ORCID Profile
0000-0003-1813-3971
Current Organisations
O&G
,
Embrace Fertility
,
Associate Professor Louise Hull Fertility Practice
,
Women's and Children's Hospital
,
University of Adelaide
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Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.FERTNSTERT.2022.04.023
Abstract: Immune cells are essential for endometrial receptivity to embryo implantation and early placental development. They exert tissue-remodeling and immune regulatory roles-acting to promote epithelial attachment competence, regulate the differentiation of decidual cells, remodel the uterine vasculature, control and resolve inflammatory activation, and suppress destructive immunity to paternally inherited alloantigens. From a biological perspective, the endometrial immune response exerts a form of "quality control"-it promotes implantation success when conditions are favorable but constrains receptivity when physiological circumstances are not ideal. Women with recurrent implantation failure and recurrent miscarriage may exhibit altered numbers or disturbed function of certain uterine immune cell populations-most notably uterine natural killer cells and regulatory T cells. Preclinical and animal studies indicate that deficiencies or aberrant activation states in these cells can be causal in the pathophysiological mechanisms of infertility. Immune cells are, therefore, targets for diagnostic evaluation and therapeutic intervention. However, current diagnostic tests are overly simplistic and have limited clinical utility. To be more informative, they need to account for the full complexity and reflect the range of perturbations that can occur in uterine immune cell phenotypes and networks. Moreover, safe and effective interventions to modulate these cells are in their infancy, and personalized approaches matched to specific diagnostic criteria will be needed. Here we summarize current biological understanding and identify knowledge gaps to be resolved before the promise of therapies to target the uterine immune response can be fully realized.
Publisher: The Endocrine Society
Date: 06-2003
Abstract: Endometriosis is a disease in which the lining of the uterus (endometrium), shed at the time of menstruation, becomes established at sites such as the peritoneum and ovaries. These explants develop a rich blood supply that enables them to survive and grow. We hypothesized that inhibitors of angiogenesis would prevent this growth by disrupting sensitive vessels supplying endometriotic lesions. Vessels sensitive to angiogenic antagonism have few associations with pericyte cells. The vessels supplying human endometriotic lesions were immunohistochemically characterized and found to be predominantly pericyte free. A model in which human endometrium is implanted into nude mice was used to test the effects of two antagonists of the angiogenic growth factor, vascular endothelial cell growth factor A. Soluble truncated receptor (flt-1 P = 0.002) and an affinity-purified antibody to human vascular endothelial cell growth factor A (P = 0.03) significantly inhibited the growth of nude mouse explants. Pericyte-free vessels were shown to supply endometrial lesions in nude mice and were disrupted in lesions taken from soluble flt-1-treated mice. In summary, antiangiogenic agents inhibited the growth of explants in an in vivo model of endometriosis by disrupting the vascular supply, and this effect is likely to apply to the human disease. These findings suggest that antiangiogenic agents may provide a novel therapeutic approach for the treatment of endometriosis.
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.FERTNSTERT.2020.11.014
Abstract: Can the priorities for future research in infertility be identified? The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, erse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were erse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require erse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. We used consensus development methods, which have inherent limitations, including the representativeness of the participant s le, methodological decisions informed by professional judgement, and arbitrary consensus definitions. We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. Not applicable.
Publisher: Oxford University Press (OUP)
Date: 07-06-2022
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.FERTNSTERT.2020.11.012
Abstract: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy) pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy) live birth gestational age at delivery birthweight neonatal mortality and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. We used consensus development methods which have inherent limitations, including the representativeness of the participant s le, Delphi survey attrition, and an arbitrary consensus threshold. Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set. This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. Core Outcome Measures in Effectiveness Trials Initiative: 1023.
Publisher: Wiley
Date: 28-09-2022
DOI: 10.1111/CEN.14604
Abstract: Women with polycystic ovary syndrome (PCOS) report delayed diagnosis of the condition and receiving inadequate information at diagnosis. No studies have investigated the diagnosis experiences of adolescents with PCOS. Our objective was to investigate the adolescents' experiences of PCOS diagnosis and their concerns about the condition. Cross‐sectional study. Eighty‐six adolescents (aged 13–19 years) were diagnosed with PCOS by a medical practitioner. Adolescents were recruited consecutively from paediatric and women's outpatient hospital clinics in South Australia and online PCOS support organisations in Australia and the United Kingdom (May 2017–June 2019). PCOS diagnosis experience and information received at the time of diagnosis were evaluated using a validated questionnaire. The majority of the adolescents ( n = 67, 78%) were diagnosed with PCOS in less than 1 year from their first doctor's visit but 11 (13%) were diagnosed more than 2 years from that visit. Fifty‐three adolescents (66%) saw 1–2 health professionals before the diagnosis was made. Forty‐nine adolescents (57%) were satisfied with the overall diagnosis experience but adolescents were either dissatisfied or reported that the information was not mentioned after diagnosis in relation to lifestyle management ( n = 47, 55%), long‐term complications ( n = 53, 62%) and emotional support and counselling ( n = 65, 76%). The majority of adolescent girls with PCOS are receiving a timely diagnosis, but delayed diagnosis still occurs in a minority of adolescents. Current information provided at diagnosis is not meeting the needs of adolescents and is a lost opportunity for preventive healthcare at a critical transition to adult care period.
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 20-04-2016
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: Springer Science and Business Media LLC
Date: 02-2018
DOI: 10.1038/S41598-018-19263-8
Abstract: Diabetes has been linked with impaired fertility but the underlying mechanisms are not well defined. Here we use a streptozotocin-induced diabetes mouse model to investigate the cellular and biochemical changes in conceptus and maternal tissues that accompany hyperglycaemia. We report that streptozotocin treatment before conception induces profound intra-cellular protein β- O -glycosylation ( O -GlcNAc) in the oviduct and uterine epithelium, prominent in early pregnancy. Diabetic mice have impaired blastocyst development and reduced embryo implantation rates, and delayed mid-gestation growth and development. Peri-conception changes are accompanied by increased expression of pro-inflammatory cytokine Trail , and a trend towards increased Il1a , Tnf and Ifng in the uterus, and changes in local T-cell dynamics that skew the adaptive immune response to pregnancy, resulting in 60% fewer anti-inflammatory regulatory T-cells within the uterus-draining lymph nodes. Activation of the heat shock chaperones, a mechanism for stress deflection, was evident in the reproductive tract. Additionally, we show that the embryo exhibits elevated hyper- O -GlcNAcylation of both cytoplasmic and nuclear proteins, associated with activation of DNA damage (ɣH2AX) pathways. These results advance understanding of the impact of peri-conception diabetes, and provide a foundation for designing interventions to support healthy conception without propagation of disease legacy to offspring.
Publisher: Springer Nature Switzerland
Date: 2022
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.2147/JPR.S219684
Publisher: World Scientific Pub Co Pte Ltd
Date: 12-2019
DOI: 10.1142/S2661318219500178
Abstract: The intravenous fat emulsion, intralipid, has been hypothesised to be an effective and safe treatment for repeated in vitro fertilisation (IVF), implantation failure and pregnancy loss. This exploratory, retrospective cohort study determined pregnancy outcomes and documented adverse events associated with intralipid use. Ninety-three women were identified as having received intralipid for a history of repeated unsuccessful IVF cycles and pre-viable pregnancy loss in two Australian IVF units that independently recruited between October 2014 and July 2016. Pregnancy outcomes and adverse events were recorded in fresh and frozen embryo transfer cycles in which the infusion was administered. The 93 women who received intralipid had a clinical pregnancy rate of 40.0%, compared with 35.0% in 651 age-matched controls undergoing IVF, which was not significantly different. The intralipid group had a livebirth rate of 35.7%. Apart from flushing, which was experienced by one in idual, there were no adverse events associated with intralipid use. As a prelude to definitive evidence of benefit, we did not identify a safety concern or reduced pregnancy rates in intralipid users compared to controls. Indeed, these outcomes were better than expected in a poor prognosis group. This data supports an argument for large, randomised controlled trials to determine the benefit of intralipid in the treatment of recurrent implantation failure or miscarriage.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.JRI.2019.01.002
Abstract: Endometriotic lesion development involves complex interactions between endometrial tissue, the peritoneum and immune cells. Macrophages are essential in this process however their precise roles are not defined. To investigate whether infiltrating macrophages acquire functionally different phenotypes during lesion development, human endometrial tissues were grafted into immunodeficient mice expressing macrophage-specific green fluorescent protein (GFP). Although the numbers of GFP-positive macrophages were similar in lesions 4, 7, 10 and 14 days after grafting, their surface markers changed over time. Inflammatory markers MHC class II (MHC II) and iNOS were present on 36% and 41% of macrophages respectively early in lesion development at day 4, whereas abundance of tissue remodelling markers peaked later, with arginase 1 most highly expressed on 57% of macrophages at day 7 and scavenger receptor A (CD204) on 66% of macrophages at day 14. This is consistent with a transition from classical M1 macrophage activity to an alternate M2 profile, which correlates to histological hallmarks of initially acute inflammation followed by tissue remodelling during lesion development. This progressive shift in phenotype is likely to be relevant to the mechanisms by which macrophages are central players in endometriosis-like lesion development.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-07-2012
Abstract: Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3 P .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P .001), debulking surgery (CCR 2 or 3 P .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P .001) were independent predictors of a poorer overall survival. The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.
Publisher: SAGE Publications
Date: 12-2022
DOI: 10.1177/22840265221141527
Abstract: This study aimed to test group Physiotherapy sessions – pain education and supervised exercise − in addition to in idual consultations, for women referred with persistent pelvic pain (with/without endometriosis), with the primary outcomes being pain scores and pain impact. Parallel study design with three treatment arms: (1) usual care: a suite of in idual Physiotherapy consultations (2) introductory group pain education session followed by usual care and (3) introductory group pain education session followed by usual care and an 8-week supervised group exercise programme. Ninety women were recruited (30/treatment arm), with 66 women (73%) completing their allocated treatment. Participants were aged between 16 and 51 years endometriosis was confirmed in 41% ( n = 27/66) of the study population. Data was analysed using descriptive and inferential statistics. Statistically significant gains ( p 0.05) in pain scores and pelvic pain impact scores were observed in all arms. Between groups, there was statistically significant improvement ( p 0.05) in pelvic pain impact score for those who attended the group pain education session followed by usual care (arm 2), compared to usual care (arm 1) alone. There was no significant added improvement with the weekly supervised group exercise programme (arm 3), when compared to those who received the group pain education programme and usual care (arm 2). This study has demonstrated positive benefits of a group pain education session on pain scores and pelvic pain impact for women referred with persistent pelvic pain, when added as a precursor to in idual Physiotherapy consultations.
Publisher: AIP Publishing
Date: 15-10-2009
DOI: 10.1063/1.3253576
Abstract: Formation of defects in hexagonal and cubic boron nitride (h-BN and c-BN, respectively) under low-energy argon or nitrogen ion-bombardment has been studied by near-edge x-ray absorption fine structure (NEXAFS) around boron and nitrogen K-edges. Breaking of B–N bonds for both argon and nitrogen bombardment and formation of nitrogen vacancies, VN, has been identified from the B K-edge of both h-BN and c-BN, followed by the formation of molecular nitrogen, N2, at interstitial positions. The presence of N2 produces an additional peak in photoemission spectra around N 1s core level and a sharp resonance in the low-resolution NEXAFS spectra around N K-edge, showing the characteristic vibrational fine structure in high-resolution measurements. In addition, several new peaks within the energy gap of BN, identified by NEXAFS around B and N K-edges, have been assigned to boron or nitrogen interstitials, in good agreement with theoretical predictions. Ion bombardment destroys the cubic phase of c-BN and produces a phase similar to a damaged hexagonal phase.
Publisher: The Endocrine Society
Date: 03-01-2019
Abstract: Despite extensive searches for novel noninvasive diagnostics, laparoscopy remains the reference test for endometriosis. Circulating miRNAs are purported endometriosis biomarkers however, the miRNA species and their diagnostic accuracy differ between studies and have not been validated in independent cohorts. Identify endometriosis-specific plasma miRNAs and determine their diagnostic test accuracy. Two university-based, public hospitals and a private gynecology practice in Australia. Four phases: (i) Explorative phase. Plasma miRNA menstrual cycle fluctuations were evaluated in women with endometriosis and asymptomatic controls (n = 16). (ii) Biomarker discovery. Endometriosis-specific plasma miRNAs were identified in (a) women with endometriosis and asymptomatic controls (n = 16) and (b) women with and without surgically defined endometriosis (n = 20). (iii) Biomarker selection. Plasma miRNAs with the best diagnostic potential for endometriosis were selected in a surgically defined selection cohort (n = 78). (iv) Biomarker validation. The diagnostic test accuracy of these miRNAs was calculated in an independent, surgically defined validation cohort (n = 119). Forty-nine miRNAs were differentially expressed in women with endometriosis. Nine maintained dysregulation in the selection cohort, but only three (miR-155, miR574-3p and miR139-3p) did so in the validation cohort. Combined, these three miRNAs demonstrated a sensitivity and specificity of 83% and 51%, respectively. Plasma miRNAs demonstrated modest sensitivity and specificity as diagnostic tests or triage tools for endometriosis. Other groups' findings were not replicated and accorded poorly with our results. Circulating miRNAs demonstrate diagnostic potential, but stringent, standardized methodological approaches are required for the development of a clinically applicable tool.
Publisher: The Endocrine Society
Date: 04-07-2022
Abstract: Regulatory T (Treg) cells are a specialized CD4+ T cell subpopulation that are essential for immune homeostasis, immune tolerance, and protection against autoimmunity. There is evidence that sex-steroid hormones estrogen and progesterone modulate Treg cell abundance and phenotype in women. Since natural oscillations in these hormones are modified by hormonal contraceptives, we examined whether oral contraception (OC) use impacts Treg cells and related T cell populations. T cells were analyzed by multiparameter flow cytometry in peripheral blood collected across the menstrual cycle from healthy women either using OC or without hormonal contraception and from age-matched men. Compared to naturally cycling women, women using OC had fewer Treg cells and an altered Treg cell phenotype. Notably, Treg cells exhibiting a strongly suppressive phenotype, defined by high FOXP3, CD25, Helios, HLADR, CTLA4, and Ki67, comprised a lower proportion of total Treg cells, particularly in the early- and mid-cycle phases. The changes were moderate compared to more substantial differences in Treg cells between women and men, wherein women had fewer Treg cells—especially of the effector memory Treg cell subset—associated with more T helper type 1 (Th1) cells and CD8+ T cells and lower Treg:Th1 cell and Treg:CD8+ T cell ratios than men. These findings imply that OC can modulate the number and phenotype of peripheral blood Treg cells and raise the possibility that Treg cells contribute to the physiological changes and altered disease susceptibility linked with OC use.
Publisher: Oxford University Press (OUP)
Date: 02-09-2016
Abstract: There is ongoing interest in immune-suppressant corticosteroid drugs such as prednisolone to treat infertility in women with repeated IVF failure and recurrent miscarriage. The rationale draws on the pervasive but flawed view that immune activation is inconsistent with normal pregnancy. This ignores clear evidence that controlled inflammation and activation of the immune response is essential for embryo implantation. Generally, the immune response actively promotes reproductive success - by facilitating endometrial receptivity and tolerance of the foreign embryo, and promoting vascular adaptation to support placental morphogenesis. The peri-conception immune response also establishes developmental trajectories that can impact on fetal growth and gestational age at birth. Here, we describe immune changes accompanying conception that could be impeded by inappropriate corticosteroid administration. While women with specific clinical conditions may benefit from the anti-inflammatory and immune-deviating actions of prednisolone and related drugs, it is incorrect to assume a 'one-size-fits-all' approach. Better diagnostics and more preclinical studies are essential to define patient groups, build evidence for efficacy and fine-tune treatments so as not to inhibit essential actions of immune cells. We argue that unless overt immune pathology is evident, utilization of corticosteroids is not warranted and may be harmful. In most women, perturbing immune adaptation at implantation is expected to adversely influence placental development and impair immune-mediated quality control mechanisms, potentially elevating risk of altered fetal growth and developmental programming, congenital anomalies and preterm birth.
Publisher: SAGE Publications
Date: 2021
DOI: 10.1177/17455065211019717
Abstract: It is important to evaluate sequalae for complex chronic health conditions such as endometriosis and mental health disorders. Endometriosis impacts 1 in 10 women. Mental health outcomes can be a primary determinant in many physical health conditions although this is an area not well researched particularly in women’s health. This has been problematic for endometriosis patients in particular, who report mental health issues as well as other key comorbidities such as chronic pelvic pain and infertility. This could be partly due to the complexities associated with comprehensively exploring overlaps between physical and mental health disorders in the presence of multiple comorbidities and their potential mechanistic relationship. In this evidence synthesis, a systematic methodology and mixed-methods approaches were used to synthesize both qualitative and quantitative data to examine the prevalence of the overlapping sequalae between endometriosis and psychiatric symptoms and disorders. As part of this, an evidence synthesis protocol was developed which included a systematic review protocol that was published on PROSPERO (CRD42020181495). The aim was to identify and evaluate mental health reported outcomes and prevalence of symptoms and psychiatric disorders associated with endometriosis. A total of 34 papers were included in the systematic review and 15 were included in the meta-analysis. Anxiety and depression symptoms were the most commonly reported mental health outcomes while a pooled analysis also revealed high prevalence of chronic pelvic pain and dyspareunia. It is evident that small-scale cross-sectional studies have been conducted in a variety of settings to determine mental health outcomes among endometriosis patients. Further research is required to comprehensively evaluate the mental health sequalae with endometriosis.
Publisher: World Scientific Pub Co Pte Lt
Date: 30-01-2021
DOI: 10.1142/S2661318221500018
Abstract: BACKGROUND: Lipiodol has a dramatic short term fertility enhancing effect for women with endometriosis. Microarray studies have shown transcriptomic regulation of molecular markers of endometrial inflammation, most notably a consistent down-regulation of endometrial osteopontin. We further explored the endometrial bathing effect of lipiodol on leukocyte expression in endometrium. METHODS: A cohort of four women, nested within a randomised trial of twelve women assessing the lipiodol uterine bathing effect, was studied as an ‘own control’ group, with their mid-luteal endometrium assessed before and after endometrial lipiodol exposure. Pipelle endometrial s ling allowed endometrial assessment by immunochemistry. Endometrial tissue s les were assessed by immunochemistry for total CD45+ leukocytes, CD68+ macrophages, CD3+ T-cells and CD56+ uterine natural killer cells. RESULTS: There was a statistically significant increase in the mean density of uterine natural killer cells in the endometrium of women post-lipiodol. No other significant differences were found in the mean densities of all leukocytes, macrophages or T cells in the endometrium of women post-lipiodol. CONCLUSIONS: These preliminary data further support the concept of a uterine bathing effect of lipiodol. Whether the increase in the mean density of uterine natural killer cells in the endometrium might contribute to an improvement in endometrial receptivity to embryo implantation merits further investigation.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Oxford University Press (OUP)
Date: 2003
Abstract: The response of the human endometrium to the ovarian hormones, estrogen and progesterone, has been the focus of decades of research. In order to understand this critical aspect of endometrial physiology, we undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle. A high-density, oligonucleotide gene array, comprising 60 000 gene targets, was used to define the gene expression profile of proliferative and secretory phase endometrium. Results from the arrays were verified using real-time PCR. The expression levels of 149 transcripts differed significantly between the two phases of the cycle determined by stringent range limits (99.99%), calculated using local variance values. These transcripts include previously documented steroidally responsive genes (such as placental protein 14 and stromelysin-3) and novel transcripts not previously linked to either endometrial physiology or steroid regulation (such as intestinal trefoil factor and a number of expressed sequence tags). Examination of the 5' promoter regions of these genes identified many putative estrogen and progesterone receptor DNA binding domains, suggesting a direct response of these genes to the ovarian hormones.
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1328
Abstract: Intravenous infusion of Intralipid is an adjunct therapy in assisted reproduction treatment (ART) when immune‐associated infertility is suspected. Here, we evaluated the effect of Intralipid infusion on regulatory T cells (Treg cells), effector T cells and plasma cytokines in peripheral blood of women undertaking IVF. This prospective, observational pilot study assessed Intralipid infusion in 14 women exhibiting recurrent implantation failure, a clinical sign of immune‐associated infertility. Peripheral blood was collected immediately prior to and 7 days after intravenous administration of Intralipid. Plasma cytokines were measured by Luminex, and T‐cell subsets were analysed by flow cytometry. A small increase in conventional CD8 + T cells occurred after Intralipid infusion, but no change was seen in CD4 + Treg cells, or naïve, memory or effector memory T cells. Proliferation marker Ki67, transcription factors Tbet and RORγt, and markers of suppressive capacity CTLA4 and HLA‐DR were unchanged. Dimensionality‐reduction analysis using the tSNE algorithm confirmed no phenotype shift within Treg cells or other T cells. Intralipid infusion increased plasma CCL2, CCL3, CXCL8, GM‐CSF, G‐CSF, IL‐6, IL‐21, TNF and VEGF. Intralipid infusion elicited elevated pro‐inflammatory cytokines, and a minor increase in CD8 + T cells, but no change in pro‐tolerogenic Treg cells. Notwithstanding the limitation of no placebo control, the results do not support Intralipid as a candidate intervention to attenuate the Treg cell response in women undergoing ART. Future placebo‐controlled studies are needed to confirm the potential efficacy and clinical significance of Intralipid in attenuating cytokine induction and circulating CD8 + T cells.
Publisher: Wiley
Date: 13-07-2016
Publisher: Bioscientifica
Date: 19-10-2021
DOI: 10.1530/RAF-21-0031
Abstract: Pouch of Douglas (POD) obliteration is a severe consequence of inflammation in the pelvis, often seen in patients with endometriosis. The sliding sign is a dynamic transvaginal ultrasound (TVS) test that can diagnose POD obliteration. We aimed to develop a deep learning (DL) model to automatically classify the state of the POD using recorded videos depicting the sliding sign test. Two expert sonologists performed, interpreted, and recorded videos of consecutive patients from September 2018 to April 2020. The sliding sign was classified as positive (i.e. normal) or negative (i.e. abnormal POD obliteration). A DL model based on a temporal residual network was prospectively trained with a dataset of TVS videos. The model was tested on an independent test set and its diagnostic accuracy including area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive value (PPV/NPV) was compared to the reference standard sonologist classification (positive or negative sliding sign). In a dataset consisting of 749 videos, a positive sliding sign was depicted in 646 (86.2%) videos, whereas 103 (13.8%) videos depicted a negative sliding sign. The dataset was split into training (414 videos), validation (139), and testing (196) maintaining similar positive/negative proportions. When applied to the test dataset using a threshold of 0.9, the model achieved: AUC 96.5% (95% CI: 90.8–100.0%), an accuracy of 88.8% (95% CI: 83.5–92.8%), sensitivity of 88.6% (95% CI: 83.0–92.9%), specificity of 90.0% (95% CI: 68.3–98.8%), a PPV of 98.7% (95% CI: 95.4–99.7%), and an NPV of 47.7% (95% CI: 36.8–58.2%). We have developed an accurate DL model for the prediction of the TVS-based sliding sign classification. Endometriosis is a disease that affects females. It can cause very severe scarring inside the body, especially in the pelvis − called the pouch of Douglas (POD). An ultrasound test called the 'sliding sign' can diagnose POD scarring. In our study, we provided input to a computer on how to interpret the sliding sign and determine whether there was POD scarring or not. This is a type of artificial intelligence called deep learning (DL). For this purpose, two expert ultrasound specialists recorded 749 videos of the sliding sign. Most of them (646) were normal and 103 showed POD scarring. In order for the computer to interpret, both normal and abnormal videos were required. After providing the necessary inputs to the computer, the DL model was very accurate (almost nine out of every ten videos was correctly determined by the DL model). In conclusion, we have developed an artificial intelligence that can interpret ultrasound videos of the sliding sign that show POD scarring that is almost as accurate as the ultrasound specialists. We believe this could help increase the knowledge on POD scarring in people with endometriosis.
Publisher: Oxford University Press (OUP)
Date: 05-12-2016
Abstract: What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis? We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis. Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis. A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken. A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken. This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements. This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries - has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis. The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer Lone Hummelshoj is an unpaid consultant to AbbVie Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet Jörg Keckstein has received a travel grant from AbbVie Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms Rulla Tamimi Hugh Taylor. N/A.
Publisher: Informa UK Limited
Date: 12-2018
DOI: 10.2147/JPR.S179409
Publisher: JMIR Publications Inc.
Date: 05-2019
Abstract: olycystic Ovary Syndrome (PCOS) is a common endocrine condition characterized by irregular periods and hyperandrogenism. Adolescents with PCOS have impaired quality of life (QOL) and increased psychological distress. Transcendental Meditation (TM) is a well-established self-management strategy that has been used to improve stress and well-being. A meta-analysis of TM trials has shown beneficial effects on stress and blood pressure in adults. Recent data are suggesting that another self-management strategy called a mindfulness stress management program has a role in improving QOL in women with PCOS, but there are no studies in adolescents. his study aims to evaluate the effect of TM on QOL and psychological distress in adolescent girls with PCOS. his study is a randomized controlled trial that will be conducted over eight weeks at the Women’s and Children’s Hospital in Adelaide, South Australia, to determine the effect of TM on QOL and psychological distress in adolescent girls (aged 12-20 years) with PCOS. A total of 40 girls will be randomized into either the TM (n=20) or control group (n=20). The TM group will be asked to practice TM in a comfortable sitting position with the eyes closed, for 15 minutes twice daily over eight weeks. The control group will be asked to sit quietly for 15 minutes twice daily for eight weeks. The primary outcomes are any effects on improving QOL and psychological distress, and the secondary outcomes are any effects on lowering blood pressure and salivary cortisol levels. he recruitment of study participants began in May 2019 and is expected to be completed by June 2020. It is expected that the adolescent girls with PCOS practicing TM over eight weeks will have a significant improvement in QOL and psychological distress compared to adolescents in the control group. Also, it is expected that adolescent girls in the TM group will have lower salivary cortisol levels and lower blood pressure. his study will be the first to evaluate the effect of TM on QOL in adolescent girls with PCOS. The study will provide valuable information on a potential self-management strategy to improve QOL and well-being in adolescent girls with PCOS. ustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN1261900019010 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376657& isReview=true RR1-10.2196/14542
Publisher: Elsevier BV
Date: 09-2008
Publisher: Oxford University Press (OUP)
Date: 15-11-2018
Publisher: Springer Science and Business Media LLC
Date: 02-2017
Publisher: The Endocrine Society
Date: 12-2001
Abstract: It has been suggested that CRH is a placental clock that controls the duration of pregnancy and that the timing of the rise in CRH may permit prediction of the onset of labor. We have performed a prospective longitudinal study, in 297 women, to examine the utility of a single second-trimester plasma CRH measurement to predict preterm delivery. Venous blood s les were taken at 4-weekly intervals, beginning at 16–20 wk gestation, until delivery for CRH and its binding protein. A time point at which a single plasma CRH test might give optimal data to predict preterm delivery was determined. Thirty-one subjects delivered prematurely (10.4%). S ling for plasma CRH at 26 wk gestation seemed the optimal time point to maximize sensitivity and specificity of the test. The mean (± sd) plasma CRH in women at this gestation who eventually delivered after spontaneous labor within 1 wk of their due date (39–41 wk, n = 127) was 34.7 ± 27.0 pm. A plasma CRH of more than 90 pm at 26 wk gestation had a sensitivity of 45% and a specificity of 94% for prediction of preterm delivery. The positive predictive value was 46.7%. Calculation of free CRH did not improve these figures. In conclusion, a single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted. These data do not support the routine clinical use of plasma CRH as a predictor of preterm labor.
Publisher: Informa UK Limited
Date: 14-06-2019
Publisher: Oxford University Press (OUP)
Date: 22-09-2009
Abstract: microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal roles in the pathogenesis of these disorders. A systematic review was undertaken of the published literature on (i) the expression and functions of miRNAs in mammalian female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease and (ii) the potential roles played by validated mRNA targets of endometriosis-associated miRNAs. The current understanding of the biology of miRNAs is overviewed and the potential diagnostic and therapeutic potential of miRNAs in endometriosis is highlighted. The differential expression of miRNAs in endometriosis, and the putative molecular pathways constituted by their targets, suggests that miRNAs may play an important role in endometriotic lesion development. Models for miRNA regulatory functions in endometriosis are presented, including those associated with hypoxia, inflammation, tissue repair, TGFbeta-regulated pathways, cell growth, cell proliferation, apoptosis, extracellular matrix remodelling and angiogenesis. In addition, specific miRNAs which may be associated with malignant progression and subfertility in endometriosis are discussed. miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.
Publisher: Wiley
Date: 26-02-2016
Publisher: Informa UK Limited
Date: 03-2021
DOI: 10.2147/JPR.S279253
Publisher: The Endocrine Society
Date: 02-2009
DOI: 10.1210/ME.2008-0387
Publisher: The American Association of Immunologists
Date: 15-10-2022
Abstract: Pregnancy depends on a state of maternal immune tolerance mediated by CD4
Publisher: Wiley
Date: 23-12-2015
Publisher: Oxford University Press (OUP)
Date: 30-11-2020
Abstract: Can the priorities for future research in infertility be identified? The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, erse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were erse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require erse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. We used consensus development methods, which have inherent limitations, including the representativeness of the participant s le, methodological decisions informed by professional judgment and arbitrary consensus definitions. We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist’s Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. N/A.
Publisher: Oxford University Press (OUP)
Date: 30-11-2020
Abstract: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? Consensus definitions for in idual core outcomes, contextual statements and a standardized reporting table have been developed. Different definitions exist for in idual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. Core Outcome Measures in Effectiveness Trials Initiative: 1023.
Publisher: Wiley
Date: 09-08-2020
DOI: 10.1111/AJO.13222
Publisher: Elsevier BV
Date: 05-2020
Publisher: Wiley
Date: 05-2016
Publisher: JMIR Publications Inc.
Date: 24-01-2020
DOI: 10.2196/14542
Abstract: Polycystic Ovary Syndrome (PCOS) is a common endocrine condition characterized by irregular periods, hirsutism, acne, or hyperandrogenemia. Adolescents with PCOS have impaired quality of life (QOL) and increased psychological distress. Transcendental Meditation (TM) is a well-established self-management strategy that has been used to improve stress and well-being. A meta-analysis of TM trials has shown beneficial effects on stress and blood pressure in adults. Recent data are suggesting that another self-management strategy called a mindfulness stress management program has a role in improving QOL in women with PCOS, but there are no studies in adolescents. This study aims to evaluate the effect of TM on QOL and psychological distress in adolescent girls with PCOS. This study is a randomized controlled trial that will be conducted over eight weeks at the Women’s and Children’s Hospital in Adelaide, South Australia, to determine the effect of TM on QOL and psychological distress in adolescent girls (aged 12-20 years) with PCOS. A total of 40 girls will be randomized into either the TM (n=20) or control group (n=20). The TM group will be asked to practice TM in a comfortable sitting position with the eyes closed, for 15 minutes twice daily over eight weeks. The control group will be asked to sit quietly for 15 minutes twice daily for eight weeks. The primary outcomes are any effects on improving QOL and psychological distress, and the secondary outcomes are any effects on lowering blood pressure and salivary cortisol levels. The recruitment of study participants began in May 2019 and is expected to be completed by June 2020. It is expected that the adolescent girls with PCOS practicing TM over eight weeks will have a significant improvement in QOL and psychological distress compared to adolescents in the control group. Also, it is expected that adolescent girls in the TM group will have lower salivary cortisol levels and lower blood pressure. This study will be the first to evaluate the effect of TM on QOL in adolescent girls with PCOS. The study will provide valuable information on a potential self-management strategy to improve QOL and well-being in adolescent girls with PCOS. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN1261900019010 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376657& isReview=true
Publisher: Cold Spring Harbor Laboratory
Date: 04-03-2022
DOI: 10.1101/2022.03.02.22271773
Abstract: Pain is a silent global epidemic impacting approximately a third of the population. Pharmacological and surgical interventions are primary modes of treatment. Cognitive/behavioural management approaches and interventional pain management strategies are approaches that have been used to assist with the management of chronic pain. Accurate data collection and reporting treatment outcomes are vital to addressing the challenges faced. In light of this, we conducted a systematic evaluation of the current digital application landscape within chronic pain medicine. The primary objective was to consider the prevalence of digital application usage for chronic pain management. These digital applications included mobile apps, web apps, and chatbots. We conducted searches on PubMed and ScienceDirect for studies that were published between 1st January 1990 and 1st January 2021. Our review included studies that involved the use of digital applications for chronic pain conditions. There were no restrictions on the country in which the study was conducted. Only studies that were peer-reviewed and published in English were included. Four reviewers had assessed the eligibility of each study against the inclusion/exclusion criteria. Out of the 84 studies that were initially identified, 38 were included in the systematic review. The AMSTAR guidelines were used to assess data quality. This assessment was carried out by 3 reviewers. The data were pooled using a random-effects model. Before data collection began, the primary outcome was to report on the prevalence of digital application usage for chronic pain conditions. We also recorded the type of digital application studied (e.g. mobile application, web application) and, where the data was available, the prevalence of pain intensity, pain inferences, depression, anxiety, and fatigue. 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The digital interventions were categorised to web and mobile applications and chatbots, with pooled prevalence of 0.22 (95% CI −0.16, 0.60), 0.30 (95% CI 0.00, 0.60) and −0.02 (95% CI −0.47, 0.42) respectively. Pooled standard mean differences for symptomatologies of pain intensity, depression, and anxiety symptoms were 0.25 (95% CI 0.03, 0.46), 0.30 (95% CI 0.17, 0.43) and 0.37 (95% CI 0.05, 0.69) respectively. A sub-group analysis was conducted on pain intensity due to the heterogeneity of the results (I 2 =82.86% p=0.02). After stratifying by country, we found that digital applications were more likely to be effective in some countries (e.g. USA, China) than others (e.g. Ireland, Norway). The use of digital applications in improving pain-related symptoms shows promise, but further clinical studies would be needed to develop more robust applications.
Publisher: Oxford University Press (OUP)
Date: 25-04-2018
Abstract: Endometriosis is a benign gynaecological disorder, which affects 10% of reproductive-aged women and is characterized by endometrial cells from the lining of the uterus being found outside the uterine cavity. However, the pathophysiological mechanisms causing the development of this heterogeneous disease remain enigmatic, and a lack of effective biomarkers necessitates surgical intervention for diagnosis. There is international recognition that accurate non-invasive diagnostic tests and more effective therapies are urgently needed. Non-coding RNA (ncRNA) molecules, which are important regulators of cellular function, have been implicated in many chronic conditions. In endometriosis, transcriptome profiling of tissue s les and functional in vivo and in vitro studies demonstrate that ncRNAs are key contributors to the disease process. In this review, we outline the biogenesis of various ncRNAs relevant to endometriosis and then summarize the evidence indicating their roles in regulatory pathways that govern disease establishment and progression. Articles from 2000 to 2016 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: ncRNA and reproduction ncRNA and endometriosis miRNA and endometriosis lncRNA and endometriosis siRNA and endometriosis endometriosis endometrial cervical ovary uterus reproductive tract. All articles were independently screened for eligibility by the authors. This review integrates extensive information from all relevant published studies focusing on microRNAs, long ncRNAs and short inhibitory RNAs in endometriosis. We outline the biological function and synthesis of microRNAs, long ncRNAs and short inhibitory RNAs and provide detailed findings from human research as well as functional studies carried out both in vitro and in vivo, including animal models. Although variability in findings between in idual studies exists, collectively, the extant literature justifies the conclusion that dysregulated ncRNAs are a significant element of the endometriosis condition. There is a compelling case that microRNAs, long non-coding RNAs and short inhibitory RNAs have the potential to influence endometriosis development and persistence through modulating inflammation, proliferation, angiogenesis and tissue remodelling. Rapid advances in ncRNA biomarker discovery and therapeutics relevant to endometriosis are emerging. Unravelling the significance of ncRNAs in endometriosis will pave the way for new diagnostic tests and identify new therapeutic targets and treatment approaches that have the potential to improve clinical options for women with this disabling condition.
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: Frontiers Media SA
Date: 02-11-2022
DOI: 10.3389/FDGTH.2022.850601
Abstract: Pain is a silent global epidemic impacting approximately a third of the population. Pharmacological and surgical interventions are primary modes of treatment. Cognitive/behavioural management approaches and interventional pain management strategies are approaches that have been used to assist with the management of chronic pain. Accurate data collection and reporting treatment outcomes are vital to addressing the challenges faced. In light of this, we conducted a systematic evaluation of the current digital application landscape within chronic pain medicine. The primary objective was to consider the prevalence of digital application usage for chronic pain management. These digital applications included mobile apps, web apps, and chatbots. We conducted searches on PubMed and ScienceDirect for studies that were published between 1st January 1990 and 1st January 2021. Our review included studies that involved the use of digital applications for chronic pain conditions. There were no restrictions on the country in which the study was conducted. Only studies that were peer-reviewed and published in English were included. Four reviewers had assessed the eligibility of each study against the inclusion/exclusion criteria. Out of the 84 studies that were initially identified, 38 were included in the systematic review. The AMSTAR guidelines were used to assess data quality. This assessment was carried out by 3 reviewers. The data were pooled using a random-effects model. Before data collection began, the primary outcome was to report on the standard mean difference of digital application usage for chronic pain conditions. We also recorded the type of digital application studied (e.g., mobile application, web application) and, where the data was available, the standard mean difference of pain intensity, pain inferences, depression, anxiety, and fatigue. 38 studies were included in the systematic review and 22 studies were included in the meta-analysis. The digital interventions were categorised to web and mobile applications and chatbots, with pooled standard mean difference of 0.22 (95% CI: −0.16, 0.60), 0.30 (95% CI: 0.00, 0.60) and −0.02 (95% CI: −0.47, 0.42) respectively. Pooled standard mean differences for symptomatologies of pain intensity, depression, and anxiety symptoms were 0.25 (95% CI: 0.03, 0.46), 0.30 (95% CI: 0.17, 0.43) and 0.37 (95% CI: 0.05, 0.69), respectively. A sub-group analysis was conducted on pain intensity due to the heterogeneity of the results ( I 2 = 82.86% p = 0.02). After stratifying by country, we found that digital applications were more likely to be effective in some countries (e.g., United States, China) than others (e.g., Ireland, Norway). The use of digital applications in improving pain-related symptoms shows promise, but further clinical studies would be needed to develop more robust applications. www.crd.york.ac.uk rospero/ , identifier: CRD42021228343.
Publisher: JMIR Publications Inc.
Date: 20-04-2023
Abstract: -health websites are being increasingly used to obtain information about endometriosis by the community and for self-learning and for recommendations to patients by clinicians. Critical evaluation is needed to inform users of their quality. o evaluate the quality of endometriosis e-health websites and provide high-quality recommendations to the community and clinicians. RISMA 2020 guidelines informed two Google searches using incognito mode of international and Australian e-health websites. The first search string used terms ‘endometriosis’, ‘adenomyosis’ or ‘pelvic pain’ whereas ‘Australia’ was added to the second search string. Only free e-health websites in English were included. ENLIGHT, a validated tool, assessed the quality of each e-health website across 7 domains. A final average score of .7 was considered high-quality. ifty-nine e-health websites were screened and 49 included. Eleven high-quality websites were identified: Endometriosis Australia Facebook Page, Endometriosis UK, National Action Plan for Endometriosis on EndoActive, Endometriosis by Jean Hailes for Women’s Health, Adenomyosis by Jean Hailes for Women’s Health, Endometriosis by IVF Australia, Adenomyosis by Sydney Morning Herald, Endometriosis by National Health System, Endometriosis by Safe Work Australia, Adenomyosis by the Medical Republic, and Endometriosis by Royal Australian College for General Practitioners. These websites provided easily understood, accurate information. The last two e-health websites were resources for clinicians. Recommendations on search engine optimisation are provided to improve reach and discoverability of e-health websites. lthough geographical location can influence the search results, we identified eleven high-quality endometriosis e-health websites that can be recommended to those with endometriosis and clinicians. To improve Google ranking, e-health websites should leverage search engine optimisation tools. systematic review protocol was developed and registered with the international prospective register of systematic reviews (PROSPERO registration CRD42020185475) after which the systematic review was conducted according to PRISMA guidelines.
Publisher: Wiley
Date: 27-07-2023
Abstract: This study aimed to assess the accuracy of transvaginal ultrasound (TVUS) for the mapping of endometriosis before surgery when performed by sonographers in an outpatient women's imaging centre. A prospective longitudinal cohort study was performed. The study group comprised of 201 women who underwent a comprehensive TVUS assessment, performed by a sonographer. Laparoscopy was performed as the reference standard. Complete TVUS and surgical data were available for 53 women who were included in the final analysis. Endometriosis was confirmed at a surgery in 50/53 (94.3%) participants, with 25/53 (47.2%) having deep endometriosis (DE) nodules and/or endometriomas present. TVUS for mapping of DE had an overall sensitivity of 84.0%, specificity of 89.3%, PPV of 87.5%, NPV of 86.2%, LR+ of 7.85, LR− of 0.18, and accuracy of 86.8% ( P 0.001). Ovarian immobility had poor sensitivity for detecting localised superficial endometriosis, DE, adhesions, and/or endometriomas (Left = 61.9% and right = 13.3%) but high specificities (left = 87.5% and right = 94.7%). Site‐specific tenderness had low sensitivities and moderate specificities for the same. All soft markers of endometriosis failed to reach statistical significance except for left ovarian immobility ( P = .001). Sonographers well experienced in obstetric and gynaecological imaging, working in an outpatient women's imaging setting can accurately map DE however, the performance of soft markers for detection of SE was poor.
Location: Australia
No related grants have been discovered for Mary Louise Hull.