, 12 Cochrane systematic reviews, and 79 randomised trials. Eighty-six definitions were entered into the consensus development meeting. Ten healthcare professionals and three researchers, including six participants who had experience of conducting research in low- and middle-income countries, participated in the consensus development process. The final core outcome set was approved by an international steering group. Consensus definitions were developed for all core outcomes. When considering stroke, pulmonary oedema, acute kidney injury, raised liver enzymes, low platelets, birth weight, and neonatal seizures, consensus definitions were developed specifically for low- and middle-income countries because of the limited availability of diagnostic interventions including computerised tomography, chest x-ray, laboratory tests, equipment, and electroencephalogram monitoring. Consensus on measurements for the pre-ecl sia core outcome set will help to ensure consistency across future randomised trials and systematic reviews. Such standardization should make research evidence more accessible and facilitate the translation of research into clinical practice. Video abstract can be available at: /ftrgvrfu0u9glqd/6.%20Standardising%20definitions%20in%20teh%20pre-ecl sia%20core%20outcome%20set%3A%20a%20consensus%20development%20study.mp4?dl=0.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.RBMO.2018.11.034
Abstract: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China? Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster s ling strategy. Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy. The prevalence of infertility in China is high, but the uptake of treatment is relatively low.
Publisher: Public Library of Science (PLoS)
Date: 02-2022
DOI: 10.1371/JOURNAL.PMED.1003892
Abstract: Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia grade 1, intraventricular hemorrhage grade 2, necrotising enterocolitis stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin ( n = 204) or placebo ( n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% ( n = 9) versus 2.6% ( n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered s le size due to the lower than expected preterm birth rates. In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. Dutch Trial Register (NL5553, NTR5675) www.trialregister.nl/trial/5553 .
Publisher: MDPI AG
Date: 14-10-2019
DOI: 10.3390/NU11102446
Abstract: Women’s lifestyle has important implications for the development and health of their offspring. Yet little is known about the association between women’s preconception dietary intake and physical activity with cardiovascular health of the offspring. We therefore examined this association in a group of Dutch women with overweight or obesity (BMI ≥ 29 kg/m2) and infertility, who participated in a 6-month randomized preconception lifestyle intervention trial, and their offspring (n = 46). Preconception dietary intake and physical activity were assessed during the 6-month intervention using a food frequency questionnaire and the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH), respectively. Offspring cardiovascular health (i.e., BMI, waist:height ratio, systolic and diastolic blood pressure, fat and fat free mass, and pulse wave velocity) was measured at age 3–6 years. Multivariable linear regression analyses were used to examine the associations between preconception lifestyle and offspring cardiovascular health. Higher preconception vegetable intake (per 10 g/day) was associated with lower offspring diastolic blood pressure (Z-score: −0.05 (−0.08 −0.01) p = 0.007) and higher preconception fruit intake (per 10 g/day) was associated with lower offspring pulse wave velocity (−0.05 m/s (−0.10 −0.01) p = 0.03). Against our expectations, higher preconception intake of sugary drinks was associated with a higher offspring fat free mass (0.54 kg (0.01 1.07) p = 0.045). To conclude, preconception dietary intake is associated with offspring health.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
Publisher: Elsevier BV
Date: 11-2020
Publisher: Oxford University Press (OUP)
Date: 05-2020
Abstract: Does exposure to preconceptional hysterosalpingography (HSG) with iodinated oil-based contrast affect neonatal thyroid function as compared to iodinated water-based contrast? Preconceptional HSG with iodinated contrast did not influence the neonatal thyroid function. HSG is a commonly applied tubal patency test during fertility work-up in which either oil- or water-based contrast is used. Oil-based contrast contains more iodine compared to water-based contrast. A previous study in an East Asian population found an increased risk of congenital hypothyroidism (CH) in neonates whose mothers were exposed to high amounts of oil-based contrast during HSG. This is a retrospective data analysis of the H2Oil study, a randomized controlled trial (RCT) comparing HSG with the use of oil- versus water-based contrast during fertility work-up. After an HSG with oil-based contrast, 214 women had an ongoing pregnancy within 6 months leading to a live birth compared to 155 women after HSG with water-based contrast. Of the 369 women who had a live born infant, 208 consented to be approached for future research and 138 provided informed consent to collect data on the thyroid function tests of their offspring (n = 140). Thyroid function tests of these children were retrieved from the Dutch neonatal screening program, which includes the assessment of total thyroxine (T4) in all newborns, followed by thyroid-stimulating hormone only in those with a T4 level of ≤ −0.8 SD score. Furthermore, amount of contrast medium used and time between HSG and conception were compared between the two study groups. Data were collected from 140 neonates conceived after HSG with oil-based (n = 76) or water-based (n = 64) contrast. The median T4 concentration was 87.0 nmol/l [76.0–96.0] in the oil group and 90.0 nmol/l [78.0–106.0] in the water group (P = 0.13). None of the neonates had a positive screening result for CH. The median amount of contrast medium used was 9.0 ml [interquartile range (IQR), 6.0–11.8] in the oil-group and 10.0 ml [IQR, 7.5–14.0] in the water group (P = 0.43). No influence of the amount of contrast on the effect of contrast group on T4 concentrations was found (P-value for interaction, 0.37). A relatively small s le size and possible attrition at follow-up are limitations of this study. Although our results suggest that the use of iodinated contrast media for HSG is safe for the offspring, the impact of a decrease in maternal thyroid function on offspring neurodevelopment could not be excluded, as data on maternal thyroid function after HSG and during conception were lacking. As HSG with oil-based contrast does not affect thyroid function of the offspring, there is no reason to withhold this contrast to infertile women undergoing HSG. Future studies should investigate whether HSG with iodinated contrast influences the periconceptional maternal thyroid function and, consequently, offspring neurodevelopment. This study received no funding. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (Academic Medical Center and VU University Medical Center) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and intrepretation of the data. I.R. reports receiving travel fee from Guerbet. C.B.L. reports speakers fee from Ferring in the past and research grants from Ferring, Merck and Guerbet. K.D. reports receiving travel fee and speakers fee from Guerbet. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. V.M. reports receiving travel fee and speakers fee as well as research grants from Guerbet. The other authors do not report conflicts of interest. Netherlands Trial Register NTR 7526 (Neonates born after the H2Oil study), NTR 3270 (original H2Oil study), www.trialregister.nl
Publisher: Wiley
Date: 20-05-2019
DOI: 10.1111/AOGS.13634
Publisher: Wiley
Date: 24-08-2020
DOI: 10.1111/AJO.13220
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.RBMO.2019.01.014
Abstract: Can women be identified, on the basis of baseline patient characteristics, as having better chances of an ongoing pregnancy with FSH instead of clomiphene citrate as stimulation agent in intrauterine insemination for unexplained subfertility? A secondary analysis of a multicentre randomized controlled superiority trial the SUPER study. Between July 2013 and March 2016, couples with unexplained subfertility undergoing intrauterine inemination (IUI) were allocated to an FSH or clomiphene citrate group. Female age, body mass index, duration of subfertility, primary versus secondary subfertility, antral follicle count and total motile count were assessed. For each of these factors, a logistic regression model was developed to assess if different estimated effects of FSH versus clomiphene citrate on ongoing pregnancy occurred within strata of each factor. A total of 684 couples received 2259 IUI cycles 338 couples were allocated to FSH, of which 84 conceived leading to ongoing pregnancy and 346 couples were allocated to clomiphene citrate, of which 71 conceived leading to ongoing pregnancy. None of the treatment selection markers was associated with better ongoing pregnancy chances after IUI with FSH compared with clomiphene citrate. In couples with unexplained subfertility undergoing IUI, no baseline treatment selection markers could be identified to determine whether ovaries should be stimulated with FSH or clomiphene citrate.
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 20-08-2020
DOI: 10.1111/AJO.13227
Publisher: Wiley
Date: 11-02-2020
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.PREGHY.2019.09.005
Abstract: In recent years, there has been an increasing amount of information published on pre-ecl sia. We analyzed trends in pre-ecl sia literature between 1997 and 2016 and reported on the quality and utility of randomized controlled trials (RCTs) between 1987 and 2016. We searched PubMed for all articles containing "pre-ecl sia" or "hypertensive disorders of pregnancy" in the title between 1997 and 2016 for the general literature and between 1987 and 2016 for RCTs. An analysis was performed based on study type, languages and publications from high-impact journals. Specific to RCTs, a quality and utility analysis based on the CONSORT guidelines and a usefulness checklist was adapted. An analysis by continents and proportion of RCTs published was also performed. Bibliometric network maps were created to determine trends in pre-ecl sia literature. In total, 9654 articles were identified, with a doubling in the number of annual average publications from 310 to 655 between 1997 and 2016. This increase occurred in both English and non-English publications. There was a decline in the proportion of publications from selected high-impact journals from 22% in 1997-2001 to 8% in 2012-2016. Out of the available 130 RCTs that we analyzed, the number of RCTs published in 5-yearly periods remained relatively stable between 1987 and 2016, with quality and utility scores increasing from 24.6 and 11.6 to 31.9 and 13.3, respectively. A geographical search by continents showed that North America produced the majority of RCTs, followed by Asia and Europe. For completed pre-ecl sia trials that were registered between 2005 and 2014, only 68% resulted in peer-reviewed publications. The yearly number of publications on pre-ecl sia has substantially increased, with a stable number of high-level study types and publications from high-impact journals. The reporting quality and usefulness of RCTs relating to pre-ecl sia have improved over time.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.EJOGRB.2019.05.022
Abstract: We studied the incidence of postpartum hemorrhage and manual removal of the placenta and their recurrence rate in a subsequent pregnancy. We hypothesized that the risk of recurrence was dependent on the gestational age at first birth and whether or not a manual removal of the placenta was necessary. Knowledge on this subject can potentially improve counselling, prevention and management in obstetric care for women at risk for PPH or identify women at low risk for recurrence. This was a retrospective national cohort study consisting of women with two consecutive singleton deliveries between 1999 and 2009 in the Netherlands. A longitudinal linked national cohort with information on subsequent singleton deliveries in the Netherlands was used. Main outcome measures were: postpartum hemorrhage (defined as ≥1000 mL after vaginal delivery or Caesarean section) and manual removal of the placenta. We calculated incidence and recurrence rates of postpartum hemorrhage and manual removal of the placenta for all women and stratified by gestational age. After application of in- and exclusion criteria 359 737 women were studied. A total of 5.4% women experienced postpartum hemorrhage in the first pregnancy and 2.7% of women had a manual removal of the placenta. The risk of postpartum hemorrhage in a subsequent pregnancy was significantly higher in women with a history of postpartum hemorrhage compared to women without a previous postpartum hemorrhage (18% vs 3.9%, adjusted odds ratio 4.5 95% confidence interval 4.3-4.7). The risk of manual removal of the placenta in the second pregnancy was only 1.4% in women without a previous manual removal compared to 17% of women with a previous manual removal of the placenta. Women with a manual removal of the placenta in the first pregnancy between 32 and 37 weeks were most at risk for recurrence (adjusted odds ratio 8.9 95% confidence interval 7.2-11). Women with a previous delivery complicated by postpartum hemorrhage or manual removal of the placenta are at increased risk for recurrence. The magnitude of this risk is highest in women with deliveries beyond 32 weeks in the first pregnancy.
Publisher: Elsevier BV
Date: 08-2019
Publisher: BMJ
Date: 02-2020
DOI: 10.1136/BMJOPEN-2019-032480
Abstract: Induction of labour (IOL) is a common practice. In Australia, up to 40% of women undergoing labour induction will ultimately have a caesarean section. As a biological role for melatonin in the onset and progress of labour has been demonstrated, we aim to test the hypothesis that addition of melatonin will reduce the need for caesarean section. This is a double-blind, randomised, placebo-controlled trial in women undergoing IOL at term. We plan to randomise 722 women (1:1 ratio) to receive either melatonin (four doses of 10 mg melatonin: first dose—in the evening at the time of cervical balloon or Dinoprostone PGE 2 vaginal pessary insertion, second dose—at time of oxytocin infusion commencement, third dose—6 hours after the second dose, fourth dose—6 hours after the third dose) or placebo (same dosing regime). Participants who are having artificial rupture of the membranes only as the primary means of labour induction will receive up to three doses of the trial intervention. The primary outcome measure will be the requirement for a caesarean section. Secondary outcomes will include duration of each stage of labour and time from induction to birth, total dose of oxytocin administration, epidural rate, indication for caesarean section, rate of instrumental deliveries, birth within 24 hours of induction commencement, estimated blood loss, Apgar score at 5 min, neonatal intensive care unit admissions and participant satisfaction. Maternal melatonin levels will be measured immediately before commencement of the oxytocin intravenous infusion and 3 hours after and at the time of birth in order to determine any differences between the two trial arms. The study is conducted in accordance with the conditions of Monash Health HREC (RES-17-0000-168A). Findings from the trial will be disseminated through peer-reviewed publications and conference presentations. V.7.0, 30 July 2019. ACTRN12616000311459, Universal trial number: (UTN) U1111-1195-3515.
Publisher: Oxford University Press (OUP)
Date: 27-09-2019
Publisher: Wiley
Date: 15-04-2022
Abstract: The efficacy and safety profile of phosphodiesterase‐5 inhibitors (PDE‐5i) in pregnancy are unclear from the few relatively small erse studies that have used them. To assess the safety profile and clinical outcomes of PDE‐5i use in pregnancy. We searched Embase, PubMed, CENTRAL, Prospero and Google Scholar to identify randomised controlled trials (RCTs) reporting the use of any PDE‐5i in pregnancy up to September 2021. RCTs reporting obstetric or perinatal outcomes or maternal adverse outcomes in women taking PDE5i in pregnancy. Risk ratios (RR), 95% confidence intervals (95% CI) and 95% prediction intervals were calculated and pooled for analysis. We identified 1324 citations, of which 10 studies including 1090 participants met the inclusion criteria. Only tadalafil and sildenafil were reported as used in pregnancy. Two studies using tadalafil and eight sildenafil. Nine of ten studies were assessed at having of low risk of bias. PDE‐5i use was associated with an increased risk of headaches (RR 1.41, 95% CI 0.97–2.05), flushing (RR 2.59, 95% CI 0.69–9.90) and nasal bleeding (RR 10.53, 95% CI 1.36–81.3) an increase in vaginal birth when used for non‐fetal growth restriction (FGR) indications (RR 1.24, 95% CI 1.00–1.55) and a reduction in risk of operative birth for intrapartum fetal compromise (RR 0.58, 95% CI 0.38–0.88). There was no evidence of any increase in risk of perinatal death (RR 0.89, 95% CI 0.56–1.43). However, use for the treatment of FGR increased the risk of persistent pulmonary hypertension of the newborn (PPHN) (RR 2.52, 95% CI 1.00–6.32). This meta‐analysis suggests PDE‐5i use in pregnancy is associated with mild maternal side effects and lower risk of operative birth for intrapartum fetal distress. Prolonged use for the treatment of FGR may increase the risk of PPHN. PDE‐5i use in pregnancy is associated with mild maternal side effects, lower operative birth for intrapartum fetal distress and a possible increase in persistent pulmonary hypertension of the newborn when used for the treatment of fetal growth restriction.
Publisher: Public Library of Science (PLoS)
Date: 16-02-2021
DOI: 10.1371/JOURNAL.PONE.0245746
Abstract: The uterine cervical length is an important risk factor for preterm birth. The aim of this study was to assess cervical length distribution in women with singleton pregnancies, measured by transvaginal ultrasound between 16 and 24 weeks, and its association with population characteristics. We searched electronic databases and other sources for studies published from April 1, 1990 to July 21, 2020. Of the 2019 retrieved publications, full-text versions of 137 articles were considered. We included 77 original articles that reported cervical length measurements of 363,431 women. The main aim of this study was to identify the pattern of cervical length in different populations. We collected demographic and clinical data concerning the population, in addition to information regarding the ultrasound examination and cervical length measurement. Regarding study bias, 56 were at low risk of bias and 21 were at medium risk of bias. The meta-analysis included 57 articles with data from 158,346 women. The mean cervical length was 37.96. mm (95% CI [36.68, 39.24]). Cervical length was shorter in women from Africa and Asia, in those from low-income countries, with a lower body weight, and in those who delivered before 37 gestational weeks. We found that the cervical length from pooled studies is longer than that usually discussed in the literature. Regarding limitations, we had difficulty assessing our main variable because there was no consistent pattern in the way authors reported cervical length measurement. Another limitation was the great heterogeneity between studies. The use of a single cutoff value to define a short cervix diagnosis, an important risk factor for preterm birth, may not be correct and cervical length must be considered according to maternal population characteristics. Future studies should identify different specific curves and cutoff values for cervical length in different populations. This meta-analysis was registered in the PROSPERO database under CRD42017070246 at www.crd.york.ac.uk rospero/display_record.php?RecordID=70246 .
Publisher: Elsevier BV
Date: 10-2020
Publisher: BMJ
Date: 08-2200
DOI: 10.1136/BMJOPEN-2018-025620
Abstract: To identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment. In idual participant data meta-analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database ( ollaboration ). Preferred Reporting Items for Systematic reviews and Meta-Analysis of In idual Participant Data Statement guidelines were followed. Major electronic databases, from inception to February 2017. Randomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary). Cochrane risk of bias tool was used. Principle measures of effect were OR and regression coefficient. Of the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B −0.055 95% CI −0.098 to −0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B −0.053 95% CI −0.069 to −0.037,p .001). Physical activity based interventions did not impact GWG when stratified by education. Pregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2019
DOI: 10.1038/S41598-019-53919-3
Abstract: It is unknown whether seasonal variation influences the outcome of in vitro fertilization (IVF). Previous studies related to seasonal variation of IVF were all small s le size, and the results were conflicting. We performed a retrospective cohort study evaluating the relationship between seasonal variability and live birth rate in the year of 2014–2017. Patients were grouped into four seasons (Winter (December-February), Spring (March-May), Summer (June-August), and Autumn (September-November)) according to the day of oocyte pick-up (OPU). Multivariate logistic regression analysis was performed to evaluate association between seasonal variation and live birth. Models were adjusted for covariates including temperature, sunshine hour, infertility type, infertility duration, infertility factor and BMI. In total 38,476 women were enrolled, of which 25,097 underwent fresh cycles, 13,379 were frozen embryo transfer. Live birth rates of fresh embryo transfer were 50.36%, 53.14%, 51.94% and 51.33% for spring, summer, autumn and winter, respectively. Clinical pregnancy rate between the calendar months varied between 55.1% and 63.4% in fresh embryo transfer (ET) and between 58.8% and 65.1% in frozen embryo transfer (FET) ( P -values 0.073 and 0.220). In the unadjusted model and adjust model, seasonal variation was not associated with live birth. In conclusion, there was no significant difference of seasonal variations in the outcome of IVF with fresh embryo transfer and frozen embryo transfer.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Wiley
Date: 13-10-2020
Publisher: Wiley
Date: 30-08-2019
DOI: 10.1111/AOGS.13709
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 15-11-2019
DOI: 10.1007/S00404-019-05380-W
Abstract: To estimate the incidence of recurrence of complaints and repeated interventions after hysteroscopic treatment for abnormal uterine bleeding in premenopausal women and to determine potential predictors for re-intervention. This is a retrospective cohort study in two secondary care centers in the Netherlands. We included 313 premenopausal women who underwent hysteroscopy for complaints of abnormal uterine bleeding and who had intrauterine pathology visualized at ultrasound. The intrauterine structure was hysteroscopically removed. These women were compared with women who had a hysteroscopy for abnormal uterine bleeding, but in whom hysteroscopy showed no abnormalities. We used Chi-squared test for categorical variables and independent-s les T test for continuous variables. p Values less than 0.05 were considered to indicate statistical significance. In total, 262 women had intrauterine pathology removed at hysteroscopy 136 (52%) women had recurrence of complaints, while 101 women (39%) underwent re-intervention. Heavy menstrual bleeding at baseline and multiparity were predictive factors for recurrence of abnormal uterine bleeding and re-intervention. In the 51 women with abnormal uterine bleeding in whom hysteroscopy showed no intrauterine abnormality, 29 women (60%) had recurrence of complaints and 12 (24%) a re-intervention. In premenopausal women with abnormal uterine bleeding, treatment of intrauterine pathology often does not reduce the complaints, thus questioning the effectiveness of hysteroscopic removal of these structures.
Publisher: Wiley
Date: 05-04-2020
DOI: 10.1111/AOGS.13828
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.EJOGRB.2019.11.001
Abstract: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 5 years of age in offspring of women with mild late preterm hypertensive disorders. We studied children born during the HYPITAT-II trial, in which 704 women with a hypertensive disorder between 34 and 37 weeks of gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire (ASQ) for developmental outcome and the Child Behavior Checklist (CBCL) for behavioral problems when their child was 5 years old. Outcomes were dichotomized and analyzed by logistic regression analysis. We also assessed factors influencing development and behavior at both 2 and 5 years after a hypertensive pregnancy. Five years after the original study 322(46%) women were contacted for follow-up, of whom 148 (46%) responded. In the delivery group 22%(n = 14/65) of the children had an abnormal ASQ score compared to 21% (n = 13/62) in the expectant monitoring group (p = 0.9). Abnormal CBCL-scores were found in 19% (n = 14/72) of the children in the delivery group versus in 27% (n = 20/75) in the expectant monitoring group (p = 0.3). The main predictor of development and behavior at 2 and 5 years was fetal growth restriction (for abnormal development OR 2.1, CI 1.0-4.4 for behavior problems OR 2.2, CI 1.1-5.5). Higher maternal education decreased abnormal behavior outcomes (OR 0.5, CI 0.2-0.9) and a similar tendency was observed for developmental problems (OR 0.6, CI 0.3 - 1.1). We did not find different developmental and behavior outcomes at 5 years of age between a management policy of immediate delivery and expectant management in preterm hypertensive disorders. The increased risk of developmental delay at 2 years of age after immediate delivery, we found in the 2 year follow up study, did not persist at 5 years of age.
Publisher: Public Library of Science (PLoS)
Date: 13-05-2019
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1186/S12884-019-2513-2
Abstract: Preterm birth is the leading cause of mortality and disability in newborn and infants. Having a short cervix increases the risk of preterm birth, which can be accessed by a transvaginal ultrasound scan during the second trimester. In women with a short cervix, vaginal progesterone and pessary can both reduce this risk, which progesterone more established than cervical pessary. The aim of this study is to compare the use of vaginal progesterone alone versus the association of progesterone plus pessary to prevent preterm birth in women with a short cervix. This is a pragmatic open-label randomized controlled trial that will take place in 17 health facilities in Brazil. Pregnant women will be screened for a short cervix with a transvaginal ultrasound between 18 0/7 until 22 6/7 weeks of gestational age. Women with a cervical length below or equal to 30 mm will be randomized to the combination of progesterone (200 mg) and pessary or progesterone (200 mg) alone until 36 + 0 weeks. The primary outcome will be a composite of neonatal adverse events, to be collected at 10 weeks after birth. The analysis will be by intention to treat. The s le size is 936 women, and a prespecified subgroup analysis is planned for cervical length (= or 25 mm). Categorical variables will be expressed as a percentage and continuous variables as mean with standard deviation. Time to delivery will be assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. I n clinical practice, the combination of progesterone and pessary is common however, few studies have studied this association. The combination of treatment might act in both the biochemical and mechanical routes related to the onset of preterm birth. Brazilian Clinical Trial Registry (ReBec) RBR-3t8prz, UTN: U1111–1164-2636 , 2014/11/18.
Publisher: Oxford University Press (OUP)
Date: 02-2020
Abstract: What are the key core outcomes to be reported in studies on polycystic ovary syndrome (PCOS)? We identified 3 generic and 30 specific core outcomes in 6 specialist domains: metabolic (8), reproductive (7), pregnancy (10), oncological (1), psychological (1) and long-term outcomes (1). Research reporting PCOS is heterogeneous with high variation in outcome selection, definition and quality. Evidence synthesis and a modified Delphi method with e-surveys were used as well as a consultation meeting. Overall, 71 health professionals and 123 lay consumers (women with lived experience of PCOS and members of advocacy and peer support groups) from 17 high-, middle- and low-income countries were involved in this analysis. The final core outcome set included 3 generic outcomes (BMI, quality of life, treatment satisfaction) that are applicable to all studies on women with PCOS and 30 specific outcomes that were categorised into six specialist domains: 8 metabolic outcomes (waist circumference, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypertension, coronary heart disease, lipid profile, venous thromboembolic disease) 7 reproductive outcomes [viable pregnancy (confirmed by ultrasound including singleton, twins and higher multiples), clinical and biochemical hyperandrogenism, menstrual regularity, reproductive hormonal profile, chronic anovulation, ovulation stimulation success including the number of stimulated follicles ≥ 12 mm, incidence and severity of ovarian hyperstimulation syndrome] 10 pregnancy outcomes (live birth, miscarriage, stillbirth, neonatal mortality, gestational weight gain, gestational diabetes, preterm birth, hypertensive disease in pregnancy, baby birth weight, major congenital abnormalities) 3 psychological outcomes (depression, anxiety, eating disorders) 1 oncological (abnormal endometrial proliferation including atypical endometrial hyperplasia and endometrial cancer) and 1 outcome in the long-term domain (long-term offspring metabolic and developmental outcomes). We involved lay consumers in all stages of study through e-surveys but not through focus groups, thereby limiting our understanding of their choices. We did not address the variations in the definitions and measurement tools for some of the core outcomes. Implementing this core outcome set in future studies on women with PCOS will improve the quality of reporting and aid evidence synthesis. Evidence synthesis was funded through the Australian government, National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS, and H.T. is funded through an NHMRC fellowship. B.H.A. is funded through an NIHR lectureship. All authors have no competing interest to declare.
Publisher: Wiley
Date: 11-2020
DOI: 10.1002/UOG.22044
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.RBMO.2018.11.015
Abstract: Does pre-IVF Lipiodol Lipiodol is known to enhance natural fertility, especially amongst women with endometriosis. The effect of Lipiodol may accrue through an impact on the endometrium that enhances receptivity to implantation. A randomized controlled trial (RCT) was carried out on 70 women due to undergo IVF. Women with endometriosis or RIF in previous IVF treatments, recruited from IVF clinics in New Zealand and in Pune, India, received either Lipiodol by hysterosalpingogram or no intervention prior to IVF treatment. Between May 2009 and January 2014, 33 women were randomized to Lipiodol plus IVF and 37 to IVF alone. When pregnancies resulting from fresh embryo transfer from the IVF cycle under study were considered, live birth rates were 8/33 (24%) in the pre-IVF Lipiodol group and 11/37 (30%) in the IVF only group (relative risk [RR] 0.81 95% confidence interval [CI] 0.37 to 1.8). Live birth rates from pregnancies within 6 months were 11/33 (33%) and 12/37 (32%) in these respective groups (RR 1.03 95% CI, 0.53 to 2.0). The trial was underpowered to detect smaller differences between treatment and control groups. No evidence was found of benefit of Lipiodol prior to fresh embryo transfer in women with endometriosis or RIF. It is suggested that this treatment should not be undertaken purely as an adjuvant in IVF other than in the context of a further well-designed RCT.
Publisher: Cold Spring Harbor Laboratory
Date: 05-10-2021
DOI: 10.1101/2021.10.04.21264500
Abstract: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many settings due to the combined impacts of maternal COVID-19 disease, disruptions to maternity care, and overloaded health systems. In 2020, Melbourne endured a unique natural experiment where strict lockdown conditions were accompanied by very low COVID-19 case numbers and the maintenance of health service capacity. The aim of this study was to compare stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. Retrospective multi-centre cohort study of perinatal outcomes before and during COVID-19 lockdown Birth outcomes from all 12 public maternity hospitals in metropolitan Melbourne Singleton births without congenital anomalies from 24 weeks’ gestation. The lockdown-exposed cohort were those women for whom weeks 20- 40 of gestation would have occurred during the lockdown period of 23 March 2020 to 14 March 2021. The control cohort comprised all pregnancies in the corresponding periods one and two years prior to the exposed cohort. Odds of stillbirth, preterm birth (PTB), birth weight 3 rd centile, and iatrogenic PTB for fetal compromise, adjusting for multiple covariates. There were 24,017 births in the exposed and 50,017 births in the control group. There was a significantly higher risk of preterm, but not term, stillbirth in the exposed group compared with the control group (0.26% vs 0.18%, aOR 1.49, 95%CI 1.08 to 2.05, P = 0.015). There was also a significant reduction in preterm birth 37 weeks (5.93% vs 6.23%, aOR 0.93, 95%CI 0.87 to 0.99, P=0.03), largely mediated by a reduction in iatrogenic PTB for live births (3.01% vs 3.27%, aOR 0.89, 95%CI 0.81 to 0.98, P = 0.015), including iatrogenic PTB for suspected fetal compromise (1.25% vs 1.51%, aOR 0.79, 95%CI 0.69 to 0.91, P= 0.001). There was no significant difference in the spontaneous PTB rate between the exposed and control groups (2.69% vs 2.82%, aOR 0.94, 95%CI 0.86 to 0.1.03, P=0.25). Lockdown restrictions in a high-income setting, in the absence of high rates of COVID-19 disease, were associated with a significant increase in preterm stillbirths, and a significant reduction in iatrogenic PTB for suspected fetal compromise. This study was registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976).
Publisher: Wiley
Date: 22-11-2016
DOI: 10.1111/AOGS.13032
Abstract: This systematic review examines whether in idualized gonadotropin dosing in in vitro fertilization (IVF) leads to better outcomes with respect to safety, costs, and live birth rates compared with standard dosing. Electronic databases searched were PubMed, Embase, and Cochrane. The primary outcome was live birth rate. The secondary outcomes included pregnancy rate, costs, and safety. Papers were critically appraised by two reviewers. A total of 7022 articles were retrieved and assessed for eligibility, of which seven randomized controlled trials were selected. All studies used gonadotropin-releasing hormone agonist co-treatment. Clinical and methodological heterogeneity was present, so data could not be pooled for meta-analysis. Only one study, that mainly included women with a good prognosis, revealed an increased chance of ongoing pregnancy in the in idualized dosing group compared with standard treatment. With respect to safety, in idualized dosing might reduce the occurrence of hyper-response and ovarian hyperstimulation syndrome, without affecting the outcome of pregnancy. In predicted poor responders, higher than standard dosages do not reduce the incidence of poor response. A cost-efficacy analysis was not performed in any of the studies included. It is currently not possible to conclude whether in idualized dosing leads to higher pregnancy or live birth rates compared with standard dosing, because evidence from well-designed studies that are adequately powered for one of these outcomes is lacking. So, large well-designed studies that evaluate the impact of in idualized dosing on live birth rates are needed to assess whether in idualized dosing should become the standard in IVF practice.
Publisher: Georg Thieme Verlag KG
Date: 04-2023
Abstract: Objective To describe a reference curve for cervical length (CL) in mid-trimester twin gestations using transvaginal ultrasound (TVU) and to investigate whether short CL increases spontaneous preterm birth (sPTB) in asymptomatic twin pregnancies. Methods This was a prospective cohort study performed at 17 outpatient antenatal facilities of Brazil with women at 18 0/7 to 22 6/7 weeks of gestation who participated in a randomized clinical trial screening phase (P5 trial) between July 2015 and March 2019. TVU was performed to provide CL measurement in all screened women. Almost all women with CL ≤ 30 mm received vaginal progesterone 200mg/day and they were also randomized to receive cervical pessary or not. We considered data from the CL distribution among asymptomatic twin pregnancies and analyzed CL and its association with PTB generating receiver operating characteristics (ROC) curves and Kaplan-Meier curves. Results A total of 253 pregnant women with twins were included in the distribution curve. The mean CL was 33.7 mm and median was 35.5mm. The 10th percentile was 17.8mm. We identified a PTB rate of 73.9% (187/253) with 33.6% of sPTB 37 (85/253) and 15% (38/253) of sPTB 34 weeks. The best cutoff point to predict sPTB 37 was 24.15 mm. However, the ROC curve showed a poor performance (0.64). The Kaplan-Meier survival curves identified that only CL values ≤ 20mm were associated to sPTB 34 weeks. Conclusion A cutoff point of CL ≤ 20 mm can be interesting point to identify short cervix in Brazilian twin pregnancies. However, in Brazilian asymptomatic twin pregnancies, CL does not show a good performance to predict PTB.
Publisher: Informa UK Limited
Date: 20-11-2019
DOI: 10.1080/14767058.2017.1401606
Abstract: The objective of this study was to assess the prevalence and sociodemographic characteristics of cesarean section in Ethiopia. We used data collected for Ethiopia Demographic and Health Surveys (DHS) conducted in 2000, 2005, 2011, and 2016. A two-stage, stratified, clustered random s ling design was used to gather information from women who gave birth within the 5-year period before each of the surveys. We analyzed the data to identify sociodemographic characteristics associated with cesarean section using log-Poisson regression models. The national cesarean section rate increased from 0.7% in 2000 to 1.9% in 2016, with increases across seven of the eleven administrative regions of Ethiopia. Addis Ababa had the highest cesarean section rate (21.4%) in 2016 and the greatest increase since 2000. In the adjusted analysis, women who gave birth in private health facility had a 78.0% higher risk of cesarean section (adjusted prevalence ratio (aPR) (95% CI) 1.78 (1.22, 2.58)) compared with women who gave birth in public health facility. Having four or more births was associated with a lower risk of cesarean section compared with first births (aPR (95% CI) 0.36 (0.16, 0.79)). The Ethiopian national cesarean section rate is about 2%, but the rate varies widely among administrative regions, suggesting unequal access. Cesarean sections were highest among urban mothers, first births, births to women with higher education, and births to women from the richest quintile of household wealth.
Publisher: Wiley
Date: 24-02-2020
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 2021
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-055902
Abstract: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births 20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random ‘signals’ in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). ACTRN12620000878976 Pre-results.
Publisher: BMJ
Date: 10-2022
DOI: 10.1136/BMJOPEN-2022-063981
Abstract: Natural cycle (NC) and hormone replacement treatment (HT) are frequently used endometrial preparation protocols prior to frozen-thawed embryo transfer in ovulatory women. It is not clear which protocol results in a higher live birth rate. It has been suggested that there is an increased risk in maternal and perinatal morbidity following HT protocol due to the lack of corpus luteum. The objective of this trial is to compare the clinical outcomes of NC and HT protocols in frozen embryo transfer. COMPETE is an open-label, single-centre, randomised controlled trial targeting to recruit 888 women, with 444 women each in two arms (1:1 treatment ratio). Women undergoing in vitro fertilisation scheduled for a frozen embryo transfer and have a regular menstrual cycle are eligible. Exclusion criteria include ovulation disorders and intrauterine adhesions. The primary outcome is live birth resulting from the first frozen embryo transfer after randomisation. Secondary outcomes include biochemical pregnancy, clinical pregnancy, multiple pregnancy, ongoing pregnancy, miscarriage, endometrial thickness, cycle cancellation, gestational diabetes mellitus, hypertensive disorders of pregnancy, antepartum haemorrhage, preterm birth, birth weight, large for gestational age, congenital anomaly and perinatal mortality. The data analysis will be following the intention-to-treat principle. This study has been approved by the Institutional Review Board of Northwest women’s and children’s hospital (2020008). Written informed consent will be obtained from each participant before randomisation. The results of the trial will be presented via publications. ChiCTR2000040640.
Publisher: Authorea, Inc.
Date: 23-02-2023
DOI: 10.22541/AU.167716085.54111521/V1
Abstract: Novel Gonadotrophin Releasing Hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix, and linzagolix have assessed treatment efficacy for fibroid related heavy menstrual blood loss in comparison to placebo. Marketing authorization has already been granted by several agencies including those in Europe, the United Kingdom, and the United States. Prior to marketing authorization, the European Medicines Agency recommends that Phase III registration trails should assess treatment efficacy in a representative study population, assess relevant outcomes with a comparison to gold-standard alternative treatment options and that long-term safety data will adequately be collected. In this review, we demonstrate limitations in the trial data generated to date, namely a lack of generalizability due to the restricted population studied, the absence of any comparison to alternative treatment methods, and findings limited to specific subgroups of patients because of the type of outcomes assessed. Symptoms related to uterine fibroids adversely affect many women’s quality of life and effective medical treatments are lacking. However, despite the urgent need for effective treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness, and cost-effectiveness in a representative population compared with alternative treatment methods before introduction into mainstream clinical practice.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Wiley
Date: 21-02-2016
DOI: 10.1111/AOGS.12849
Abstract: We recently showed that a cervical pessary prevents preterm birth and reduces poor neonatal outcomes in women with a twin pregnancy and a short cervix (<38 mm). The objective of this study was to evaluate the full potential treatment effect of the pessary in the whole group and in women with a short cervix. We performed a per-protocol analysis of a multicenter randomized controlled trial (ProTWIN trial, NTR1858) where we excluded women who were allocated to the pessary but never had it placed. Women who had the pessary removed before 36 gestational weeks and did not deliver within 7 days after removal, were excluded. Analyses were performed on all women and in those with a cervical length <38 mm. In 23 (6%) women the pessary was not placed. In women with a cervical length <38 mm (25th percentile) the pessary reduced poor perinatal outcome (relative risk 0.32, 95% confidence interval 0.13-0.78) and birth at <32 weeks (relative risk 0.41, 95% confidence interval 0.20-0.87). After excluding 47 (12%) women, the time to delivery was longer in the pessary group than in the control group (whole group: hazard ratio 0.68, 95% confidence interval 0.55-0.82, cervical length <38 mm: hazard ratio 0.35, 95% confidence interval 0.22-0.57). The analysis confirms the principal findings of the intention-to-treat analysis. Time to delivery was longer in the pessary group than in the control group when censored data were used. This implies the pessary should not be removed until labor is evident.
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2018-027497
Abstract: To examine the impact of caesarean section on breastfeeding indicators—early initiation of breastfeeding, exclusive breastfeeding under 6 months and children ever breastfed (at least once)—in sub-Saharan Africa. Secondary analysis of Demographic and Health Surveys (DHS). Thirty-three low-income and middle-income countries with a survey conducted between 2010 and 2017/2018. Women aged 15–49 years with a singleton live last birth during the 2 years preceding the survey. We analysed the DHS data to examine the impact of caesarean section on breastfeeding indicators using the modified Poisson regression models for each country adjusted for potential confounders. For each breastfeeding indicator, the within-country adjusted prevalence ratios (aPR) were pooled in random-effects meta-analysis. The within-country analyses showed, compared with vaginal birth, caesarean section was associated with aPR for early initiation of breastfeeding that ranged from 0.24 (95% CI 0.17 to 0.33) in Tanzania to 0.89 (95% CI 0.78 to 1.00) in South Africa. The aPR for exclusive breastfeeding under 6 months ranged from 0.58 (95% CI 0.34 to 0.98) in Angola to 1.93 (95% CI 0.46 to 8.10) in Cote d'Ivoire, while the aPR for children ever breastfed ranged from 0.91 (95% CI 0.82 to 1.02) in Gabon to 1.02 (95% CI 0.99 to 1.04) in Gambia. The meta-analysis showed caesarean section was associated with a 46% lower prevalence of early initiation of breastfeeding (pooled aPR, 0.54 (95% CI 0.48 to 0.60)). However, meta-analysis indicated little association with exclusive breastfeeding under 6 months (pooled aPR, 0.94 (95% CI 0.88 to 1.01)) and children ever breastfed (pooled aPR, 0.98 (95% CI 0.98 to 0.99)) among caesarean versus vaginally born children. Caesarean section had a negative influence on early initiation of breastfeeding but showed little difference in exclusive breastfeeding under 6 months and children ever breastfed in sub-Saharan Africa.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
Publisher: Wiley
Date: 17-06-2019
DOI: 10.1111/CEN.14013
Abstract: Polycystic ovary syndrome (PCOS) has a prevalence of 8%-13%. Given the prevalence, erse health impacts and variation in care, rigorous evidence-based guidelines are needed in PCOS management. This systematic review with meta-analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines. Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta-analyses were conducted, where appropriate. Fifty-six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low-quality evidence in adolescents, meta-analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] -4.02 [-5.23, -2.81], P < 0.001) COCP was better than metformin for menstrual regulation (MD -0.19 [-0.25, -0.13], P < 0.00001). In low-quality evidence in adults, meta-analyses demonstrated that metformin was better than placebo for BMI (MD -0.48 [-0.94, -0.02], P = 0.04) metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti-androgen for BMI (MD -3.04 [-5.45, -0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI. This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti-androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SINY.2018.10.001
Abstract: Infants born in the late preterm period and via non-labour caesarean section in the early term period are at increased risk of respiratory morbidity when compared to their term-born counterparts. The morbidity in these infants is less frequent and severe than in early preterm infants. Antenatal corticosteroids reduce respiratory morbidity in these populations however, the magnitude of the reduction appears to be small and predominantly in the self-limiting condition of transient tachypnoea of the neonate. The smaller benefit, along with possible harmful effects of corticosteroids, raises a question about the role of antenatal corticosteroids in this population. Special obstetric populations such as twin pregnancies and pregnancies complicated by diabetes and growth restriction are at increased risk of prematurity and more vulnerable to its complications. Nevertheless, there is limited evidence regarding the benefits of corticosteroids in these populations and potential concern regarding adverse effects. We recommend an in idualised approach when administering corticosteroids at later gestations. In these specific obstetric populations, we do not currently recommend administering corticosteroids in the late preterm/early term periods until more evidence is available.
Publisher: Wiley
Date: 04-09-2019
DOI: 10.1002/UOG.20417
Abstract: The Hypertension and Preecl sia Intervention Trial At near Term-I (HYPITAT-I) randomized controlled trial showed that, in women with gestational hypertension or mild pre-ecl sia at term, induction of labor, compared with expectant management, was associated with improved maternal outcome without compromising neonatal outcome. The aim of the current study was to evaluate the impact of these findings on obstetric management and maternal and perinatal outcomes in The Netherlands. We retrieved data for the period 2000-2014 from the Dutch National Perinatal Registry, including 143 749 women with gestational hypertension or pre-ecl sia and a singleton fetus in cephalic presentation, delivered between 36 + 0 and 40 + 6 weeks of gestation (hypertensive disorder of pregnancy (HDP) group). Pregnant women without HDP were used as the reference group (n = 1 649 510). The HYPITAT-I trial was conducted between 2005 and 2008. To study the impact of HYPITAT-I, we compared rate of induction of labor, mode of delivery and maternal and perinatal outcomes in the periods before (2000-2005) and after (2008-2014) the trial. We also differentiated between hospitals that participated in HYPITAT-I and those that did not. In the HDP group, the rate of induction of labor increased from 51.1% before the HYPITAT-I trial to 64.2% after it (relative risk (RR), 1.26 95% CI, 1.24-1.27). Maternal mortality decreased from 0.022% before the trial to 0.004% after it (RR, 0.20 95% CI, 0.06-0.70) and perinatal death decreased from 0.49% to 0.27% (RR, 0.54 95% CI, 0.45-0.65), which was attributable mostly to a decrease in fetal death. Both the increase in induction rate and the reduction in hypertensive complications were more pronounced in hospitals that participated in the HYPITAT-I trial than in those that did not. Following HYPITAT-I, the rate of induction of labor also increased (by 4.6 percentage points) in the reference group however, the relative increase in the HDP group (13.1 percentage points) was significantly greater (P < 0.001 for the interaction). The reduction in maternal and perinatal deaths did not differ significantly between the HDP and reference groups. There was a decreased incidence of placental abruption in both HDP and reference groups, which was significantly greater in the HDP than in the reference group (P < 0.001 for the interaction). There was also an increased incidence of emergency Cesarean section in both HDP and reference groups however, this change was significantly greater in the reference than in the HDP group (P < 0.001 for the interaction). Following the HYPITAT-I trial, there was a higher rate of induction of labor and improved obstetric outcome in term pregnancies complicated by HDP in The Netherlands. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Springer Science and Business Media LLC
Date: 21-04-2020
DOI: 10.1186/S12884-020-02940-W
Abstract: Preterm birth is the leading cause of perinatal mortality and neonatal morbidity worldwide. Many factors have been associated with preterm birth, including parity. The aim of the present study was to investigate associations between parity and risk of spontaneous preterm birth. We conducted a retrospective study including live singleton births (≥22 weeks) of women with a first, second, third, fourth or fifth pregnancy in The Netherlands from 2010 through 2014. Our primary outcome was risk of spontaneous preterm birth 37 weeks. Secondary outcomes were spontaneous preterm birth 32 and 28 weeks. We studied 802,119 pregnancies, including 30,237 pregnancies that ended spontaneously 37 weeks. We identified an increased risk for spontaneous preterm birth 37 weeks in nulliparous women (OR 1.95, 95% CI 1.89–2.00) and women in their fifth pregnancy (OR 1.26, 95% CI 1.13–1.41) compared to women in their second pregnancy. Similar results were seen for spontaneous preterm birth 32 and 28 weeks. Our data show an independent association between nulliparity and spontaneous preterm birth 37, 32 and 28 weeks. Furthermore, we observed an increased risk for spontaneous preterm birth in women in their fifth pregnancy, with highest risk for preterm birth at early gestational age.
Publisher: Wiley
Date: 12-02-2021
DOI: 10.1002/UOG.23126
Publisher: National Institute for Health and Care Research
Date: 12-2020
DOI: 10.3310/HTA24720
Abstract: Pre-ecl sia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. To assess the performance of existing pre-ecl sia prediction models and to develop and validate models for pre-ecl sia using in idual participant data meta-analysis. We also estimated the prognostic value of in idual markers. This was an in idual participant data meta-analysis of cohort studies. Source data from secondary and tertiary care. We identified predictors from systematic reviews, and prioritised for importance in an international survey. Early-onset (delivery at 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-ecl sia. We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I 2 and τ 2 . A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of in idual predictors for pre-ecl sia as odds ratios with 95% confidence and prediction intervals. The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-ecl sia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-ecl sia, and lowest for the first-trimester clinical characteristics models to predict any pre-ecl sia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-ecl sia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-ecl sia. Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the in idual participant data. For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. This study is registered as PROSPERO CRD42015029349. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
Publisher: Public Library of Science (PLoS)
Date: 27-03-2020
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-030366
Abstract: Intracytoplasmic sperm injection (ICSI), originally introduced as add-on to in vitro fertilisation (IVF) for couples with severe male infertility, is in current clinical practice also used in couples with mild male or even unexplained infertility. However, ICSI has involved unresolved concerns regarding the selection and damage to gametes and the health conditions of the offspring, and it is also labour intensive and therefore more expensive than conventional IVF. High-quality well-powered randomised clinical trials (RCTs) comparing ICSI and IVF are lacking. We propose a multicentre, open-label RCT in 10 reproductive medical centres across China. We will study couples with non-severe male infertility (defined as a semen concentrate 5–15×10 6 /mL or sperm with a progressive motility 10%–32%) scheduled for their first or second ICSI or IVF cycle, as low fertility rate after fertilisation are more frequent in this population, which could lead to controversy about ICSI or conventional IVF for fertilisation. On the day of oocyte retrieval, eligible participants are after informed consent be randomised to undergo either ICSI or conventional IVF in a 1:1 treatment ratio. Other standard assisted reproductive treatments are similar and parallel between two groups. Our primary outcome is ongoing pregnancy leading to live birth after the first cycle with embryo transfer. To demonstrate or refute a difference of 7% between ICSI and conventional IVF, we need to include 2346 women (1173 in each intervention arm). In addition, we will follow-up neonatal outcomes after delivery to identify the influence of ICSI on offspring. Ethical approval was obtained from Peking University Third Hospital medical science research ethics committee. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. ClinicalTrials.gov registry ( NCT03298633 ).
Publisher: BMJ
Date: 06-2020
DOI: 10.1136/BMJOPEN-2019-036587
Abstract: Women with twin pregnancies and a short cervix are at increased risk for preterm birth (PTB). Given the burden of prematurity and its attendant risks, the quest for effective interventions in twins has been an area of considerable research. Studies investigating the effectiveness of cervical cerclage, cervical pessary and vaginal progesterone in preventing PTB have yielded conflicting results. The aim of this study is to compare the effectiveness of cervical pessary and cervical cerclage with or without vaginal progesterone to prevent PTB in women with twin pregnancies and a cervical length (CL) ≤ 28 mm. This multicentre, randomised clinical trial will be conducted at My Duc Hospital and My Duc Phu Nhuan Hospital, Vietnam. Asymptomatic women with twin pregnancies and a CL ≤28 mm, measured at 16–22 weeks’ gestation, will be randomised in a 1:1:1:1 ratio to receive a cerclage, pessary, cerclage plus progesterone or pessary plus progesterone. Primary outcome will be PTB weeks. Secondary outcomes will be maternal and neonatal complications. We preplanned a subgroup analysis according to CL from all women after randomisation and ided into four quartiles. Analysis will be conducted on an intention-to-treat basis. The rate of PTB weeks’ gestation in women with twin pregnancies and a cervix ≤28 mm and treated with pessary in our previous study at My Duc Hospital was 24.2%. A s le size of 340 women will be required to show or refute that cervical cerclage decreases the rate of PTB weeks by 50% compared with pessary (from 24.2% to 12.1%, α level 0.05, power 80%, 5% lost to follow-up and protocol deviation). This study is not to be powered to assess interactions between interventions. Ethical approval was obtained from the Institutional Ethics Committee of My Duc Hospital and informed patient consent was obtained before study enrolment. Results of the study will be submitted for publication in a peer-reviewed journal. NCT03863613 (date of registration: 4 March 2019).
Publisher: Wiley
Date: 16-01-2019
Publisher: Wiley
Date: 19-09-2015
DOI: 10.1111/AOGS.12757
Abstract: Pregnancies complicated by chronic hypertension are at increased risk of adverse pregnancy outcomes. To assess whether planned early delivery might prevent some of these adverse outcomes, we studied maternal and neonatal outcomes of pregnancy in women with chronic hypertension, including gestational-age-specific outcomes. We performed a retrospective, population-based cohort study, using data from the Netherlands Perinatal Register. We included women with chronic hypertension and normotensive controls who delivered a singleton without congenital anomalies in 2002-2007. We calculated crude and adjusted odds ratios (OR) with 95% CI, compared delivery and ongoing pregnancy using moving averages, and used multiple Cox regression to adjust for differences in baseline characteristics and to examine adverse neonatal outcomes across subgroups of hypertensive disorder. Main outcome measures were composite adverse maternal and neonatal outcomes. We included 3457 (0.3%) women with chronic hypertension and 984 932 normotensive controls. Women with chronic hypertension had adverse maternal outcomes more often (28.7% vs. 6.6%, adjusted OR 5.7, 95% CI 5.3-6.2). Their offspring had an increased rate of neonatal morbidity (17.4% vs. 13.2%, adjusted OR 1.2, 95% CI 1.1-1.4) but not of severe adverse neonatal outcomes (2.5% vs. 2.2%, adjusted OR 0.8, 95% CI 0.6-1.0). The increased risk of adverse maternal outcomes for ongoing pregnancy remained stable around 17% at term. The risk of severe adverse neonatal outcomes for birth was at its lowest between 38 and 40 weeks, mainly in women with iatrogenic onset of delivery. Women with chronic hypertension are at increased risk of adverse maternal and neonatal outcomes compared with controls throughout pregnancy, including at term. Our results suggest that the optimal timing of delivery might be between 38 and 40 weeks of gestation, but prospective randomized studies should confirm this.
Publisher: Public Library of Science (PLoS)
Date: 06-07-2021
DOI: 10.1371/JOURNAL.PMED.1003686
Abstract: Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. Pregnant women included in the analyses were 22 +0 to 34 +6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an in idual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016 1,783 women mean age 29.7 years median BMI 24.8 kg/m 2 67.6% White 11.7% smokers 51.8% nulliparous 10.4% with multiple pregnancy 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018 2,924 women mean age 28.2 years median BMI 25.4 kg/m 2 88.2% White 21% smokers 35.2% nulliparous 3.5% with multiple pregnancy 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R 2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R 2 of 36% (95% CI: 34% to 38%). Recalibration of the model’s intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than “treat all” or “treat none” strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry ( ISRCTN 41598423 ) and NIHR Portfolio (CPMS: 31277).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Oxford University Press (OUP)
Date: 30-04-2020
Abstract: Does septum resection improve reproductive outcomes in women with a septate uterus? In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management. The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2–2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies. We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK. We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders. In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49–1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52–1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81–3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52–3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24–1.33)). Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding. Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or in iduals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. A travel for JFWR to Chicago was supported by the Jo Kolk Studyfund. Otherwise, no specific funding was received for this study. The Department of Obstetrics and Gynaecology, University Medical Centre, Groningen, received an unrestricted educational grant from Ferring Pharmaceutical Company unrelated to the present study. BWM reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck, personal fees from Guerbet, other payment from Guerbet and grants from Merck, outside the submitted work. The other authors declare no conficts of interest. N/A
Publisher: Cold Spring Harbor Laboratory
Date: 18-05-2023
DOI: 10.1101/2023.05.16.23289144
Abstract: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. To compare the rates of adverse perinatal outcomes in twin pregnancies exposed and unexposed to lockdown restrictions in Melbourne. Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. We compared perinatal outcomes between a pre- pandemic group (‘unexposed’) and two lockdown-exposed groups: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. We analyzed routinely-collected maternity data on all twin births ≥ 20 weeks where outcomes were available for both infants. The primary outcomes were rates of preterm birth weeks and all-cause stillbirth. Multivariable log-binomial regression models were used to compare perinatal outcomes between the pre-pandemic group and women in whom weeks 20 +0 to 40 +0 of their pregnancy occurred entirely during each lockdown-exposure period. Perinatal outcomes were calculated per infant maternal outcomes were calculated per pregnancy. We included 2267 women birthing twins. Total preterm births weeks were significantly lower in the exposure 1 group compared with the pre-pandemic group (63.1% vs 68.3% respectively adjusted risk ratio, aRR 0.92 95% CI 0.87-0.98, p=0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3% aRR 0.95 95%CI 0.90- 0.99, p=0.04) and a trend to fewer iatrogenic preterm births (44.1% vs 48.1% aRR 0.97 95%CI 0.92-1.03, p=0.39). There were also significantly lower rates of preterm birth weeks in the exposure 1 group compared with the pre-pandemic group (19.9% vs 23.0%, aRR 0.93 95%CI 0.89-0.98 p=0.01). Total iatrogenic births for fetal compromise were significantly lower (13.4% vs 20.4% aRR 0.94 95%CI 0.89–0.98, p=0.01). There were fewer special care nursery admissions (38.5% vs 43.4% aRR 0.91 95%CI 0.87-0.95, p .001). There was no associated difference in all-cause stillbirths (1.5% vs 1.6% aRR 1.00 95%CI 0.99-1.01, p=0.82), birthweight rd centile (5.7% vs 6.0% aRR 1.00, 95%CI 0.98-1.02 p=0.74) or neonatal intensive care unit admissions in the exposure 1 group compared to the pre-pandemic group. In contrast, when comparing the pre-pandemic group with exposure 2 group, there was no significant difference in the rates of preterm birth or weeks. However, during exposure 2 the rate of preterm birth weeks was significantly higher (7.2% vs 4.8% aRR 1.03 95%CI 1.01-1.05, p=0.04) and infants were more likely to be admitted to a neonatal intensive care unit (25.0% vs 19.6% aRR 1.06 95%CI 1.03-1.10, p .0001) compared with the pre-pandemic period. Melbourne’s first lockdown-exposure period was associated with fewer twin preterm births and weeks without significant differences in stillbirths or adverse newborn outcomes. These lower rates were not sustained in the second exposure period. Pandemic conditions may provide important lessons for future antenatal care of twin pregnancies, including prevention of preterm birth and optimal timing of birth.
Publisher: Wiley
Date: 20-02-2023
Publisher: Massachusetts Medical Society
Date: 24-01-2019
DOI: 10.1056/NEJME1815042
Publisher: Wiley
Date: 08-02-2023
Abstract: The performance of cell‐free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear. This was a systematic review and meta‐analysis to investigate the sensitivity, specificity and positive predictive value (PPV) of cfDNA screening for CNVs. Articles published in EMBASE, PubMed or Web of Science before November 2022 were screened for inclusion. This protocol was registered with PROSPERO (23 March 2021, CRD42021250849) prior to initiation. Articles published in English, detailing diagnostic outcomes for at least 10 high‐risk CNV results with cfDNA were considered for inclusion. The PPV was calculated and pooled with random‐effects models for double‐arcsine transformed proportions, using cases with diagnostic confirmation. Overall sensitivity, specificity and a summary receiver‐operating characteristics (ROC) curve were calculated using bivariate models. The risk of bias was assessed using QUADAS‐2. In all, 63 articles were included in the final analysis, detailing 1 591 459 cfDNA results. The pooled PPV was 37.5% (95% confidence interval [CI] 30.6–44.8), with substantial statistical heterogeneity ( I 2 = 93.9%). Bivariate meta‐analysis estimated sensitivity and specificity to be 77.4% (95% CI 65.7–86.0) and 99.4% (95% CI 98.0–99.8), respectively, with an area under the summary ROC curve of 0.947 (95% CI 0.776–0.984). Approximately one‐third of women who screen high‐risk for CNVs with cfDNA will have an affected fetus. This value is of importance for screening counselling.
Publisher: Wiley
Date: 05-10-2021
DOI: 10.1111/AJO.13438
Abstract: COVID‐19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID‐19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P 0.0001). Uptake of telehealth and a shift from in‐person care has been a major contributor to maintaining pregnancy care during pandemic restrictions. However, further research is required to understand women’s perspectives and health outcomes.
Publisher: Wiley
Date: 29-12-2016
DOI: 10.1111/AOGS.13051
Abstract: If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk. We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities. We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p = 0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p < 0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, 0.45, respectively). In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.
Publisher: Wiley
Date: 09-11-2019
DOI: 10.1111/AJO.12907
Abstract: The long-acting oxytocic agent carbetocin, has been consistently shown to reduce the need for additional uterotonics at caesarean section, but not postpartum haemorrhage (PPH). While promising, current evidence is limited by heterogenicity in study design and findings. To examine whether carbetocin confers clinical or economic benefit compared to oxytocin at caesarean section in an all-risk Australian population. A retrospective cohort study was undertaken of all singleton caesarean sections at a public tertiary hospital from 2008 to 2010 (n = 2499). From 1 January 2008 to 24 March 2009 all women received prophylactic oxytocin 5-10 units slow push intravenously at delivery, after which all patients received 100 μg intravenous carbetocin. Outcomes were PPH (≥1000 mL) and the requirement of secondary uterotonics. A post hoc cost analysis was also performed. A total of 1467 and 1024 patients received carbetocin and oxytocin, respectively. Incidence of PPH ≥1000 mL was 7.8% for carbetocin compared to and 9.7% for oxytocin (odds ratio (OR) 0.79, 95% CI 0.59-1.05). Moderate blood loss >500 mL was significantly reduced with carbetocin occurring in 27.3% versus 39.4% (OR 0.57, 95% CI 0.49-0.68). There was a 20.0% reduction in secondary uterotonic treatment with carbetocin (OR 0.42, 95% CI 0.35-0.49). Average drug costs were lower with oxytocin at $4.74 versus $36.42 atient. However, the 1.9% reduction in PPH with carbetocin resulted in a $63.46 reduction in cost per patient, with a cost-effectiveness ratio of $1667 to prevent one case of PPH ≥1000 mL. Carbetocin reduced moderate blood loss >500 mL, but not PPH ≥1000 mL. Carbetocin conferred a 20% reduction in secondary uterotonic treatment, as well as lowering direct medical costs.
Publisher: Elsevier BV
Date: 06-2020
DOI: 10.1016/J.AJOG.2019.12.272
Abstract: In routine antenatal care, blood pressure is used as a screening tool for preecl sia and its associated adverse outcomes. As such women with a blood pressure greater than 140/90 mm Hg undergo further investigation and closer follow-up, whereas those with lower blood pressures receive no additional care. In the nonpregnant setting, the American College of Cardiology now endorses lower hypertensive thresholds and it remains unclear whether these lower thresholds should also be considered in pregnancy. (1) To examine the association between lower blood pressure thresholds (as per the American College of Cardiology guidelines) and pregnancy outcomes and (2) to determine whether there is a continuous relationship between blood pressure and pregnancy outcomes and identify the point of a change at which blood pressure is associated with an increased risk of such outcomes. This was a retrospective study of singleton pregnancies at Monash Health, Australia. Data were obtained with regards to maternal characteristics and blood pressure measurements at varying gestational ages. Blood pressures were then categorized as (1) mean arterial pressure and (2) normal, elevated, stage 1 and stage 2 hypertension, as per the American College of Cardiology guidelines. Multivariable regression analysis was performed to identify associations between blood pressure categories and pregnancy outcomes. This study included 18,243 singleton pregnancies. We demonstrated a positive dose-response relationship between mean arterial pressure and the development of preecl sia in later pregnancy. Across all gestational ages, the risk of preecl sia was greater in those with "elevated blood pressure" and "stage 1 hypertension" in comparison with the normotensive group (adjusted risk ratio 2.45, 95% confidence interval, 1.74-3.44 and adjusted risk ratio, 6.60 95% confidence interval, 4.98-8.73 respectively, at 34-36 weeks' gestation). There was also an association between stage 1 hypertension, preterm birth, and adverse perinatal outcomes. This study demonstrated that preecl sia and the associated adverse outcomes are not exclusive to those with blood pressures greater than 140/90 mm Hg. As such, those with prehypertensive blood pressures may also benefit from closer monitoring. Further research is essential to determine whether lowering the blood pressure threshold in pregnancy would improve detection and outcomes.
Publisher: BMJ
Date: 11-2022
DOI: 10.1136/BMJOPEN-2022-065206
Abstract: Dietary and/or physical activity interventions are often recommended for women with overweight or obesity as the first step prior to fertility treatment. However, randomised controlled trials (RCTs) so far have shown inconsistent results. Therefore, we propose this in idual participant data meta-analysis (IPDMA) to evaluate the effectiveness and safety of dietary and/or physical activity interventions in women with infertility and overweight or obesity on reproductive, maternal and perinatal outcomes and to explore if there are subgroup(s) of women who benefit from each specific intervention or their combination (treatment–covariate interactions). We will include RCTs with dietary and/or physical activity interventions as core interventions prior to fertility treatment in women with infertility and overweight or obesity. The primary outcome will be live birth. We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials and trial registries to identify eligible studies. We will approach authors of eligible trials to contribute in idual participant data (IPD). We will perform risk of bias assessments according to the Risk of Bias 2 tool and a random-effects IPDMA. We will then explore treatment–covariate interactions for important participant-level characteristics. Formal ethical approval for the project (Venus-IPD) was exempted by the medical ethics committee of the University Medical Center Groningen (METc code: 2021/563, date: 17 November 2021). Data transfer agreement will be obtained from each participating institute/hospital. Outcomes will be disseminated internationally through the collaborative group, conference presentations and peer-reviewed publication. CRD42021266201.
Publisher: Wiley
Date: 03-01-2017
DOI: 10.1111/AOGS.13059
Abstract: Large practice variation exists in mode of delivery after cesarean section, suggesting variation in implementation of contemporary guidelines. We aim to evaluate this practice variation and to what extent this can be explained by risk factors at patient level. This retrospective cohort study was performed among 17 Dutch hospitals in 2010. Women with one prior cesarean section without a contraindication for a trial of labor were included. We used multivariate logistic regression analysis to develop models for risk factor adjustments. One model was derived to adjust the elective repeat cesarean section rates a second model to adjust vaginal birth after cesarean rates. Standardized rates of elective repeat cesarean section and vaginal birth after cesarean per hospital were compared. Pseudo-R In all, 1068 women had a history of cesarean section, of whom 71% were eligible for inclusion. A total of 515 women (67%) had a trial of labor, of whom 72% delivered vaginally. The elective repeat cesarean section rate at hospital level ranged from 6 to 54% (mean 29.8, standard deviation 11.8%). Vaginal birth after cesarean rates ranged from 50 to 90% (mean 71.8%, standard deviation 11.1%). More than 85% of this practice variation could not be explained by risk factors at patient level. A large practice variation exists in elective repeat cesarean section and vaginal birth after cesarean rates that can only partially be explained by risk factors at patient level.
Publisher: Wiley
Date: 05-02-2018
DOI: 10.1002/UOG.18809
Publisher: Elsevier BV
Date: 06-2021
DOI: 10.1016/J.EJOGRB.2021.04.018
Abstract: In 2019, a randomized controlled trial (RCT) authored by Dr. Ismail was retracted due to concerns about data integrity. Since there are no policies in place to investigate other publications of authors of retracted studies, we investigated Dr. Ismail's other trials. We searched for RCTs authored by Dr. Ismail. We made pairwise comparisons of values in baseline and outcome tables between trials. We assessed whether the distributions of baseline characteristics were compatible with properly conducted randomization, using Monte Carlo simulations and the Kolmogorov-Smirnov test. We read the publications carefully for unusual features. Dr. Ismail was author in eight published and one unpublished trial. In three of his first author studies we found multiple identical values in the baseline and/or outcome tables from different trials. At least some of the trials were unlikely to have followed a proper randomization process. There were a number of other unusual features in the papers we reviewed. It is probable that other trials published by Dr. Ismail contain questionable data. We call for a thorough investigation of the original trial data and related official documents. Our exercise suggests that the practice to assess research integrity should include all publications of authors with retracted fabricated articles.
Publisher: BMJ
Date: 07-2021
DOI: 10.1136/BMJOPEN-2020-046927
Abstract: The anti-Mullerian hormone (AMH) test has been promoted as a way to inform women about their future fertility. However, data consistently show the test is a poor predictor of natural fertility potential for an in idual woman. As fertility centre websites are often a primary source of information for reproductive information, it is essential the information provided is accurate and reflects the available evidence. We aimed to systematically record and categorise information about the AMH test found on Australian and New Zealand fertility clinic websites. Content analysis of online written information about the AMH test on fertility clinic websites. Accredited Australian and New Zealand fertility clinic websites. Data were extracted between April and June 2020. Any webpage that mentioned the AMH test, including blogs specifically about the AMH test posted since 2015, was analysed and the content categorised. Of the 39 active accredited fertility clinics’ websites, 25 included information about the AMH test. The amount of information varied widely, and embodied four overarching categories (1) the utility of the AMH test, (2) who the test is suitable for, (3) possible actions in response to the test and (4) caveats and limitations of the test. Eight specific statements about the utility of the test were identified, many of which are not evidence-based. While some websites were transparent regarding the test’s limitations, others mentioned no caveats or included persuasive statements actively promoting the test as empowering for a range of women in different circumstances. Several websites had statements about the utility of the AMH test that are not supported by the evidence. This highlights the need for higher standards for information provided on fertility clinic websites to prevent women being misled to believe the test can reliably predict their fertility.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.EJOGRB.2019.02.035
Abstract: To assess the capacity of transvaginal hydrolaparoscopy (THL) versus hysterosalpingography (HSG) as a primary tool to diagnose tubal pathology. We performed a multicenter RCT (NTR3462) in 4 teaching hospitals in the Netherlands, comparing THL and HSG as first line tubal test in subfertile women. The primary outcome of the trial was cumulative live birth rate at 24 months. Here, we present the secondary outcomes, the diagnostic findings of both THL and HSG as well as performance defined as failures, complications and pain- and acceptability scores. Between May 2013 and October 2016, we allocated 149 women to THL and 151 to HSG, of which 17 women in the THL group (11.4%) and 12 in the HSG group (7.9%) conceived naturally before the scheduled procedure, while 13 HSGs and 5 THLs were not performed for other reasons (withdrawal of informed consent, not willing to undergo tubal testing and protocol violations). A total of 119 THLs and 134 HSGs were carried out. Failures were seen more in the THL group (n = 8, 5.6%) than in the HSG group (n = 1, 0.7%) (p = 0.014). Complications did not differ significantly between the groups (THL n = 4 2.8% vs HSG n = 1 0.7%) (p = 0.20). Bilateral tubal occlusion was detected in one versus three women (0.9% versus 2.2%) of the THL group and HSG group, while unilateral tubal occlusion was detected in seven (6.2%) versus eight (5.9%) women, respectively. Normal findings were seen in 96 (79.3%) women randomised to THL and in 119 (87.5%) in women randomised for HSG (RR 0.91 95%CI 0.81-1.01, p = 0.08). The pain score was significantly less for THL (VAS 4.7 (SD: 2.5)) than for HSG (VAS 5.4 (SD:2.5)) (p 0.038). The acceptability rate of THL and was high and comparable. THL and HSG have a comparable capacity in diagnosing tubal pathology with comparable performance in safety, pain and acceptability.
Publisher: Wiley
Date: 29-03-2020
Publisher: Informa UK Limited
Date: 31-03-2023
Publisher: Wiley
Date: 30-05-2021
Abstract: To assess the association of baseline anti‐Müllerian hormone (AMH) levels with ovulation, time to ovulation and fertility outcomes in women with polycystic ovary syndrome (PCOS) receiving clomiphene citrate (CC) and compare this with placebo. Secondary analysis of the PCOSAct trial (NCT01573858). 27 trial centres in mainland China. 1000 infertile women with PCOS receiving either CC or placebo. Baseline serum AMH was measured and analysed as a continuous and as a categorical variable. Interaction between AMH and CC was tested. Predictive values of AMH for ovulation, time to ovulation and fertility outcomes were assessed. Ovulation and time to ovulation. 900 baseline AMH data were available for analysis. There were no significant interactions with ovulation or conception for AMH and CC treatment ( P = 0.782 and 0.419, respectively). Women in the upper quartile of AMH .88 ng/ml had significant lower ovulation (odds ratio [OR] 0.34, 95% CI 0.20–0.58) and conception rates (OR 0.65, 95% CI 0.42–1.00) compared with women in the lower quartile. Associations of AMH with clinical pregnancy (OR 0.98, 95% CI 0.95–1.01) and live birth (OR 0.98, 95% CI 0.96–1.01) were not significant. Ovulation rate increased until baseline AMH levels ≥7.0 ng/ml in women treated with CC but decreased when AMH increased in women with placebo. When AMH .0 ng/ml, an AMH threshold at 4.11 ng/ml predicted ovulation in women receiving CC (area under the curve [AUC] 0.64, 95% CI 0.42–0.86), with a sensitivity of 64% and a specificity of 62%, whereas prediction was poor for AMH ≥7.0 ng/ml (AUC 0.38, 95% CI 0.28–0.47). Median time to ovulation was 35 days in the lower quartile for women with placebo but this was significantly prolonged up to 98 days in the upper quartile. CC significantly shortened the time to ovulation up to 56 days. Among women with PCOS, high baseline AMH levels were associated with a 20.1% lower chance of ovulation with a 63‐day longer time to ovulation. AMH can predict ovulation only when the baseline AMH level was .0 ng/ml in women with PCOS undergoing ovulation induction with CC. Ovulation rate increased until baseline AMH levels ≥7.0 ng/ml in women treated with CC a successful ovulation and time to ovulation was highly associated with baseline AMH level in these women.
Publisher: Oxford University Press (OUP)
Date: 09-06-2023
Abstract: Ectopic pregnancy is a risk of both spontaneous and assisted reproduction pregnancies. The majority of ectopic pregnancies abnormally implant within a fallopian tube (extrauterine pregnancies). In haemodynamically stable women, medical or expectant treatment can be offered. Currently accepted medical treatment is using a drug called methotrexate. However, methotrexate has potential adverse effects, and a significant proportion of women will still require emergency surgery (up to 30%) to remove the ectopic pregnancy. Mifepristone (RU-486) has anti-progesterone effects and has a role in managing intrauterine pregnancy loss and termination of pregnancy. On reviewing the literature and given progesterone’s pivotal role in sustaining pregnancy, we propose that we may have overlooked the role of mifepristone in the medical management of tubal ectopic pregnancy in haemodynamically stable women.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 05-09-2019
Abstract: To quantify the effect of different methodological decisions on the identification of potential core outcomes to inform the development of recommendations for future core coutcome set developers. Mixed methods study. A core outcome set for pre-ecl sia was used as an exemplar. A long list of potential core outcomes was developed by undertaking a systematic review of pre-ecl sia trials and performing a thematic analysis of in-depth patient interviews. Specific methods used to generate long lists of potential core outcomes were evaluated. Different methodological decisions had a substantial impact on the identification of potential core outcomes. Extracting outcomes from published pre-ecl sia trials was an effective way of identifying 48 maternal, eight fetal, 25 neonatal outcomes, and eight patient-reported outcomes. Limiting the extraction of outcomes to primary outcomes or outcomes commonly reported in pre-ecl sia trials reduced the number and ersity of potential core outcomes identified. Thematic analysis of in-depth patient interviews ensured an additional five patient reported outcomes and six outcomes related to future child health were identified. Future core outcome set developers should use quantitative and qualitative methods when developing a long list of potential core outcomes. TWEETABLE ABSTRACT: @OfficialNIHR research published in @BJOGtweets informs new recommendations for future @coreoutcomes developers.
Publisher: Wiley
Date: 09-06-2022
DOI: 10.1111/AJO.13547
Abstract: Fetal growth restriction (FGR) is an obstetric complication associated with adverse perinatal outcomes. Doppler ultrasound can improve perinatal outcomes through monitoring at‐risk fetuses and helping time delivery. To investigate the prognostic value of different Doppler ultrasound measurements for adverse perinatal outcomes. In idual participant data. We performed a pooled analysis on in idual participant data. We compared six prognostic models using multilevel logistic regression, where each subsequent model added a new variable to a base model that included maternal characteristics. Estimated fetal weight (EFW) and four Doppler ultrasound measurements were added in turn: umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), cerebroplacental ratio (CPR), and mean uterine artery pulsatility index (mUtA PI). The primary outcome was a composite adverse perinatal outcome, defined as perinatal mortality, emergency caesarean delivery for fetal distress, or neonatal admission. Discriminative ability was quantified with area under the curve (AUC). Three data sets ( N = 3284) were included. Overall, the model that included EFW and UA PI improved AUC from 0.650 (95% CI 0.624–0.676) to 0.673 (95% CI 0.646–0.700). Adding more ultrasound measurements did not improve further the discriminative ability. In subgroup analysis, the addition of EFW and UA PI improved AUC in both preterm (AUC from 0.711 to 0.795) and small for gestational age pregnancies (AUC from 0.729 to 0.770), but they did not improve the models in term delivery or normal growth subgroups. Umbilical artery pulsatility index added prognostic value for adverse perinatal outcomes to the already available information, but the combination of other Doppler ultrasound measurements (MCA PI, CPR or UtA PI) did not improve further prognostic performance.
Publisher: Oxford University Press (OUP)
Date: 13-06-2023
Abstract: What is the anti-Mullerian hormone (AMH) test usage, awareness, and perceived reasons for testing in a representative community s le of women in Australia? : Among women aged 18–55 years, 13% had heard about AMH testing and 7% had had an AMH test, with the top three reasons for testing including due to infertility investigations (51%), considering pregnancy and wanting to understand their chances (19%) or to find out if a medical condition had affected fertility (11%). The growing availability of direct-to-consumer AMH testing has raised concerns about overuse, however as most AMH tests are paid for privately by consumers, data on test usage is not publicly available. National cross-sectional survey of 1773 women, conducted in January 2022. Females aged 18–55 years were recruited from the representative ‘Life in Australia’ probability-based population panel and completed the survey online or by telephone. Main outcome measures included if and how participants had heard about AMH testing, whether they had ever had an AMH test, main reason for testing and test access. Of the 2423 women who were invited 1773 responded (73% response rate). Of these, 229 (13%) had heard about AMH testing and 124 (7%) had had an AMH test. Testing rates were highest among those currently aged 35–39 years (14%) and associated with educational attainment. Almost all accessed the test through their general practitioner or fertility specialist. Reasons for testing were: part of an infertility investigation (51%), considering pregnancy and wanting to understand chances of conceiving (19%), finding out if a medical condition had affected fertility (11%), curiosity (9%), considering egg freezing (5%), and considering delaying pregnancy (2%). Although the s le was large and mostly representative, it was over-represented by people holding a university degree and under-represented by people aged 18–24, however, we used weighted data where possible to account for this. All data were self-reported so there is a risk of recall bias. The number of survey items was also restricted, so the type of counselling women received prior to testing, reasons for declining an AMH test or test timing were not measured. Whilst most women reported having an AMH test for appropriate reasons, about one third had it for reasons not supported by evidence. Public and clinician education about the lack of utility of AMH testing for women not undergoing infertility treatment is needed. This project was supported by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence grant (1104136) and Program grant (1113532). T.C. is supported by an NHMRC Emerging Leader Research Fellowship (2009419). B.W.M. reports research funding, consultancy and travel support from Merck. D.L. is the Medical Director of City Fertility NSW and reports consultancy for Organon, Ferring, Besins and Merck. The authors have no other competing interests. N/A.
Publisher: Wiley
Date: 19-01-2018
DOI: 10.1111/AOGS.13283
Abstract: Curettage is more effective than expectant management in women with suspected incomplete evacuation after misoprostol treatment for first-trimester miscarriage. The cost-effectiveness of curettage vs. expectant management in this group is unknown. From June 2012 until July 2014 we conducted a randomized controlled trial and parallel cohort study in the Netherlands, comparing curettage with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first-trimester miscarriage. Successful treatment was defined as a sonographic finding of an empty uterus 6 weeks after study entry, or an uneventful course. Cost-effectiveness and cost-utility analyses were performed. We included costs of healthcare utilization, informal care and lost productivity. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated using bootstrapping. We included 256 women from 27 hospitals 95 curettage and 161 expectant management. Treatment was successful in 96% of the women treated with curettage vs. 83% of the women after expectant management (mean difference 13%, 95% confidence interval 5-20). Mean costs were significantly higher in the curettage group (mean difference €1157 95% C confidence interval €955-1388). The incremental cost-effectiveness ratio for curettage vs. expectant management was €8586 per successfully treated woman. The cost-effectiveness acceptability curve showed that at a willingness-to-pay of €18 200/extra successfully treated women, the probability that curettage is cost-effective is 95%. Curettage is not cost-effective compared with expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment. This indicates that curettage in this group should be restrained.
Publisher: Oxford University Press (OUP)
Date: 05-01-2023
Abstract: Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro-conceived (IVF, ICSI or IVM) and in vivo-conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/567379
Abstract: Objective . To evaluate the relationship of physical activity (PA) and sedentary behaviour with gestational weight gain (GWG) and birth weight. Design . Combined data from two prospective studies: (1) nulliparous pregnant women without BMI restrictions and (2) overweight and obese pregnant women at risk for gestational diabetes. Methods . Daily PA and sedentary behaviour were measured with an accelerometer around 15 and at 32–35 weeks of gestation. The association between time spent in moderate-to-vigorous PA (MVPA) and in sedentary activities with GWG and birth weight was determined. Main outcome measures were GWG between 15 and 32 weeks of gestation, average GWG per week, and birth weight. Results . We studied 111 women. Early in pregnancy, 32% of women spent ≥30 minutes/day in at least moderate PA versus 12% in late pregnancy. No significant associations were found between time spent in MVPA or sedentary behaviour with GWG or birth weight. Conclusions. We found no relation between MVPA and sedentary behaviour with GWG or birth weight. The small percentage of women meeting the recommended levels of PA indicates the need to inform and support pregnant women to maintain regular PA, as there seems to be no adverse effect on birth weight and maintaining PA increases overall health.
Publisher: Wiley
Date: 05-09-2019
Publisher: Elsevier BV
Date: 10-2020
Publisher: Oxford University Press (OUP)
Date: 03-01-2023
Abstract: Several GnRH antagonist protocols are currently used during COS in the context of ART treatments however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist assisted reproduction treatment randomized controlled trial (RCT). Only studies published in English were included. The search strategy resulted in 6738 in idual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0% 6 RCTs n = 907 participants low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92 I2 = 0% 5 RCTs, n = 1318 participants low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99 moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2020
Publisher: Wiley
Date: 12-07-2021
DOI: 10.1002/UOG.23148
Abstract: To review the accuracy of different imaging modalities for the detection of rectosigmoid deep endometriosis (DE) in women with clinical suspicion of endometriosis, and to determine the optimal modality. A search was conducted using PubMed, MEDLINE, Scopus, EMBASE and Google Scholar to identify studies using imaging to evaluate women with suspected DE, published from inception to May 2020. Studies were considered eligible if they were prospective and used any imaging modality to assess preoperatively for the presence of DE in the rectum/rectosigmoid, which was then correlated with the surgical diagnosis as the reference standard. Eligibility was restricted to studies including at least 10 affected and 10 unaffected women. The QUADAS‐2 tool was used to assess the quality of the included studies. Mixed‐effects diagnostic meta‐analysis was used to determine the overall pooled sensitivity and specificity of each imaging modality for rectal/rectosigmoid DE, which were used to calculate the likelihood ratio of a positive (LR+) and negative (LR–) test and diagnostic odds ratio (DOR). Of the 1979 records identified, 30 studies (3374 women) were included in the analysis. The overall pooled sensitivity and specificity, LR+, LR– and DOR for the detection of rectal/rectosigmoid DE using transvaginal sonography (TVS) were, respectively, 89% (95% CI, 83–92%), 97% (95% CI, 95–98%), 30.8 (95% CI, 17.6–54.1), 0.12 (95% CI, 0.08–0.17) and 264 (95% CI, 113–614). For magnetic resonance imaging (MRI), the respective values were 86% (95% CI, 79–91%), 96% (95% CI, 94–97%), 21.0 (95% CI, 13.4–33.1), 0.15 (95% CI, 0.09–0.23) and 144 (95% CI, 70–297). For computed tomography, the respective values were 93% (95% CI, 84–97%), 95% (95% CI, 81–99%), 20.3 (95% CI, 4.3–94.9), 0.07 (95% CI, 0.03–0.19) and 280 (95% CI, 28–2826). For rectal endoscopic sonography (RES), the respective values were 92% (95% CI, 87–95%), 98% (95% CI, 96–99%), 37.1 (95% CI, 21.1–65.4), 0.08 (95% CI, 0.05–0.14) and 455 (95% CI, 196–1054). There was significant heterogeneity and the studies were considered methodologically poor according to the QUADAS‐2 tool. The sensitivity of TVS for the detection of rectal/rectosigmoid DE seems to be slightly better than that of MRI, although RES was superior to both. The specificity of both TVS and MRI was excellent. As TVS is simpler, faster and more readily available than the other methods, we believe that it should be the first‐line diagnostic tool for women with suspected DE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology
Publisher: Informa UK Limited
Date: 21-06-2022
DOI: 10.1080/14767058.2022.2089550
Abstract: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10 .79) and OR 1.49 (95% CI: 1.06 .10) respectively. Depression, anxiety, and PTSD symptoms are common years after HG occurred.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.RBMO.2018.11.005
Abstract: Hysterosalpingography (HSG) with an oil-based contrast has been shown to increase ongoing pregnancy rates compared with HSG with water-based contrast, but it remains unclear if an effect of HSG occurs compared with no HSG. A secondary data-analysis of a prospective cohort study among 4556 couples that presented with unexplained subfertility in 38 clinics in the Netherlands between January 2002 and December 2004. A time-varying Cox regression with inverse probability of treatment weighing was used to analyse ongoing pregnancy rates in women after undergoing the HSG procedure (with the use of either water- or oil-based contrast media) compared with women who did not undergo HSG. The probability of natural conception within 24 months after first presentation at the fertility clinic was increased after HSG, regardless of the type of contrast medium used, compared with no HSG (adjusted hazard ratio 1.48, 95% CI 1.26 to 1.73, corresponding to an absolute increase in 6-month pregnancy rate of +6%). When this analysis was limited to HSGs that were made with water-contrast, the treatment effect remained (adjusted hazard ratio 1.40, 95% CI 1.16 to 1.70). HSG increases the ongoing pregnancy rate of couples with unexplained subfertility compared with no HSG, regardless of the contrast medium used. Results need to be validated in future, preferably randomized, studies.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.RBMO.2019.02.003
Abstract: Does the addition of human growth hormone (HGH) to an IVF cycle improve the live birth rate in previously documented poor responders to FSH? Double-blind, placebo-controlled, randomized clinical trial comparing HGH to placebo in maximal stimulation in an IVF cycle. The study was stopped after 4 years. Women receiving ovarian stimulation in one IVF cycle, having failed to produce more than 5 eggs in a previous cycle with more than 250 IU/day of FSH were included. Basal FSH was ≤15 IU/l, body mass index <33 kg/m The live birth rates following an IVF cycle were 9/62 (14.5%) for growth hormone and 7/51 (13.7%) for the placebo group (risk difference 0.8%, 95% confidence interval [CI] -12.1 to 13.7% odds ratio [OR] 1.07, 95% CI 0.37-3.10). There was a greater odds of oocyte retrieval with growth hormone (OR 5.67, 95% CI 1.54-20.80) but no better chance of embryo transfer (OR 1.42, 95% CI 0.50-4.00). Birth weights were comparable. Planned participant numbers were not reached. It was not possible to demonstrate an increase in live birth rate from the addition of growth hormone in women with a previous poor ovarian response to IVF.
Publisher: Oxford University Press (OUP)
Date: 19-06-2023
Abstract: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed. This in idual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study s les, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis. A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET. Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as ‘low’ for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02–1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96–1.54] OR 1.25 [95% CI 0.99–1.57] OR 1.26 [95% CI 1.03–1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause. This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties.
Publisher: Wiley
Date: 12-03-2021
DOI: 10.1111/AOGS.14131
Abstract: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG. We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4. Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg β = 2.00, 95% CI 0.47‐3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion ( β = 1.74, 95% CI 0.36‐3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty‐one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis ( p = 0.03). Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.
Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 20-02-2023
Abstract: In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates. Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit. We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women. This trial was conducted at the Mater Mothers’ Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group. The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09 risk difference −0.02, 95% CI −0.11 to 0.07 P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82–1.11 P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96–1.72 P = 0.096) or more (RR 0.79, 95% CI 0.53–1.19 P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38 95% CI 0.69 to 2.78 P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes. Our study was single centre and did not reach the planned s le size because it was stopped prematurely at an interim analysis. We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research. Mothers’ and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. ACTRN12611000405910 19 April 2011 06 February 2012
Publisher: Elsevier BV
Date: 08-2019
Publisher: Elsevier BV
Date: 12-2020
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJOPEN-2021-054845
Abstract: Tubal patency testing is an essential part in the fertility workup of many subfertile women. Hysterosalpingography (HSG) has long been the test of choice in many clinics. There is evidence from a large randomised multicentre trial and from a recent meta-analysis that women who had HSG using oil soluble contrast medium (OSCM) had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast. However, the field is moving away from HSG and nowadays hysterosalpingo-foam sonography (Hyfosy) using ultrasound guidance is considered as the first line office tubal patency test. Therefore, a large multicentre randomised clinical trial (RCT) will be initiated to evaluate if flushing the fallopian tubes with OSCM after a normal Hyfosy showing at least one patent fallopian tube will increase the live birth rate as compared with no flushing. We plan a multicentre two arm, 1:1 randomised, open-label pragmatic comparative trial in 12 Belgian centres. After informed consent, we will randomise infertile women between 18 and 40 years of age, undergoing Hyfosy as part of the fertility workup to Hyfosy with additional tubal flushing with OSCM versus Hyfosy without additional flushing. Infertility is defined as lack of conception despite 12 months of unprotected intercourse, or three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy, all three in combination with at least one patent tube on Hyfosy. Primary endpoint will be live birth with conception within 6 months after randomisation. Approval on 11 May 2021 by the Ethics Committee from ZNA Hospital Antwerp who was the central Ethics Committee for the Clinical Trial Regulation Pilot (Pilot 412) in the 12 centres. The findings from this RCT will be disseminated in peer-reviewed publications and presentations at scientific international meetings. EudraCT number: 2020-002135-30 and NCT04379973 .
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.EJOGRB.2019.06.020
Abstract: Low-positioned placentas which are located in the lower uterine segment (LUS), either a low-lying placenta or a placenta previa, are associated with increased obstetric risks. However, most second trimester low-positioned placentas resolve during pregnancy and have a higher position in the third trimester, without posing any risks. We performed a systematic review and meta-analysis to evaluate the proportion of second trimester low-positioned placentas that have a position towards the fundus in the third trimester. Our aim was to find a cut-off value that included all women in whom the placenta will remain low in the third trimester, thus who are at increased risk of obstetric complications. Subsequently, we assessed whether an anterior or posterior placental location influenced this proportion. We searched MEDLINE and EMBASE and clinicaltrials.gov up to April 2019 for studies on the sonographic follow-up of second trimester low-positioned placentas, with a distance between the placenta and the internal os of the cervix of 20 mm or less at a gestational age of above 15 week and a follow up after 28 weeks. Studies were scored on methodological quality using the Newcastle-Ottowa Scale (NOS). A meta-analysis was conducted to summarize the proportion of second trimester low-positioned placentas with a position towards the fundus in the third trimester. We calculated the proportion at different cut-off values of the distance from the placental edge to the internal os of the cervix (0 mm, 10 mm and 20 mm). Also, anteriorly and posteriorly located placentas and women with and without a prior cesarean delivery were compared. We included 11 eligible studies which reported on 3586 women with a low-positioned placenta in the second trimester. Proportions of placentas with a position towards the fundus in the third trimester ranged between 0.63 and 1.0. Pooled proportions were 0.90 (95% CI 0.87-0.93) for IOD <10 mm and 0.80 (95% CI 0.74-0.85) for IOD < 0 mm. Due to heterogeneity between studies, the subgroup of <20 mm could not be pooled. Overall, anteriorly located placentas more often had a position towards the fundus in the third trimester, but studies did report conflicting results. Prior cesarean section had no influence except for an IOD of <0 mm, in which women without a prior cesarean delivery more often had a placenta towards the fundus. The majority of second trimester low-positioned placentas will be located towards the fundus at the time of follow-up. However, we could not determine a cut-off value for anterior and posterior placentas that included all women at high risk. The cut-off value, placental side and prior cesarean section should be assessed in a large prospective observational study.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-11-2019
Abstract: Women with a history of preecl sia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high‐risk group, remains unclear. This review aims to determine whether women with a history of preecl sia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. A systematic search of MEDLINE , EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preecl sia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preecl sia and nonpreecl sia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preecl sia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m 2 (95% CI , 2.08, 6.42) and 0.03 (95% CI , 0.01, 0.05), respectively. In comparison with the nonpreecl sia population, they also demonstrated a lower E/A and a higher E/e′ ratio with a mean difference of −0.08 (95% CI , −0.15, −0.01) and 0.84 (95% CI , 0.41, 1.27), respectively. In comparison with women who had a normotensive pregnancy, women with a history of preecl sia demonstrated a trend toward altered cardiac structure and function. Further studies with larger s le sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high‐risk population group.
Publisher: Wiley
Date: 10-03-2019
Abstract: Low-lying placentas are positioned close to the internal os of the cervix. The preferred way of delivery within this group is unclear. To review the literature on the success of a vaginal delivery with a low-lying placenta. We searched OVID EMBASE and MEDLINE for studies on vaginal delivery with a low-lying placenta. Data was extracted on successful vaginal delivery and emergency caesarean section due to haemorrhage. We distinguished between different distances between the cervical os and the placenta (internal os distance, IOD) 0-10, 11-20, and >20 mm. A meta-analysis of proportions was made for successful vaginal delivery and emergency caesarean section at every cut-off value. Maternal morbidity (i.e. antepartum blood loss, postpartum haemorrhage and blood transfusion) at different cut-off values was evaluated. Of the 999 articles retrieved, 10 articles met our inclusion criteria. A vaginal delivery was successful at an IOD of 0-10 mm in 43%, at an IOD of 11-20 mm in 85%, and at an IOD of >20 mm in 82%. A shorter IOD had a higher chance of antepartum haemorrhage, whereas a larger IOD needed postpartum blood transfusion more often. Postpartum haemorrhage did not depend on IOD. A low-lying placenta is not a contraindication for a trial of labour, and the morbidity in these women is not increased. However, women with a low-lying placenta have a higher chance of an emergency caesarean section compared with women with a placenta outside the lower uterine segment. Therefore, shared decision-making is mandatory in case of a trial of labour. This systematic review demonstrates the possibility of a vaginal delivery in women with a low-lying placenta within 20 mm of the cervix.
Publisher: BMJ
Date: 11-2019
DOI: 10.1136/BMJOPEN-2019-029101
Abstract: Preterm birth complicates million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed. We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A s le size of 760 participants (380 per group) will detect a reduction in adverse neonatal outcome from 11.95% to 6% (alpha error 0.05, beta error 0.2). A cost-effectiveness analysis will be performed from a societal perspective. This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. Nederlands Trial Register (Trial NL6469).
Publisher: Wiley
Date: 26-05-2020
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.RBMO.2019.10.011
Abstract: To evaluate the findings of outpatient transvaginal hydrolaparoscopy (THL) in comparison with diagnostic laparoscopy combined with chromopertubation in subfertile women. In a retrospective study in four large teaching hospitals, all subfertile women who underwent a THL and a conventional laparoscopy as part of their fertility work-up in the period between 2000 and 2011 were studied. Findings at THL were compared with findings at diagnostic and therapeutic laparoscopies. Tubal occlusion, endometriosis and adhesions were defined as abnormalities. Out of 1119 women, 1103 women underwent THL. A complete evaluation or incomplete but diagnostic procedure could be performed in 989 (89.7%) and 28 (2.5%), respectively. An incomplete non-diagnostic procedure was performed in 11 (1.0%) women. Failure of THL occurred in 75 women (6.8%) and 40 of these women (3.6%) subsequently underwent laparoscopy. Laparoscopy was performed in a total of 126 patients with a median time interval of 7 weeks (interquartile range [IQR] 3-13 weeks). Of 64 patients who successfully underwent both THL and laparoscopy, concordant findings were found in 53 women and discordant results in 11 women, 6 of which were caused by tubal spasm. Sensitivity of THL in detecting abnormalities was 100% and specificity was 22.2%, with a likelihood ratio of 1.29. THL in an outpatient setting can detect anatomical abnormalities comparable to the more invasive reference standard diagnostic laparoscopy. If THL succeeds, there is no need to add a diagnostic laparoscopy in the work-up.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.RBMO.2018.12.012
Abstract: What are the roles of serum progesterone and endometrial thickness as biomarkers in the decision between a freeze-only and fresh embryo transfer in IVF for women without polycystic ovary syndrome (PCOS)? This was a secondary analysis of a randomized controlled trial including 782 couples who were followed up until the end of the first completed cycle. Couples scheduled for their first or second IVF cycle with a FSH/gonadotrophin-releasing hormone antagonist protocol were randomized to a freeze-only (n = 391) or fresh embryo transfer (n = 391) strategy. The endpoint for this analysis was live birth rate (LBR) after the first embryo transfer. There was no significant difference in LBR after the first cycle between a freeze-only and fresh transfer strategy. When serum progesterone levels at trigger were in the third quartile (Q3, 1.14-1.53 ng/ml), LBR was significantly higher in the freeze-only versus fresh transfer group (P = 0.01) when serum progesterone was ≥1.14 ng/ml, LBR was significantly better in the freeze-only group (37.4% versus 23.8% in the fresh transfer group P = 0.004). LBRs in the freeze-only and fresh embryo transfer groups were similar across all quartiles of endometrial thickness, although a small advantage for freeze-only in women with a very thin endometrium could not be excluded. Serum progesterone level on the day of trigger may have potential as a biomarker on which to base a prospective decision about whether to use a freeze-only or fresh embryo transfer strategy in women undergoing IVF.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: Wiley
Date: 30-03-2020
Abstract: To develop a core outcome set for endometriosis. Consensus development study. International. One hundred and sixteen healthcare professionals, 31 researchers and 206 patient representatives. Modified Delphi method and modified nominal group technique. The final core outcome set includes three core outcomes for trials evaluating potential treatments for pain and other symptoms associated with endometriosis: overall pain improvement in the most troublesome symptom and quality of life. In addition, eight core outcomes for trials evaluating potential treatments for infertility associated with endometriosis were identified: viable intrauterine pregnancy confirmed by ultrasound pregnancy loss, including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy live birth time to pregnancy leading to live birth gestational age at delivery birthweight neonatal mortality and major congenital abnormalities. Two core outcomes applicable to all trials were also identified: adverse events and patient satisfaction with treatment. Using robust consensus science methods, healthcare professionals, researchers and women with endometriosis have developed a core outcome set to standardise outcome selection, collection and reporting across future randomised controlled trials and systematic reviews evaluating potential treatments for endometriosis. TWEETABLE ABSTRACT: @coreoutcomes for future #endometriosis research have been developed @jamesmnduffy.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.RBMO.2019.09.004
Abstract: What is the cost-effectiveness of gonadotrophins compared with clomiphene citrate in couples with unexplained subfertility undergoing intrauterine insemination (IUI) with ovarian stimulation under strict cancellation criteria? A cost-effectiveness analysis alongside a randomized controlled trial (RCT). Between July 2013 and March 2016, 738 couples were randomized to gonadotrophins (369) or clomiphene citrate (369) in a multicentre RCT in the Netherlands. The direct medical costs of both strategies were compared. Direct medical costs included costs of medication, cycle monitoring, insemination and, if applicable, pregnancy monitoring. Non-parametric bootstrap res ling was used to investigate the effect of uncertainty in estimates. The cost-effectiveness analysis was performed according to intention-to-treat. The incremental cost-effectiveness ratio (ICER) between gonadotrophins and clomiphene citrate for ongoing pregnancy and live birth was assessed. The mean costs per couple were €1534 for gonadotrophins and €1067 for clomiphene citrate (mean difference of €468 95% confidence interval [CI] €464-472). As ongoing pregnancy rates were 31% in women allocated to gonadotrophins and 26% in women allocated to clomiphene citrate (relative risk 1.16, 95% CI 0.93-1.47), the ICER was €21,804 (95% CI €11,628-31,980) per additional ongoing pregnancy with gonadotrophins and €17,044 (95% CI €8998-25,090) per additional live birth with gonadotrophins. Gonadotrophins are more expensive compared with clomiphene citrate in couples with unexplained subfertility undergoing IUI with adherence to strict cancellation criteria, without being significantly more effective.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 04-2020
Publisher: JMIR Publications Inc.
Date: 09-05-2019
DOI: 10.2196/11442
Publisher: Wiley
Date: 04-11-2019
Publisher: Wiley
Date: 04-11-2020
Publisher: Oxford University Press (OUP)
Date: 05-12-2019
Abstract: IUI for unexplained infertility can be performed in a natural cycle or in combination with ovarian stimulation. A disadvantage of ovarian stimulation is an increased risk of multiple pregnancies with its inherent maternal and neonatal complication risks. Stimulation agents for ovarian stimulation are clomiphene citrate (CC), Letrozole or gonadotrophins. Although studies have compared two or three of these drugs to each other in IUI, they have never been compared to one another in one analysis. The objective of this network meta-analysis was to compare the effectiveness and safety of IUI with CC, Letrozole or gonadotrophins with each other and with natural cycle IUI. We searched PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL and the Clinical Trial Registration Database indexed up to 16 August 2018. We included randomized controlled trials that compared a stimulation regimen with CC, Letrozole or gonadotrophins to each other or to natural cycle IUI among couples with unexplained infertility. We performed the network meta-analysis within a multivariate random effects model. We identified 26 studies reporting on 5316 women. The relative risk (RR) for live birth/ongoing pregnancy rates comparing IUI with CC to natural cycle IUI was 1.05 (95% CI 0.63–1.77, low quality of evidence), while comparing IUI with Letrozole to natural cycle IUI was 1.15 (95% CI 0.63–2.08, low quality of evidence) and comparing IUI with gonadotrophins to natural cycle IUI was 1.46 (95% CI 0.92–2.30, low quality of evidence). The RR for live birth/ongoing pregnancy rates comparing gonadotrophins to CC was 1.39 (95% CI 1.09–1.76, moderate quality of evidence), comparing Letrozole to CC was 1.09 (95% CI 0.76–1.57, moderate quality of evidence) and comparing Letrozole to gonadotrophins was 0.79 (95% CI 0.54–1.15, moderate quality of evidence). We did not perform network meta-analysis on multiple pregnancy due to high inconsistency. Pairwise meta-analyses showed an RR for multiple pregnancy rates of 9.11(95% CI 1.18–70.32) comparing IUI with gonadotrophins to natural cycle IUI. There was no data available on multiple pregnancy rates following IUI with CC or Letrozole compared to natural cycle IUI. The RR for multiple pregnancy rates comparing gonadotrophins to CC was 1.42 (95% CI 0.68–2.97), comparing Letrozole to CC was 0.97 (95% CI 0.47–2.01) and comparing Letrozole to gonadotrophins was 0.29 (95% CI 0.14–0.58). In a meta-analysis among studies with adherence to strict cancellation criteria, the RR for live births/ongoing pregnancy rates comparing gonadotrophins to CC was 1.20 (95% CI 0.95–1.51) and the RR for multiple pregnancy rates comparing gonadotropins to CC was 0.80 (95% CI 0.38–1.68). Based on low to moderate quality of evidence in this network meta-analysis, IUI with gonadotrophins ranked highest on live birth/ongoing pregnancy rates, but women undergoing this treatment protocol were also at risk for multiple pregnancies with high complication rates. IUI regimens with adherence to strict cancellation criteria led to an acceptable multiple pregnancy rate without compromising the effectiveness. Within a protocol with adherence to strict cancellation criteria, gonadotrophins seem to improve live birth/ongoing pregnancy rates compared to CC. We, therefore, suggest performing IUI with ovarian stimulation using gonadotrophins within a protocol that includes strict cancellation criteria. Obviously, this ignores the impact of costs and patients preference.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 06-2021
DOI: 10.1016/J.EJOGRB.2021.04.031
Abstract: Randomized controlled trials (RCTs) are a cornerstone for the assessment of the effectiveness of interventions. Appropriate randomization, design, s le size, statistical analyses, and conduct that reduces the risk of bias, enhance the chance they will deliver true research findings. The credibility of RCTs is difficult to assess without objective evidence of compliance with Good Clinical Practice standards. Remarkably, no mechanisms are in place both in the initial peer review process and during meta-analysis to assess these, and little guidance on how to assess data where research integrity cannot be confirmed (e.g. where data originated from a setting without established infrastructure or an era preceding current standards). We describe the case of the use of antenatal steroids. When these drugs are used in early preterm birth, their benefits outweigh the harms. However, later in pregnancy, and specifically at term, this balance is less clear. We describe that the four randomised clinical trials that inform clinical practice through the Cochrane meta-analysis, for various reasons, lack clear governance which makes it difficult to verify provenance and reliability of the data. We conclude that transparency and assessment of data credibility need to be inbuilt both at the time of publication and at the time of meta-analysis. This will drive up standards and encourage appropriate interpretation of results and the context from which they were derived.
Publisher: Oxford University Press (OUP)
Date: 30-10-2018
Publisher: Elsevier BV
Date: 09-2023
Publisher: Wiley
Date: 16-04-2019
Publisher: Georg Thieme Verlag KG
Date: 2020
Abstract: Unexplained infertility represents up to 30% of all cases of infertility. It is a diagnosis of exclusion, where no cause for infertility may be identified in the investigation of the couple, be it anovulation, fallopian tube blockage, or severe male factor. Unexplained infertility therefore cannot be considered a diagnosis to which a specific treatment is directed, rather that it indicates a failure to reach a diagnosis of the true cause of infertility. In this review, we explore the evidence base and potential limitations of the current routine infertility assessment. We also aim to highlight the importance of considering the prognosis of each in idual couple through the process of assessment and propose a reconsidered approach to treatment, targeted to the prognosis rather than the diagnosis. Ultimately, a better understanding of the mechanisms of infertility will reduce the number of couples diagnosed with “unexplained” infertility.
Publisher: Georg Thieme Verlag KG
Date: 2020
Abstract: The uterine junctional zone represents the juncture between endometrium and myometrium. The junctional zone is hormonally dependent and displays continuous peristaltic activity throughout the menstrual cycle in the nonpregnant state which is concerned with sperm transport and embryo implantation. Peristalsis may be observed using various invasive and noninvasive modalities, of which ultrasound is the most readily applied in the clinical setting. Women with pelvic pathology display alterations in uterine peristalsis which may contribute to infertility. Characterization of peristalsis in infertility subgroups, the development of a subjective peristalsis tool, and the application of potential therapeutics to an assisted reproductive treatment setting are the subject of ongoing investigation. Meta-analysis indicates a potential role for oxytocin antagonist in the improvement of fertility treatments.
Publisher: Cold Spring Harbor Laboratory
Date: 23-07-2021
DOI: 10.1101/2021.07.22.21261008
Abstract: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to the delivery of maternity care globally and has been associated with regional changes in perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne endured one of the longest and most stringent lockdowns in 2020. This paper presents the protocol for a collaborative maternity dashboard project to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. De-identified maternal and newborn outcomes will be collected monthly from all public maternity services in Melbourne, allowing rapid analysis of a multitude of perinatal indicators. Weekly outcomes will be displayed as run charts according to established methods for detecting non-random ‘signals’ in health care. A pre-pandemic median for all indicators will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≤ six consecutive weeks, all above or below the pre-pandemic median. Additional statistical analyses such as regression, time-series, and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. This study has been registered as an observational study with the Australian and New Zealand Clinical Trials Registry (ACTRN12620000878976). ⍰ This project is the first clinician-led, multi-centre perinatal data collection system for metropolitan Melbourne. ⍰ It complements the state government data collection, with the significant benefits of more timely and flexible reporting of outcomes, and granular detail on emerging areas of concern. ⍰ The study relies on primary source coding of exposure and outcomes from each hospital that have not been internally validated during the study period. ⍰ Data from private maternity hospitals, containing 25% of Melbourne births, are not available. ⍰ This resource will support data-informed hospital pandemic responses through to the end of 2022.
Publisher: Wiley
Date: 04-2019
DOI: 10.1002/UOG.20224
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 09-2021
Abstract: Do mental health and sexual function differ between women with or without polycystic ovary syndrome (PCOS) with comparable BMI and fertility characteristics? Women with PCOS have a poorer mental quality of life than women without PCOS, but there were no differences in symptoms of depression, anxiety, physical quality of life or sexual function. Various studies suggest that women with PCOS have poorer mental health, such as higher symptoms of anxiety and depression with a lower quality of life, and have an impaired sexual function compared to women without PCOS. However, in most studies, BMI and infertility status differ between women with and without PCOS, which may h er comparability. This study is a cross-sectional analysis of a 5-year follow-up of a randomized controlled trial (RCT) among women with obesity and a history of infertility. Participants in this follow-up study of an RCT were women with obesity and infertility randomized to a lifestyle intervention followed by infertility treatment or prompt infertility treatment (control), stratified by ovulatory status and trial centre. In total, 173 (30.0%) women of the 577 women randomized in the initial trial participated in this follow-up study, with a mean follow-up of 5.5 years (range 3.7–7.0 years) of these women 73 had been diagnosed with PCOS and 100 did not have PCOS. Participants completed questionnaires on symptoms of anxiety and depression (Hospital Anxiety and Depression scale (HADS)), quality of life (36-item Short Form Health Survey (SF-36)) and sexual function (McCoy Female Sexuality Questionnaire (MFSQ)). We also compared quality of life subscale scores in women with and without PCOS and compared them to an age-matched Dutch reference population with average BMI. Effect sizes were calculated to assess the differences. Symptoms of anxiety and depression, physical quality of life and sexual function did not differ significantly between obese women with and without PCOS. However, women with PCOS had a worse mental quality of life summary component score (−3.60 [95% CI −6.72 to −0.56]), mainly due to a lower score on the subscale ‘role limitations due to emotional problems’ (−12.41 [95% CI −22.78 to −2.28]), compared to women without PCOS. However, compared to an age-matched Dutch reference population, the obese infertile women with and without PCOS both scored lower on almost all physical and mental quality of life subscales. These are secondary analyses of the follow-up study of the RCT. No power analysis was performed for the outcomes included in this analysis and, as our study had a relatively small s le size, the null findings could be based on insufficient power to detect small differences between the groups. Our study population had a high mean BMI (average total group 34.5 [SD ± 5.1]) therefore, our results may only be generalizable to women with obesity. Our results indicate that PCOS status is associated with impaired mental quality of life. Anxiety and depression, physical quality of life and sexual function in obese infertile women with PCOS seem more related to the obesity than the PCOS status. The initial study and follow-up were supported by grants from: ZonMw (50-50110-96-518), the Dutch Heart Foundation (2013T085) and the European Commission (633595). The Department of Obstetrics and Gynaecology of the UMCG received an unrestricted educational grant from Ferring pharmaceuticals BV, The Netherlands, outside the submitted work. A.H. reports consultancy for Ferring pharmaceuticals. B.W.J.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.J.M. reports consultancy for ObsEva, Merck Merck KGaA, iGenomix and Guerbet. All other authors declare no competing interests. The initial trial was registered on 16 November 2008 in the Dutch trial register clinical trial registry number NTR1530.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.JCLINEPI.2019.07.016
Abstract: The objective of this study was to assess if there is evidence of publication bias in prognostic accuracy studies of middle cerebral artery (MCA) or cerebroplacental ratio (CPR) for adverse perinatal outcome. We queried PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov and searched abstract books of five perinatal conferences (1989-2017). We included prognostic accuracy studies on MCA and/or CPR. Highest reported accuracy estimates, s le size, study design, and conclusion positivity were extracted and compared. We included 127 full-text articles and 51 conference abstracts, 29 of which had not been reported as full-text article. In conference abstracts not reported in full, median negative predictive value was significantly lower compared to full-text articles (0.79 [interquartile range 0.67-0.97] vs. 0.95 [0.89-0.99] P < 0.001). No significant difference was identified for positive predictive value (0.62 vs. 0.59 P = 0.827), sensitivity (0.67 vs. 0.71 P = 0.159), and specificity (0.86 vs. 0.86 P = 0.632). Study design differed significantly as well (P = 0.030), with fewer prospective studies in conference abstracts not reported in full compared to full-text articles (28% vs. 54%). We found no significant differences in s le size or conclusion positivity. Possibly, a publication bias in previously published meta-analyses of MCA and CPR has led to overly generous estimates of prognostic performance.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cold Spring Harbor Laboratory
Date: 18-09-2020
DOI: 10.1101/2020.09.14.20194605
Abstract: To balance the costs and effects comparing a strict lockdown versus a flexible social distancing strategy for societies affected by Coronavirus-19 Disease (COVID-19). Cost-effectiveness analysis. We used societal data and COVID-19 mortality rates from the public domain. The intervention was a strict lockdown strategy that has been followed by Denmark. Reference strategy was flexible social distancing policy as was applied by Sweden. We derived mortality rates from COVID-19 national statistics, assumed the expected life years lost from each COVID-19 death to be 11 years and calculated lost life years until 31 st August 2020. Expected economic costs were derived from gross domestic productivity (GDP) statistics from each country’s official statistics bureau and forecasted GDP. The incremental financial costs of the strict lockdown were calculated by comparing Sweden with Denmark using externally available market information. Calculations were projected per one million inhabitants. In sensitivity analyses we varied the total cost of the lockdown (range −50% to +100%). Financial costs per life years saved. In Sweden, the number of people who died with COVID-19 was 577 per million inhabitants, resulting in an estimated 6,350 life years lost per million inhabitants. In Denmark, where a strict lockdown strategy was installed for months, the number of people dying with COVID-19 was on average 111 per million, resulting in an estimated 1,216 life years per million inhabitants lost. The incremental costs of strict lockdown to save one life year was US$ 137,285, and higher in most of the sensitivity analyses. Comparisons of public health interventions for COVID-19 should take into account life years saved and not only lost lives. Strict lockdown costs more than US$ 130,000 per life year saved. As our all our assumptions were in favour of strict lockdown, a flexible social distancing policy in response to COVID19 is defendable.
Publisher: Wiley
Date: 08-06-2020
Publisher: Hindawi Limited
Date: 08-2019
DOI: 10.1155/2019/2675101
Abstract: In this review, we discuss the recent literature regarding the prevention of preecl sia and aim to answer common questions that arise in the routine antenatal care of pregnant women. Prescription of low-dose aspirin for high-risk patients has been shown to reduce the risk of preecl sia (PE). A daily dose between 100 and 150 mg taken in the evening should be initiated prior to 16 weeks of gestation and can be continued until delivery. Calcium supplementation seems to be advantageous but currently it is only considered for patients with poor dietary intake and high risk for PE. Recent data about heparin are still conflicting, and therefore, heparin can currently not be recommended in the prevention of PE.
Publisher: Wiley
Date: 13-06-2016
DOI: 10.1111/AOGS.12929
Abstract: Fetal gender is associated with preterm birth however, a proper sub ision by onset of labor and corresponding neonatal outcome by week of gestation is lacking. Data from the Netherlands Perinatal Registry (1999-2010) were used to calculate relative risk ratios for gender by week of gestation and gender-related risk on adverse neonatal outcomes using a moving average technique. White European women with an alive fetus at onset of labor were included. Adverse neonatal outcomes were defined as neonatal mortality and a composite of neonatal morbidity. Onset of labor was categorized as spontaneous onset with intact membranes, premature rupture of membranes, and induction or elective cesarean section. The study population comprised 1 736 615 singleton deliveries (25(+0) -42(+6) weeks). Male fetuses were at increased risk of spontaneous preterm birth with intact membranes compared with a female fetus with a peak between 27 and 31 weeks [relative risk (RR) 1.5 95% CI 1.4-1.6]. Male fetuses were also at increased risk of preterm premature rupture of membranes between 27 and 37 weeks (RR 1.2 95% CI 1.16-1.23). No gender effect was seen for medically indicated preterm birth. No significant differences were seen for neonatal mortality. Males were at significantly increased risk of composite neonatal morbidity from 29 weeks onwards (RR 1.3 95% CI 1.3-1.4). Male fetal gender is a relevant risk factor for spontaneous preterm birth, both for intact membranes and for preterm premature rupture of membranes in white European women. In addition, male infants are at increased risk of neonatal morbidity.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2020
DOI: 10.1186/S12916-020-01766-9
Abstract: Pre-ecl sia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-ecl sia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-ecl sia using in idual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-ecl sia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-ecl sia as an outcome were included for validation. We reported the model predictive performance as discrimination ( C -statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C -statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-ecl sia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. PROSPERO ID: CRD42015029349 .
Publisher: Wiley
Date: 27-07-2021
Abstract: To compare adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) versus laparoscopy. Parallel group, 1:1 single‐centre single‐blinded randomised trial, designed as non‐inferiority study with a margin of 15%. Belgian teaching hospital. Non‐pregnant non‐virgin women with an intact uterus and without obliteration of the pouch of Douglas scheduled to undergo removal of an adnexal mass assessed to be benign on ultrasound by IOTA criteria. Randomisation to laparoscopy (control group) or vNOTES (experimental group). Stratification according to adnexal size. Blinding of participants and outcome assessors by sham incisions. The primary outcome measure was adnexectomy by the allocated technique. Secondary outcomes included duration of surgery, pain scores and analgesics used, quality of life and adverse events. We randomly assigned 67 participants (34 to the vNOTES group and 33 to the laparoscopy group). The primary end point was always reached in both groups: there were no conversions. We performed a sensitivity analysis for the primary outcome, assuming one conversion in the vNOTES group and no conversions in the laparoscopy group: the one‐sided 95% upper limit for the differences in proportions of conversion was estimated as 13%, which is below the predefined non‐inferiority margin of 15%. The secondary outcomes demonstrated a shorter duration of surgery, lower pain scores, lower total dose of analgesics and a trend for more adverse events in the vNOTES group. vNOTES is non‐inferior to laparoscopy for a successful adnexectomy without conversion. vNOTES allowed shorter operating times and less postoperative pain but there was a trend for more adverse events.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.PREGHY.2018.10.010
Abstract: To estimate preecl sia occurrence and recurrence risk in the 2nd pregnancy and analyze associated risk factors such as 1st pregnancy maximum diastolic blood pressure (maxDBP) and gestational age at delivery (GA). Linked cohort of 1st and 2nd pregnancies of 272,551 women from the Dutch Perinatal Registry collected between 2000 and 2007. We defined preecl sia as hypertension (maxDBP ≥90 mmHg or documented hypertension) plus proteinuria (≥300 mg/24 h) and analyzed its 2nd pregnancy occurrence with logistic regression. Early and late onset preecl sia were defined by delivery before and after the 34th week, respectively. Preecl sia prevalences in the 1st and 2nd pregnancies were 2.5% and 0.9%, respectively. Women with prior preecl sia had a 10.5% risk of recurrence. For women with term 1st pregnancies and maxDBP <80 mmHg, the 2nd pregnancy preecl sia rate was 0.2% (95% CI 0.17%-0.23%), while for those whom presented maxDBP ≥110 mmHg it was 4.2% (95% CI 3.6%-4.8%). First pregnancy late onset preecl sia was associated with increased preecl sia recurrence risk proportional to 1st pregnancy maxDBP: in women with a maxDBP between 100 and 109 mmHg the recurrence risk was 8.3%, while for women with a maxDBP ≥110 mmHg this risk was 11% (difference 2.7% 95% CI 1.0%-4.4%). In 1st pregnancy early onset preecl sia corresponding rates were 14.8% and 19.3% (difference 4.5% 95% CI -1.3%-9.7%). Preecl sia recurrence risk is 10%. Preecl sia risk in the 2nd pregnancy increases proportionally to 1st pregnancy maxDBP. Earlier onsets of 1st pregnancy preecl sia further increase recurrence risk.
Publisher: Public Library of Science (PLoS)
Date: 25-02-2019
Publisher: Wiley
Date: 08-04-2022
DOI: 10.1111/AJO.13527
Abstract: We evaluated the impact of the COVID‐19 pandemic and Melbourne's multiple community lockdowns (between 2020–21) on total live birth rates and preterm births in a large health network. Analysis revealed a decrease in total live birth rates following easing of initial lockdowns, and a sharp increase in births at one stage in between lockdowns. The proportion and number of preterm births ( weeks gestation) decreased at the start of initial lockdowns with the strongest decrease after the end of the second lockdown period. Births weeks gestation also decreased during lockdowns, but no significant change was identified for births weeks gestation.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 08-02-2023
DOI: 10.1111/AJO.13648
Abstract: Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity worldwide. A shortened cervix is a recognised risk factor for PTB, and amniotic fluid sludge (AFS) diagnosed on ultrasound may be suggestive of underlying inflammation or infection. The aim is to determine if azithromycin, administered in cases of a shortened cervix, results in prolongation of gestation with improvements in neonatal outcomes. We performed a retrospective cohort study at three tertiary maternity services in Melbourne, Australia, between 2015 and 2020. Women with a singleton pregnancy were included if they had a cervical length of 15 mm or less at 13–24 weeks' gestation, with or without AFS. Exclusion criteria comprised multiple pregnancy, major fetal congenital anomaly, placenta praevia, prelabour premature rupture of membranes, vaginal bleeding and/or clinical signs suggestive of chorioamnionitis at the time of diagnosis of the short cervix. The results of antibiotic treatment with azithromycin were compared to those of no antibiotic treatment. The outcomes of interest were PTB, prelabour premature rupture of membranes (PPROM), chorioamnionitis and neonatal morbidity. A total of 374 women were included in the study, of whom 129 received azithromycin and 245 received no antibiotics. When adjusting for potential confounders, the adjusted risk of PTB overall was higher in the treatment group (adjusted hazard ratio 1.36 (95% confidence interval 1.04–1.77) P = 0.023) with no differences found for PPROM, chorioamnionitis or neonatal morbidity. These data do not support the routine use of azithromycin in women with a short cervix, including those with AFS detected on ultrasound.
Publisher: BMJ
Date: 04-2020
DOI: 10.1136/BMJOPEN-2019-035334
Abstract: Polycystic ovary syndrome (PCOS) is the first common cause of anovulatory infertility. Currently, in vitro fertilisation (IVF) is recommended when conventional attempts have failed. In vitro maturation (IVM) of human oocytes is an emerging treatment option in infertile women with PCOS. It is a patient-friendly intervention, avoiding the risk of ovarian hyperstimulation syndrome, which is a serious complication of controlled ovarian stimulation in the standard IVF procedure. We plan a randomised controlled trial (RCT) to evaluate whether IVM is non-inferior to the standard IVF for live birth in women with PCOS. This is a single-centre, open-label, non-inferiority RCT performed in a large reproductive medicine centre in China. Infertile women with PCOS will be randomised to receive either IVM or standard IVF in a 1:1 treatment ratio after informed consent. IVF procedures used in our study are all standard treatments and other standard-assisted reproductive technologies will be similar between the two groups. The primary outcome is ongoing pregnancy leading to live birth within 6 months of the first oocyte retrieval cycle after randomisation. Pregnancy outcome, maternal safety and obstetric and perinatal complications will be secondary outcomes. The planned s le size is 350 (175 per group). Ethical permission was acquired from the Ethics Committee of Peking University Third Hospital. The results will be issued to publications through scientific journals and conference reports. NCT03463772 .
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 03-2019
Publisher: Wiley
Date: 24-04-2019
Publisher: Elsevier BV
Date: 11-2022
Publisher: Wiley
Date: 27-03-2019
Abstract: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. An economic analysis alongside a randomised clinical trial (the APOSTEL III study). Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)] multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.
Publisher: Oxford University Press (OUP)
Date: 15-12-2019
Abstract: In IVF/ICSI treatment, the FSH starting dose is often increased in predicted low responders from the belief that it improves the chance of having a baby by maximizing the number of retrieved oocytes. This intervention has been evaluated in several randomized controlled trials, and despite a slight increase in the number of oocytes—on average one to two more oocytes in the high versus standard dose group—no beneficial impact on the probability of a live birth has been demonstrated (risk difference, −0.02 95% CI, −0.11 to 0.06). Still, many clinicians and researchers maintain a highly ingrained belief in ‘the more oocytes, the better’. This is mainly based on cross-sectional studies, where the positive correlation between the number of retrieved oocytes and the probability of a live birth is interpreted as a direct causal relation. If the latter would be present, indeed, maximizing the oocyte number would benefit our patients. The current paper argues that the use of high FSH doses may not actually improve the probability of a live birth for predicted low responders undergoing IVF/ICSI treatment and exemplifies the flaws of directly using cross-sectional data to guide FSH dosing in clinical practice. Also, difficulties in the de-implementation of the increased FSH dosing strategy are discussed, which include the prioritization of intermediate outcomes (such as cycle cancellations) and the potential biases in the interpretation of study findings (such as confirmation or rescue bias).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2019
DOI: 10.1097/AOG.0000000000003136
Abstract: To compare the effectiveness of cervical pessary to vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and short cervix. This randomized controlled trial was conducted at My Duc Hospital, Vietnam. Asymptomatic women with twin pregnancies and cervical length less than 38 mm were randomized to Arabin pessary or vaginal progesterone (400 mg once a day) group. The primary outcome was preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse maternal and perinatal complications. We planned a subgroup analysis according to quartile of cervical length. Analysis was conducted on an intention-to-treat basis. We estimated that the primary outcome would occur in 28.4% of women treated with progesterone. Thus a total s le size of 290 women ided equally into two groups was required to detect a 14% absolute risk difference in the primary outcome between the two groups (power 80%, alpha-error 5%, 10% loss to follow-up). Between March 2016 and June 2017, we randomized 300 women, 150 women in each group. Preterm birth at less than 34 weeks of gestation occurred in 24 (16%) women in the pessary group and 33 (22%) women in the progesterone group (relative risk [RR] 0.73, 95% CI 0.46–1.18). The use of pessary significantly reduced the composite of poor perinatal outcomes (19% vs 27% RR 0.70, 95% CI 0.43–0.93). In women with cervical length of 28 mm or less (25th percentile), pessary significantly reduced the preterm birth rate at less than 34 weeks of gestation from 46% (16/35) to 21% (10/47) (RR 0.47, 95% CI 0.24–0.90) and significantly improved the composite of poor perinatal outcomes. Cervical pessary and 400 mg vaginal progesterone resulted in similar rates of preterm birth at less than 34 weeks of gestation in women with twin pregnancies and cervical length less than 38 mm. ClinicalTrials.gov, NCT02623881.
Publisher: BMJ
Date: 08-2019
DOI: 10.1136/BMJOPEN-2019-029808
Abstract: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. NTR6134 Pre-results.
Publisher: BMJ
Date: 11-2020
DOI: 10.1136/BMJOPEN-2020-038657
Abstract: The time-lapse imaging system (TLS) is a newly developed non-invasive embryo assessment system. Compared with conventional incubators, a TLS provides stable culture conditions and consistent observations of embryo development, thereby potentially improving embryo quality and selection of the best quality embryo. Although TLSs have been routinely used in many in vitro fertilisation (IVF) centres globally, there is insufficient evidence to indicate that TLSs result in higher cumulative live birth rates over conventional incubators. The purpose of this study is to compare the cumulative live birth rates and safety including miscarriage in infertile patients with diminished ovarian reserve (DOR) from both TLSs and conventional incubators. This study is a double-blind randomised controlled clinical trial (1:1 treatment ratio of TLSs vs conventional incubator). A total of 730 patients with DOR undergoing the first or second cycle of IVF or intracytoplasmic sperm injection (ICSI) will be enrolled and randomised into two parallel groups. Participants will undergo embryo culture in the TLSs (group A) or the conventional incubators (group B), respectively. Embryos are selected for transfer in both groups by the morphological characteristics. The embryo selection algorithm software is not used in the TLSs. The primary outcome is the cumulative live birth rate of the trial IVF/ICSI cycle within 12 months after randomisation. This study is powered to detect an absolute difference of 10% (35% vs 25%) at the significance level of 0.05% and 80% statistical power based on a two-sided test. This trial has been approved by the Institutional Ethical Committee of Shanghai First Maternity and Infant Hospital (KS1958). All participants in the trial will provide written informed consent. The study will be conducted according to the principles outlined in the Declaration of Helsinki and its amendments. Results of this study will be disseminated in peer-reviewed scientific journals. Chinese Clinical Trial Registry (ChiCTR1900027746).
Publisher: Wiley
Date: 22-10-2020
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 02-05-2020
Publisher: Wiley
Date: 20-07-2020
Publisher: Informa UK Limited
Date: 04-01-2019
Publisher: BMJ
Date: 06-2021
DOI: 10.1136/BMJOPEN-2020-046046
Abstract: Late preterm prelabour rupture of membranes (PROM between 34 +0 and 36 +6 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed. The PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL ( ISRCTN29313500 ) and PPROMEXIL-2 trial ( ISRCTN05689407 ), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359 total EM n=352). At 10–12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up. The study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results. NL6623 (NTR6953).
Publisher: World Scientific Pub Co Pte Lt
Date: 12-2019
DOI: 10.1142/S266131821950018X
Abstract: Background: Embryo quality is an important predictor of successful outcome in in vitro fertilization (IVF). However, current knowledge on the live birth rate after transfer of poor quality embryos is limited. This study investigated the live birth rate after transfer of only poor quality day-3 embryos in women undergoing IVF. Methods: This retrospective study included 153 couples who underwent IVF at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam between June 2014 and January 2017 and had only poor quality day-3 embryos available for fresh (n [Formula: see text] 102) or frozen (n [Formula: see text] 51) transfer. The control group included patients who had transfer of one good embryo (n [Formula: see text] 64). Embryos were rated using the Istanbul criteria. Results: In the poor quality embryo group, the mean number of oocytes retrieved and number of embryos were 7.5 ± 4.4 and 1.8 ± 0.9, respectively. Mean number of embryos transferred was 1.6 ± 0.5 in the fresh transfer group and 2.0 ± 0.2 in the freeze-only group. Live births did occur after transfer of poor quality embryos, but the implantation, clinical pregnancy and live birth rates were significantly lower than after fresh or frozen transfer of a single good quality embryo (9.5 vs. 26.6%, p 0.001 13.7 vs. 26.6%, p 0.001 and 7.2 vs. 18.8%, p [Formula: see text] 0.02, respectively). Conclusions: Live birth was achieved after transfer of only poor quality embryos in women undergoing IVF. This suggests that transfer of poor quality embryos could be an option when higher grade embryos are not available, after the chances of live birth have been discussed with the patient.
Publisher: National Institute for Health and Care Research
Date: 09-2021
DOI: 10.3310/HTA25520
Abstract: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an in idual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. Pregnant women at 22 +0 –34 +6 weeks’ gestation with signs and symptoms of preterm labour. Quantitative fetal fibronectin. Spontaneous preterm birth within 7 days. The in idual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R 2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 52. See the NIHR Journals Library website for further project information.
Publisher: BMJ
Date: 07-2023
DOI: 10.1136/BMJOPEN-2022-070950
Abstract: A uterine niche is a defect at the site of the uterine caesarean scar that is associated with gynaecological symptoms and infertility. Promising results are reported in cohort studies after a laparoscopic niche resection concerning reduction of gynaecological symptoms in relation to baseline and concerning pregnancy outcomes. However, randomised controlled trials to study the effect of a laparoscopic niche resection on reproductive outcomes in infertile women are lacking. This study will answer the question if laparoscopic niche resection in comparison to expectant management improves reproductive outcomes in infertile women with a large uterine niche. The LAPRES study is a randomised, non-blinded, controlled trial, including 200 infertile women with a total follow-up of 2 years. Women with the presence of a large niche in the uterine caesarean scar and unexplained infertility of at least 1 year or failed IVF will be randomly allocated to a laparoscopic niche resection within 6 weeks or to expectant management for at least 9 months. A large niche is defined as a niche with a depth of % of the myometrial thickness and a residual myometrium of ≤3 mm on transvaginal ultrasound. Those receiving expectant management will be allowed to receive fertility therapies, including assisted reproductive techniques, if indicated. The primary outcome is time to ongoing pregnancy, defined as a viable intrauterine pregnancy at 12 weeks’ gestation. Secondary outcome measures are time to conception leading to a live birth, other pregnancy outcomes, received fertility therapies after randomisation, menstruation characteristics, patient satisfaction, quality of life, additional interventions, and surgical and ultrasound outcomes (intervention group). Questionnaires will be filled out at baseline, 6, 12 and 24 months after randomisation. Ultrasound evaluation will be performed at baseline and at 3 months after surgery. The study protocol was approved by the medical ethics committee of the Amsterdam University Medical Centre. (Ref. No. 2017.030). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.RBMO.2019.06.013
Abstract: This systematic review and meta-analysis determined the association between aspirated after ovarian stimulation and top/good quality embryos obtained in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). MEDLINE, EMBASE, Scopus, CINAHL and Web of Science were searched for English-language publications on top/good-quality embryos at cleavage (day 2/3) and/or blastocyst (day 5/6) developmental stages, up to 18 November 2017. Twenty-eight studies (three prospective and 25 retrospective) reporting data on 291,752 assisted reproductive technology (ART) cycles were considered eligible. We confirmed a strong positive association between oocytes retrieved and top/good-quality day 2/3 embryos (weighted correlation coefficient [r
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.RBMO.2019.06.014
Abstract: The study aimed to evaluate the associations of endocrine and ultrasound characteristics with metabolic syndrome in women with polycystic ovary syndrome (PCOS), and whether these associations were modified by body mass index (BMI). The study was a secondary analysis of baseline data from a randomized controlled trial of induction of ovulation in women with PCOS. Among 947 Chinese women with PCOS, 153 (16.2%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome in women with normal (<24 kg/m The associations of endocrine characteristic with metabolic syndrome were modified by BMI in women with PCOS. Women with PCOS and normal BMI did not have an increased risk of metabolic syndrome.
Publisher: BMJ
Date: 04-2019
DOI: 10.1136/BMJOPEN-2018-025809
Abstract: Pre-ecl sia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far more fetal losses. There is no definitive treatment other than delivery. A therapeutic that could quench the disease process would be useful to treat preterm pre-ecl sia, as it could allow these pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have published preclinical data to show that metformin, a drug known to be safe in pregnancy and commonly used to treat gestational diabetes, has potent biological effects making it another promising candidate to treat pre-ecl sia. Here, we describe a phase II clinical trial to examine whether administering extended-release metformin may be effective in treating women with preterm pre-ecl sia (PI2 Trial). The PI2 Trial is a phase II, double blind, randomised controlled trial that aims to recruit 150 women with preterm pre-ecl sia (gestational age 26+0 to 31+6 weeks) who are being managed expectantly. Participants will be randomised to receive either 3 g of metformin or placebo daily. The primary outcome is time from randomisation until delivery. A delay in delivery of 5 days is assumed to be clinically relevant. The secondary outcomes will be a maternal composite and neonatal composite outcome. All other outcomes will be exploratory. We will record adverse events. This study has ethical approval (Protocol number M16/09/037 Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), is registered with the Pan African Clinical Trial Registry (PACTR201608001752102) and the South African Medicine Control Council (20170322). Data will be presented at international conferences and published in peer-reviewed journals. PACTR201608001752102 Pre-results.
Publisher: Royal College of Psychiatrists
Date: 06-12-2019
DOI: 10.1192/BJP.2019.260
Abstract: Perinatal depression and anxiety are associated with unfavourable child outcomes. To assess among women with antenatal depression or anxiety the effectiveness of prenatally initiated cognitive–behavioural therapy (CBT) on mother and child compared with care as usual (CAU). Trial registration: Netherlands Trial Register number NTR2242. Pregnant women ( n = 282) who screened positive for symptoms of depression and/or anxiety were randomised to either CBT ( n = 140) or CAU ( n = 142). The primary outcome was child behavioural and emotional problems at age 18 months, assessed using the Child Behavior Checklist (CBCL). Secondary outcomes were maternal symptoms during and up to 18 months after pregnancy, neonatal outcomes, mother–infant bonding and child cognitive and motor development at age 18 months. In total, 94 (67%) women in the CBT group and 98 (69%) in the CAU group completed the study. The mean CBCL Total Problems score was non-significantly higher in the CBT group than in the CAU group (mean difference: 1.38 (95% CI −1.82 to 4.57) t = 0.85, P = 0.399). No effects on secondary outcomes were observed except for depression and anxiety, which were higher in the CBT group than in the CAU group at mid-pregnancy. A post hoc analysis of the 98 women with anxiety disorders showed lower infant gestational age at delivery in the CBT than in the CAU group. Prenatally initiated CBT did not improve maternal symptoms or child outcomes among non-help-seeking women with antenatal depression or anxiety. Our findings are not in line with present recommendations for universal screening and treatment for antenatal depression or anxiety, and future work may include the relevance of baseline help-seeking.
Publisher: Wiley
Date: 30-04-2020
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 15-06-2020
DOI: 10.1111/DMCN.14585
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2020
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000526020
Abstract: b i Introduction: /i /b Midtrimester prelabor rupture of membranes (PROM) between 16 and 24 weeks of gestational age is a major obstetric complication with high rates of perinatal morbidity and mortality. Amnioinfusion has been proposed in women with midtrimester PROM to target oligohydramnios and subsequently enhance pulmonary development and perinatal outcomes. b i Material and Methods: /i /b The purpose of this study was to perform a systematic review and meta-analysis including all randomized clinical trials investigating amnioinfusion versus no intervention in women with PROM between 16 sup +0 /sup and 24 sup +0 /sup weeks of gestational age. Databases Central, Embase, Medline, ClinicalTrials.gov and references of identified articles were searched from inception of database to December 2021. The primary outcome was perinatal mortality. Secondary outcomes included neonatal, maternal, and long-term developmental outcomes as defined in the core outcome set for preterm birth studies. Summary measures were reported as pooled relative risk (RR) or mean difference with corresponding 95% confidence interval (CI). b i Results: /i /b Two studies (112 patients, 56 in the amnioinfusion group and 56 in the no intervention group) were included in this review. Pooled perinatal mortality was 66.1% (37/56) in the amnioinfusion group compared with 71.4% (40/56) in no intervention group (RR 0.92, 95% CI: 0.72–1.19). Other neonatal and maternal core outcomes were similar in both groups, although due to the relatively small number of events and wide CIs, there is a possibility that amnioinfusion can be associated with clinically important benefits and harms. Long-term healthy survival was seen in 35.7% (10/28) of children assessed for follow-up and treated with amnioinfusion versus 28.6% (8/28) after no intervention (RR 1.30, 95% CI: 0.47–3.60, “best case scenario”). b i Conclusions: /i /b Based on these findings, the benefits of amnioinfusion for midtrimester PROM & #x3c weeks of gestational age are unproven, and the potential harms remain undetermined.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Informa UK Limited
Date: 25-11-2018
Publisher: Oxford University Press (OUP)
Date: 23-10-2019
Abstract: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. In idual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment–covariate interaction analyses and therefore offers an opportunity for personalised medicine. We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17–1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23–1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38–2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01–1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00–1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00–1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87–1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01–1.06). In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2019
DOI: 10.1038/S41372-019-0361-6
Abstract: Our aim was to investigate the association between large-for-gestational-age and the risk of spontaneous preterm birth. We studied nulliparous women with a singleton gestation using data from the Dutch perinatal registry from 1999 to 2010. Neonates were categorized according to the Hadlock fetal weight standard, into 10th to 90th percentile, 90th to 97th percentile, or above 97th percentile. Outcomes were preterm birth <37 We included 547,418 women. The number of spontaneous preterm births p97) compared with fetuses with a normal growth (p10-p90) (11.3% vs. 7.3%, odds ratio (OR) 1.8 95% CI 1.7-1.9). The same results were found when limiting analyses to women with certain pregnancy duration (after in vitro fertilization). Large-for-gestational-age increases the risk of spontaneous preterm delivery from 25 weeks of gestation onwards.
Publisher: Wiley
Date: 07-2019
DOI: 10.1002/UOG.20117
Abstract: Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-ecl sia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-ecl sia, to identify high-value avenues for future research and to minimize future research waste in this field. MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-ecl sia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, s le size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding. From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-ecl sia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-ecl sia, 31 (24.6%) investigated genetic associations with pre-ecl sia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-ecl sia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through in idual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-ecl sia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 11-2021
DOI: 10.1002/UOG.23743
Abstract: To investigate the effect of restriction measures implemented to mitigate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission during the coronavirus disease 2019 (COVID‐19) pandemic on pregnancy duration and outcome. A before‐and‐after study was conducted with cohort s ling in three maternity hospitals in Melbourne, Australia, including women who were pregnant when restriction measures were in place during the COVID‐19 pandemic (estimated conception date between 1 November 2019 and 29 February 2020) and women who were pregnant before the restrictions (estimated conception date between 1 November 2018 and 28 February 2019). The primary outcome was delivery before 34 weeks' gestation or stillbirth. The main secondary outcome was a composite of adverse perinatal outcomes. Pregnancy outcomes were compared between women exposed to restriction measures and unexposed controls using the χ‐square test and modified Poisson regression models, and duration of pregnancy was compared between the groups using survival analysis. In total, 3150 women who were exposed to restriction measures during pregnancy and 3175 unexposed controls were included. Preterm birth before 34 weeks or stillbirth occurred in 95 (3.0%) exposed pregnancies and in 130 (4.1%) controls (risk ratio (RR), 0.74 (95% CI, 0.57–0.96) P = 0.021). Preterm birth before 34 weeks occurred in 2.4% of women in the exposed group and in 3.4% of women in the control group (RR, 0.71 (95% CI, 0.53–0.95) P = 0.022), without evidence of an increase in the rate of stillbirth in the exposed group (0.7% vs 0.9% RR, 0.83 (95% CI, 0.48–1.44) P = 0.515). Competing‐risks regression analysis showed that the effect of the restriction measures on spontaneous preterm birth was stronger and started earlier (subdistribution hazard ratio (HR), 0.81 (95% CI, 0.64–1.03) P = 0.087) than the effect on medically indicated preterm birth (subdistribution HR, 0.89 (95% CI, 0.70–1.12) P = 0.305). The effect was stronger in women with a previous preterm birth (RR, 0.42 (95% CI, 0.21–0.82) P = 0.008) than in parous women without a previous preterm birth (RR, 0.93 (95% CI, 0.63–1.38) P = 0.714) ( P for interaction = 0.044). Composite adverse perinatal outcome was less frequent in the exposed group than in controls (all women: 2.1% vs 2.9% RR, 0.73 (95% CI, 0.54–0.99) P = 0.042) women with a previous preterm birth: 4.5% vs 8.4% RR, 0.54 (95% CI, 0.25–1.18) P = 0.116). Restriction measures implemented to mitigate SARS‐CoV‐2 transmission during the COVID‐19 pandemic were associated with a reduced rate of preterm birth before 34 weeks. This reduction was mainly due to a lower rate of spontaneous prematurity. The effect was more substantial in women with a previous preterm birth and was not associated with an increased stillbirth rate. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: National Institute for Health and Care Research
Date: 06-2023
DOI: 10.3310/NNZF1037
Abstract: Tubal ectopic pregnancies can cause significant morbidity or even death. Current treatment is with methotrexate or surgery. However, methotrexate treatment can fail in approximately 30% of women. Gefitinib, an epidermal growth factor receptor inhibitor, may improve the effects of methotrexate. We assessed the efficacy of administering oral gefitinib with methotrexate, versus methotrexate alone, to treat a tubal ectopic pregnancy. To test the hypothesis a combination of gefitinib with methotrexate can increase resolution of stable tubal ectopic pregnancy without the need for surgery, compared with methotrexate alone. A randomised, double-blind, placebo-controlled, multicentre, superiority trial. Fifty UK hospitals. A target of 328 women with a stable, tubal ectopic pregnancy. Women were randomised to combination of methotrexate and gefitinib or methotrexate and placebo. All participants received a single intramuscular dose of methotrexate 50 mg/m 2 and were randomised in a 1:1 ratio of oral gefitinib (250 mg daily for 7 days) or placebo. The primary outcome was surgical intervention for resolution of ectopic pregnancy. Secondary outcomes were the need for an additional dose of methotrexate, time to resolution of the ectopic pregnancy, number of treatment-associated hospital visits, safety and tolerability, acceptability of treatment and return to menses. Between 2 November 2016 and 6 October 2021, 328 women were randomly allocated to methotrexate and gefitinib ( n = 165) or methotrexate and placebo ( n = 163). Three women in the placebo group withdrew. Surgical intervention occurred in 30% (50/165) of the gefitinib group and in 29% (47/160) of the placebo group (adjusted risk ratio 1.15, 95% confidence interval 0.85 to 1.58 adjusted risk difference −0.01, 95% confidence interval −0.10 to 0.09 p = 0.37). Without surgical intervention, median time to resolution was 28.0 days in the gefitinib group and 28.0 days in the placebo group (subdistribution hazard ratio 1.03, 95% confidence interval 0.75 to 1.40). The need for additional methotrexate doses, number of additional hospital visits, participant acceptability, time to return of menses and serious adverse events were similar in both groups. Diarrhoea and rash were more common in the gefitinib group. The addition of gefitinib to standard medical management with methotrexate to treat tubal ectopic pregnancy is not clinically effective as it does not reduce subsequent surgical intervention and is associated with higher rates of reported symptoms than placebo. We were unable to investigate how different gefitinib doses or modes of delivery would impact on the results. Questions that remain unaddressed relate to the use of methotrexate and gefitinib combination treatment for other extrauterine and uterine ectopic pregnancy, such as caesarean scar pregnancies, or in the management of choriocarcinoma. This trial is registered as ISRCTN 67795930 and EudraCT 2015-005013-76. This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme and will be published in full in Efficacy and Mechanistic Evaluation Vol. 10, No. 1. The gefitinib and placebo were supplied by Astra Zeneca. See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.YGYNO.2014.06.021
Abstract: Models to predict the probability of recurrence free survival exist for various types of malignancies, but a model for recurrence free survival in in iduals with an adult granulosa cell tumor (GCT) of the ovary is lacking. We aimed to develop and internally validate such a prognostic model. We performed a multicenter retrospective cohort study of patients with a GCT. Demographic, clinical and pathological information were considered as potential predictors. Univariable and multivariable analyses were performed using a Cox proportional hazards model. Using backward stepwise selection we identified the combination of predictors that best predicted recurrence free survival. Discrimination (c-statistic) and calibration were used to assess model performance. The model was internally validated using bootstrapping techniques to correct for overfitting. To increase clinical applicability of the model we developed a nomogram to allow in idual prediction of recurrence free survival. We identified 127 patients with a GCT (median follow-up time was 131 months (IQR 70-215)). Recurrence of GCT occurred in 81 out of 127 patients (64%). The following four variables jointly best predicted recurrence free survival clinical stage, Body Mass Index (BMI), tumor diameter and mitotic index. The model had a c-statistic of 0.73 (95% CI 0.66-0.80) and showed accurate calibration. Recurrence free survival in patients with an adult GCT of the ovary can be accurately predicted by a combination of BMI, clinical stage, tumor diameter and mitotic index. The introduced nomogram could facilitate in counseling patients and may help to guide patients and caregivers in joint decisions on post-treatment surveillance.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2020
DOI: 10.1186/S12884-020-03169-3
Abstract: Medical practice variation in caesarean section rates is the most studied type of practice variation in the field of obstetrics and gynaecology. This has not resulted in increased homogeneity of treatment between geographic areas or healthcare providers. Our study aim was to evaluate whether current study designs on medical practice variation of caesarean section rates were optimized to identify the unwarranted share of practice variation and could contribute to the reduction of unwarranted practice variation by meeting criteria for audit and feedback. We searched PubMed, Embase, EBSCO/CINAHL and Wiley/Cochrane Library from inception to March 24th, 2020. Studies that compared the rate of caesarean sections between in iduals, institutions or geographic areas were included. Study design was assessed on: selection procedure of study population, data source, case-mix correction, patient preference, aggregation level of analysis, maternal and neonatal outcome, and determinants (professional and organizational characteristics). A total of 284 studies were included. Most studies (64%) measured the caesarean section rate in the entire study population instead of using a s le (30%). (National) databases were most often used as information source (57%). Case-mix correction was performed in 87 studies (31%). The Robson classification was used in 20% of the studies following its endorsement by the WHO in 2015. The most common levels of aggregation were hospital level (35%) and grouped hospitals (35%) e.g. private versus public. The percentage of studies that assessed the relationship between variation in caesarean section rates and maternal outcome was 9%, neonatal outcome 19%, determinants (professional and organizational characteristics) 21% and patient preference 2%. Study designs of practice variation in caesarean sections varied considerably, raising questions about their appropriateness. Studies focused on measuring practice variation, rather than contributing to the reduction of unwarranted practice variation. Future studies should correct for differences in patient characteristics (case-mix) and patient preference to identify unwarranted practice variation. Practice variation studies could be used for audit and feedback if results are presented at lower levels of aggregation, and appeal to intrinsic motivation of physicians, for ex le by including the health effects on mother and child.
Publisher: Informa UK Limited
Date: 02-10-2021
Publisher: Wiley
Date: 19-11-2020
Abstract: To examine early and late pregnancy loss in women with and without polycystic ovary syndrome (PCOS) undergoing IVF/ICSI transfers. Retrospective cohort study. Reproductive medicine centre at a tertiary hospital. We studied women with a positive β‐human chorionic gonadotropin (β‐hCG) after in vitro fertilisation/intra‐cytoplasmic sperm injection (IVF/ICSI) treatment from May 2014 to April 2019. Odds ratios (OR) for early (≤13 weeks) and late ( weeks) pregnancy loss were calculated among women with and without PCOS for plurality of the pregnancy with adjustment for confounding factors. Early pregnancy loss (EPL) and late pregnancy loss (LPL). From 21 820 women identified with a positive β‐hCG, 2357 (10.8%) women had PCOS, and 19 463 (89.2%) women did not. EPL occurred in 16.6% (391) of women with PCOS versus 18.3% (3565) in women with non‐PCOS (OR 0.89, 95% CI 0.79–0.99, P = 0.04). After adjustment for age and other confounders, the rate of EPL was not statistically significantly associated with PCOS status (adjusted OR [aOR] 0.91, 95% CI 0.80–1.05). Women with PCOS demonstrated a higher rate of LPL (6.4% in PCOS versus 3.6% in non‐PCOS, OR 1.81, 95% CI 1.48–2.21, P 0.001). In multivariable analysis, the potential impact of PCOS was less strong (aOR 1.38, 95% CI 0.96–1.98), with BMI and maternal comorbidities also associated with LPL (aOR 1.08, 95% CI 1.04–1.1 and aOR 2.07, 95% CI 1.43–3.00, respectively). Polycystic ovary syndrome was not independently associated with EPL. There was an increased risk of LPL but this difference was not statistically significant. Polycystic ovary syndrome women are at increased risk of late pregnancy loss, partly driven by elevated BMI and maternal comorbidities.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2019
Publisher: Wiley
Date: 04-03-2020
Publisher: Wiley
Date: 18-05-2020
DOI: 10.1111/AJO.13179
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 04-2021
DOI: 10.1002/UOG.21907
Abstract: To evaluate whether there is a differential benefit of planned Cesarean delivery (CD) over planned vaginal delivery (VD) in women with a twin pregnancy and the first twin in cephalic presentation, depending on prespecified baseline maternal and pregnancy characteristics, and/or gestational age (GA) at delivery. This was a secondary analysis of the Twin Birth Study, which included 2804 women with a twin pregnancy and the first twin (Twin A) in cephalic presentation between 32 + 0 and 38 + 6 weeks' gestation at 106 centers in 25 countries. Women were assigned randomly to either planned CD or planned VD. The main outcome measure was composite adverse perinatal outcome, defined as the occurrence of perinatal mortality or serious neonatal morbidity in at least one twin. The baseline maternal and pregnancy characteristics (markers) considered were maternal age, parity, history of CD, use of antenatal corticosteroids, estimated fetal weight (EFW) of Twin A, EFW of Twin B, 25% difference in EFW between the twins, presentation of Twin B, chorionicity on ultrasound, method of conception, complications of pregnancy, ruptured membranes at randomization and GA at randomization. Separate logistic regression models were developed for each marker in order to model composite adverse perinatal outcome as a function of the specific marker, planned delivery mode and the interaction between these two terms. In addition, multivariable logistic regression analysis with backward variable elimination was performed separately in each arm of the trial. The association between planned mode of delivery and composite adverse perinatal outcome, according to GA at delivery, was assessed using logistic regression analysis. Of the 2804 women initially randomized, 1391 were included in each study arm. None of the studied baseline markers was associated with a differential benefit of planned CD over planned VD in the rate of composite adverse perinatal outcome. GA at delivery was associated differentially with composite adverse perinatal outcome in the treatment arms ( P for interaction 0.001). Among pregnancies delivered at 32 + 0 to 36 + 6 weeks, there was a trend towards a lower rate of composite adverse perinatal outcome in those in the planned‐VD group compared with those in planned‐CD group (29 (2.2%) vs 48 (3.6%) cases odds ratio (OR) 0.62 (95% CI, 0.37–1.03)). In pregnancies delivered at or after 37 + 0 weeks, planned VD was associated with a significantly higher rate of composite adverse perinatal outcome, as compared with planned CD (23 (1.5%) vs 10 (0.7%) cases OR, 2.25 (95% CI, 1.06–4.77)). The perinatal outcome of twin pregnancies with the first twin in cephalic presentation may differ depending on GA at delivery and planned mode of delivery. At 32–37 weeks, planned VD seems to be favorable, while, from around 37 weeks onwards, planned CD might be safer. The absolute risks of adverse perinatal outcomes at term are low and must be weighed against the increased maternal risks associated with planned CD. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Wiley
Date: 28-06-2020
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.AJOG.2021.11.1371
Abstract: As the understanding of the pathophysiology of preecl sia has improved, its diagnostic criteria have evolved. The classical triad of hypertension, edema, and proteinuria has become hypertension and organ dysfunction-renal, hepatic, neurologic, hematological, or uteroplacental. However, the most recent definitions have largely been based off consensus and expert opinion, not primary research. In this review, we explore how the criteria have evolved, particularly through the second half of the 20
Publisher: BMJ
Date: 08-2021
DOI: 10.1136/BMJOPEN-2020-045770
Abstract: Recently, the rate of caesarean sections (CS) worldwide has risen and CS-associated complications such as niche have increased substantially. Until now, evidence-based clinical guidelines for the treatment of niche-related symptoms remain absent. In patients with postmenstrual spotting, it has not been studied if the effect of levonorgestrel 52 mg intrauterine system (LNG-IUS 52 mg) is superior to that of hysteroscopy. This study will answer the question of whether LNG-IUS 52 mg is more effective in improving postmenstrual spotting than hysteroscopic niche resection in women with niche-related spotting at 6 months after randomisation. This is a randomised controlled trial. A total of 208 women with postmenstrual spotting related to niche in the caesarean uterine scar of at least 2 mm and residual myometrium of at least 2.2 mm evaluated by MRI will be included. Women desiring to conceive within 1 year, with contraindications for LNG-IUS 52 mg or hysteroscopic surgery will be excluded. After informed consent is obtained, eligible women will be randomly allocated to LNG-IUS 52 mg or hysteroscopic niche resection at 1:1. The primary outcome is the efficacy in reducing postmenstrual spotting at 6 months after randomisation. The secondary outcomes include menstrual pattern, total days of blood loss per month, rate of amenorrhoea, side effects and complications.We will use a Visual Analogue Scale for chronic pelvic pain, urological symptoms and women’s satisfaction (five-point Likert scale). The study was approved by the local medical ethics committee and by the Institutional Review Board of the International Peace Maternity and Child Health Hospital, Shanghai, China (No. GKLW 2019-08). Participants will sign a written informed consent before participation. The results of this study will be submitted to a peer-reviewed journal for publication. ChiCTR1900025677.
Publisher: Wiley
Date: 16-07-2019
Publisher: Wiley
Date: 20-03-2023
Abstract: Cervical length is widely used to assess a woman's risk of spontaneous preterm birth (SPTB). To summarise and critically appraise the evidence from systematic reviews on the prognostic capacity of transvaginal sonographic cervical length in the second trimester in asymptomatic women with singleton or twin pregnancy. Searches were performed in Medline, Embase, CINAHL and grey literature from 1 January 1995 to 6 July 2021, including keywords ‘cervical length’, ‘preterm birth’, ‘obstetric labour, premature’, ‘review’ and others, without language restriction. We included systematic reviews including women who did not receive treatments to reduce SPTB risk. From 2472 articles, 14 systematic reviews were included. Summary statistics were independently extracted by two reviewers, tabulated and analysed descriptively. The ROBIS tool was used to evaluate risk of bias of included systematic reviews. Twelve reviews performed meta‐analyses: two were reported as systematic reviews of prognostic factor studies, ten used diagnostic test accuracy methodology. Ten systematic reviews were at high or unclear risk of bias. Meta‐analyses reported up to 80 combinations of cervical length, gestational age at measurement and definition of preterm birth. Cervical length was consistently associated with SPTB, with a likelihood ratio for a positive test of 1.70–142. The ability of cervical length to predict SPTB is a prognostic research question systematic reviews typically analysed diagnostic test accuracy. In idual participant data meta‐analysis using prognostic factor research methods is recommended to better quantify how well transvaginal ultrasonographic cervical length can predict SPTB.
Publisher: Informa UK Limited
Date: 28-05-2018
Publisher: Wiley
Date: 23-03-2019
Publisher: Wiley
Date: 12-06-2023
Abstract: To investigate whether Day 3 (D3) embryo status matter to reproductive outcomes of blastocyst transfer cycles. Retrospective cohort study. Assisted Reproduction Department of Shanghai Ninth People's Hospital, Shanghai, China. A total of 6906 vitrified–thawed single blastocyst transfer cycles in 6502 women were included. Generalised estimated equation regression models were used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between embryo status and pregnancy outcomes. Biochemical pregnancy, miscarriage, live birth. High‐quality blastocysts derived from poor‐grade D3 embryos had comparable pregnancy outcomes to those derived from high‐grade D3 embryos (40.0% versus 43.2%, aOR 1.00, 95% CI 0.85–1.17 for live birth rate 8.3% versus 9.5%, aOR 0.82, 95% CI 0.63–1.07 for miscarriage rate). Cycles with low D3 cell number (five cells or fewer) had significantly higher miscarriage rate (9.2% versus 7.6%, aOR 1.33, 95% CI 1.02–1.75) compared with cycles with eight cells on D3. Poor‐quality cleavage embryos should be cultivated to the blastocyst stage because high‐quality blastocysts derived from poor‐grade D3 embryos had acceptable pregnancy outcomes. When the blastocyst grade is identical, choosing embryos with higher D3 cell number (eight or more cells) for transfer could reduce the risk of early miscarriage.
Publisher: BMJ
Date: 10-2023
Publisher: Wiley
Date: 22-02-2023
DOI: 10.1111/AOGS.14520
Abstract: The incidence of induction of labor, for both medical reasons and as an elective procedure, has been rising and a further increase in induction of labor following the ARRIVE trial may be expected. The effects of induction of labor at term on childhood neurodevelopment, however, are not well studied. We aimed to study the influence of elective induction of labor for each week of gestation separately from 37 to 42 weeks on offspring school performance at 12 years of age after uncomplicated pregnancies. We performed a population‐based study among 226 684 liveborn children from uncomplicated singleton pregnancies, born from 37 +0 to 42 +0 weeks of gestation in cephalic presentation in 2003–2008 (no hypertensive disorders, diabetes or birthweight ≤p5) in the Netherlands. Children with congenital anomalies, of non‐white mothers and born after planned cesarean section were excluded. Birth records were linked with national data on school achievement. We compared, using a fetus‐at‐risk approach and per week of gestation, school performance score and secondary school level at age 12 in those born after induction of labor to those born after non‐intervention, ie spontaneous onset of labor in the same week plus all those born at later gestations. Education scores were standardized to a mean of 0 and a standard deviation of 1 and adjusted in the regression analyses. For each gestational age up to 41 weeks, induction of labor was associated with decreased school performance scores compared with non‐intervention (at 37 weeks −0.05 SD, 95% confidence interval [CI] −0.10 to −0.01 SD adjusted for confounding factors). After induction of labor, fewer children reached higher secondary school level (at 38 weeks 48% vs 54% adjusted odds ratio [aOR] 0.88, 95% CI 0.82–0.94). In women with uncomplicated pregnancies at term, consistently, at every week of gestation from 37 to 41 weeks, induction of labor is associated with lower offspring school performance at age 12 and lower secondary school level compared with non‐intervention, although residual confounding may remain. These long‐term effects of induction of labor should be incorporated in counseling and decision making.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2018
Publisher: Informa UK Limited
Date: 27-12-2020
DOI: 10.1080/10641955.2019.1708383
Abstract: Intracranial hemorrhage and stroke are primary causes of maternal mortality in pregnancies affected by hypertensive disorders. As such antihypertensive therapy plays a crucial role in the management of severe hypertension. However, the target level to achieve the best outcome for both - mother and fetus - is still unclear. Moreover, given the lack of well-designed randomized controlled trials with standardized key outcomes, the current choice of antihypertensive medications depends rather on clinicians' preference. Furthermore, data on long-term outcomes of offspring is not available. Therefore, there is an urgent need for randomized trials comparing different anti-hypertensive options to address efficacy and safety questions.
Publisher: JMIR Publications Inc.
Date: 29-06-2018
Abstract: regnant women are often unaware of the potential risks that working conditions can cause to them and their unborn child. A mobile health (mHealth) app, the Pregnancy and Work (P and W) app, developed by a multidisciplinary team and based on an evidence-based guideline for occupational physicians, aims to provide advice on work adjustment during pregnancy. his study evaluates the usability of the mHealth P and W app and the perceived usefulness of the work advice, the main goal of the app, by potential end users. total of 12 working pregnant women participated in think aloud usability sessions and performed 9 tasks. All think aloud sessions were recorded, transcribed, and coanalyzed. The usability problems were rated for their severity in accordance with Nielsen severity scale. The completion rates and time taken for completion of tasks were registered. In addition, participants were questioned on demographics and user characteristics and were asked to evaluate the value of the app by filling in the Intrinsic Motivation Inventory (IMI) score and the System Usability Scale (SUS) questionnaire. n total, 82 usability problems with a severity ≥1 were identified, of which 40 had severity ≥3. The main usability problems concerned the interpretation of terminology used in the app’s questionnaires and difficulties in finding and understanding the work advice. Furthermore, 10 out of 12 participants were able to open the work advice page in the app. Only 7 out of these 10 participants understood and intended to follow the work advice. The overall mean IMI score was relatively high (5 out of 7), indicating that the participants did indeed value the use of the app. This IMI score corresponded to the overall mean SUS score (68 out of 100) and the mean grade given to the P and W app (7 out of 10). his think aloud usability study showed that the information provided in the P and W app was considered valuable by the end users, working pregnant women, and it meets their needs however, usability issues severely impacted the perceived usefulness of the work advice given in the app.
Publisher: Oxford University Press (OUP)
Date: 23-09-2020
Abstract: Questions continue to be raised regarding the benefit of genetic assessment of embryos prior to transfer in IVF, specifically with regards to preimplantation genetic testing for aneuploidy (PGT-A). To evaluate and quantify these concerns, we appraised the most recent (2012–2019) randomized controlled trials on the topic. Only two of these six studies listed cumulative live birth rates per started cycle, with both eliciting a statistically non-significant result. This article describes the concern that a focus on results from the first embryo transfer compared to cumulative outcomes falsely construes PGT-A as having superior outcomes, whilst its true benefit is not confirmed, and it cannot actually improve the true pregnancy outcome of an embryo pool.
Publisher: Wiley
Date: 07-07-2023
DOI: 10.1111/AOGS.14626
Abstract: Evidence comparing double‐balloon versus single‐balloon catheter for induction of labor is ided. We aim to compare the efficacy and safety of double‐ versus single‐balloon catheters using in idual participant data. A search of Ovid MEDLINE, Embase, Ovid Emcare, CINAHL Plus, Scopus, and clinicaltrials.gov was conducted for randomized controlled trials published from March 2019 until April 13, 2021. Earlier trials were identified from the Cochrane Review on Mechanical Methods for Induction of Labour. Randomized controlled trials that compared double‐balloon with single‐balloon catheters for induction of labor in singleton gestations were eligible. Participant‐level data were sought from trial investigators and an in idual participant data meta‐analysis was performed. The primary outcomes were rates of vaginal birth achieved, a composite measure of adverse maternal outcomes and a composite measure of adverse perinatal outcomes. We used a two‐stage random‐effects model. Data were analyzed from the intention‐to‐treat perspective. Of the eight eligible randomized controlled trials, three shared in idual‐level data with a total of 689 participants, 344 women in the double‐balloon catheter group and 345 women in the single‐balloon catheter group. The difference in the rate of vaginal birth between double‐balloon catheter and single‐balloon catheter was not statistically significant (relative risk [RR] 0.93, 95% confidence interval [CI] 0.86–1.00, p = 0.050 I 2 0% moderate‐certainty evidence). Both perinatal outcomes (RR 0.81, 95% CI 0.54–1.21, p = 0.691 I 2 0% moderate‐certainty evidence) and maternal composite outcomes (RR 0.65, 95% CI 0.15–2.87, p = 0.571 I 2 55.46% low‐certainty evidence) were not significantly different between the two groups. Single‐balloon catheter is at least comparable to double‐balloon catheter in terms of vaginal birth rate and maternal and perinatal safety outcomes.
Publisher: American College of Physicians
Date: 07-2023
DOI: 10.7326/M22-2974
Publisher: Wiley
Date: 05-05-2020
Publisher: Public Library of Science (PLoS)
Date: 28-07-2020
Publisher: Wiley
Date: 15-10-2020
Publisher: Wiley
Date: 18-08-2020
DOI: 10.1002/SMI.2976
Publisher: American Diabetes Association
Date: 11-07-2019
DOI: 10.2337/DC19-0958
Publisher: Wiley
Date: 22-06-2023
DOI: 10.1111/AJO.13724
Abstract: Placenta accreta spectrum disorder is an increasingly prevalent cause of maternal morbidity in developed countries. This study aimed to review the management and outcomes of cases of placenta accreta spectrum, and compare blood loss and blood transfusion rates, over time after an institutional change in planned primary surgeon from gynaecological oncologists to experienced obstetricians. This retrospective cohort study included all cases of suspected or confirmed placenta accreta spectrum disorder (PASD) between 1999 and 2021 at Monash Health. Data were collected by reviewing medical records to obtain baseline characteristics, details of surgical planning and management and major maternal morbidity outcomes over a 20‐year period. The primary surgical lead was recorded as either gynaecological oncologist or experienced obstetricians. The primary outcomes were estimated maternal blood loss and number of units of blood transfused. A total of 88 patients were identified: 43 between 1999 and 2015 where gynaecological oncologists were the primary surgeon in 79% of cases and 45 between 2016 and 2021 where experienced obstetricians were the primary surgeon in 73.3% of cases. There was no statistically significant difference in the estimated blood loss between the two time periods (median: 2000 vs 2500 mL, P = 0.669). Hysterectomy rates were significantly reduced in the second time period, from 100 to 73.3%, P 0.001. Management of cases of PASDs has improved over time with changes in antenatal diagnosis and perioperative management, and management by experienced obstetricians has similar maternal outcomes compared to those whose management includes the presence of gynaecological oncologists.
Publisher: Wiley
Date: 13-10-2020
Publisher: Georg Thieme Verlag KG
Date: 03-03-2022
DOI: 10.1055/A-1787-7744
Publisher: Wiley
Date: 10-04-2018
DOI: 10.1002/UOG.19029
Abstract: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group odds ratio (OR), 0.13 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Wiley
Date: 12-02-2021
DOI: 10.1111/AOGS.14074
Abstract: Preterm birth is a major cause of perinatal morbidity and mortality worldwide. In many countries preterm birth rates are increasing, largely as a result of increases in iatrogenic preterm birth, whereas in other countries rates are stable or even declining. The objective of the study is to describe trends in singleton preterm births in Victoria from 2007 to 2017 in relation to trends in perinatal mortality to identify opportunities for improvements in clinical care. We conducted a consecutive cross‐sectional study in all women with a singleton pregnancy giving birth at ≥20 weeks of pregnancy in Victoria, Australia, between 2007 and 2017, inclusive. Rates of preterm birth and perinatal mortality were calculated and trends were analyzed in all pregnancies, in pregnancies complicated by fetal growth problems, hypertension, (pre)ecl sia or prelabor rupture of membranes (PROM), and in (low‐risk) pregnancies not complicated by any of these conditions. There were 811 534 singleton births between 2007 and 2017. Preterm birth increased from 5.9% (4074 births) to 6.4% (4893 births P .001), due to an increase in iatrogenic preterm birth from 2.5% (1730 births) to 3.6% (2730 births P .001). Comparable trends were seen in pregnancies complicated by fetal growth problems and hypertension and in pregnancies not complicated by small for gestational age (SGA), hypertension, (pre)ecl sia or PROM (all P .001). In pregnancies complicated by SGA, hypertension, (pre)ecl sia or PROM the perinatal mortality rate from 20 weeks of gestation fell (13 to 12 per 1000 births P .001). In pregnancies not complicated by SGA, hypertension, (pre)ecl sia or PROM there was no significant change in the perinatal mortality from 28 weeks and no decrease in the preterm weekly prospective stillbirth risk. The singleton preterm birth rate in Victoria is increasing, driven by an increase in iatrogenic preterm birth, both in pregnancies complicated by SGA and hypertension, and in pregnancies not complicated by SGA, hypertension, (pre)ecl sia or PROM. While perinatal mortality decreased in the pregnancies complicated by SGA, hypertension, (pre)ecl sia or PROM, no significant reduction in perinatal mortality from 28 weeks or in preterm weekly prospective stillbirth risk was noted in the pregnancies not complicated by any of these conditions.
Publisher: American Geophysical Union (AGU)
Date: 03-2020
DOI: 10.1029/2019WR024987
Publisher: Wiley
Date: 13-10-2020
DOI: 10.1002/UOG.21903
Abstract: The majority of cases of placenta previa or a low‐lying placenta in the second trimester will have a normal placental position in the third trimester. The aim of this study was to assess the accuracy of the distance between the placenta and the internal os of the cervix (IOD) in the second trimester for the prediction of third‐trimester low‐positioned placenta, and to define a cut‐off value at which all cases of third‐trimester low‐positioned placenta are identified. This was a prospective cohort study including women undergoing a transvaginal ultrasound examination between 18 and 24 weeks' gestation who had a low‐positioned placenta, defined as an IOD of 20 mm. Low‐positioned placenta included placenta previa, defined as a placenta covering the internal os of the cervix, and a low‐lying placenta, defined as a placenta lying near to (within 20 mm) but not overlying the internal os. All women were re‐evaluated in the third trimester. Relative risks for a low‐positioned placenta in the third trimester were calculated for women with placenta previa vs a low‐lying placenta, posterior vs anterior placenta and positive vs negative history of Cesarean section. Multilevel likelihood ratios for ranges of IOD in the prediction of a low‐positioned placenta in the third trimester were calculated separately for anteriorly and posteriorly located placentae. Corresponding receiver‐operating‐characteristics curves were constructed. In total, 958 women were included in the study. In the second trimester, placentae were more frequently located on the posterior side (62.0%) than on the anterior side (38.0%). In the third trimester, 48/958 (5.0%) placentae persisted as a low‐positioned placenta. Women with placenta previa in the second trimester had a higher risk of a low‐positioned placenta in the third trimester than did those with a low‐lying placenta in the second trimester (37/181 (20.4%) vs 11/777 (1.4%) relative risk (RR), 17.9 (95% CI, 8.9–36.0)). Women with a posterior placenta had a higher risk of a low‐positioned placenta in the third trimester than did those with an anterior placenta (38/594 (6.4%) vs 10/364 (2.7%) RR, 2.4 (95% CI, 1.2–4.9)), as did women with a history of Cesarean section compared with those without such a history (14/105 (13.3%) vs 34/853 (4.0%) RR, 3.7 (95% CI, 1.9–7.2)). The cut‐off value of IOD in the second trimester to identify all cases of an abnormally located placenta in the third trimester was 15.5 mm for posteriorly located placentae, while for anteriorly located placentae the IOD cut‐off was lower, namely –4.5 mm, representing a 4.5‐mm overlap of the placental edge over the internal os of the cervix. With incorporation of a safety margin of 5 mm and ensuring that all women with placenta previa undergo a follow‐up scan, we recommend lowering the IOD cut‐off value for follow‐up in cases of an anterior low‐positioned placenta from 20 to 5 mm, which would decrease the number of unnecessary follow‐up ultrasound examinations without missing any high‐risk women. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Wiley
Date: 21-06-2019
DOI: 10.1111/AOGS.13664
Abstract: The OPTIMIST trial revealed that for women starting in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment, no substantial differences exist in first cycle and cumulative live birth rates between an antral follicle count (AFC)-based in idualized follicle-stimulating hormone (FSH) dose and a standard dose. Female age and body weight have been suggested to cause heterogeneity in the effect of FSH dose in idualization. The objective of the current study is to evaluate whether these patient characteristics modify the effect of AFC-based in idualized FSH dosing in IVF/ICSI treatment. A secondary data-analysis of the OPTIMIST trial. Women initiating IVF/ICSI treatment were classified as predicted poor (AFC 0-7), suboptimal (AFC 8-10) or hyper responders (AFC >15), and randomly allocated to a standard FSH dose (150 IU/d) or an in idualized FSH dose (450, 225 or 100 IU/d for predicted poor, suboptimal and hyper responders, respectively). In each predicted response category, logistic regression models with interaction terms were used to evaluate the presence of effect modification. The first cycle was analyzed, and the primary outcomes were first complete cycle live birth rate (including fresh plus frozen-thawed embryo transfers) and ovarian hyperstimulation syndrome (OHSS) risks. No effect modification was revealed in the predicted poor (n = 234) and suboptimal (n = 277) responders. In the predicted hyper responders (n = 521), the effect of the in idualized FSH dose on the first cycle live birth rate was modified by female age (P = 0.02) and the effect on OHSS risks was modified by body weight (P = 0.02). A dose reduction from 150 to 100 IU/d generally decreased the OHSS risks in predicted hyper responders, but also reduced the chance of a live birth in young women, and had no beneficial impact on OHSS risks in women with a relatively low body weight. In women with a predicted hyper response undergoing IVF/ICSI treatment, female age and body weight seem to modify the effect of FSH dose in idualization. Although a reduced FSH starting dose generally decreases the OHSS risks, it may also reduce the chance of a live birth, specifically for young women. Future studies could consider these findings when investigating the optimal approach to reduce OHSS risks while maintaining the probability of a live birth for predicted hyper responders in IVF/ICSI treatment.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.EJOGRB.2019.09.026
Abstract: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have h ered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 05-2022
DOI: 10.1002/UOG.24851
Abstract: To assess the performance of placental, fetal and maternal cardiovascular markers in the prediction of adverse perinatal and maternal outcomes in women with suspected or confirmed pre‐ecl sia. This was a prospective prognostic accuracy study of women with suspected or confirmed pre‐ecl sia who underwent a series of investigations to measure maternal hemodynamic indices, mean arterial pressure, augmentation index, ophthalmic artery peak systolic velocity (PSV) ratio, uterine artery pulsatility index (UtA‐PI), fetal biometric and Doppler parameters, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF). The performance of these markers, in idually or in combination, in predicting adverse perinatal and maternal outcomes was then assessed using receiver‐operating‐characteristics (ROC)‐curve analysis. Adverse maternal outcome was defined as one or more of severe hypertension, admission to the intensive care unit, ecl sia, placental abruption, HELLP syndrome, disseminated intravascular coagulation, platelets 100 × 10 9 /L, creatinine 90 μ mol/L and alanine aminotransferase 100 U/L. Adverse perinatal outcome was defined as one or more of preterm birth at or before 34 + 0 weeks, neonatal intensive care unit admission for 48 h, respiratory distress syndrome, intraventricular hemorrhage, hypoxic ischemic encephalopathy, necrotizing enterocolitis, retinopathy of prematurity and confirmed fetal infection. We recruited 126 women with suspected ( n = 31) or confirmed ( n = 95) pre‐ecl sia at a median gestational age of 33.9 weeks (interquartile range, 30.9–36.3 weeks). Pregnancies with adverse perinatal outcome compared to those without had a higher median UtA‐PI (1.3 vs 0.8 P 0.001), ophthalmic artery PSV ratio (0.8 vs 0.7 P = 0.01) and umbilical artery PI percentile (82.0 vs 68.5 P 0.01) and lower median estimated fetal weight percentile (4.0 vs 43.0 P 0.001), abdominal circumference percentile (4.0 vs 63.0 P 0.001), middle cerebral artery PI percentile (28.0 vs 58.5 P 0.001) and cerebroplacental ratio percentile (18.0 vs 46.5 P 0.001). Pregnancies with adverse perinatal outcome also had a higher median sFlt‐1 (8208.0 pg/mL vs 4508.0 pg/mL P 0.001), lower PlGF (27.2 pg/mL vs 76.3 pg/mL P 0.001) and a higher sFlt‐1/PlGF ratio (445.4 vs 74.4 P 0.001). The best performing in idual marker for predicting adverse perinatal outcome was the sFlt‐1/PlGF ratio (area under the ROC curve (AUC), 0.87 (95% CI, 0.81–0.93)), followed by estimated fetal weight (AUC, 0.81 (95% CI, 0.73–0.89)). Women who experienced adverse maternal outcome had a higher median sFlt‐1 level (7471.0 pg/mL vs 5131.0 pg/mL P 0.001) and sFlt‐1/PlGF ratio (204.3 vs 93.3 P 0.001) and a lower PlGF level (37.0 pg/mL vs 66.1 pg/mL P = 0.01) and estimated fetal weight percentile (16.5 vs 37.0 P = 0.04). All markers performed poorly in predicting adverse maternal outcome, with sFlt‐1 (AUC, 0.69 (95% CI, 0.60–0.79)) and sFlt‐1/PlGF ratio (AUC, 0.69 (95% CI, 0.59–0.78)) demonstrating the best in idual performance. The addition of cardiovascular, fetal or other placental indices to the sFlt‐1/PlGF ratio did not improve the prediction of adverse maternal or perinatal outcomes. The sFlt‐1/PlGF ratio performs well in predicting adverse perinatal outcomes but is a poor predictor of adverse maternal outcomes in women with suspected or diagnosed pre‐ecl sia. The addition of cardiovascular or fetal indices to the model is unlikely to improve the prognostic performance of the sFlt‐1/PlGF ratio. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Wiley
Date: 26-06-2021
DOI: 10.1111/AOGS.14197
Abstract: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well‐being. We know very little about HG’s long‐term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies. We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy‐three women were included in this follow‐up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies. Thirty‐five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty‐four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3–130.5, p = 0.03). High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Georg Thieme Verlag KG
Date: 10-07-2023
Abstract: Objective Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. Study Design In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective in idual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). Results Results will be published in phases as the in idual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. Key Points
Publisher: Wiley
Date: 02-11-2021
DOI: 10.1111/AJO.13273
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.AJOG.2019.03.024
Abstract: Management of preterm hypertensive disorders remains a clinical dilemma. The maternal benefits of delivery need to be weighed against the adverse neonatal consequences of preterm birth. Long-term consequences of obstetric management in offspring of women with hypertensive disorders in preterm pregnancy are largely unknown. We report child neurodevelopmental and behavioral outcomes at 2 years after the Hypertension and Preecl sia Intervention Trial at near Term (HYPITAT-II) trial, which compared immediate delivery versus expectant monitoring in mild late preterm hypertensive disorders of pregnancy. To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 2 years of age in offspring of women with mild late preterm hypertensive disorders. We studied children born in the HYPITAT-II trial, a study in which women (n = 704) with hypertensive disorders of pregnancy who were between 34 and 37 weeks' gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire for developmental outcome and the Child Behavior Checklist for behavioral problems when their toddlers were 2 years old. We approached 545 of 704 randomized women (77%) 330 of 545 (61%) returned the questionnaires. In the immediate delivery group, 45 of 162 infants (28%) had an abnormal Ages and Stages Questionnaire score compared to 27 of 148 (18%) in the expectant monitoring group (risk difference, 9.6% 95% CI, 0.3-18.0%) P = .045. In the pregnancies (n = 94) that delivered before reaching 36 weeks, 27% (n = 25) had an abnormal Ages and Stages Questionnaire score compared to 22% (n = 47) when delivered after 36 weeks (odds ratio, 0.77 confidence interval, 0.44-1.34). An abnormal Child Behavior Checklist outcome was found in 31 of 175 (18%) in the delivery group vs 24 of 166 (15%) in the expectant monitoring group (risk difference, 3.2% 95% CI, -4.6% to 11.0%). After correction for maternal education, management strategy remained an independent predictor of abnormal Ages and Stages Questionnaire score (odds ratio, 0.48 confidence interval, 0.24 to -0.96, P = .03). In multivariable analyses, low birth weight, low maternal education, and immediate delivery policy were all significantly associated with an abnormal Ages and Stages Questionnaire score. In this study, we found that early delivery in women with late preterm hypertensive disorders is associated with poorer neurodevelopmental outcomes in their children at 2 years of age. These findings indicate an increased risk of developmental delay after early delivery compared to expectant monitoring. This follow-up study underlines the conclusion of the original HYPITAT-II study that, until the clinical situation deteriorates, expectant monitoring remains the most appropriate management strategy in the light of short- and long-term neonatal outcomes in women with preterm hypertensive disorders.
Publisher: Informa UK Limited
Date: 23-05-2022
DOI: 10.1080/01443615.2022.2054679
Abstract: Hysterosalpingographies (HSGs) have formed an essential part of the fertility workup for more than a century. More recently, tubal flushing, especially with oil-based contrast, has been shown to significantly improve the natural conception rates. Critically, the mechanism of this fertility-enhancing effect during tubal flushing is still unclear. This article postulates hypotheses, based on published and own research, on the potential mechanisms and root cause of tubal flushing fertility enhancement. Possible explanations for the increased fertility rates, especially with oil-based contrast, are ided into the biochemical and interfacial effects derived from the contrast properties. The biochemical effects may include the immunological response of the endometrium or peritoneum, the impact on the endometrial opioid receptors or the iodine content. The interfacial effects may include improvement of interfacial factors due to the lubricant effect or dislodgement of mucus debris within the Fallopian tubes. Impact Statement
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research. Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research. Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health’s consensus development conference. An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for in idual core outcomes. This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Gr ian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests. Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586. N/A. N/A.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.AJOG.2014.04.023
Abstract: The objective of the study was to assess in trichorionic triplet pregnancies the effectiveness of elective reduction to twins. This was a nationwide retrospective cohort study. We compared the time to delivery and perinatal mortality in trichorionic triplet pregnancies electively reduced to twins with ongoing trichorionic triplets and primary dichorionic twins. We identified 86 women with reduced trichorionic triplet pregnancies, 44 with ongoing trichorionic triplets, and 824 with primary twins. Reduced triplets had a median gestational age at delivery of 36.1 weeks (interquartile range [IQR], 33.3-37.5 weeks) vs 33.3 (IQR, 28.1-35.2) weeks for ongoing triplets and 37.1 (IQR, 35.3-38.1) weeks for primary twins (P < .001). The total number of surviving children in the reduced group was 155 (90%) vs 114 (86%) in the ongoing triplet group. After reduction, 75 of women (87%) had all their fetuses surviving, compared with 36 (82%) (relative risk [RR], 1.3 95% confidence interval [CI], 0.72-2.3) for ongoing triplets and 770 (93%) (RR, 0.91 95% CI, 0.82-1) for primary twins. There were 6 women without any surviving children (7%) after reduction vs 5 (11.4%) (RR, 0.81 95% CI, 0.47-1.4) among women with ongoing triplets and 32 (3.9%) (RR, 1.7 95% CI, 0.8-3.7) in women with primary twins. In women with a triplet pregnancy, fetal reduction increases gestational age at birth with 3 weeks as compared with ongoing triplets. However, there the impact on neonatal survival is limited.
Publisher: Wiley
Date: 05-04-2020
Publisher: Oxford University Press (OUP)
Date: 09-2021
Abstract: Is there an ideal imaging modality for the detection of uterosacral ligaments/torus uterinus (USL), rectovaginal septum (RVS) and vaginal deep endometriosis (DE) in women with a clinical history of endometriosis? The sensitivity for the detection of USL, RVS and vaginal DE using MRI seems to be better than transvaginal ultrasonography (TVS), whilst the specificity of both were excellent. The surgical management of women with DE can be complex and requires advanced laparoscopic skills with maximal cytoreduction being vital at the first procedure to provide the greatest symptomatic benefit. Owing to a correlation of TVS findings with surgical findings, preoperative imaging has been used to adequately consent women and plan the appropriate surgery. However, until publication of the consensus statement by the International Deep Endometriosis Analysis Group in 2016, there were significant variations within the terms and definitions used to describe DE in the pelvis. A systematic review and meta-analysis was conducted using Embase, Google Scholar, Medline, PubMed and Scopus to identify studies published from inception to May 2020, of which only those from 2010 were included owing to the increased proficiency of the sonographers and advancements in technology. All prospective studies that preoperatively assessed any imaging modality for the detection of DE in the USL, RVS and vagina and correlated with the reference standard of surgical data were considered eligible. Study eligibility was restricted to those including a minimum of 10 unaffected and 10 affected participants. There were 1977 references identified from which 10 studies (n = 1188) were included in the final analysis. For the detection of USL DE, the overall pooled sensitivity and specificity for all TVS techniques were 60% (95% CI 32–82%) and 95% (95% CI 90–98%), respectively, and for all MRI techniques were 81% (95% CI 66–90%) and 83% (95% CI 62–94%), respectively. For the detection of RVS DE, the overall pooled sensitivity and specificity for all TVS techniques were 57% (95% CI 30–80%) and 100% (95% CI 92–100%), respectively. For the detection of vaginal DE, the overall pooled sensitivity and specificity for all TVS techniques were 52% (95% CI 29–74%) and 98% (95% CI 95–99%), respectively, and for all MRI techniques were 64% (95% CI 40–83%) and 98% (96% CI 93–99%). Pooled analyses were not possible for other imaging modalities. There was a low quality of evidence given the high risk of bias and heterogeneity in the included studies. There are also potential biases secondary to the risk of misdiagnosis at surgery owing to a lack of either histopathological findings or expertise, coupled with the surgeons not being blinded. Furthermore, the varying surgical experience and the lack of clarity regarding complete surgical clearance, thereby also contributing to the lack of histopathology, could also explain the wide range of pre-test probability of disease. MRI outperformed TVS for the per-operative diagnosis of USL, RVS and vaginal DE with higher sensitivities, although the specificities for both were excellent. There were improved results with other imaging modalities, such as rectal endoscopy-sonography, as well as the addition of bowel preparation or ultrasound gel to either TVS or MRI, although these are based on in idual studies. No funding was received for this study. M.L. reports personal fees from GE Healthcare, grants from the Australian Women’s and Children’s Foundation, outside the submitted work. B.W.M. reports grants from NHMRC, outside the submitted work. G.C. reports personal fees from GE Healthcare, outside the submitted work and is on the Endometriosis Advisory Board for Roche Diagnostics. Prospective registration with PROSPERO (CRD42017059872) was obtained.
Publisher: Oxford University Press (OUP)
Date: 12-2019
Abstract: Do randomised controlled trials (RCTs) evaluating endometrial scratching suffer from methodological issues including insufficient trial registration, statistical errors or irreproducibility, randomisation errors or miscellaneous issues? The majority of RCTs investigating endometrial scratching have methodological issues. A large number of small RCTs investigating the effectiveness of endometrial scratching prior to in vitro fertilisation (IVF) and intrauterine insemination (IUI)/intercourse have reported favourable findings. Subsequently, systematic reviews incorporating these RCTs yielded meta-analyses in favour of endometrial scratching. Endometrial scratching has been widely adopted by infertility specialists around the world. Recently, an international RCT including 1364 women reported no benefit from endometrial scratching before IVF. We evaluated several methodological issues of RCTs investigating the effectiveness of endometrial scratching prior to IVF and IUI/intercourse. We identified 25 RCTs for IVF and 12 RCTs for IUI/intercourse with full-text publication. We assessed the RCTs on the following criteria: adequacy of trial registration, statistical issues (description of statistical methods and reproducibility of univariable statistical analysis), excessive similarity or difference in baseline characteristics that is not compatible with chance (Monte Carlo simulations and Kolmogorov–Smirnov test) and miscellaneous methodological issues. Of 25 RCTs evaluating endometrial scratching prior to IVF, only eight (32%) had adequate trial registration. In total, 10 (40%) RCTs had issues regarding statistical methods. Nine (69%, 13 applicable) RCTs had at least one inconsistency between reported and reproduced univariable statistical analysis for categorical baseline/intermediate characteristics. Statistical results of at least one outcome were not reproducible in 14 (74%, 19 applicable) RCTs. Only two (8%) RCTs had none of the above issues. Suggested by the simulations, these RCTs did not significantly violate the null hypothesis that the baseline characteristics were the results of a properly conducted randomisation process (P = 0.4395). Of 12 IUI/intercourse RCTs, only 2 (17%) had adequate trial registration. In total, five (42%) studies had issues of statistical methods. Inconsistency between reported and reproduced univariable analysis for baseline/intermediate categorical variable(s) was found in four (57%, 7 applicable) RCTs. Statistical analysis was not reproducible for at least one outcome in eight (80%, 10 applicable) studies. All RCTs had at least one of the above issues. These RCTs were inconsistent with the null hypothesis that their baseline characteristics were the results of proper randomised allocation (P = 1.659*10−7). We were unable to assess RCTs which were not published as full-text papers. We could not analyse in idual participant data to investigate possible reasons for statistical inconsistencies. The method to infer the likelihood of proper random s ling rests on assumptions including independent baseline characteristics, simple randomisation and no publication bias. The methodological issues common to RCTs evaluating endometrial scratching may have biased the results of the trials. Further development and validation of these novel methods may be helpful for the critical appraisal of RCTs. No external funding was sought to support this work. B.W.M. is supported by a National Health Medical Research Council (NHMRC) Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. D.W. is supported by a grant from the Paracelsus Medical University Salzburg, Austria (PMU Research Fund—PMU FFF Number: L-18/02/006-WET) and by Drs Haackert Foundation, Germany. S.L. is an author of a trial included in this study, an author of an included systematic review and a Cochrane editor. All other authors have no conflicts of interest. N/A
Publisher: Oxford University Press (OUP)
Date: 20-12-2018
Abstract: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC? Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC. In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown. We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization. We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap res ling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle. We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were €4495 versus €3006 (cost difference of €1475 (95% CI: €1457-€1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24:95% CI: 1.05-1.46). The ICER was €15 258 (95% CI: €8721 to €63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were €4497 versus €3005 (cost difference of €1510 (95% CI: €1492-€1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14:95% CI: 0.97-1.35). The ICER was €24 361 (95% CI: €-11 290 to €85 172) per additional live birth with IUI. We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC. Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines. This trial was funded by the Netherlands Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). The Eudract number for this trial is 2008-006171-73. The Sponsor's Protocol Code Number is P08-40. CBLA reports unrestricted grant support from Merck and Ferring. BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva and Guerbet. NTR1449.
Publisher: Oxford University Press (OUP)
Date: 12-2019
Abstract: Does pain or volume of used contrast medium impact the effectiveness of oil-based contrast during hysterosalpingography (HSG)? In women who report moderate to severe pain during HSG, the use of oil-based contrast resulted in more ongoing pregnancies compared to the use of water-based contrast, whereas in women who reported mild or no pain, no difference in ongoing pregnancies was found. We recently showed that in infertile women undergoing HSG, the use of oil-based contrast results in more ongoing pregnancies within 6 months as compared to the use of water-based contrast. However, the underlying mechanism of this fertility-enhancing effect remains unclear. We performed a post-hoc analysis of the H2Oil study, a multicentre randomised controlled trial (RCT) evaluating the therapeutic effect of oil- and water-based contrast at HSG. Here, we evaluated the impact of pain experienced at HSG and volume of used contrast media during HSG on ongoing pregnancy. In a subset of 400 participating women, pain during HSG by means of the Visual Analogue Scale (VAS) (range: 0.0–10.0 cm) was reported, while in 512 women, we registered the volume of used contrast (in millilitres). We used logistic regression analyses to assess whether pain and volume of used contrast media modified the effect of oil-based contrast on ongoing pregnancy rates. Data were analysed according to intention-to-treat principle. In 400 women in whom pain scores were reported, the overall median pain score was 5.0 (Interquartile range (IQR) 3.0–6.8) (oil group (n = 199) 4.8 (IQR 3.0–6.4) water group (n = 201) 5.0 (IQR 3.0–6.7) P-value 0.28). There was a significant interaction between pain (VAS ≤5 versus VAS ≥6) and the primary outcome ongoing pregnancy (P-value 0.047). In women experiencing pain (VAS ≥6), HSG with oil-based contrast resulted in better 6-month ongoing pregnancy rates compared to HSG with water-based contrast (49.4% versus 29.6% RR 1.7 95% CI, 1.1–2.5), while in women with a pain score ≤5, 6-month ongoing pregnancy rates were not significantly different between the use of oil- (28.8%) versus water-based contrast (29.2%) (RR 0.99 95% CI, 0.66–1.5). In the 512 women in whom we recorded contrast, median volume was 9.0 ml (IQR 5.7–15.0) in the oil group versus 8.0 ml (IQR 5.9–13.0) in the water group, respectively (P-value 0.72). Volume of used contrast was not found to modify the effect of oil-based contrast on ongoing pregnancy (P-value for interaction 0.23). This was a post-hoc analysis that should be considered as hypothesis generating. The RCT was restricted to infertile ovulatory women, younger than 39 years of age and with a low risk for tubal pathology. Therefore, our results should not be generalised to infertile women who do not share these features. The underlying mechanism of the fertility-enhancing effect induced by HSG with the use of oil-based contrast remains unclear. However, these findings suggest a possible mechanistic pathway, that is increasing intrauterine pressure occurring prior to dislodging pregnancy hindering debris or mucus plugs from the proximal part of otherwise normal fallopian tubes. This information might help in the search of the underlying fertility-enhancing mechanism found by using oil-based contrast during HSG. The original H2Oil RCT was an investigator-initiated study that was funded by the two academic institutions (AMC and VUmc) of the Amsterdam UMC. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports consultancy for Guerbet. H.V. reports consultancy fees from Ferring. C.B.L. reports speakers’ fees from Ferring and research grants from Ferring, Merck and Guerbet. V.M. reports receiving travel and speakers fees as well as research grants from Guerbet. B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research grants from Merck KGaA and Guerbet. The other authors do not report conflict of interests. The H2Oil study was registered at the Netherlands Trial Registry (NTR 3270). 1 February 2012. 3 February 2012.
Publisher: Oxford University Press (OUP)
Date: 13-05-2023
Abstract: What is the capacity of the change between Day 1 and Day 4 post-treatment serum human chorionic gonadotropin (hCG) levels for predicting single-dose methotrexate treatment success in tubal ectopic pregnancy? Any fall in Days 1–4 serum hCG signified an 85% (95% CI 76.8–90.6) likelihood of treatment success for women with tubal ectopic pregnancy (initial hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate. For those with tubal ectopic pregnancy managed by single-dose methotrexate, current guidelines advocate intervention if Days 4–7 hCG fails to fall by & %. The trajectory of hCG over Days 1–4 has been proposed as an early indicator that predicts treatment success, allowing early reassurance for women. However, almost all prior studies of Days 1–4 hCG changes have been retrospective. This was a prospective cohort study of women with tubal ectopic pregnancy (pre-treatment hCG of ≥1000 and ≤5000 IU/l) managed with single-dose methotrexate. The data were derived from a UK multicentre randomized controlled trial of methotrexate and gefitinib versus methotrexate and placebo for treatment of tubal ectopic pregnancy (GEM3). For this analysis, we include data from both treatment arms. Participants were categorized according to single-dose methotrexate treatment success or failure. Treatment success for this analysis was defined as complete and uneventful resolution of tubal ectopic pregnancy to serum hCG & IU/l following single-dose methotrexate treatment without additional treatment. Patient characteristics of the treatment success and failure groups were compared. Changes in Days 1–4, 1–7, and 4–7 serum hCG were evaluated as predictors of treatment success through receiver operating characteristic curve analysis. Test performance characteristics were calculated for percentage change ranges and thresholds including optimal classification thresholds. A total of 322 women with tubal ectopic pregnancy were treated with single-dose methotrexate. The overall single-dose methotrexate treatment success rate was 59% (n = 189/322). For any fall in serum hCG on Days 1–4, likelihood ratios were & , while for any fall of serum hCG & % on Days 1–7, likelihood ratios reached 5. Any rise of serum hCG on Days 1–7 and 4–7 strongly reduced the chance of success. Any fall in Days 1–4 hCG predicted single-dose methotrexate treatment success with a sensitivity of 58% and specificity 84%, resulting in positive and negative predictive values of 85% and 57%, respectively. Any rise in Days 1–4 serum hCG & % was identified as an optimal test threshold that predicted treatment success with 79% sensitivity and 74% specificity, resulting in 82% positive predictive value and 69% negative predictive value. Our findings may be limited by intervention bias resulting from existing guidelines which influences evaluation of hCG changes reliant on Day 7 serum hCG levels. Examining a large prospective cohort, we show the value of Days 1–4 serum hCG changes in predicting single-dose methotrexate treatment success in tubal ectopic pregnancy. We recommend that clinicians provide early reassurance to women who have a fall or only a modest (& %) rise in Days 1–4 serum hCG levels, that their treatment will likely be effective. This project was supported by funding from the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership (grant reference number 14/150/03). A.W.H. has received honoraria for consultancy for Ferring, Roche, Nordic Pharma and AbbVie. W.C.D. has received honoraria from Merck and Guerbet and research funding from Galvani Biosciences. L.H.R.W. has received research funding from Roche Diagnostics. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437). B.W.M. also reports consultancy for ObsEva and Merck and travel support from Merck. The other authors declare no competing interests. This study is a secondary analysis of the GEM3 trial (ISRCTN Registry ISRCTN67795930).
Publisher: Wiley
Date: 03-2020
DOI: 10.1002/UOG.20848
Abstract: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix. Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed. During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%) relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 € absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035). In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: Oxford University Press (OUP)
Date: 16-09-2020
Abstract: In our recent in idual participant data (IPD) meta-analysis evaluating the effectiveness of first-line ovulation induction for polycystic ovary syndrome (PCOS), IPD were only available from 20 studies of 53 randomized controlled trials (RCTs). We noticed that the summary effect sizes of meta-analyses of RCTs without IPD sharing were different from those of RCTs with IPD sharing. Granting access to IPD for secondary analysis has implications for promoting fair and transparent conduct of RCTs. It is, however, still common for authors to choose to withhold IPD, limiting the impact of and confidence in the results of RCTs and systematic reviews based on aggregate data. We performed a meta-epidemiologic study to elucidate if RCTs without IPD sharing have lower quality and more methodological issues than those with IPD sharing in an IPD meta-analysis evaluating first-line ovulation induction for PCOS. We included RCTs identified for the IPD meta-analysis. We dichotomized RCTs according to whether they provided IPD (shared group) or not (non-shared group) in the IPD meta-analysis. We restricted RCTs to full-text published trials written in English. We assessed and compared RCTs in the shared and non-shared groups on the following criteria: Risk of Bias (RoB 2.0), GRADE approach, adequacy of trial registration description of statistical methods and reproducibility of univariable statistical analysis excessive similarity or difference in baseline characteristics that is not compatible with chance and other miscellaneous methodological issues. In total, 45 trials (8697 women) were included in this study. IPD were available from 17 RCTs and 28 trials were categorized as the non-shared IPD group. Pooled risk rates obtained from the shared and non-shared groups were different. Overall low risk of bias was associated with 13/17 (76%) of shared RCTs versus 7/28 (25%) of non-shared RCTs. For RCTs that started recruitment after 1 July 2005, adequate trial registration was found in 3/9 (33%) of shared IPD RCTs versus 0/16 (0%) in non-shared RCTs. In total, 7/17 (41%) of shared RCTs and 19/28 (68%) of non-shared RCTs had issues with the statistical methods described. The median (range) of inconsistency rate per study, between reported and reproduced analyses for baseline variables, was 0% (0–92%) (6 RCTs applicable) in the shared group and 54% (0–100%) (13 RCTs applicable) in the non-shared group. The median (range) of inconsistency rate of univariable statistical results for the outcome(s) per study was 0% (0–63%) (14 RCTs applicable) in the shared group and 44% (0–100%) (24 RCTs applicable) in the non-shared group. The distributions of simulation-generated P-values from comparisons of baseline continuous variables between intervention and control arms suggested that RCTs in the shared group are likely to be consistent with properly conducted randomization (P = 0.163), whereas this was not the case for the RCTs in the non-shared group (P = 4.535 × 10−8). IPD meta-analysis on evaluating first-line ovulation induction for PCOS preserves validity and generates more accurate estimates of risk than meta-analyses using aggregate data, which enables more transparent assessments of benefits and risks. The availability of IPD and the willingness to share these data may be a good indicator of quality, methodological soundness and integrity of RCTs when they are being considered for inclusion in systematic reviews and meta-analyses.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Wiley
Date: 11-03-2023
DOI: 10.1111/AOGS.14545
Abstract: Preterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high‐risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid‐trimester short cervical length. This was a follow‐up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ‐3) and a red flag questionnaire. In surviving children, we compared the mean ASQ‐3 scores, abnormal ASQ‐3 scores, the number of children with any abnormal ASQ‐3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ‐3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm ( th percentile). In the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow‐up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ‐3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ‐3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ‐3 score in unselected women and in those with cervical length ≤28 mm. Cervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.
Publisher: Wiley
Date: 2022
DOI: 10.1002/UOG.24764
Abstract: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one‐fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS. This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non‐linear relationship with outcome. Optimal cut‐offs for those characteristics with a non‐linear pattern were determined based on the maximum area under the receiver‐operating‐characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome. Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31–35 years compared with younger women (aOR, 1.51 (95% CI, 1.15–1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34–12.18)) and in Sub‐Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33–3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04–1.08)). High birth‐weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74–4.07) for birth weight between the 80.0 th and 89.9 th percentiles and aOR, 4.08 (95% CI, 2.75–6.05) for birth weight ≥ 90 th percentile, as compared with birth weight between the 20.0 th and 49.9 th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05–1.12)) and BMI (aOR, 1.05 (95% CI, 1.03–1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76–9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23–5.10)). Birth weight 10.0 th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22–3.05)), as compared with birth weight between the 20.0 th and 49.9 th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC. In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth‐weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Publisher: Authorea, Inc.
Date: 15-10-2023
Publisher: Wiley
Date: 07-03-2019
DOI: 10.1111/AOGS.13558
Publisher: Wiley
Date: 14-09-2018
DOI: 10.1111/AOGS.13438
Publisher: Oxford University Press (OUP)
Date: 14-07-2020
Abstract: Network meta-analysis allows researchers to synthesise both direct and indirect evidence, thus enabling simultaneous comparisons of multiple treatments. A relatively recent addition to evidence synthesis in reproductive medicine, this approach has become increasingly popular. Yet, the underlying assumptions of network meta-analyses, which drive the validity of their findings, have been frequently ignored. In this article, we discuss the strengths and limitations of network meta-analyses. In addition, we present an overview of published network meta-analyses in reproductive medicine, summarize their challenges and provide insights into future research opportunities.
Publisher: Oxford University Press (OUP)
Date: 26-02-2020
Abstract: What are clinicians’ views about the diagnosis of polycystic ovary syndrome (PCOS), and how do they handle any complexities and uncertainties in practice? Clinicians have to navigate many areas of complexity and uncertainty regarding the diagnosis of PCOS, related to the diagnostic criteria, limitations in current evidence and misconceptions surrounding diagnosis, and expressed concern about the risk and consequences of both under- and overdiagnosis. PCOS is a complex, heterogeneous condition with many areas of uncertainty, raising concerns about both underdiagnosis and overdiagnosis. Quantitative studies with clinicians have found considerable variation in diagnostic criteria used and care provided, as well as a lack of awareness around the breadth of PCOS features and poor uptake of recommended screening for metabolic complications. Clinicians’ views about the uncertainties and complexities of diagnosing PCOS have not been explored. Semi-structured telephone interviews were conducted with clinicians from September 2017 to July 2018 to explore their perceptions about the diagnosis of PCOS, including how they handle any complexities and uncertainties in practice. A group of 36 clinicians (15 general practitioners, 10 gynaecologists and 11 endocrinologists) currently practicing in Australia, were recruited through advertising via professional organisations, contacting a random s le of endocrine and gynaecology teams across Australia and snowballing. Transcribed audio-recordings were analysed thematically using Framework analysis. Clinicians expressed a range of uncertainties and complexities regarding the diagnosis of PCOS, which were organised into three areas: (i) establishing diagnosis (e.g. lack of standardisation regarding diagnostic cut-offs, risk of misdiagnosis), (ii) factors influencing the diagnostic process (e.g. awareness of limitations in evidence and consideration of the benefits and harms) and (iii) strategies for handling challenges and uncertainties (e.g. using caution and communication of uncertainties). Clinicians also varied in their concerns regarding under- and overdiagnosis. Overall, most felt the diagnosis was beneficial for women provided that it was the correct diagnosis and time was taken to assess patient expectations and dispel misconceptions, particularly concerning fertility. There is possible selection bias, as clinicians who are more knowledgeable about PCOS may have been more likely to participate. Clinicians’ views may also differ in other countries. These findings underscore the vital need to first consider PCOS a diagnosis of exclusion and use caution before giving a diagnosis in order to reduce misdiagnosis, as suggested by clinicians in our study. Until there is greater standardisation of diagnostic criteria, more transparent conversations with women may help them understand the uncertainties surrounding the criteria and limitations in the evidence. Additionally, clinicians emphasised the importance of education and reassurance to minimise the potential harmful impact of the diagnosis and improve patient-centred outcomes. The study was funded by the University of Sydney Lifespan Research Network and an NHMRC Program Grant (APP1113532). T.C. is supported by an Australian Government Research Training Program (RTP) Scholarship and a Sydney Medical School Foundation Scholarship, from the The University of Sydney, Australia. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. No further competing interests exist. N/A
Publisher: Informa UK Limited
Date: 10-2023
Publisher: Oxford University Press (OUP)
Date: 24-09-2020
Abstract: Is one cycle of IVM non-inferior to one cycle of conventional in IVF with respect to live birth rates in women with high antral follicle counts (AFCs)? We could not demonstrate non-inferiority of IVM compared with IVF. IVF with ovarian hyperstimulation has limitations in some subgroups of women at high risk of ovarian stimulation, such as those with polycystic ovary syndrome. IVM is an alternative ART for these women. IVM may be a feasible alternative to IVF in women with a high AFC, but there is a lack of data from randomized clinical trials comparing IVM with IVF in women at high risk of ovarian hyperstimulation syndrome. This single-center, randomized, controlled non-inferiority trial was conducted at an academic infertility center in Vietnam from January 2018 to April 2019. In total, 546 women with an indication for ART and a high AFC (≥24 follicles in both ovaries) were randomized to the IVM (n = 273) group or the IVF (n = 273) group each underwent one cycle of IVM with a prematuration step versus one cycle of IVF using a standard gonadotropin-releasing hormone antagonist protocol with gonadotropin-releasing hormone agonist triggering. The primary endpoint was live birth rate after the first embryo transfer. The non-inferiority margin for IVM versus IVF was −10%. Live birth after the first embryo transfer occurred in 96 women (35.2%) in the IVM group and 118 women (43.2%) in the IVF group (absolute risk difference –8.1% 95% confidence interval (CI) –16.6%, 0.5%). Cumulative ongoing pregnancy rates at 12 months after randomization were 44.0% in the IVM group and 62.6% in the IVF group (absolute risk difference –18.7% 95% CI –27.3%, –10.1%). Ovarian hyperstimulation syndrome did not occur in the IVM group, versus two cases in the IVF group. There were no statistically significant differences between the IVM and IVF groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications. The main limitation of the study was its open-label design. In addition, the findings are only applicable to IVM conducted using the prematuration step protocol used in this study. Finally, the single ethnicity population limits the external generalizability of the findings. Our randomized clinical trial compares live birth rates after IVM and IVF. Although IVM is a viable and safe alternative to IVF that may be suitable for some women seeking a mild ART approach, the current study findings approach inferiority for IVM compared with IVF when cumulative outcomes are considered. Future research should incorporate multiple cycles of IVM in the study design to estimate cumulative fertility outcomes and better inform clinical decision-making. This work was partly supported by Ferring grant number 000323 and funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) and by the Fund for Research Flanders (FWO). LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring RJN has received conference and scientific board fees from Ferring, is a minor shareholder in an IVF company, and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant RBG reports grants and fellowships from the NHMRC of Australia JS reports lecture fees from Ferring Pharmaceuticals, Biomérieux, Besins Female Healthcare and Merck, grants from Fund for Research Flanders (FWO), and is co-inventor on granted patents on CAPA-IVM methodology in the US (US10392601B2) and Europe (EP3234112B1) TDP, VQD, VNAH, NHG, AHL, THP and RW have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. NCT03405701 (www.clinicaltrials.gov). 16 January 2018. 25 January 2018.
Publisher: Wiley
Date: 06-2019
DOI: 10.1111/AJO.12975
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 05-04-2019
DOI: 10.1007/S00404-019-05136-6
Abstract: This study explored the probability and outcome of delivery in women with placenta accreta spectrum (PAS) according to gestational age at delivery. A retrospective cohort study among women with PAS who had cesarean section was conducted. The gestational week (gw) of delivery and estimated blood loss (EBL) were recorded. The proportion of urgent delivery beyond 32 gw and EBL in women with or without antepartum suspected diagnosis of placenta accreta was compared. Totally, 180 women with PAS were enrolled. Of these, 54 (30.0%, 95% CI 23.8-37.1%) were delivered by urgent cesarean delivery and 126 (70.0%, 95% CI 62.9-76.2%) by elective cesarean section. The probability of emergent delivery was increased from 3.1 to 5.7% at 33-36 weeks, and increased by > 10% beyond 37 weeks. Among 121 antenatal suspected PAS patients, 25 (20.7%, 95% CI 14.4-28.7%) had emergency cesarean section, and 96 (79.3%, 95% CI 71.3-85.6%) experienced elective cesarean. The EBL of PAS in both emergent group (r = - 0.276, p = 0.044) and elective group (r = - 0.370, p < 0.001) was significantly decreased with gestational age progression. The antepartum hemorrhage increased the risk of urgent delivery [OR 2.54 (1.19, 5.44)] (p = 0.016), while PAS with antepartum diagnosis decreased the risk [OR 0.21 (0.10, 0.43)] (p < 0.001). Although the incidence of emergency operation in PAS patients was increased at 32-36 gw, there was no significant difference among the groups. The decision of timing for pregnancy termination should be made cautiously. We recommend scheduled operation at around 36-37 gw. In serious cases, the termination time could be arranged as early as appropriate.
Publisher: S. Karger AG
Date: 2022
DOI: 10.1159/000523996
Abstract: b i Introduction: /i /b Cervical length is an important predictor of spontaneous preterm birth. So far, the best way to measure cervical length has not been established. We aimed to compare the incidence of short cervical length between three methods of cervical length measurement with and without the inclusion of cervico-isthmic complex (CIC) (six methods in total) and to determine the positive predictive value for spontaneous preterm birth. b i Material and Methods: /i /b We performed a prospective single-center cohort study in women with a singleton pregnancy between August 2014 and December 2018. During the routine fetal anomaly scan (18–22 weeks), women were offered transvaginal ultrasound for cervical length measurement to screen for the risk of spontaneous preterm birth. Each cervix was measured in six different ways: single-line, two-line, and tracing method between the internal and external os of the cervix with and without CIC. We evaluated the predictive value of the different measurements for spontaneous delivery before 37 weeks using positive predictive values. b i Results: /i /b Our final study population comprised 1,691 women. The overall rate of preterm birth & #x3c weeks was 8.0% (4.6% spontaneous, 3.4% iatrogenic preterm birth). The mean gestational age at cervical length measurement was 19+6 weeks. The different measuring techniques resulted in significant different cervical lengths, showing a maximum difference of & #x3e mm between the techniques (41.04 mm [SD 7.1] with one-line without CIC and 49.18 [SD 9.05] mm with trace with CIC) with an incidence of short cervical length below & #x3c mm ranging from 0.4% to 1.1% ( i /i = 0.18). The positive predictive values for spontaneous preterm birth & #x3c weeks ranged from 42.9% to 20.0%. b i Conclusion: /i /b Different measurement methods for cervical length resulted in statistically significant differences in measured cervical length. Depending on the chosen cut-off this translates to different incidences of short cervical length and influences the number of women designated as high risk for preterm birth and receiving treatment. For interpretation and comparability between (inter-) national studies, it is important to adequately report on the employed technique. Future research should focus on determining the optimal measuring technique and a universal method of measurement.
Publisher: SAGE Publications
Date: 04-01-2019
Abstract: Responsiveness and the minimal important change (MIC) are important measurement properties to evaluate treatment effects and to interpret clinical trial results. The International Knee Documentation Committee (IKDC) Subjective Knee Form is a reliable and valid instrument for measuring patient-reported knee-specific symptoms, functioning, and sports activities in a population with meniscal tears. However, evidence on responsiveness is of limited methodological quality, and the MIC has not yet been established for patients with symptomatic meniscal tears. To evaluate the responsiveness and determine the MIC of the IKDC for patients with meniscal tears. Cohort study (design) Level of evidence 2. This study was part of the ESCAPE trial: a noninferiority multicenter randomized controlled trial comparing arthroscopic partial meniscectomy with physical therapy. Patients aged 45 to 70 years who were treated for a meniscal tear by arthroscopic partial meniscectomy or physical therapy completed the IKDC and 3 other questionnaires (RAND 36-Item Health Survey, EuroQol-5D-5L, and visual analog scales for pain) at baseline and 6-month follow-up. Responsiveness was evaluated by testing predefined hypotheses about the relation of the change in IKDC with regard to the change in the other self-reported outcomes. An external anchor question was used to distinguish patients reporting improvement versus no change in daily functioning. The MIC was determined by the optimal cutoff point in the receiver operating characteristic curve, which quantifies the IKDC score that best discriminated between patients with and without improvement in daily function. Data from all 298 patients who completed baseline and 6-month follow-up questionnaires were analyzed. Responsiveness of the IKDC was confirmed in 7 of 10 predefined hypotheses about the change in IKDC score with regard to other patient-reported outcome measures. One hypothesis differed in the expected direction, while 2 hypotheses failed to meet the expected magnitude by 0.02 and 0.01 points. An MIC of 10.9 points was calculated for the IKDC of middle-aged and older patients with meniscal tears. This study showed that the IKDC is responsive to change among patients aged 45 to 70 years with meniscal tears, with an MIC of 10.9 points. This strengthens the value of the IKDC in quantifying treatment effects in this population.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ben Willem Mol.