ORCID Profile
0000-0002-3118-3896
Current Organisation
University of Adelaide
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Publisher: Oxford University Press (OUP)
Date: 19-07-2018
Publisher: Wiley
Date: 10-07-2009
Publisher: Wiley
Date: 03-1930
Publisher: Elsevier BV
Date: 07-2023
Publisher: Oxford University Press (OUP)
Date: 24-08-2018
Abstract: Is a freeze-only strategy more cost-effective from a patient perspective than fresh embryo transfer (ET) after one completed In Vitro Fertilization/ Intracytoplasmic Sperm Injection (IVF/ICSI) cycle in women without polycystic ovary syndrome (PCOS)? There is a low probability of the freeze-only strategy being cost-effective over the fresh ET strategy for non-PCOS women undergoing IVF/ICSI. Conventionally, IVF embryos are transferred in the same cycle in which oocytes are collected, while any remaining embryos are frozen and stored. We recently evaluated the effectiveness of a freeze-only strategy compared with a fresh ET strategy in a randomized controlled trial (RCT). There was no difference in live birth rate between the two strategies. A cost-effectiveness analysis (CEA) was performed alongside the RCT to compare a freeze-only strategy with a fresh ET strategy in non-PCOS women undergoing IVF/ICSI. The effectiveness measure for the CEA was the live birth rate. Data on the IVF procedure, pregnancy outcomes and complications were collected from chart review additional information was obtained using patient questionnaires, by telephone. For all patients, we measured the direct medical costs relating to treatment (cryopreservation, pregnancy follow-up, delivery), direct non-medical costs (travel, accommodation) and indirect costs (income lost). The direct cost data were calculated from resources obtained from patient records and prices were applied based on a micro-costing approach. Indirect costs were calculated based on responses to the questionnaire. Patients were followed until all embryos obtained from a single controlled ovarian hyperstimulation cycle were used or a live birth was achieved. The incremental cost-effectiveness ratio (ICER) was based on the incremental cost per couple and the incremental live birth rate of the freeze-only strategy compared with the fresh ET strategy. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were also performed. Between June 2015 and April 2016, 782 couples were randomized to a freeze-only (n = 391) or a fresh ET strategy (n = 391). Baseline characteristics including mean age, Body Mass Index (BMI), anti-Mullerian hormone, total dose of Follicle Stimulating Hormone (FSH), number of oocytes obtained, good quality Day 3 embryos, fertility outcomes and treatment complications were comparable between the two groups. The live birth rate (48.6% vs. 47.3%, respectively risk ratio, 1.03 95% Confidence Interval [CI], 0.89, 1.19 P = 0.78) and the average cost per couple (3906 vs. 3512 EUR, respectively absolute difference 393.6, 95% CI, -76.2, 863.5 P = 0.1) were similar in the freeze-only group versus fresh ET. Corresponding costs per live birth were 8037 EUR versus 7425 EUR in the freeze-only versus fresh ET group, respectively. The incremental cost for the freeze-only strategy compared with fresh ET was 30 997 EUR per 1% additional live birth rate. The direct non-medical costs and indirect costs of infertility treatment strategies represented ~45-52% of the total cost. PSA shows that the 95% CI of ICERs was -263 901 to 286 681 EUR. Out of 1000 simulations, 44% resulted in negative ICERs, including 13.0% of simulations in which the freeze-only strategy was dominant (more effective and less costly than fresh ET), and 31% of simulations in which the fresh embryo strategy was dominant. In the other 560 simulations with positive ICERs, the 95% CI of ICERs ranged from 2155 to 471 578 EUR. The CEAC shows that at a willingness to pay threshold of 300 000 EUR, the probability of the freeze-only strategy being cost-effective over the fresh ET strategy would be 58%. Data were collected from a single private IVF center study in Vietnam where there is no public or insurance funding of IVF. Unit costs obtained might not be representative of other settings. Data obtained from secondary sources (medical records, financial and activity reports) could lack authenticity, and recall bias may have influenced questionnaire responses on which direct costs were based. In non-PCOS women undergoing IVF/ICSI, the results suggested that the freeze-only strategy was not cost-effective compared with fresh ET from a patient perspective. These findings indicate that other factors could be more important in deciding whether to use a freeze-only versus fresh ET strategy in this patient group. This study was funded by My Duc Hospital no external funding was received. Ben Willem J. Mol is supported by an NHMRC Practioner Fellowship (GNT 1082548) and reports consultancy for Merck, ObsEva and Guerbet. Robert J. Norman has shares in an IVF company and has received support from Merck and Ferring. All other authors have no conflicts of interest to declare. Not applicable.
Publisher: The Endocrine Society
Date: 11-2003
DOI: 10.1210/EN.2003-0584
Publisher: Wiley
Date: 19-10-2019
DOI: 10.1111/OBR.12762
Abstract: Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta-analysis and meta-regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta-regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high-density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2-hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA-IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.
Publisher: Elsevier BV
Date: 04-1997
DOI: 10.1111/J.1467-842X.1997.TB01670.X
Abstract: We conducted a brief health survey of adults in an isolated Northern Territory Aboriginal community, whose standardised mortality rates are the second highest in Australia. The screen revealed high rates of smoking and excessive drinking, of preventable infections and their sequelae, and of hypertension, insulin resistance, diabetes and renal disease. The infectious morbidities were more pronounced and the life-style morbidities almost entirely new since a health screen in 1957. Most morbidities were strongly associated with identifiable risk factors, such as overweight, smoking, excessive drinking, skin sores and scabies, all of which which are amenable to modification. Problems with food supply and pricing, poor food choices and ersion of money to cigarettes, beer and gambling all contributed to poor nutrition. Low birthweight probably compounds the risk for serious adult disease associated with these environmental influences. This profile highlights the failure of current systems to deal with health needs. Improvements in infrastructure, education and employment, and reinvigoration of preventive and primary health care programs, assumption of responsibility for health by the community and by in iduals themselves, and better management of existing morbidities are essential to rectifying this shameful situation.
Publisher: Elsevier BV
Date: 04-0006
DOI: 10.1016/0022-4731(87)90059-8
Abstract: Cytoplasmic and nuclear receptors for oestrogen and progesterone were measured in non-pregnant myometrium and endometrium and compared to concentrations found in decidua of ectopic pregnancy (6-8 weeks gestation) and therapeutic abortions (8-16 weeks). Amnion, chorion, placenta, decidua and myometrium at full term pregnancy were also assayed for the same receptors. High affinity binding was confirmed in the non-pregnant tissue in early pregnancy, decreases in concentrations of cytoplasmic receptors were demonstrated, these decreases becoming more marked as pregnancy progressed in the 1st trimester. Nuclear receptor concentrations were not significantly different. Significant decreases in the occurrence of positive receptors with the progression of pregnancy were also demonstrated for cytoplasmic and nuclear oestrogen and nuclear progesterone receptors. Tissue at full term pregnancy had no detectable receptors, irrespective of whether the patients were in labour or not. Increasing the range of the labelled steroids failed to demonstrate any low affinity binding sites and pre-assay removal of endogenous hormones also had no effect on receptor status. When endogenous hormones were removed, displaceable binding was demonstrated in the presence of excess unlabelled ligand. However, this binding did not conform with receptor dynamics on Scatchard analysis. Heating the cytosol prior to assay or failure to remove endogenous steroid hormones eliminated this binding. Cytosolic oestrogen and progesterone levels increased significantly in the decidua of therapeutic abortions, whilst term pregnant tissue had the highest concentration of endogenous hormones.
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: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.TEM.2014.12.003
Abstract: Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women, with reproductive, cardiometabolic, and psychological features. The heterogeneity in insulin resistance, obesity, and cardiometabolic features has led to controversy on the independent contributions of PCOS status, diagnostic criteria, phenotype, and adiposity. It now appears that women with PCOS have an increased risk of insulin resistance and cardiometabolic features, which is independent of, but worsened by, adiposity and central adiposity, and is unrelated to reproductive phenotype. Obesity may be more prevalent in the more severe phenotypes, which suggests either an exacerbation of the reproductive features or a more likely diagnosis in overweight women with PCOS. Therefore, all women with PCOS should be targeted for prevention, screening, and management of cardiometabolic features.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.FERTNSTERT.2007.02.065
Abstract: Mounting evidence has shown that increased body mass index has a significant adverse effect on pregnancy and miscarriage rates in women seeking to conceive naturally. Several studies have sought to determine the effects of obesity on the endometrium by analyzing outcomes in patients receiving ovum donation.
Publisher: The Endocrine Society
Date: 14-02-2008
DOI: 10.1210/EN.2007-1570
Abstract: Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg·d sodium salicylate, IκK inhibitor that reverses insulin resistance, 50 mg/kg·d or peroxisome proliferator activated receptor-γ agonist rosiglitazone, 10 mg/kg·d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating indicates that peroxisome proliferator activated receptor-γ is a key target for metabolic regulation of ovarian function and oocyte quality.
Publisher: SAGE Publications
Date: 2021
Abstract: Human growth hormone has found favour as a co-gonadotrophin in assisted reproduction particularly in the circumstances of a poor response to stimulation. Its use has been based on animal studies suggesting insulin-like growth factor-1 enhances granulosa and cumulus cell function and possibly oocyte quality. While there is limited ovarian cellular information in women, the use of human growth hormone is alleged to improve egg numbers, embryo quality, clinical pregnancies and live birth in women with a poor ovarian response. A number of cohort studies have claimed these benefits compared with prior nil treatment, but there are a limited number of quality randomised controlled studies. The few good randomised trials indicate an enhanced ovarian response in terms of oestradiol secretion and oocyte maturity with controversial improvement in ongoing pregnancy and live birth. Given the cost of the medication, the lack of convincing data on enhanced clinical outcomes and the theoretical possibility of side effects, we propose it is still too early to determine human growth hormone’s true cost-benefit for widespread use. However, a number of emerging randomised trials may tilt the equation to a positive outlook in the future. Meanwhile, the hormone should only be used after full informed consent from the patient as to its effectiveness and efficacy.
Publisher: Oxford University Press (OUP)
Date: 19-03-2012
Abstract: The effectiveness of aromatase inhibitors (AIs) in the treatment of anovulatory polycystic ovary syndrome (PCOS) remains unclear. The objective was to determine whether AIs are effective in improving fertility outcomes in women with PCOS. Databases were searched until July 2011. Inclusion criteria were women with PCOS, who are infertile, receiving any type, dose and frequency of AI compared with placebo, no other treatment or other infertility treatment. Outcomes were rates of: ovulation, pregnancy, live birth, multiple pregnancies, miscarriage and adverse events, as well as quality of life and cost effectiveness. Data were extracted and risk of bias was assessed. A random-effects model was used for the meta-analyses, using odds ratios (ORs) and rate ratios (RRs). The search returned 4981 articles, 78 articles addressed AIs and 13 randomized controlled trials (RCTs) met the inclusion criteria. No RCTs compared AIs versus placebo or no treatment, in therapy naïve women with PCOS. Meta-analyses of six RCTs comparing letrozole with clompihene citrate (CC) demonstrated that letrozole improved the ovulation rate per patient [OR 2.90 (95% confidence interval (CI) 1.72, 4.88), I(2) = 0%, P < 0.0001] however, there was no statistical difference for the ovulation rate per cycle or the pregnancy, live birth, multiple pregnancy or miscarriage rates. Letrozole also did not improve pregnancy or live birth rates compared with placebo or with CC plus metoformin in women with CC-resistant PCOS. Results of comparisons of letrozole and anastrozole in women with CC-resistant PCOS were conflicting in terms of ovulation and pregnancy rates. In the absence of supportive high-quality evidence, AIs should not be recommended as the first-line pharmacological therapy for infertility in women with PCOS, and further research is needed.
Publisher: Oxford University Press (OUP)
Date: 05-2004
Publisher: Springer Science and Business Media LLC
Date: 12-04-2006
Abstract: Ovarian folliculogenesis is regulated by both endocrine and intraovarian mechanisms that coordinate the processes of oocyte growth and somatic cell proliferation and differentiation. Within the follicle, paracrine interactions between the oocyte and surrounding granulosa cells are critical for normal cell development and function. This review focuses on the role of paracrine interactions during early oocyte and follicular development that ensure proper coordination of oocyte and somatic cell function. Particular emphasis is given to granulosa cell-derived Kit Ligand (KitL), whose functional importance for oocyte growth has been demonstrated by a wide range of in vivo and in vitro studies. Reported interactions between KitL and oocyte-derived growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) suggest the molecular basis of oocyte-granulosa cell interactions, but also hint at the complexity of these communications. These paracrine interactions and the structure of the oocyte-granulosa cell interface are follicle stage-specific and regulated by FSH. Elucidation of the molecular mechanisms that promote the development of healthy oocytes with good developmental competence has potential applications for improving fertility and for in vitro growth systems for oocytes from domestic animals and humans.
Publisher: AMPCo
Date: 10-2018
DOI: 10.5694/MJA18.00635
Publisher: Oxford University Press (OUP)
Date: 03-2004
Publisher: Wiley
Date: 09-2011
DOI: 10.5694/MJA11.10915
Publisher: Informa UK Limited
Date: 1989
Publisher: Oxford University Press (OUP)
Date: 03-2000
DOI: 10.1095/BIOLREPROD62.3.704
Abstract: During the estrous cycle and early pregnancy, lymphohemopoietic cytokines and chemokines contribute to the regulation of ovarian function by orchestrating the recruitment and activation of leukocytes associated with the ovulatory follicle and corpus luteum. The purpose of this study was to investigate the physiological role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the ovary, utilizing mice genetically deficient in GM-CSF. Our results show that the mean duration of the estrous cycle in GM-CSF-deficient (GM-/-) mice was extended by 1.5 days (mean +/- SE, 4.9 +/- 0.3 vs. 6.5 +/- 0.5 days for GM+/+ and GM-/- mice, respectively). Similar ovulation rates were observed in immature superovulated mice (31.8 +/- 7.7 vs. 28.9 +/- 6.4 oocytes per mouse) and adult naturally cycling mice (10.4 +/- 0.8 vs. 10.3 +/- 0.8 oocytes per mouse). Furthermore, comparable numbers of oocytes were released from GM+/+ and GM-/- ovaries in an in vitro perfusion model. However, ovaries in pregnant GM-/- mice were found to comprise fewer cells and synthesize less progesterone (141.6 +/- 10.3 vs. 116.5 +/- 6 nM plasma), although the duration of pseudopregnancy was unaltered by GM-CSF deficiency (11.0 +/- 0.2 vs. 11.0 +/- 0.5 days). Immunohistochemical staining of leukocytes in the ovary during the periovulatory period indicated that the size and composition of ovarian leukocyte populations were unaltered in the absence of GM-CSF. However, an effect of GM-CSF deficiency on the activation phenotype of ovarian leukocytes was indicated by a 57% increase in mean secretion of nitric oxide in in vitro-perfused GM-/- ovaries, and diminished major histocompability complex (MHC) class II (Ia) expression in ovarian macrophages and/or dendritic cells (30.5 +/- 7. 2% vs. 9.1 +/- 1.8% positive stain in GM+/+ and GM-/- ovaries, respectively). Furthermore, ovarian macrophages and neutrophils were diminished in number after parturition, with significantly decreased CD11b+ (Mac-1) staining in the stromal region of postpartum GM-/- ovaries (6.7 +/- 0.6 vs. 3.6 +/- 0.7% positive stain). In summary, GM-CSF does not appear to be essential for ovarian function but may play a role in fine-tuning the activation status and adhesive properties of ovarian myeloid leukocytes. Aberrant activation of these cells appears to compromise the luteinization process and the steroidogenic capacity of the corpus luteum during early pregnancy in GM-CSF-deficient mice.
Publisher: Oxford University Press (OUP)
Date: 10-1997
DOI: 10.1093/HUMREP/12.10.2162
Abstract: The optimal time period for intrauterine insemination (IUI) in relation to either luteinizing hormone (LH) surge or human chorionic gonadotrophin (HCG) administration leading to the best pregnancy rates has not been determined. In this study, 856 consecutive human menopausal gonadotrophin (HMG)-stimulated and 49 natural unstimulated IUI cycles carried out at a reproductive medicine unit affiliated with a tertiary centre were analysed in a retrospective fashion. There were three scenarios in the temporal relationship of the LH surge, HCG administration and artificial insemination. These were (group A) subjects who had an endogenous LH surge but were not given HCG (group B) subjects who were given HCG after an observed LH surge, and (group C) subjects who were given HCG before the LH surge. The overall pregnancy rate (PR) was 16% per cycle. The PR was 9% in group A, 20% in group B and 14% in group C. The PR in group B was significantly better than group C (P = 0.04). In group B, the longer the time interval between the LH surge and HCG administration, the better the PR up to 20 h (P = 0.025) the timing of IUI based on the LH surge was not critical to the achievement of pregnancy within 3 days. In group C, PR improved with the increasing interval between HCG and IUI from <28 h up to 60 h. We conclude that a better PR is achieved if a spontaneous LH surge occurs before HCG administration, especially where the administration of HCG is delayed 8-20 h after an observed LH surge the timing of IUI based on the LH surge is not critical to the achievement of pregnancy within 3 days.
Publisher: The Endocrine Society
Date: 02-2003
Abstract: Overweight women with polycystic ovary syndrome (PCOS) were randomized to a high protein (HP 40% carbohydrate and 30% protein n = 14) or a low protein (LP 55% carbohydrate and 15% protein) diet (n = 14). The intervention consisted of 12 wk of energy restriction (∼6000 kJ/d), followed by 4 wk of weight maintenance. Pregnancies (two HP and one LP) improvements in menstrual cyclicity, lipid profile, and insulin resistance (as measured by the homeostasis model) and decreases in weight (7.5%) and abdominal fat (12.5%) occurred independently of diet composition. Improvements in menstrual cyclicity were associated with greater decreases in insulin resistance and fasting insulin (P = 0.011). On the LP diet, high density lipoprotein cholesterol decreased 10% during energy restriction (P = 0.008), and the free androgen index increased 44% in weight maintenance stages (P = 0.027). Weight loss leads to improvements in cardiovascular and reproductive parameters potentially mediated by improvements in surrogate measures of insulin resistance. An HP weight loss diet may result in minor differential endocrine and metabolic improvements.
Publisher: Elsevier BV
Date: 05-1990
DOI: 10.1016/0090-8258(90)90343-J
Abstract: A low-molecular-weight glycoprotein containing sequences of the beta subunit of human chorionic gonadotropin (hCG) has been found in the urine of patients with carcinoma of the cervix using an immunoradiometric assay. This fragment has chromatographic and immunological identity with hCG beta core. This molecule was present in 52 to 77% of all patients with invasive disease, while between 11 and 27% of patients with cervical intraepithelial neoplasia (CIN) also exhibited significant hCG beta-core immunoactivity. Few patients had either a positive assay for intact hCG or a positive assay directed at an epitope on the beta subunit (beta-hCG radioimmunoassay) in serum. However, between 17 and 40% of patients with invasive disease were positive for free beta-subunit immunoactivity in the blood. The origin of the beta-core immunoactivity in the urine is uncertain while tumor production cannot be excluded, it is possible that the molecule originates from renal metabolism of small quantities of the beta subunit of hCG. Regardless of the source of the molecule, hCG beta core is a far more sensitive marker of hCG production by tumors than is serum hCG.
Publisher: Wiley
Date: 13-10-2006
DOI: 10.1111/J.1471-0528.2006.01090.X
Abstract: There remains a large degree of disagreement about the association of polycystic ovary syndrome (PCOS) with impaired endothelial dysfunction and cardiovascular disease (CVD) risk. The purpose of this study was to determine whether overweight and obese women with PCOS have impaired endothelial function compared with weight-matched controls without PCOS and whether endothelial function is associated with cardiovascular risk markers and hormonal parameters. Cross-sectional analysis. An outpatient trial at the Commonwealth Scientific Industrial Research Organisation Clinical Research Unit. Overweight and obese women with PCOS (n= 12) and weight-matched controls without PCOS (n= 10). Endothelial function, cardiovascular risk markers and hormonal parameters were assessed in the patients. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound. Lipid profile, fasting insulin level, glucose level, insulin resistance, C-reactive protein level, folate level, Vitamin B(12) level and hormonal parameters. Women with PCOS had significantly higher testosterone levels (P < 0.001) and free androgen index (P= 0.006) compared with the controls without PCOS. Both groups were normoinsulinaemic, and there were no significant differences in any of the markers of CVD between women with and without PCOS. Furthermore, FMD was similar in both groups (PCOS 6.1 +/- 1.2% versus control 5.6 +/- 1.0%, P= 0.77). Compared with a group of weight-matched women with similar metabolic profiles, normoinsulinemic, overweight and obese women with PCOS did not show any greater impairment in endothelial function assessed by FMD. A normoinsulinemic phenotype of PCOS with low metabolic risk factors may reduce the risk of endothelial dysfunction in overweight and obese women with this syndrome. Further studies are required that directly compare FMD in normoinsulinemic and hyperinsulinaemic women with PCOS.
Publisher: Oxford University Press (OUP)
Date: 06-12-2018
Publisher: Oxford University Press (OUP)
Date: 06-11-2011
Abstract: Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age. We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of hirsutism. The prevalence of hirsutism is ~10% in most populations, with the important exception of Far-East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention. Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint.
Publisher: Oxford University Press (OUP)
Date: 10-2005
DOI: 10.1095/BIOLREPROD.104.039362
Abstract: In this study, we test the hypothesis that the growth-promoting action of androgens on granulosa cells requires paracrine signaling from the oocyte. Mural granulosa cells (MGCs) from small antral (1-3 mm) prepubertal pig follicles were cultured in the presence or absence of denuded oocytes (DO) from the same follicles to determine whether mitogenic and/or steroidogenic responses, to combinations of FSH, insulin-like growth factor 1 (IGF1), and dihydrotestosterone (DHT) were influenced by oocyte-secreted factors (OSFs). To further explore the identity of such factors we performed the same experiments, substituting growth differentiation factor 9 (GDF9), a known OSF, for the DO. OSFs and GDF9 both potently enhanced IGF1-stimulated proliferation, and inhibited FSH-stimulated progesterone secretion. Alone, DHT had little effect on DNA synthesis, but significantly enhanced the mitogenic effects of OSFs or GDF9 in the presence of IGF1. Denuded oocytes, GDF9, and DHT independently inhibited FSH-stimulated progesterone secretion, and androgen, together with DO or GDF9, caused the most potent steroidogenic inhibition. Focusing on mitogenic effects, we demonstrate that both natural androgen receptor (AR) agonists, testosterone and DHT, dose-dependently augmented the mitogenic activity of DO or GDF9. Antiandrogen (hydroxyflutamide) treatment, which is used to block androgen receptor activity, opposed the interaction between androgen and GDF9. In conclusion, androgens stimulate porcine MGC proliferation in vitro by potentiating the growth-promoting effects of oocytes or GDF9, via a mechanism that involves the AR. These signaling pathways are likely to be important regulators of folliculogenesis in vivo, and may contribute to the excess follicle growth that is observed in androgen-treated female animals.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.FERTNSTERT.2007.09.041
Abstract: The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.PSYNEUEN.2010.02.013
Abstract: Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are no published prospective studies where prenatal androgen exposure has been measured and correlated with digit ratio in adult life. We aimed to establish the prospective relationship between prenatal androgen exposure in the second and third trimesters of pregnancy (as measured by maternal circulating androgen concentrations and umbilical cord androgen concentrations) and digit ratio in adolescent girls. Androgen concentrations (testosterone, free androgen index, androstenedione, DHEAS) and sex hormone binding globulin (SHBG) were measured in stored plasma s les from pregnant mothers at 18 (n=118) and 34/36 (n=114) weeks of gestation and in cord blood (n=82) from the Western Australian Pregnancy (Raine) Cohort Study (www.rainestudy.org.au). Digit ratio was measured in 244 female offspring from this cohort at age 14-16 years. Only one borderline statistically significant correlation between maternal circulating androstenedione levels at 18 weeks of gestation and left hand digit ratio was seen. No other statistically significant relationship between maternal androgen concentrations or umbilical cord androgen concentrations and digit ratio in adolescence were observed. These findings suggest that variation in 2D:4D in girls is not established as a result of testosterone concentrations in the second and third trimesters. We conclude that prenatal androgen exposure as measured by maternal circulating androgen concentrations at 18 and 34/36 weeks of gestation or in the umbilical cord at birth may not predict digit ratio in girls.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/08977190802707571
Abstract: We report the presence of KIT variants in granulosa and thecal cells of the follicle and endothelial and steroidogenic cells of the corpus luteum. Transcripts of both full-length splice variants, KIT and KITA, were ubiquitously detected in all cell types, in contrast to transcripts for truncated KIT. RT-PCR with exon-intron-specific primers suggested that KIT transcripts retained intron sequences. We used domain-specific KIT antibodies to identify truncated KIT proteins in cell conditioned media and lysates. These proteins represented soluble KIT and a so far disregarded intracellular KIT fragment, and were ubiquitously present. In contrast, glycosylated variants of full-length KIT were predominantly detected in thecal and endothelial cells. All KIT variants were encountered again in COS-7 cells transfected with a vector containing KITA. Phorbol 12-myristate-13-acetate treatment induced levels of truncated KITs, and this effect was repressed by the metalloproteinase inhibitor TAPI-1. Our findings show that ectodomain cleavage of full-length KIT generates an intracellular KIT. Our experiments suggest that replenishing full-length KIT differs among various ovarian cell types.
Publisher: BMJ
Date: 21-12-2010
DOI: 10.1136/BMJ.C6945
Publisher: Wiley
Date: 08-1988
DOI: 10.1111/J.1471-0528.1988.TB06551.X
Abstract: Uterine activity was assessed by measuring the uterine activity integral (UAI) in 116 black multigravid patients in spontaneous active labour at term. Although in idual patients showed a wide range of mean UAI levels, normal labour (group I, n = 54) was associated with a mean UAI level of 1640 kPas/15 min which was higher than the mean level observed in patients in whom delay in cervical dilatation occurred in active labour. The patients who failed to progress in labour were treated with oxytocin infusion and 32 of them made good progress in labour and achieved vaginal delivery (group IIa: mean UAI pre-oxytocin treatment 1040 (SD 424) kPas/15 min, post-oxytocin 1890 (SD 559) kPas/15 min). The other 23 patients required operative delivery (group IIb) despite correction of uterine activity after oxytocin treatment (pre-oxytocin mean UAI 1230 (SD 570) kPas/15 min, post-oxytocin 1815 (SD 650) kPas/15 min). The rate of oxytocin infusion varied between patients from 2 to 16 mU/min but in 75% uterine activity was corrected to normal levels by a dose of less than or equal to 8 mU/min. It is concluded that delay in progress in labour is associated with lower intrauterine pressures than are present in normal labour, and that management of patients presenting with inefficient uterine action may benefit from the use of uterine activity integral measurements.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JNEUMETH.2016.09.008
Abstract: Transcranial direct current stimulation (tDCS) has been shown to perturb both cortical neural activity and hemodynamics during (online) and after the stimulation, however mechanisms of these tDCS-induced online and after-effects are not known. Here, online resting-state spontaneous brain activation may be relevant to monitor tDCS neuromodulatory effects that can be measured using electroencephalography (EEG) in conjunction with near-infrared spectroscopy (NIRS). We present a Kalman Filter based online parameter estimation of an autoregressive (ARX) model to track the transient coupling relation between the changes in EEG power spectrum and NIRS signals during anodal tDCS (2mA, 10min) using a 4×1 ring high-definition montage. Our online ARX parameter estimation technique using the cross-correlation between log (base-10) transformed EEG band-power (0.5-11.25Hz) and NIRS oxy-hemoglobin signal in the low frequency (≤0.1Hz) range was shown in 5 healthy subjects to be sensitive to detect transient EEG-NIRS coupling changes in resting-state spontaneous brain activation during anodal tDCS. Conventional sliding window cross-correlation calculations suffer a fundamental problem in computing the phase relationship as the signal in the window is considered time-invariant and the choice of the window length and step size are subjective. Here, Kalman Filter based method allowed online ARX parameter estimation using time-varying signals that could capture transients in the coupling relationship between EEG and NIRS signals. Our new online ARX model based tracking method allows continuous assessment of the transient coupling between the electrophysiological (EEG) and the hemodynamic (NIRS) signals representing resting-state spontaneous brain activation during anodal tDCS.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.FERTNSTERT.2007.10.039
Abstract: To assess the practicality of using power Doppler (PD) to assess follicular vascularity at the time of oocyte retrieval. Prospective study. University-affiliated IVF unit. Twenty-six women undergoing IVF treatment. Evaluation of follicular vascularity by using PD during oocyte retrieval. Subjective assessment of the impact of PD estimation of follicle vascularity during oocyte retrieval reproducibility of grading of follicle vascularity. Assessment of follicle vascularity by using PD during oocyte retrieval was found to be reproducible and to add minimally to the workload of the clinician and embryologist. The grade of follicle vascularity did not correlate with the yield of oocytes, fertilization rate, or concentration of hormones in follicular fluid. Although the study group was small, there was a statistically significant trend toward higher clinical pregnancy rates when the embryo transfer cohort contained at least one embryo from a highly vascular follicle (50% vs. 15.4%). Assessment of follicle vascularity by using PD at the time of oocyte retrieval was found to be a practical alternative to other methods.
Publisher: CSIRO Publishing
Date: 1995
DOI: 10.1071/RD9950021
Abstract: The cellular composition of cells collected from the follicular fluid obtained during the IVF procedure and cultured in vitro was examined, as well as the effects of two cytokines, interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF alpha), on the proliferation of in idual cell types. After 48 h in culture, most of the cells were granulosa-lutein cells exhibiting positive staining against 3-beta-hydroxysteroid dehydrogenase (3 beta-HSD). About one-third of the total cell population stained positive with monoclonal antibodies against specific antigen sites on lymphohaemopoietic cells, including B-lymphocytes, T-lymphocytes, natural killer cells, monocytes and macrophages. During this 48-h period, IL-2 and TNF alpha significantly (P 0.05) increased the proportion of leukocyte common antigen (LCA)-positive cells and monocytes. At the end of 144 h in culture, although LCA-positive cells and monocytes were still present, there were fewer. The main targets for the proliferative effects of IL-2 and TNF alpha in this culture system during the first 48 h are leukocytes rather than steroid-producing cells. Thus, any observed effects from the addition of cytokines in this system may be due to indirect effects of cytokine-activated leukocytes on granulosa-lutein cells.
Publisher: Oxford University Press (OUP)
Date: 19-08-2009
Publisher: Oxford University Press (OUP)
Date: 12-2002
Abstract: In order to carry out preimplantation genetic diagnosis (PGD) for beta-thalassaemia, we have applied direct sequencing of single cell PCR products to detect mutations and polymorphic loci within the beta-globin gene. Conventional duplex PCR was used to lify two regions of the beta-globin gene with an lification efficiency of 79% for blastomeres. Sequencing data were obtained for 100% of lified products, with 12% having confirmed allele drop-out (ADO). A double ADO event was observed at least twice, confirming the real risk of such an event during PGD. In one couple, the presence of a polymorphism linked to the female partner's mutation enabled us to eliminate the risk of misdiagnosis due to double ADO without having to lify both mutations within the same PCR product. We present here the data from eight clinical PGD cycles for three couples resulting in a singleton pregnancy and a twin pregnancy with all babies confirmed to be free from beta-thalassaemia (major).
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/S1472-6483(10)60128-9
Abstract: The aim of this study was to assess the effectiveness and safety of a low-dose step-up protocol with a recombinant FSH starting dose of 25 IU for ovulation induction in anovulatory patients with polycystic ovary syndrome (PCOS) and a normal or low body mass index (BMI). In this prospective, non-comparative, open trial, 183 PCOS patients who had three unsuccessful cycles of ovulation induction with clomiphene citrate received recombinant FSH (Puregon((R))) 25 IU/day for 14 days, the dose was then increased by 25 IU every 5 days if there was no follicle of >12 mm diameter (maximum 150 IU/day). Human chorionic gonadotrophin was administered when the lead follicle was >/=18 mm, and intrauterine insemination was performed 36 h later. Duration of stimulation was 15.9 +/- 4.8 days and total FSH dose was 484 +/- 257 IU. A developing follicle was observed in 96.7% of cycles, of which 62.1% had unifollicular development and 15.8% were cancelled due to over-response. The clinical and ongoing pregnancy rates were 35.5% and 33.9%, respectively. There were no multiple pregnancies, and only one case of mild ovarian hyperstimulation syndrome. A low-dose step-up protocol with a recombinant FSH starting dose of 25 IU/day is effective and safe in anovulatory Vietnamese PCOS patients with a low or normal BMI.
Publisher: Bioscientifica
Date: 11-2000
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine secreted by lymphohaemopoietic and other cell lineages, is known to influence ovarian cyclicity and embryo development. The aim of this study was to examine the effect of GM-CSF on ovarian follicular cell function using GM-CSF-deficient (GM -/-) mice. Immature GM -/- and GM +/+ mice were stimulated with eCG, and cumulus-oocyte complexes and mural granulosa cells were collected 48 h later. Expression of GM-CSF receptor (GM-CSFR) alpha and beta mRNA subunits by cumulus-oocyte complexes and mural granulosa cells was examined using RT-PCR. Cumulus-oocyte complexes from both genotypes were found to express mRNA for the GM-CSFRalpha-subunit only, while the mural granulosa cells expressed both the alpha and beta receptor subunits. Cumulus-oocyte complexes recovered from GM -/- mice had approximately twice the number of cumulus cells per cumulus-oocyte complex than did those of GM +/+ mice (P 0.05), even though the growth-promoting activity of denuded GM -/- oocytes was found to be equivalent to that of wild-type oocytes. GM-CSF deficiency was associated with marginally increased DNA synthesis in cumulus cells and significantly (P 0.05) lower progesterone production by mural granulosa cells recovered from GM -/- compared with those recovered from GM +/+ mice. The addition of rec-mGM-CSF in vitro did not affect DNA synthesis in either cell type or progesterone production by mural granulosa cells, irrespective of GM-CSF status. There was no effect of GM-CSF deficiency on the capacity of FSH and insulin-like growth factor I to stimulate DNA synthesis in cumulus-oocyte complexes (approximately 15- and threefold, respectively) and in mural granulosa cells (approximately two- and threefold, respectively). Taken together, these data show that GM-CSF influences events associated with follicular maturation in mice. The effects of GM-CSF are not exerted directly in granulosa or cumulus cells, but appear to be mediated indirectly, perhaps through the agency of steroidogenesis-regulating secretions of local macrophage populations residing in the theca.
Publisher: Oxford University Press (OUP)
Date: 12-2010
DOI: 10.1095/BIOLREPROD.110.084145
Abstract: Oocyte and embryo metabolism are closely linked with their subsequent developmental capacity. Lipids are a potent source of cellular energy, yet little is known about lipid metabolism during oocyte maturation and early embryo development. Generation of ATP from lipids occurs within mitochondria via beta-oxidation of fatty acids, with the rate-limiting step catalyzed by carnitine palmitoyl transferase I (CPT1B), a process also requiring carnitine. We sought to investigate the regulation and role of beta-oxidation during oocyte maturation and preimplantation development. Expression of Cpt1b mRNA, assessed by real-time RT-PCR in murine cumulus-oocyte complexes (COCs), increased following hormonal induction of oocyte maturation and ovulation in vivo with human chorionic gonadotropin (5 IU) and in embryos reaching the blastocyst stage. Beta-oxidation, measured by the production of (3)H(2)O from [(3)H]palmitic acid, was significantly increased over that in immature COCs following induction of maturation in vitro with epidermal growth factor (3 ng/ml) and follicle-stimulating hormone (50 mIU/ml). The importance of lipid metabolism for oocyte developmental competence and early embryo development was demonstrated by assessing the rate of embryo development following inhibition or upregulation of beta-oxidation with etomoxir (an inhibitor of CPT1B) or L-carnitine, respectively. Inhibition of beta-oxidation during oocyte maturation or zygote cleavage impaired subsequent blastocyst development. In contrast, L-carnitine supplementation during oocyte maturation significantly increased beta-oxidation, improved developmental competence, and in the absence of a carbohydrate energy supply, significantly increased 2-cell cleavage. Thus, carnitine is an important cofactor for developing oocytes, and fatty acids are an important energy source for oocyte and embryo development.
Publisher: CSIRO Publishing
Date: 2012
DOI: 10.1071/RD11904
Abstract: Obesity can have detrimental effects on pregnancy rates in natural conceptions and also in women undergoing IVF or intracytoplasmic sperm injection (ICSI). This review summarises the most recent clinical literature investigating whether obesity impacts oocyte quality and early embryo growth. In other tissues, obesity leads to lipotoxicity responses including endoplasmic reticulum stress, mitochondrial dysfunction and apoptosis. Recent reports indicate that lipotoxicity is a mechanism by which obesity may impact oocyte quality.
Publisher: Elsevier BV
Date: 06-2004
Publisher: Oxford University Press (OUP)
Date: 20-05-2022
Abstract: Is there any difference in developmental outcomes in children born after capacitation IVM (CAPA IVM) compared with conventional IVF? Overall development up to 24 months of age was comparable in children born after CAPA IVM compared with IVF. IVM has been shown to be a feasible alternative to conventional IVF in women with a high antral follicle count (AFC). In addition to live birth rate, childhood development is also a relevant metric to compare between the two approaches to ART and there are currently no data on this. This study was a follow-up of babies born to women who participated in a randomized controlled trial comparing IVM with a pre-maturation step (CAPA IVM) and IVF. Developmental assessments were performed on 231 children over 24 months of follow-up. Participants in the randomized controlled trial had an indication for ART and a high AFC (≥24 follicles in both ovaries). They were randomized to undergo one cycle of either IVM (n = 273) or IVF (n = 273). Of these, 96 women and 118 women, respectively, had live births. Seventy-six women (94 children, 79.2%) and 104 women (137 children, 88.1%), respectively, completed Ages & Stages Third Edition Questionnaire assessment (ASQ-3), and underwent evaluation of Developmental Red Flags at 6, 12 and 24 months of age. Baseline characteristics of participants in the follow-up study between the IVM and IVF groups were comparable. Overall, there were no significant differences in ASQ-3 scores at 6, 12 and 24 months between children born after IVM or IVF. The proportion of children with developmental red flags was low and did not differ between the two groups. Slightly, but significantly, lower ASQ-3 problem solving and personal-social scores in twins from the IVM versus IVF group at 6 months were still within the normal range and had caught up to the IVF group in the 12- and 24-month assessments. The number of children confirmed to have abnormal mental and/or motor development after specialist assessment was four in the IVM group and two in the IVF group (relative risk 2.91, 95% CI 0.54-15.6 P = 0.23). This study is an open-label follow-up of participants in a randomized controlled trial, and not all original trial subjects took part in the follow-up. The self-selected nature of the follow-up population could have introduced bias, and the s le size may have been insufficient to detect significant between-group differences in developmental outcomes. Based on the current findings at 2 years of follow-up, there does not appear to be any significant concern about the effects of IVM on childhood development. These data add to the evidence available to physicians when considering different approaches to fertility treatment, but require validation in larger studies. This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number FWO.106-YS.2017.02. L.N.V. 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 T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring R.J.N. has receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia B.W.M. has acted as a paid consultant to Merck, ObsEva and Guerbet and is the recipient of grant money from an NHMRC Investigator Grant J.E.J.S. reports lecture fees from Ferring Pharmaceuticals, Biomérieux and Besins Female Healthcare, grants from Fund for Research Flanders (FWO) and is co-inventor on granted patents on CAPA-IVM methodology in the USA (US10392601B2) and Europe (EP3234112B1) T.D.P., M.H.N.N., N.A.N., T.T.L., V.T.T.T., N.T.N., H.L.T.H. and X.T.H.L. have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. NCT04296357 (www.clinicaltrials.gov). 5 March 2020. 7 March 2020.
Publisher: Oxford University Press (OUP)
Date: 30-05-2012
Abstract: Lifestyle has been shown to affect fertility in both males and females, with compelling evidence that smoking and being under or overweight impairs natural and assisted fertility, and other factors such as stress and caffeine have also been implicated. The objective of this study was to determine whether providing infertile couples with in idualized lifestyle assessments and ongoing support facilitates positive lifestyle changes enhancing healthy fertility. We conducted a prospective cohort pilot study of 23 infertile couples attending an Adelaide-based fertility clinic for advice and treatment relating to infertility. The intervention was a comprehensive assessment interview with the couple, focused on health and lifestyle. Motivational interviewing techniques were used and ongoing support provided. The assessment was repeated after 4 months and included an exit questionnaire. The main outcome measure(s) was self-reported lifestyle changes, including increased exercise, modified diet, reduced caffeine and alcohol consumption, ceased or reduced smoking and decreased psychological stress. Following the initial lifestyle assessment interview, all participants reported adverse lifestyle behaviour. The results suggest that the FAST (Fertility ASsessment and advice Targeting lifestyle choices and behaviours) approach of an in idualized assessment of current lifestyle practice followed by ongoing one to two weekly telephone support is effective in promoting healthy lifestyle change. Larger studies using this methodology are now required.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
Publisher: American Medical Association (AMA)
Date: 15-05-2018
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.PHYSBEH.2009.05.020
Abstract: Reproductive disorders and psychological distress are common co-morbidities of obesity in young women. Psychological and reproductive disturbances may also be associated with increased food cravings but the relationships between these factors have not been explored. This study aimed to explore the pattern of food cravings and to determine the relationship between psychological distress, reproductive health and food cravings in overweight and obese young women using baseline data in a weight loss trial. A total of 198 young women were included in this analysis (BMI 33.3+/-0.3 kg/m(2), age 28+/-0.3 years). The most frequently craved food item was chocolate (3.9+/-0.08 i.e., sometimes-often). The most frequently craved food categories were fast foods (2.6+/-0.07) and sweets (2.5+/-0.05). Psychological distress was significantly correlated with food cravings (R(2)=0.18, P<0.05). High fat (r=0.2), sweets (r=0.17) and overall cravings (r=0.20) were significantly correlated with energy intake (P 0.05). Participants with menstrual disturbances had greater fast food cravings independent of age, BMI and PCOS status (P<0.05). Participants with hyperandrogenemia had greater high fat food cravings independent of age, BMI and PCOS status (P 0.05). These results suggest that psychological distress, hyperandrogenemia and menstrual disturbances are associated with greater food cravings. Further investigations are required to elucidate the relationship between hyperandrogenemia and food cravings in young women.
Publisher: Elsevier BV
Date: 02-1982
DOI: 10.1016/S0262-1746(82)80009-7
Abstract: Family members are prominent providers of necessary care to persons with dementia. The psychological, emotional, and social costs of care have led to the development of interventions to support these families. Although evidence supports the effectiveness of dementia caregiver interventions, few have been implemented into practice. Stakeholder involvement may increase the potential for interventions to be integrated into community contexts. Utilization of community advisory boards (CABs) have been identified as a successful strategy to engage stakeholders in research and intervention development. Yet, little is known about the use of CABs when developing and refining interventions in dementia care. This article presents a case study of a CAB intended to inform the development and translation of an online dementia caregiver resource: Care to Plan. Qualitative thematic analysis of transcripts from seven CAB meetings over a 3-year period identified two major categories. First, the CAB process: who participated, how meetings were conducted, and issues that arose. Second, Care to Plan improvement: how CAB members provided key stakeholder perspectives resulting in changes in language, functionality, substance, and dissemination. Findings demonstrate how CABs can inform gerontological social work when facilitating the development, translation, and implementation of meaningful, community-based resources for dementia caregivers.
Publisher: Oxford University Press (OUP)
Date: 20-04-2009
Publisher: Georg Thieme Verlag KG
Date: 2018
Abstract: In this paper, we describe the robust governance structures and processes underpinning the development of the first International Evidence-Based Guideline for the Assessment and Management Polycystic Ovary Syndrome (2018). The guideline was an outcome of the Centre of Research Excellence for Polycystic Ovary Syndrome, and an ex le of a transformative, strategic research initiative to impact delivery model. The governance structure supported and delivered critical ethical and regulatory outcomes, including: broad and erse representation across health professional and consumer groups and exceeded regulatory standards adherence to rigorous knowledge creation processes and compliance with the standards for guidelines set by the approval body, the Australian National Health and Medical Research Council (NHMRC). Well-articulated and appropriately implemented governance structures that meet the complex nature of contemporary research and translation activities are essential to enable distributed leadership and to deliver key outcomes.
Publisher: Georg Thieme Verlag KG
Date: 2018
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.NIOX.2011.06.005
Abstract: Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects this may contribute to the increased cardiovascular risk associated with this syndrome.
Publisher: The Endocrine Society
Date: 12-2009
DOI: 10.1210/JC.2009-1342
Abstract: Context: Adequate uterine volume and ovarian reserve are essential for reproductive health. Antenatal events such as restricted fetal growth and maternal tobacco smoking are hypothesized to impact on reproductive function in later life, although not studied in a large prospective normal pregnancy population to date. Objective: The objective of the study was to determine the relationship between intrauterine growth, birth weight, and maternal tobacco smoking on uterine volume and ovarian reserve in adolescence. Design and Setting: This was a prospective study in which half the cohort underwent intensive ultrasound monitoring in utero. Participants: Intrauterine growth was measured using ultrasound at 18, 24, 28, and 34/36 wk gestation (n = 115 girls). Maternal smoking data were prospectively collected at 18 and 34/36 wk from the whole cohort. Uterine (n = 229) and early follicular ovarian volume and antral follicle count (n = 225) were measured using transabdominal ultrasound (n = 230). Ovarian reserve was estimated using early follicular phase anti-Mullerian hormone, inhibin B, and FSH (n = 213). Main Outcome Measures: The relationship between maternal tobacco smoking, intrauterine growth trajectories, and markers of ovarian reserve and uterine size in adolescence was measured. Results: Linear regression showed that daughters of mothers who smoked had a significantly smaller uterus compared with nonsmokers (P = 0.019). No significant relationship between maternal tobacco smoking and ovarian volume (P = 0.164) or markers of ovarian reserve (antral follicle count, plasma FSH, anti-Mullerian hormone, and inhibin B) in adolescence was determined. Conclusions: Our findings indicate that maternal smoking, but not variations in fetal growth, may lead to a reduction in uterine volume and does not appear to impact ovarian reserve.
Publisher: Elsevier BV
Date: 10-1987
DOI: 10.1016/0090-6980(87)90093-1
Abstract: The regulatory effect of amniotic fluid factors on prostaglandin production by sheep seminal vesicle prostaglandin synthetase was determined using s les obtained before and after the onset of labor. Variations in the enzyme incubation conditions permitted the effects on both prostaglandin E (PGE) and prostaglandin F (PGF) production to be assessed. Amniotic fluid obtained before the onset of labor and during early labor resulted in a net stimulation of PGE production and no difference was observed between these two groups. S les obtained before and during early labor had no net effect on PGF production. However, when s les obtained late in labor were tested, there was a greater stimulation of PGF and less of PGE compared to early labor suggesting a preference for PGF production rather than PGE in late labor. When s les obtained from patients in dysfunctional labor were compared to normal labor, no difference on the effect of either PGE or PGF production was observed. This implies that the decreased PGF previously described in dysfunctional labor is due to an intrinsic abnormality of the fetal membranes rather than inhibition of prostaglandin production by factors mediated via the amniotic fluid.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2021
DOI: 10.1371/JOURNAL.PCBI.1009386
Abstract: Transcranial direct current stimulation (tDCS) has been shown to evoke hemodynamics response however, the mechanisms have not been investigated systematically using systems biology approaches. Our study presents a grey-box linear model that was developed from a physiologically detailed multi-compartmental neurovascular unit model consisting of the vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. Then, model linearization was performed on the physiologically detailed nonlinear model to find appropriate complexity (Akaike information criterion) to fit functional near-infrared spectroscopy (fNIRS) based measure of blood volume changes, called cerebrovascular reactivity (CVR), to high-definition (HD) tDCS. The grey-box linear model was applied on the fNIRS-based CVR during the first 150 seconds of anodal HD-tDCS in eleven healthy humans. The grey-box linear models for each of the four nested pathways starting from tDCS scalp current density that perturbed synaptic potassium released from active neurons for Pathway 1, astrocytic transmembrane current for Pathway 2, perivascular potassium concentration for Pathway 3, and voltage-gated ion channel current on the smooth muscle cell for Pathway 4 were fitted to the total hemoglobin concentration (tHb) changes from optodes in the vicinity of 4x1 HD-tDCS electrodes as well as on the contralateral sensorimotor cortex. We found that the tDCS perturbation Pathway 3 presented the least mean square error (MSE, median .5%) and the lowest Akaike information criterion (AIC, median -1.726) from the in idual grey-box linear model fitting at the targeted-region. Then, minimal realization transfer function with reduced-order approximations of the grey-box model pathways was fitted to the ensemble average tHb time series. Again, Pathway 3 with nine poles and two zeros (all free parameters), provided the best Goodness of Fit of 0.0078 for Chi-Square difference test of nested pathways. Therefore, our study provided a systems biology approach to investigate the initial transient hemodynamic response to tDCS based on fNIRS tHb data. Future studies need to investigate the steady-state responses, including steady-state oscillations found to be driven by calcium dynamics, where transcranial alternating current stimulation may provide frequency-dependent physiological entrainment for system identification. We postulate that such a mechanistic understanding from system identification of the hemodynamics response to transcranial electrical stimulation can facilitate adequate delivery of the current density to the neurovascular tissue under simultaneous portable imaging in various cerebrovascular diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0EE00527D
Publisher: Proceedings of the National Academy of Sciences
Date: 29-09-1998
Abstract: Membrane growth factors that are processed to produce soluble ligands may function both as soluble factors and as membrane factors. The membrane growth factor Kit-ligand (KL), the ligand of the Kit receptor tyrosine kinase, is encoded at the Sl locus, and mice carrying Sl mutations have defects in hematopoiesis, gametogenesis, and melanogenesis. Two alternatively spliced KL transcripts encode two cell-associated KL protein products, KL-1 and KL-2. The KL-2 protein lacks the major proteolytic cleavage site for the generation of soluble KL, thus representing a more stable cell-associated form of KL. We investigated the consequences of exclusive expression of KL-2 in vivo . The KL gene in embryonic stem cells was modified and KL exon 6 was replaced with a PGKneoNTRtkpA cassette by homologous recombination, and mice carrying the Sl KL2 allele were obtained. Sl KL2 /Sl KL2 mice had only slightly reduced levels of soluble KL in their serum, suggesting that in vivo KL-2 may be processed to produce soluble KL-2S. The steady-state characteristics of the hematopoietic system and progenitor numbers were normal, and the mutant animals were not anemic. However, mast cell numbers in the skin and peritoneum were reduced and the mutant animals displayed increased sensitivity to sublethal doses of γ-irradiation. Therefore, KL-2 may substitute for KL-1 in most situations with the exception of the production of mast cells, and induced proteolytic cleavage of KL-1 to produce soluble KL may have a role in the regeneration of hematopoietic tissue after radiation injury.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.MCE.2004.09.012
Abstract: The distribution of the tyrosine kinase receptor c-Kit and its ligand stem cell factor (SCF) was evaluated by immunohistochemistry in primordial germ cells (PGCs) and human embryonic gonads during weeks 5-8 of prenatal life, and fetal ovaries during weeks 9-36 of prenatal life. Distinct c-Kit and SCF staining was present in primordial germ cells in the wall of the hindgut and in the dorsal mesentery, particularly on level with the 10th thoracic columnar segment. Several PGCs were in close contact with c-Kit-negative but SCF-positive autonomic nerve fibers of the dorsal mesentery. Many fibroblasts and mesothelial cells of the dorsal mesentery were clearly stained for SCF, but not for c-Kit. Prominent c-Kit and SCF staining was present in germ cells of the embryonic gonadal anlage and in oogonia during further ovarian development. However, oocytes were either unstained or faintly stained for SCF. Oocytes not yet enclosed in follicles or present in primordial follicles were either unstained or exhibited faint cytoplasmic c-Kit staining, whereas oocytes of growing preantral follicles again showed distinct cell membrane staining which decreased during further follicular growth. Theca cells did not stain for c-Kit. Some pregranulosa cells and the first formed granulosa cells of primordial follicles were c-Kit stained. Granulosa cells of other follicles were not c-Kit stained. In the inner part of the cortex, SCF immunolabeling was detected in some pregranulosa cells surrounding cords containing germ cells and involved in formation of primordial follicles. Granulosa cells of primordial and growing follicles, including medium-sized antral follicles also revealed SCF staining. In conclusion, this first report on SCF in human PGCs and embryonic and fetal ovaries together with the c-Kit data lend substantial countenance to the notion that c-Kit and SCF play important roles during ascent of primordial germ cells towards the gonadal anlage, and during oogenesis and folliculogenesis in the human fetal ovary. We suggest that both autocrine and paracrine mechanisms are involved in the proposed anti-apoptotic effect of the c-Kit/SCF duet while PGCs are present in the dorsal mesentery. The SCF-positive autonomic nerve fibers of the dorsal mesentery, mesothelial cells and fibroblasts may nurse and perhaps guide PGCs during their ascent.
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S1043-2760(02)00612-4
Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic consequences, including anovulation, infertility and an increased prevalence of diabetes mellitus. Obesity, central obesity and insulin resistance are strongly implicated in its etiology and reduction of these risk factors should be a central treatment focus. Short-term weight loss has been consistently successful in reducing insulin resistance and restoring ovulation and fertility. However, problems arise with maintaining weight loss and precisely quantifying the associated long-term benefits of risk factor change. Although recent research indicates modest long-term lifestyle changes might reduce the extent of impaired glucose tolerance and delay the conversion to diabetes mellitus in the general population, this has not yet been examined in women with PCOS. Current conservative treatment should emphasize sustainable weight loss through dietary modification and exercise. Modifying additional lifestyle factors, including alcohol consumption, psychosocial stressors and smoking, are also crucial in long-term treatment of PCOS.
Publisher: Hindawi Limited
Date: 2008
DOI: 10.1155/2008/243791
Abstract: Peroxisome proliferator-activated receptor gamma (PPARG) regulates cellular functions such as adipogenesis and immune cell activation. However, new information has indicated additional roles of PPARG directing the cyclic changes that occur within ovarian tissue of female mammals, including those that facilitate the release of oocytes each estrous cycle. In addition to ovarian PPARG expression and function, many PPARG actions within adipocytes and macrophages have additional direct and indirect implications for ovarian function and female fertility. This encompasses the regulation of lipid uptake and transport, insulin sensitivity, glucose metabolism, and the regulation of inflammatory mediator synthesis and release. This review discusses the developing links between PPARG activity and female reproductive function, and highlights several mechanisms that may facilitate such a relationship.
Publisher: Elsevier BV
Date: 03-1982
Publisher: The Endocrine Society
Date: 11-2004
DOI: 10.1210/JC.2004-0643
Abstract: Recently, we proposed an oocyte-growth differentiation factor-9 hypothesis that predicts alterations in the initial stages of folliculogenesis in polycystic ovary syndrome (PCOS) ovaries. Here, we test this hypothesis by scoring the composition of follicles in normal and PCOS ovaries. Follicles were classified as primordial, transitional primary, classic primary, secondary, and Graafian. A total of 2274 follicles were scored. The total number of growing follicles was significantly greater in PCOS ovaries than normal, but the number of nongrowing primordial follicles did not differ. Consequently, the increase in growing follicles in PCOS cannot be explained by increased primordial follicle recruitment. Differential counts showed that the number of growing follicles at each stage of development was significantly greater: PCOS had 2.7-fold more primary, 1.8-fold more secondary, and 2-fold more Graafian follicles than normal. The greatest effect was on the classic primary follicles where the number was almost 5-fold greater in PCOS ovaries. The absence of apoptosis in normal and PCOS preantral follicles argues that the increase in growing follicles in PCOS cannot be explained by changes in atresia. We conclude, therefore, that primary follicle growth is abnormally slow in PCOS and the dynamics are reflected in a stockpiling of classic primary follicles.
Publisher: American Chemical Society (ACS)
Date: 31-08-2010
DOI: 10.1021/JP1063403
Publisher: Springer Science and Business Media LLC
Date: 18-05-2012
Publisher: Wiley
Date: 11-2002
DOI: 10.1046/J.1523-5408.2002.05604.X
Abstract: Overweight and obesity are serious and prevalent conditions in Western countries and carry many health consequences, including reproductive dysfunction. In particular, excess fat in the abdominal area is strongly related to disorders of the reproductive system. Moderate weight loss and reduction of abdominal fat improves menstrual regularity, ovulation, and infertility in women. This may be etiologically related to insulin resistance, particularly in a subset of infertile women with polycystic ovary syndrome. As such, weight loss should be promoted as an initial treatment option for obese women with infertility. However, the most effective method for achieving and maintaining weight loss is unclear. Gradual weight loss is best achieved through a sensible eating plan that can be maintained over long periods of time. The likelihood of maintaining weight loss is increased when diet is combined with regular exercise, cognitive behavior therapy, and a supportive group environment. Adoption of these principles in a primary healthcare setting can therefore aid in treatment of infertility related to obesity.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/J.MCE.2004.10.006
Abstract: Stem cell factor (SCF), another alternative name is kit ligand, is essential for the development of early follicles. However, the underlying molecular mechanism remains to be defined. By using cultured ovaries that are rich in primordial follicles, the action of SCF (kit ligand) on early follicular development and the activated signal transduction pathways were investigated. SCF (kit ligand) promoted early follicle development. PKC and MEK but not PKA were involved in the signal transduction of SCF (kit ligand) as indicated by results using their specific pharmacological inhibitors. SCF (kit ligand) also enhanced the phosphorylation of two MEK substrates, Erk1 and 2 (Erk1/2) in thecal-interstitial cells where PKC might play an important role indicated by results using its inhibitors. SCF (kit ligand) elevated the expression of steroidogenic factor 1 (SF-1) in thecal-interstitial cells probably through a pathway that consists of Erk1/2. These results suggest that SCF (kit ligand) promotes follicular growth by stimulating the function of thecal-interstitial cells through the Erk1/2 pathway.
Publisher: Wiley
Date: 2000
Publisher: BMJ
Date: 05-11-1988
DOI: 10.1136/BMJ.297.6657.1195-C
Abstract: Enterolith is a rare clinical entity that may be found on imaging or at surgery. We report an unusual case of intestinal obstruction caused by a large uric acid containing enterolith which was formed in the absence of any bowel inflammation, stricture or erticulum.
Publisher: Bioscientifica
Date: 04-1997
Abstract: Two ovine stem cell factor (oSCF) cDNAs (822 bp and 738 bp) were generated from ovarian follicle mRNA by RT-PCR. Nucleotide sequencing revealed that the oSCF 822 bp cDNA encodes a precursor protein of 274 amino acids. An amino acid change 109 E to 109 Q was the only sequence difference from that previously described for this species. The smaller (738 bp) oSCF cDNA was shown by nucleotide sequencing to be an mRNA splice variant, equivalent to that found in other mammals, in which an exon (84 bp) encoding a potential proteolytic cleavage site is removed. Northern analysis revealed a single transcript of approximately 6·5 kb in follicles, corpora lutea and stroma of mid-luteal sheep ovaries. In situ hybridization was used to detect oSCF mRNA within ovaries of fetal sheep on days 90, 100, 120 and 135 of gestation (term=147) and of adult sheep within the breeding season. In fetal and adult ovaries, oSCF mRNA was detected in the granulosa cells of follicles at all stages of follicle growth (primordial through to antral). The SCF gene was also expressed in granulosa cells of atretic follicles but appeared to be down-regulated in the cumulus cells surrounding the oocyte at more advanced stages of atresia. In fetal ovaries at day 90 of gestation (90DG), oSCF was expressed in the subepithelial mesenchymal cells of the ovarian cortex. By 100DG the gene expression in the subepithelial cells became restricted to a narrow region below the epithelium, and areas of expression were observed in groups of cells around isolated oocytes, primordial and primary follicles. oSCF gene expression also occurred in the surface epithelial cells of 90DG ovaries, the expression was absent from these cells by 135DG and in adult ovaries. Localization of oSCF mRNA was observed in the ovarian rete and endothelial cells of blood vessels of fetal ovaries. These results suggest that oSCF may have an important and continuous role in the development and/or maintenance of germ cells during follicle growth and atresia in sheep.
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0303-7207(98)00216-0
Abstract: The luteinizing hormone receptor (LHR) is alternatively spliced. It is not known if the alternatively spliced mRNAs are translated in vivo, or indeed if they have any vital role to play. The B splice form has been detected in every species examined, and it encodes a putative protein with a high affinity LH/CG binding domain but no trans-membrane or intra-cellular domains. We raised antisera that recognize the putative protein of the B form, and the closely related G form, and showed that the B form mRNA is translated in the ovine ovary, but not kidney or liver. It localized to the luteal cytosolic and microsomal fractions and the levels declined during regression induced by treatment with prostaglandin F2alpha. We examined alternative splicing by RNase protection analyses and RT-PCR analyses of healthy pre-ovulatory follicles, atretic or steroidogenically-inactive follicles, and of newly formed, mid-luteal and regressing corpora lutea. There was approximately 5-fold more B form mRNA than A form. Thus we have evidence that the LHR B form is translated in vivo, but no evidence that alternative splicing of the LHR mRNA is differentially regulated, throughout the oestrous cycle.
Publisher: Wiley
Date: 1983
DOI: 10.1111/J.1471-0528.1983.TB06746.X
Abstract: The phospholipid composition of amniotic fluid has been examined in 30 twin pregnancies with a mean gestation of 37.7 weeks. Before the onset of labour there was no difference in ratios of lecithin (L), phosphatidylinositol (PI), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) to sphingomyelin (S) between the first and second twin. With the start of contractions (6 patients) there was a significant increase in the L/S and PE/S ratios in the first twin (L/S ratio twin I 10.8 +/- 5.2, twin II 7.0 +/- 3.8 PE/S ratio twin I 0.7 +/- 0.2, twin II 0.4 +/- 0.1). Growth retardation of one fetus did not alter the phospholipid profile in the amniotic fluid. Amniotic fluid concentrations of glucocorticoids, measured before and during labour in both twins by specific immunoassay, were the same in both sacs before labour. During labour concentrations of unconjugated and conjugated glucocorticoids were significantly increased in the first sac (twin I unconjugated 113.2 +/- 16.6, conjugated 505.1 +/- 115.9 twin II unconjugated 69.5 +/- 41.4, conjugated 284.3 +/- 124 nmol/l). Amniotic fluid from growth retarded fetuses did not show higher glucocorticoid levels. In subsequent studies the glucocorticoids were separated by chromatography and only cortisol reacted significantly with the antibody used under the conditions of the assay.
Publisher: Wiley
Date: 09-1981
Publisher: Oxford University Press (OUP)
Date: 12-10-2010
Publisher: Wiley
Date: 14-11-2006
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.BJA.2018.07.002
Abstract: Cancellation of planned surgery impacts substantially on patients and health systems. This study describes the incidence and reasons for cancellation of inpatient surgery in the UK NHS. We conducted a prospective observational cohort study over 7 consecutive days in March 2017 in 245 NHS hospitals. Occurrences and reasons for previous surgical cancellations were recorded. Using multilevel logistic regression, we identified patient- and hospital-level factors associated with cancellation due to inadequate bed capacity. We analysed data from 14 936 patients undergoing planned surgery. A total of 1499 patients (10.0%) reported previous cancellation for the same procedure contemporaneous hospital census data indicated that 13.9% patients attending inpatient operations were cancelled on the day of surgery. Non-clinical reasons, predominantly inadequate bed capacity, accounted for a large proportion of previous cancellations. Independent risk factors for cancellation due to inadequate bed capacity included requirement for postoperative critical care [odds ratio (OR)=2.92 95% confidence interval (CI), 2.12-4.02 P<0.001] and the presence of an emergency department in the treating hospital (OR=4.18 95% CI, 2.22-7.89 P<0.001). Patients undergoing cancer surgery (OR=0.32 95% CI, 0.22-0.46 P<0.001), obstetric procedures (OR=0.17 95% CI, 0.08-0.32 P<0.001), and expedited surgery (OR=0.39 95% CI, 0.27-0.56 P<0.001) were less likely to be cancelled. A significant proportion of patients presenting for surgery have experienced a previous cancellation for the same procedure. Cancer surgery is relatively protected, but bed capacity, including postoperative critical care requirements, are significant risk factors for previous cancellations.
Publisher: Wiley
Date: 1986
Publisher: Wiley
Date: 2004
DOI: 10.1002/MRD.20142
Abstract: Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti-apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3'-end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti-apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis-related gene products, the Bcl-2 family proteins, in response to SCF treatment were also investigated. While SCF up-regulated the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, it did the opposite to the pro-apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl-xL and Bax but not on Bcl-2. Therefore, it seemed that SCF initiated an anti-apoptotic signal starting from its membrane receptor c-kit to Bcl-2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.FERTNSTERT.2010.02.057
Abstract: In overweight women with polycystic ovary syndrome, weight loss improves arterial compliance and postprandial lipidemia. Modifying dietary carbohydrate or protein in weight loss provided similar improvements in arterial compliance and postprandial lipidemia.
Publisher: Elsevier BV
Date: 08-1997
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1093/AJCN/NQY248
Abstract: As a public health intervention, front-of-pack labels (FoPLs) have the potential to reach large numbers of consumers and promote healthier food choices. Of the different FoPLs, those that summarize a product's overall nutritional profile tend to be most effective in guiding healthier choices. However, information is lacking as to whether FoPLs are as effective when nutrient or health claims also appear on-pack. The aim of this study was to examine how the choice of foods of varying levels of healthfulness (less healthy, moderately healthy, and healthier) is affected by the appearance of various FoPLs (Daily Intake Guide, Multiple Traffic Lights, Health Star Rating) when shown in combination with different claim conditions (no claim, nutrient claim, general-level health claim, and higher-level health claim). Adults and children (n = 2069) completed a discrete-choice experiment online. Respondents were shown 8 choice sets, each containing 4 alternatives of the same food type (cookies, cornflakes, pizza, or yogurt) of varying levels of healthfulness and were asked which product they would likely purchase (or they could select none). Respondents were randomly assigned to view 1 of the 3 FoPLs across all choice sets. Claim type and healthfulness varied within choice sets in accordance with a D-efficient design. The probability of choosing a healthy product and avoiding an unhealthy product was greatest when only an FoPL (especially the Health Star Rating) appeared on-pack. The addition of a nutrient or health claim did not affect the likelihood of picking healthier products but did increase the likelihood of selecting less healthy foods across all FoPL conditions. FoPLs are most effective in helping consumers make better food choices when nutrient and health claims are not present. Policies are required to control how nutrient and health claims are applied to less healthy foods. This trial was registered as ACTRN12617000015347 (www.anzctr.org.au/Trial/Resgistration/TrialReview.aspx?id=372055&isReview=true).
Publisher: Wiley
Date: 2005
DOI: 10.1002/PROS.20154
Abstract: Although up to 30% of men who undergo radical prostatectomy for clinically organ-confined prostate cancer will relapse with disseminated disease, currently it is not possible to predict these patients. Androgen receptor (AR) immunoreactivity in stromal and epithelial compartments of tumor foci was evaluated by video image analysis in 53 radical prostatectomy specimens. Kaplan-Meier and Cox Regression analyses were used to determine whether AR immunostaining was related to rate and risk of relapse, respectively. Ninety-eight percent (52/53) of the tumors contained AR positive malignant epithelial cells. Kaplan-Meier analysis indicated that patients with high AR levels (>64% AR positive nuclear area) in the malignant epithelial cells or low AR levels (<or=45% AR positive nuclear area) in the peritumoral stroma cells, were more likely to relapse earlier following radical prostatectomy. The shortest time to relapse and the highest relapse rate was for patients with both high AR in the malignant epithelial cells and low AR in the peritumoral stromal cells. These findings suggest that AR is an important determinant of disease relapse in early stage prostate cancer, and that altered AR levels in the malignant epithelial cells or in the peritumoral stroma is indicative of non-organ confined prostate cancer.
Publisher: Bioscientifica
Date: 09-2000
Abstract: Evidence from mouse mutants indicates that the Kit gene encoding KIT, a receptor present on the oocyte and theca cells, and the Mgf gene encoding KIT LIGAND, the ligand of KIT, are important regulators of oogenesis and folliculogenesis. Recently, in vitro cultures of fetal gonads, of follicles and of oocytes have identified specific targets for the KIT-KIT LIGAND interaction. In fetal gonads, an anti-apoptotic effect of KIT-KIT LIGAND interactions on primordial germ cells, oogonia and oocytes has been demonstrated. In postnatal ovaries, the initiation of follicular growth from the primordial pool and progression beyond the primary follicle stage appear to involve KIT-KIT LIGAND interactions. During early folliculogenesis, KIT together with KIT LIGAND controls oocyte growth and theca cell differentiation, and protects preantral follicles from apoptosis. Formation of an antral cavity requires a functional KIT-KIT LIGAND system. In large antral follicles, the KIT-KIT LIGAND interaction modulates the ability of the oocyte to undergo cytoplasmic maturation and helps to maximize thecal androgen output. Hence, many steps of oogenesis and folliculogenesis appear to be, at least in part, controlled by paracrine interactions between these two proteins.
Publisher: Wiley
Date: 06-2002
DOI: 10.1038/OBY.2002.74
Abstract: This study examines the relationship between body mass and the risk of spontaneous abortion in a large cohort of patients who received infertility treatment. This is a retrospective study using data on pregnancies (n = 2349) achieved after treatment in a tertiary medical center from 1987 to 1999. One pregnancy per subject was included, and the subjects were stratified into five body mass groups based on body mass index (BMI): underweight, or =35 kg/m(2). Logistical regression analysis was used. The overall incidence of spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of spontaneous abortion was significant after adjusting for several independent risk factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m(2)), underweight women had a similar risk of spontaneous abortion, whereas there was progressive increase of risk in overweight, obese, and very obese groups (p < 0.05, p < 0.01, and p < 0.001, respectively). Of all known risk factors for spontaneous abortion, the control of obesity has great significance because it is noninvasive, potentially modifiable, possibly amenable to low cost, and self-manageable by patients. This study established a positive relationship between BMI and the risk of spontaneous abortion in women who became pregnant after assisted reproductive technology treatment.
Publisher: Oxford University Press (OUP)
Date: 02-2004
Abstract: There has been increasing number of pregnancies following assisted reproductive technology treatment and their survival is understandably a matter of interest. The relative risk of spontaneous abortion in these pregnancies remains unclear. The objectives of this study were to quantify the relative risk in assisted reproductive technology pregnancies in relation to two cohorts of naturally conceived pregnancies and to assess the possible risk factors for spontaneous abortion among assisted reproductive technology pregnancies. Three cohorts of pregnancies, 1945 pregnancies conceived following assisted reproductive technology treatment in a tertiary infertility clinic, 549 natural pregnancies in a prospective study of lifestyle and pregnancy (the Ford cohort), and 4265 pregnancies from another cohort (the Treloar cohort), were used in the study. After adjusting for age, the relative risk of spontaneous abortion was 1.20 (95% CI 1.03-1.46) in the assisted reproductive technology cohort in comparison with the Ford cohort. Within the assisted reproductive technology cohort, a history of spontaneous abortion predicted increased risk, while a low level of ovarian stimulation seemed to be related to a reduced risk. The study showed that the risk of spontaneous abortion was slightly increased in the assisted reproductive technology pregnancies after adjusting for maternal age and previous spontaneous abortion. Within the assisted reproductive technology cohort, several variables, including the level of stimulation, appeared to be linked with the risk of spontaneous abortion.
Publisher: Elsevier BV
Date: 03-2004
Publisher: Bioscientifica
Date: 04-2006
DOI: 10.1530/REP.1.00868
Abstract: The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit using in situ hybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian follicles in vitro . Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.
Publisher: Frontiers Media SA
Date: 04-06-2018
Publisher: The Endocrine Society
Date: 05-2009
DOI: 10.1210/JC.2008-2648
Abstract: Context: Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period. Objective: This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence. Design, Setting, and Participants: Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33 BMI 20–24.9 kg/m2), overweight (n = 31 BMI 25–29.9 kg/m2), and obese (n =32 BMI ≥30 kg/m2). Intervention: For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes. Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance. Results: Increasing BMI was associated with increased follicular fluid insulin (P & 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P & 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women. Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.FERTNSTERT.2011.09.024
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females, with a high prevalence. The etiology of this heterogeneous condition remains obscure, and its phenotype expression varies. Two widely cited previous ESHRE/ASRM sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008), respectively. The present third PCOS consensus report summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health, and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.
Publisher: Oxford University Press (OUP)
Date: 06-2002
Abstract: Embryo transfer has changed little since originally described in 1978. Clinicians rate the type of catheter used as the third most important variable in embryo transfer, but there are no adequately powered randomized trials. We compared the clinical pregnancy rates with the single lumen catheter (TCC) and the double lumen catheter (CC) in a randomized single blind trial. A total of 650 cycles of women from the Adelaide University reproductive medicine units in Australia were included in this trial. Patients were 10 IU/l, previous difficult embryo transfer and pre-implantation genetic diagnosis. Cycles were randomized from numbered sealed envelopes immediately prior to embryo transfer with stratification for fresh or frozen cycles. There was a significantly higher pregnancy rate in the group treated with the CC compared with the TCC catheter [29.6 versus 20.5% per embryo transfer, odds ratio (OR) = 1.63 (95% confidence interval: 1.14-2.30), P = 0.0076]. The point estimate for the OR was similar for fresh and frozen cycles. The pregnancy rate was increased by 50% and this justifies the increased cost of the soft double lumen catheter and the training of clinical staff required.
Publisher: Wiley
Date: 08-1984
DOI: 10.1111/J.1471-0528.1984.TB04850.X
Abstract: Concentrations of prostaglandins E (PGE), F2 alpha (PGF), 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM), 6-keto F1 alpha and thromboxane B2 were measured by specific radioimmunoassay in s les of amniotic fluid from 22 multigravid patients during labour. Normal labour in 10 patients was associated with a significant increase of PGE, PGF and PGFM with close correlation to cervical dilatation (P less than 0.05). In the 12 patients with clinically delayed labour, in the absence of cephalopelvic disproportion, there were significantly lower PGF (P less than 0.002) and PGFM (P less than 0.05) concentrations obtained while no differences were observed in the other prostanoids measured. Administration of oxytocin to the latter group to enhance labour did not have any effect on the concentrations of prostaglandins obtained in spite of an improvement in intrauterine pressures and accelerated progress of labour.
Publisher: The Endocrine Society
Date: 06-1988
Abstract: We studied the cause of the low serum progesterone, 17 beta-estradiol, and 17-hydroxyprogesterone levels that occur in women with an ectopic pregnancy. Only women who had been amenorrheic for less than 8 weeks were studied in order to assess corpus luteum rather than placental biosynthesis of these steroids each woman with an ectopic pregnancy was matched to a woman with a normal intrauterine pregnancy on the basis of serum intact hCG levels within 10% of one another to obviate the influence of different levels of this luteotropic hormone. Every woman with an ectopic pregnancy had lower serum progesterone, estradiol, and 17-hydroxyprogesterone levels than her matched normal pregnant pairmate (median values: progesterone, 27.9 vs. 83.5 mmol/L estradiol, 0.36 vs. 1.79 nmol/L 17-hydroxyprogesterone, 4.95 vs. 22.1 nmol/L, respectively all P less than 0.002). The ratios of intact hCG, measured by immunoradiometric assay, to hCG, measured by a hCG beta-specific RIA, were similar in the two groups. Serum hCG bioactivity was assayed by measuring the ability of serum to stimulate testosterone secretion from mouse Leydig cells. The mean biological to intact immunological hCG ratios were 2.06 +/- 1.39 (+/- SD) for ectopic pregnancy and 1.91 +/- 0.81 for normal pregnancy (P greater than 0.05). The biological hCG to immunoreactive hCG beta ratios were 1.98 +/- 0.75 and 2.02 +/- 0.82, respectively. Serum hCG from both groups of women stimulated cAMP generation by testicular cells similarly. We conclude that the lower serum steroid levels in women with ectopic pregnancy cannot be explained by altered hCG bioactivity. The lower steroid levels may thus reflect a primary defect of the corpus luteum, absence of another stimulator of ovarian steroid biosynthesis, or more subtle alterations in hCG glycosylation which are important in vivo but not assessed by the in vitro bioassay.
Publisher: Elsevier BV
Date: 2005
DOI: 10.1016/S1472-6483(10)61157-1
Abstract: The Australian experience of gonadotrophin stimulation is a useful ex le of steps that lead to a country deciding to use recombinant FSH solely.
Publisher: Elsevier BV
Date: 09-1989
DOI: 10.1016/0002-9378(89)90414-6
Abstract: To evaluate the association between lipid-lowering agents, antihypertensive medications, and colorectal cancer risk. We hypothesized a reduction in colorectal cancer risk with 3-hydroxy-3-methylglutaryl coA reductase inhibitors (statins) and angiotensin-converting enzyme inhibitors. We conducted a case-control study at Group Health Cooperative, an integrated delivery system in Washington State. Incident colorectal cancer cases diagnosed between January 1, 2000, and December 31, 2003, were identified from the western Washington Surveillance, Epidemiology, and End Results cancer registry. Controls were matched by age, sex, and duration of enrollment. Data on medication use and potential confounders were obtained from health plan records. We estimated odds ratios and 95% confidence intervals (95% CI) using multivariate conditional logistic regression. Risk for colorectal cancer was not associated with use of statins (odds ratio, 1.02 95% CI, 0.65-1.59), other lipid-lowering agents (odds ratio, 1.31 95% CI, 0.70-2.47), angiotensin-converting enzyme inhibitors (odds ratio, 0.98 95% CI, 0.67-1.43), calcium channel blockers (odds ratio, 1.06 95% CI, 0.72-1.55), or diuretics (odds ratio, 1.00 95% CI, 0.70-1.44). Risk did not differ by duration of medication use, including long-term use. Risk for colorectal cancer was not reduced by use of statins or angiotensin-converting enzyme inhibitors. Other lipid-lowering and antihypertensive medications were also not associated with colorectal cancer risk.
Publisher: Oxford University Press (OUP)
Date: 2003
DOI: 10.1373/49.1.144
Abstract: Background: The currently used standards for human chorionic gonadotropin (hCG) and its α and β subunits (hCGα and hCGβ) contain substantial amounts of contaminating variants of hCG and other impurities. Furthermore, some partially degraded forms of hCG and its subunits have become of potential clinical importance, e.g., “nicked” forms of hCG (hCGn) and hCGβ (hCGβn), which contain cuts in the peptide backbone between amino acids 44–45 or 47–48 in hCGβ, and a fragment of hCGβ (hCGβcf) consisting of amino acids 6–40 and 55–92 bound together by disulfide bridges. The IFCC appointed a working group with the aim of preparing new standards for hCG and related substances to improve standardization of their immunoassays. Methods: Large amounts of hCG and its subunits as well as of hCGn, hCGβn, and hCGβcf were prepared by previously developed purification methods in combination with hydrophobic interaction chromatography and reversed-phase HPLC. Each preparation was characterized on the basis of amino acid and sequence analyses, carbohydrate composition, and electrophoretic patterns. Immunoassays for relevant contaminating proteins were also performed. Results: The major preparations were homogeneous and free of contaminating proteins. Concentrations of the final preparations were determined by amino acid analysis. Conclusions: Calibrated in substance concentrations (mol/L) based on amino acid analyses, these preparations will facilitate improved standardization of immunoassays for hCG and its metabolites. The six preparations have now been established by the WHO as new 1st Reference Reagents for immunoassays with the following codes: hCG 99/688, hCGβ 99/650, hCGα 99/720, hCGn 99/642, hCGβn 99/692, and hCGβcf 99/708. In contrast to the 3rd International Standard (75/537), the clinically most important Reference Reagent for hCG (99/688) contains no hCGn and negligible amounts of free subunits.
Publisher: The Endocrine Society
Date: 11-2006
DOI: 10.1210/JC.2006-0178
Abstract: Objective: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. Participants: Participants included expert investigators in the field. Evidence: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. Consensus Process: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. Conclusions: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.
Publisher: Bioscientifica
Date: 10-1998
Abstract: A specific and sensitive ELISA for measuring marmoset chorionic gonadotrophin (mCG) in culture medium, urine and plasma was developed using a polyclonal antibody raised against recombinant mCG, tagged with six histidine molecules (rmCG-6His), as the capture antibody. A well-characterised monoclonal antibody (518B7), which was generated against bovine luteinising hormone (bLH) and has been shown to detect CG and LH in Callithrichid monkeys, was biotinylated and used as the secondary antibody. Purified rmCG, calibrated against human CG (hCG CR127) by bioassay, or the beta-subunit (rmCGbeta), quantified from amino acid analysis and carbohydrate analysis, was used as the standard. The assay was able to detect CG activity in medium collected from cultured marmoset embryos before attachment and through to the trophoblastic vesicle stage, plasma and urine collected from pregnant marmosets, marmoset placenta and pituitary homogenates. The assay was validated and its performance compared with a bioassay based on MA10 cell response to CG, with hCG as the standard. The sensitivity was 103 pg/ml (5 pg/well) of rmCGbeta and 476 pg/ml (24 pg/well) of the heterodimer rmCG. The mean recovery of standard added to embryo culture medium, marmoset urine and plasma was 104, 112 and 92% respectively. The intra- and interassay variation was less than 10 and 16% respectively. The low cross-reactivity with cynomolgus monkey and baboon LH, their beta-subunits, cynomolgus monkey and baboon follicle-stimulating hormone and hCG suggests that the assay is specific for mCG.
Publisher: Elsevier BV
Date: 04-2002
Publisher: The Endocrine Society
Date: 11-2007
DOI: 10.1210/JC.2007-0729
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, but its etiology remains obscure. Recent data suggest that an intrinsic abnormality of early follicle development in the ovary is key to the pathogenesis of PCOS. We have recently found that in PCOS the proportion of primordial follicles is decreased with a reciprocal increase in the proportion of primary follicles. Our aim was to examine whether the accelerated transition of follicles from primordial to primary stages in polycystic ovaries (PCO) is due to increased granulosa cell (GC) ision. This study is a comparison of expression of minichromosome maintenance protein 2 (MCM2) (present in the nuclei of cells that are licensed to ide) in archive tissue from normal and PCO. This is a laboratory-based study. There were 16 women with regular cycles (six with normal and 10 with PCO) and five anovulatory women with PCO, classified histologically, with reference to menstrual history and ultrasound. The presence of MCM2 expression in the GCs of 1,371 follicles was determined. GC proliferation was increased in anovulatory PCO compared with both normal and ovulatory PCO, with an increased proportion of preantral follicles with MCM2-positive GCs (P <or= 0.015). The number of GCs differed significantly among the three types of ovary at the transitional (P = 0.013) and primary (P = 0.0096) stages. This was accompanied by an altered relationship (P < 0.0001) between oocyte growth and GC ision/cuboidalization. These findings provide evidence for increased GC proliferation in early-growing follicles in PCOS. This offers an explanation for the increased proportion of primary follicles in PCOS.
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1016/J.FERTNSTERT.2004.02.146
Abstract: To investigate the immunocytochemical expression and presence of mRNA transcripts of stem cell factor (SCF) and its receptor (SCF-R) in ovaries from human adults and fetuses. Immunocytochemical and reverse transcription polymerase chain reaction (RT-PCR) study. Major tertiary care and referral academic centers. Seven women and girls undergoing laparoscopic ovarian biopsy and 13 women undergoing second and third trimester pregnancy terminations. None. Microscopic morphometric analysis, immunocytochemistry for SCF and SCF-R, and RT-PCR analyses. There was strong to moderate immunocytochemical staining for SCF and its receptor in oocytes from primordial stages onward, but not in granulosa cells, in both fetal and adult ovarian s les. Transcripts of SCF and SCF-R RNA were detected by RT-PCR analyses for SCF and SCF-R. The expression of SCF and its receptor in ovarian tissue from fetuses and women suggests a possible role of SCF in growth initiation of human primordial follicles.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.FERTNSTERT.2008.09.018
Abstract: To summarize current evidence on lifestyle management (dietary, exercise, or behavioral interventions) of obesity in women with polycystic ovary syndrome (PCOS), to indicate gaps in knowledge, and to review the medical and surgical alternatives for weight management. Expert panel appointed by the Androgen Excess and PCOS Society (AEPCOS Society) to review the literature and draft the initial report after a consensus process via electronic communication. The initial report was reviewed and critiqued by all expert panel members and the AEPCOS Society Board of Directors and modified based on their comments. Lifestyle management should be used as the primary therapy in overweight and obese women with PCOS for the treatment of metabolic complications. For reproductive abnormalities, lifestyle modification may improve ovulatory function and pregnancy. Data are preliminary for improvement in pregnancy and live-birth rates, and further research is needed. There is currently no evidence that modifying dietary macronutrient composition offers additional benefits over conventional dietary approaches for weight loss, and further research is needed. Emerging evidence suggests that exercise offers additional benefits to dietary energy restriction for reproductive features of PCOS.
Publisher: American Physiological Society
Date: 08-2007
DOI: 10.1152/AJPENDO.00172.2007
Abstract: The receptor, c-Kit, and its ligand, stem cell factor (SCF), are critical for hematopoietic stem cell differentiation and have been implicated in the development, function, and survival of rodent islets. Previously, we reported that exogenous SCF treatments of cultured human fetal (14–16 wk fetal age) islet-epithelial clusters enhanced islet cell differentiation and proliferation (Li J, Goodyer CG, Fellows F, Wang R. Int J Biochem Cell Biol 38: 961–972, 2006). In the present study, we examined the expression pattern of c-Kit in early to midgestation human fetal pancreata and the relevance of c-Kit receptor tyrosine kinase for insulin gene expression and β-cell survival. c-Kit is expressed in the intact pancreas in a cell-specific manner, with a significant decrease in immunoreactivity in the duct regions from 8 to 21 wk fetal age, paralleled by a significant increase in expression within endocrine regions. These c-Kit-positive cells are highly proliferative and show frequent coexpression with insulin and glucagon. Treatment of islet-epithelial clusters with anti-ACK45 antibody stimulates c-Kit phosphorylation paralleled by a significant increase in PDX-1 and insulin expression, increased cell proliferation, and reduced β-cell death. In contrast, transient transfection with c-Kit siRNA results in a three- to fourfold decrease in c-Kit, PDX-1, and insulin expression and decreased cell proliferation. This study describes important changes in the distribution and dynamics of c-Kit-expressing cells during human fetal pancreatic neogenesis, suggesting that c-Kit may be a marker for human pancreatic islet progenitor cells. Functional analysis of the c-Kit receptor tyrosine kinase provides evidence that phosphorylation of c-Kit receptor may be involved in mediating early β-cell differentiation and survival.
Publisher: Informa UK Limited
Date: 1987
Publisher: Bioscientifica
Date: 02-2004
Abstract: The pituitary gonadotrophins LH and FSH are responsible for regulation of gametogenesis in the testis and ovary. Chorionic gonadotrophin (CG), a third closely related glycoprotein hormone derived by gene duplication of the LHbeta gene and secreted by the placenta in primates, is essential for the rescue of the corpus luteum and maintenance of pregnancy. We have recently shown that marmoset (m) CGbeta mRNA is highly expressed in the pituitary of the common marmoset (Callithrix jacchus) and that LH is less active than human CG in activating the human LH receptor lacking exon 10. To investigate further which gonadotrophin is the actual ligand of the LH receptor (LHR) of the marmoset monkey that naturally lacks exon 10, we identified and characterised the genomic organisation of the mLHbeta gene and its expression. Intergenic PCR lification of the region encompassing the mLHbeta and the mCGbeta genes revealed that, surprisingly, mCGbeta is located 20 kbp upstream of the LHbeta gene, whereas in other species the intergenic distance is approximately 2-3 kbp. Sequence analysis of the mLHbeta coding region showed 70% identity to mCGbeta and 90% identity to human LHbeta at the amino acid level. Both gonadotrophin beta subunits are present at the genomic level, but RT-PCR of pituitary and placental total RNA using specific oligonucleotides for mCGbeta and mLHbeta showed high expression of mCGbeta mRNA in both tissues, whereas LHbeta was expressed neither in the pituitary nor in the placenta. Thus mLHbeta mRNA is lacking in the marmoset pituitary. Immunohistochemistry of marmoset pituitaries showed that mCG was confined to the gonadotrophes, and partly co-localised in cells stained positively for FSH. Western blot analysis confirmed the presence of mCG in the pituitary. Northern blot analysis using mCGbeta as a probe displayed one transcript of 0.7 kb in the pituitary and detected two transcripts of 1.1 kb and 2 kb in the marmoset placenta. Our results suggest that, in the common marmoset, CG is the only gonadotrophin with luteinising function that is present in the pituitary. We postulate that, owing to an unknown mutational event in evolution, expression of mLH was completely abolished, and CG - which, unlike LH, acts normally even when exon 10 is missing from the LHR - took over its function.
Publisher: The Endocrine Society
Date: 04-1991
Abstract: The effects of human interleukin-1 (IL-1) and IL-2 on human granulosa-luteal cell progesterone production were examined with or without hCG stimulation in vitro. Human granulosa-luteal cells were recovered from follicular fluid obtained from women undergoing in vitro fertilization procedures and cultured for up to 7 days before supernatant progesterone level measurement. Lymphokine-rich conditioned medium was prepared from mitogen-stimulated human peripheral blood leukocytes (HPL-CM). The influence of HPL-CM on both granulosa-luteal cell progesterone production and cell growth was inhibitory. In contrast, supernatants of the IL-2-producing cell line MLA-144 (MLA-CM) stimulated both basal progesterone secretion and cell proliferation. Human recombinant IL-2 (from 0.1-100 IU) alone did not change progesterone levels, compared to control values, after 24 h of cell culture. However, 1, 10, and 100 IU IL-2 significantly inhibited progesterone secretion from cells stimulated by 5 IU hCG (P less than 0.01). The enhanced progesterone levels stimulated by forskolin were also significantly inhibited by 10 IU IL-2 (P = 0.01). This effect was not mediated through decreased cAMP, since the forskolin-enhanced cAMP level was not influenced by IL-2, IL-1, with or without hCG, did not show any effect on progesterone production during either 24 or 48 h of cell culture. It is concluded that 1) human recombinant IL-2 significantly inhibits progesterone production stimulated by hCG in human granulosa-luteal cells 2) IL-2 also had a marked inhibitory effect on forskolin-induced progesterone release, but did not influence the increased cAMP level stimulated by forskolin 3) the inhibitory influence of IL-2 on progesterone synthesis may be down-stream in the signal transduction pathway from cAMP activation and 4) HPL-CM and MLA-CM produced inhibitory and stimulatory effects, respectively, on both basal and hCG-stimulated progesterone levels as well as on granulosa-luteal cell proliferation. These activities cannot be completely attributed to IL-2, and other mediators of leukocyte origin may, therefore, exist.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/S1472-6483(10)62130-X
Abstract: Women with polycystic ovary syndrome (PCOS) have a high risk of abnormal glucose metabolism, which deteriorates gradually over time. This study was designed to assess contributing factors to the rate of deterioration of glucose metabolism over the 4- to 7-year follow-up period. The study group included 67 PCOS women who had normal glucose tolerance in the initial test in 1990-1992. There was a significant increase in both fasting and 2-h glucose concentrations, and body weight, over the follow-up period. The initial obesity, expressed as waist:hip ratio and BMI, was significantly related to the increase of glucose concentrations, while weight gain was not a significant factor. The overweight/obese PCOS women have a faster deterioration of glucose metabolism over the follow-up period than the non-obese ones. Moderate weight gain has no significant detrimental effect on the rate of deterioration of glucose metabolism.
Publisher: Oxford University Press (OUP)
Date: 11-11-2004
DOI: 10.1373/CLINCHEM.2004.038679
Abstract: The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group to investigate means of improving the comparability of immunoassays for human chorionic gonadotropin (hCG), which was selected as a prototype glycoprotein analyte. The Working Group identified development of unambiguous nomenclature and production of new highly purified International Reference Reagents calibrated in substance concentrations as its primary objectives. Preparations of intact hCG, nicked hCG, hCG beta-subunit, nicked hCG beta-subunit, hCG alpha-subunit, and hCG beta-core fragment were purified from a crude urinary hCG preparation, ouled, lyophilized, and assigned values in substance concentrations (mol/L). Value assignment and accelerated degradation studies were carried out in accordance with WHO protocols for International Reference Reagents. The ouled standards were assigned final values based on the recovery of immunoreactive material after reconstitution. The degradation studies showed that the standards were highly stable. The nomenclature of hCG-related molecules and immunoassays has been adopted by the IFCC, and the standards prepared and characterized by the Working Group have been formally adopted by the WHO as the First International Reference Reagents for six hCG-related molecules. These developments will enable better understanding of what assays for hCG measure and should ultimately help to improve the clinical application of these assays.
Publisher: JMIR Publications Inc.
Date: 24-06-2020
DOI: 10.2196/17109
Abstract: There is increasing information characterizing menstrual cycle length in women, but less information is available on the potential differences across lifestyle variables. This study aimed to describe differences in menstrual cycle length, variability, and menstrual phase across women of different ages and BMI among a global cohort of Flo app users. We have also reported on demographic and lifestyle characteristics across median cycle lengths. The analysis was run based on the aggregated anonymized dataset from a menstrual cycle tracker and ovulation calendar that covers all phases of the reproductive cycle. Self-reported information is documented, including demographics, menstrual flow and cycle length, ovulation information, and reproductive health and diseases. Data from women aged ≥18 years and who had logged at least three cycles (ie, 2 completed cycles and 1 current cycle) in the Flo app were included (1,579,819 women). Of the 1.5 million users, approximately half (638,683/1,579,819, 40.42%) were aged between 18 and 24 years. Just over half of those reporting BMIs were in the normal range (18.5-24.9 kg/m2 202,420/356,598, 56.76%) and one-third were overweight or obese ( kg/m2 120,983/356,598, 33.93%). A total of 16.32% (257,889/1,579,819) of women had a 28-day median cycle length. There was a higher percentage of women aged ≥40 years who had a 27-day median cycle length than those aged between 18 and 24 years (22,294/120,612, 18.48% vs 60,870/637,601, 9.55%), but a lower percentage with a 29-day median cycle length (10,572/120,612, 8.77% vs 79,626/637,601, 12.49%). There were a higher number of cycles with short luteal phases in younger women, whereas women aged ≥40 years had a higher number of cycles with longer luteal phases. Median menstrual cycle length and the length of the follicular and luteal phases were not remarkably different with increasing BMI, except for the heaviest women at a BMI of ≥50 kg/m2. On a global scale, we have provided extensive evidence on the characteristics of women and their menstrual cycle length and patterns across different age and BMI groups. This information is necessary to support updates of current clinical guidelines around menstrual cycle length and patterns for clinical use in fertility programs.
Publisher: Springer Science and Business Media LLC
Date: 30-09-1999
Abstract: Alternate splicing of mRNA encoding c-KIT results in isoforms which differ in the presence or absence of four amino acids (GNNK) in the juxtamembrane region of the extracellular domain of the receptor. In this study we show that these isoforms of human c-KIT, expressed at similar levels in NIH3T3 cells, display differential effects on various attributes of transformation. The GNNK- isoform strongly promoted anchorage independent growth (colony formation in semi-solid medium), loss of contact inhibition (focus formation), and led to tumorigenicity in nude mice. In contrast, the GNNK+ isoform elicited colony formation but relatively poor focus formation and no tumorigenicity. Saturation binding analysis indicated that the isoforms do not differ significantly in their affinity for the KIT ligand, Steel Factor (SLF). Negligible ligand-independent receptor phosphorylation was observed in either case but, after ligand stimulation, the GNNK- isoform displayed more rapid and extensive tyrosine autophosphorylation and faster internalization. Both isoforms recruited the p85 subunit of phosphatidylinositol 3-kinase and led to similar phosphorylation of its downstream effector c-Akt, but the GNNK- isoform gave rise to more MAP kinase phosphorylation. Thus the c-KIT isoforms display different signalling characteristics and have different transforming activity in NIH3T3 cells.
Publisher: The Endocrine Society
Date: 12-2012
DOI: 10.1210/JC.2012-3606
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.FERTNSTERT.2012.02.034
Abstract: To determine whether the high lipid content of human follicular fluid influences oocyte maturation. Mouse oocytes as substitutes for human oocytes were exposed to follicular fluids of differing lipid content with outcome monitoring. Private infertility clinic and university laboratory. Seventy-four women seeking assisted reproduction, and gonadotropin-stimulated mice. Assay of follicular fluids for triglyceride and free fatty acids, and stimulation of mouse cumulus-oocyte complexes (COCs) to maturity in vitro in the presence of lipid-rich or lipid-poor follicular fluid. Oocyte lipid content, expression of endoplasmic reticulum stress marker genes, and oocyte maturation assessed in mouse COCs exposed to lipid-rich follicular fluid were compared with complexes exposed to lipid-poor follicular fluid and complexes matured in vivo. Follicular fluids were obtained from women of known body mass index undergoing oocyte aspiration at a private infertility clinic, and the follicular fluids were assayed for triglyceride and free fatty acids those with the highest and lowest levels of these lipids were selected. The mouse COCs exposed to lipid-rich follicular fluid during their maturation had increased oocyte lipid content, induction of endoplasmic reticulum stress markers, and impaired oocyte nuclear maturation. Increased body mass index is associated with elevated triglycerides and free fatty acids in ovarian follicular fluid. Maturation within this lipid-rich environment is detrimental to oocytes.
Publisher: SAGE Publications
Date: 05-1987
DOI: 10.1177/000456328702400305
Abstract: One hundred and seven patients with suspected ectopic pregnancy were tested for HCG at the bedside using the Tandem Icon. The test was performed by ward doctors with no formal laboratory experience. The patients were managed conservatively or by surgery as dictated by the clinical picture and the Icon test result. Retrospective categorisation of the 107 patients by laboratory analysis and clinical outcome showed that 21 were pregnant (17 ectopic, 4 intrauterine) and 86 non-pregnant. At the bedside the Icon was reported as negative in one pregnant patient and three patients who were not pregnant were found to give Icon-positive results. In the laboratory the Icon correctly categorised all patients. Three of the four discrepant results were found to be a direct result of the operator's inexperience in analytical procedure and interpretation. The Tandem Icon HCG urine assay can reliably be used at the bedside of patients with suspected ectopic pregnancy provided that the operator has had sufficient experience in its use.
Publisher: CSIRO Publishing
Date: 1990
DOI: 10.1071/RD9900563
Abstract: Dysfunctional labour was studied in relation to prostaglandin concentrations in amniotic fluid and production by fetal membranes. Initial clinical validation of the model established the presence of hypokinetic labour with no evidence of obstruction to the fetal progress. Prostaglandin F2 alpha (PGF2 alpha) and 13, 14 dihydro-15-keto-prostaglandin-F2 alpha concentrations in the amniotic fluid were low despite relatively normal concentrations of prostaglandin E2. Membranes removed from patients with the condition released very low concentrations of PGF2 alpha from the amniotic side with no alteration on the choriodecidual side of the membrane. Studies of free and phospholipid-associated arachidonic acid indicated normal release of arachidonic acid in dysfunctional labour. No changes in amniotic fluid-related inhibitors and stimulators of prostaglandin synthetase were detected. It is suggested that PGF2 alpha production is impaired in dysfunctional labour and that this prostaglandin is primarily involved in the progress of labour.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.FERTNSTERT.2007.12.002
Abstract: To determine the first-line medication to be used in anovulatory patients with polycystic ovary syndrome (PCOS) for ovulation induction and pregnancy achievement. Randomized controlled trial. Infertility unit of a public hospital. One hundred fifteen newly diagnosed patients with PCOS based on ESHRE/ASRM criteria. These patients were assigned to three groups: group 1 (38 patients) received 500 mg of metformin three times a day group 2 (39 patients) received clomiphene citrate (CC) at an incremental dose group 3 (38 patients) received both medications. Rates of ovulation, pregnancy (PR), and live birth. The ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4% in the combination treatment group. This was translated into a similar PR and live birth rate, which were higher in the CC and combination groups compared to the metformin group (PR: 7.9%, 15.4%, and 21.1% live birth rate: 7.9%, 15.4%, and 18.4% in metformin, CC, and combination treatment groups, respectively), although statistically the differences were not significant. There were no multiple pregnancies and the rate of spontaneous first trimester loss was similar to the general population. Clomiphene citrate should be the first-line treatment for ovulation induction in anovulatory patients with PCOS.
Publisher: Elsevier BV
Date: 07-2009
Publisher: Oxford University Press (OUP)
Date: 04-05-2018
Abstract: Is preconception dietary intake associated with reduced fecundity as measured by a longer time to pregnancy (TTP)? Lower intake of fruit and higher intake of fast food in the preconception period were both associated with a longer TTP. Several lifestyle factors, such as smoking and obesity, have consistently been associated with a longer TTP or infertility, but the role of preconception diet in women remains poorly studied. Healthier foods or dietary patterns have been associated with improved fertility, however, these studies focused on women already diagnosed with or receiving treatments for infertility, rather than in the general population. This was a multi-center pregnancy-based cohort study of 5628 nulliparous women with low-risk singleton pregnancies who participated in the Screening for Pregnancy Endpoints (SCOPE) study. A total of 5598 women were included. Data on retrospectively reported TTP and preconception dietary intake were collected during the first antenatal study visit (14-16 weeks' gestation). Dietary information for the 1 month prior to conception was obtained from food frequency questions for fruit, green leafy vegetables, fish and fast foods, by a research midwife. Use of any fertility treatments associated with the current pregnancy was documented (yes, n = 340, no, n = 5258). Accelerated failure time models with log normal distribution were conducted to estimate time ratios (TR) and 95% CIs. The impact of differences in dietary intake on infertility (TTP >12 months) was compared using a generalized linear model (Poisson distribution) with robust variance estimates, with resulting relative risks (RR) and 95% CIs. All analyses were controlled for a range of maternal and paternal confounders. Sensitivity analyses were conducted to explore potential biases common to TTP studies. Lower intakes of fruit and higher intakes of fast food were both associated with modest increases in TTP and infertility. Absolute differences between the lowest and highest categories of intake for fruit and fast food were in the order of 0.6-0.9 months for TTP and 4-8% for infertility. Compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day (TR = 1.06, 95% CI: 0.97-1.15), 1-6 times/week (TR = 1.11, 95% CI: 1.01-1.22) or <1-3 times/month (TR = 1.19, 95% CI: 1.03-1.36), corresponded to 6, 11 and 19% increases in the median TTP (Ptrend = 0.007). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2- 0-<2 times/week (TR 0.79, 95% CI 0.69-0.89) or no fast food (TR = 0.76, 95% CI: 0.61-0.95), corresponded to an 11, 21 and 24% reduction in the median TTP (Ptrend <0.001). For infertility, compared with women who consumed fruit ≥3 times/day, the adjusted effects of consuming fruit ≥1-<3 times/day, 1-6 times/week or <1-3 times/month corresponded to a 7, 18 and 29% increase in risk of infertility (Ptrend = 0.043). Similarly, compared with women who consumed fast food ≥4 times/week, the adjusted effects of consuming fast food ≥2- 0-<2 times/week, or no fast food, corresponded to an 18, 34 and 41% reduced risk of infertility (Ptrend <0.001). Pre-pregnancy intake of green leafy vegetables or fish were not associated with TTP or infertility. Estimates remained stable across a range of sensitivity analyses. Collection of dietary data relied on retrospective recall and evaluated a limited range of foods. Paternal dietary data was not collected and the potential for residual confounding cannot be eliminated. Compared to prospective TTP studies, retrospective TTP studies are prone to a number of potential sources of bias. These findings underscore the importance of considering preconception diet for fecundity outcomes and preconception guidance. Further research is needed assessing a broader range of foods and food groups in the preconception period. The SCOPE database is provided and maintained by MedSciNet AB (medscinet.com). The Australian SCOPE study was funded by the Premier's Science and Research Fund, South Australian Government (www.dfeest.sa.gov.au/science-research remiers-research-and-industry-fund). The New Zealand SCOPE study was funded by the New Enterprise Research Fund, Foundation for Research Science and Technology Health Research Council (04/198) Evelyn Bond Fund, Auckland District Health Board Charitable Trust. The Irish SCOPE study was funded by the Health Research Board of Ireland (CSA/2007/2 www.hrb.ie). The UK SCOPE study was funded by National Health Service NEAT Grant (Neat Grant FSD025), Biotechnology and Biological Sciences Research council (www.bbsrc.ac.uk/funding GT084) and University of Manchester Proof of Concept Funding (University of Manchester) Guy's and St. Thomas' Charity (King's College London) and Tommy's charity (www.tommys.org/ King's College London and University of Manchester) and Cerebra UK (www.cerebra.org.uk University of Leeds). L.E.G. is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship (ID 1070421). L.J.M. is supported by a SACVRDP Fellowship a program collaboratively funded by the National Heart Foundation, the South Australian Department of Health and the South Australian Health and Medical Research Institute. L.C.K. is supported by a Science Foundation Ireland Program Grant for INFANT (12/RC/2272). C.T.R. was supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (GNT1020749). There are no conflicts of interest to declare. Not applicable.
Publisher: Springer Science and Business Media LLC
Date: 1999
Publisher: Oxford University Press (OUP)
Date: 12-2002
DOI: 10.1093/HUMREP/17.12.3220
Abstract: In women treated by assisted reproductive technology (ART), early pregnancy loss (EPL) reduces the initial success. Risk factors for EPL, however, have not been comprehensively studied. This study assesses some potential risk factors in ART pregnancies. Altogether 1196 pregnancies, defined as serum hCG >or=10 IU/l on day 16 +/- 1 after oocyte retrieval, were included in this study. EPL was defined as pregnancy loss that occurred before 6-7 weeks gestation. Risk factors investigated were maternal age, body mass index (BMI), smoking and polycystic ovary syndrome (PCOS) status, infertility aetiology, response to stimulation, quality and number of embryos replaced and treatment type. Overall EPL was 16%. The risk of EPL was not linearly related to either age or BMI. Though women >40 years old had an increased risk, this was not significant after adjusting for other factors. The risk in both lean (BMI 35 kg/m(2)) women was also not significantly higher in multivariate analysis. There was no effect of PCOS. Smoking or transfer of 'poor quality' embryo(s) was associated with a significant increased risk of EPL after adjusting for other factors. Smoking and transferring poor quality embryos increased EPL, while the effects of age, obesity and other risk factors were not significant in a multivariate analysis.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2008
DOI: 10.1097/GME.0B013E318174F16E
Abstract: Oral estrogen therapy suppresses insulin like growth factor I (IGF-I) levels, whereas conventional dose transdermal estradiol (E2) does not. However, it has been proposed that if sufficiently high serum E2 levels are achieved, nonoral E2 will also suppress serum IGF-I. The aim of the study was to investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in postmenopausal women. This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n = 41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41) for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3, glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge, and the homeostasis model assessment for insulin resistance were assessed at baseline and after 52 weeks of treatment. The two groups were well matched for all clinical and biochemical parameters at baseline. There were no significant between-group differences for fasting and 120-minute glucose, insulin, homeostasis model assessment for insulin resistance, and IGF binding protein 3. The mean IGF-I level at week 52 was significantly lower for women treated with oral versus intranasal therapy (116 +/- 21 [SD] versus 134 +/- 33 [SD], P = 0.005) and the mean difference in change over 52 weeks in IGF-I was significantly different between groups (-19, 95% CI:-37 to -1, P = 0.04). In healthy postmenopausal women, intranasal E2 at a dose that results in serum levels that exceed the proposed threshold for growth hormone and IGF-I effects, does not alter IGF-I levels. This suggests that the effect of exogenous estrogen on IGF-I is a function of the method of administration rather than being dose related.
Publisher: Wiley
Date: 12-1988
DOI: 10.1111/J.1365-2265.1988.TB03706.X
Abstract: The relative influences of the putative thyroid stimulator, pregnancy state and non-thyroidal illnesses, were assessed in 52 patients with gestational trophoblastic neoplasia (GTN). In this study biochemical thyroid status was assessed with the aid of thyrotrophin (TSH) measurements by a sensitive immunoradiometric assay and measurement of total and free thyroid hormone concentrations. The reference group consisted of 63 patients with normal pregnancy. Thyroid function in the GTN patients was also compared with that in 36 female patients with Graves' disease and 34 female patients with non-thyroidal illnesses. We found the major influence on thyroid functions in Group I ('Hyperthyroid') patients with GTN to be the presence of the thyroid stimulator, while non-thyroidal illnesses played an important role in Group II ('High T4 syndrome') and III ('euthyroid') patients with GTN. Thyroid function was also stimulated in Group II patients. The influence of pregnancy was seen in all three groups of patients with GTN, who had higher TBG concentrations than non-pregnant patients. We conclude that there is a spectrum of thyroid function abnormalities in GTN, and that thyroid function in an in idual patient is determined by the relative influence of the thyroid stimulator, non-thyroidal illnesses and the pregnancy.
Publisher: BMJ
Date: 03-1986
Abstract: Diabetic retinopathy is a leading cause of acquired blindness. Available treatments are not very effective. We investigated the effect of a weekly application of retinal ischemia pulses (ischemic conditioning) on retinal damage induced by experimental diabetes. Diabetes was induced by an intraperitoneal injection of streptozotocin. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 minutes this maneuver started 3 days after streptozotocin injection and was weekly repeated in one eye, whereas the contralateral eye was submitted to a sham procedure. Diabetic retinopathy was evaluated in terms of i) retinal function (electroretinogram and oscillatory potentials), ii) integrity of blood-retinal barrier (by albumin-Evans blue complex leakage and astrocyte glial fibrillary acidic protein IHC), iii) optical and electron microscopy histopathologic studies, and iv) vascular endothelial growth factor levels (using Western blot analysis and IHC). Brief ischemia pulses significantly preserved electroretinogram a- and b-wave and oscillatory potentials, avoided albumin-Evans blue leakage, prevented the decrease in astrocyte glial fibrillary acidic protein levels, reduced the appearance of retinal edemas, and prevented the increase in vascular endothelial growth factor levels induced by experimental diabetes. When the application of ischemia pulses started 6 weeks after diabetes onset, retinal function was significantly preserved. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies for diabetic retinopathy treatment.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.RBMO.2018.12.038
Abstract: This was a systematic review and meta-analysis to examine the efficacy, effectiveness and safety of acupuncture as an adjunct to embryo transfer compared with controls to improve reproductive outcomes. The primary outcome was clinical pregnancy. Twenty trials and 5130 women were included in the review. The meta-analysis found increased pregnancies (risk ratio [RR] 1.32, 95% confidence interval [CI] 1.07-1.62, 12 trials, 2230 women), live births (RR 1.30, 95% CI 1.00-1.68, 9 trials, 1980 women) and reduced miscarriage (RR 1.43, 95% CI 1.03-1.98, 10 trials, 2042 women) when acupuncture was compared with no adjunctive control. There was significant heterogeneity, but no significant differences between acupuncture and sham controls. Acupuncture may have a significant effect on clinical pregnancy rates, independent of comparator group, when used in women who have had multiple previous IVF cycles, or where there was a low baseline pregnancy rate. The findings suggest acupuncture may be effective when compared with no adjunctive treatment with increased clinical pregnancies, but is not an efficacious treatment when compared with sham controls, although non-specific effects may be active in both acupuncture and sham controls. Future research examining the effects of acupuncture for women with poorer IVF outcomes is warranted.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0303-7207(02)00062-X
Abstract: Hyperandrogenaemia in women presents in a variety of ways, including problems with the reproductive system. The commonest cause is polycystic ovary syndrome (PCOS), a condition found in 5-10% of all women. PCOS has origins that are genetic and environmental but the end organ, the ovary, exhibits excessive androgen production with enhanced sensitivity to luteinising hormone and insulin. Interventions include approaches that target both these hormones as well as the ovary itself.
Publisher: Wiley
Date: 2000
DOI: 10.1002/(SICI)1098-2795(200001)55:1<55::AID-MRD8>3.0.CO;2-L
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.MRFMMM.2007.11.007
Abstract: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and reproductive and metabolic abnormalities. The potential genetic contributors to PCOS are unclear. We tested the hypothesis that genomic instability (chromosome malsegregation and DNA damage) is increased in PCOS. Overweight age, weight and BMI-matched women with (n=14) and without (n=16) PCOS (age 34.2+/-6.0 years, weight 90.7+/-14.5 kg, BMI 34.0+/-5.6 kg/m(2), mean+/-S.D.) were assessed for chromosome malsegregation (assessed by X chromosome chromogenic in situ hybridisation) and micronucleus frequency (assessed by the cytokinesis block micronucleus index) in lymphocytes. Women with PCOS had significantly elevated genomic instability as demonstrated by a significantly higher number of binucleated lymphocytes containing micronuclei, total number of micronuclei, a higher proportion of aneuploid X chromosome signals (2:1 X and 3:1 X) and a lower proportion of normal X chromosome segregation signals (2:2 X) in binucleated lymphocytes than women without PCOS. Surrogate measures of insulin resistance positively correlated with the proportion of aneuploid cells (2:1 3:1 X chromosome signals) and inversely with the proportion of normal cells (2:2 X chromosome signals). Women with PCOS display increased genomic instability (higher micronuclei and chromosome malsegregation) compared to women without PCOS and this increase may be related to the insulin resistance phenotype.
Publisher: Oxford University Press (OUP)
Date: 27-02-2022
Abstract: In a country with supportive funding for medically assisted reproduction (MAR) technologies, what is the proportion of MAR births over-time? In 2017, 6.7% of births were conceived by MAR (4.8% ART and 1.9% ovulation induction (OI)/IUI) with a 55% increase in ART births and a stable contribution from OI/IUI births over the past decade. There is considerable global variation in utilization rates of ART despite a similar infertility prevalence worldwide. While the overall contribution of ART to national births is known in many countries because of ART registries, very little is known about the contribution of OI/IUI treatment or the socio-demographic characteristics of the parents. Australia provides supportive public funding for all forms of MAR with no restrictions based on male or female age, and thus provides a unique setting to investigate the contribution of MAR to national births as well as the socio-demographic characteristics of parents across the different types of MAR births. This is a novel population-based birth cohort study of 898 084 births using linked ART registry data and administrative data including birth registrations, medical services, pharmaceuticals, hospital admissions and deaths. Birth (a live or still birth of at least one baby of ≥400 g birthweight or ≥20 weeks' gestation) was the unit of analysis in this study. Multiple births were considered as one birth in our analysis. This study included a total of 898 084 births (606 488 mothers) in New South Wales and the Australian Capital Territory, Australia 2009-2017. We calculated the prevalence of all categories of MAR-conceived births over the study period. Generalized estimating equations were used to examine the association between parental characteristics (parent's age, parity, socio-economic status, maternal country of birth, remoteness of mother's dwelling, pre-existing medical conditions, smoking, etc.) and ART and OI/IUI births relative to naturally conceived births. The proportion of MAR births increased from 5.1% of all births in 2009 to 6.7% in 2017, representing a 30% increase over the decade. The proportion of OI/IUI births remained stable at around 2% of all births, representing 32% of all MAR births. Over the study period, ART births conceived by frozen embryo-transfer increased nearly 3-fold. OI/IUI births conceived using clomiphene citrate decreased by 39%, while OI/IUI births conceived using letrozole increased 56-fold. Overall, there was a 55% increase over the study period in the number of ART-conceived births, rising to 56% of births to mothers aged 40 years and older. In 2017, almost one in six births (17.6%) to mothers aged 40 years and over were conceived using ART treatment. Conversely, the proportion of OI/IUI births was similar across different mother's age groups and remained stable over the study period. ART children, but not OI/IUI children, were more likely to have parents who were socio-economically advantaged compared to naturally conceived children. For ex le, compared to naturally conceived births, ART births were 16% less likely to be born to mothers who live in the disadvantaged neighbourhoods after accounting for other covariates (adjusted relative risk (aRR): 0.84 [95% CI: 0.81-0.88]). ART- or OI/IUI-conceived children were 25% less likely to be born to immigrant mothers than births after natural conception (aRR: 0.75 [0.74-0.77]). The social inequalities that we observed between the parents of children born using ART and naturally conceived children may not directly reflect disparities in accessing fertility care for in iduals seeking treatment. With the ubiquitous decline in fertility rates around the world and the increasing trend to delay childbearing, this population-based study enhances our understanding of the contribution of different types of MARs to population profiles among births in high-income countries. The parental socio-demographic characteristics of MAR-conceived children differ significantly from naturally conceived children and this highlights the importance of accounting for such differences in studies investigating the health and development of MAR-conceived children. This study was funded through Australian National Health and Medical Research Council (NHMRC) grant: APP1127437. G.M.C. is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand. C.V. is an employee of The University of New South Wales (UNSW), Director of Clinical Research of IVFAustralia, Member of the Board of the Fertility Society of Australia and New Zealand, and Member of Research Committee of School of Women's and Children's Health, UNSW. C.V. reports grants from Australian National Health and Medical Research Council (NHMRC), and Merck KGaA. C.V. reports consulting fees, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript, writing or educational events or attending meeting or travel from Merck, Merck Sparpe & Dohme, Ferring, Gedon-Richter and Besins outside this submitted work. C.V. reported stock or stock options from Virtus Health Limited outside this submitted work. R.J.N. is an employee of The University of Adelaide, and Chair DSMC for natural therapies trial of The University of Hong Kong. R.J.N. reports grants from NHMRC. R.J.N. reports lecture fees and support for attending or travelling for lecture from Merck Serono which is outside this submitted work. L.R.J. is an employee of The UNSW and Foundation Director of the Centre for Big Data Research in Health at UNSW Sydney. L.R.J. reports grants from NHMRC. The other co-authors have no conflict of interest. N/A.
Publisher: American Chemical Society (ACS)
Date: 23-06-1999
DOI: 10.1021/LA990111F
Publisher: Oxford University Press (OUP)
Date: 2004
Abstract: Since the 1990 NIH-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome and, as such, no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include: menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
Publisher: The Endocrine Society
Date: 07-2004
Publisher: Oxford University Press (OUP)
Date: 11-04-2008
Publisher: Elsevier BV
Date: 1996
DOI: 10.1016/0163-7258(95)02064-0
Abstract: The ovary and testis are sites for interaction between the endocrine and immune system via leukocytes and their secreted products, the cytokines. There are convincing data available to show that the gonads are sites of cytokine action and production. In the ovary, cytokines and leukocytes are intimately involved in follicular development, ovulation, and luteal function. A variety of clinical situations may be due to cytokine action in the gonads, and therapeutic manipulation of the immune system may affect reproductive function.
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.1385/ENDO:30:1:35
Publisher: Oxford University Press (OUP)
Date: 07-2004
Publisher: Oxford University Press (OUP)
Date: 2010
Abstract: BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women associated with impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and the metabolic syndrome. METHODS A literature search was conducted (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) identifying studies reporting prevalence or incidence of IGT, DM2 or metabolic syndrome in women with and without PCOS. Data were presented as odds ratio (OR) [95% confidence interval (CI)] with fixed- and random-effects meta-analysis by Mantel-Haenszel methods. Quality testing was based on Newcastle-Ottawa Scaling and The Cochrane Collaboration's risk of bias assessment tool. Literature searching, data abstraction and quality appraisal were performed by two investigators. RESULTS A total of 2192 studies were reviewed and 35 were selected for final analysis. Women with PCOS had increased prevalence of IGT (OR 2.48, 95% CI 1.63, 3.77 BMI-matched studies OR 2.54, 95% CI 1.44, 4.47), DM2 (OR 4.43, 95% CI 4.06, 4.82 BMI-matched studies OR 4.00, 95% CI 1.97, 8.10) and metabolic syndrome (OR 2.88, 95% CI 2.40, 3.45 BMI-matched studies OR 2.20, 95% CI 1.36, 3.56). One study assessed IGT/DM2 incidence and reported no significant differences in DM2 incidence (OR 2.07, 95% CI 0.68, 6.30). One study assessed conversion from normal glucose tolerance to IGT/DM2 (OR 2.4, 95% CI 0.7, 8.0). No studies reported metabolic syndrome incidence. CONCLUSIONS Women with PCOS had an elevated prevalence of IGT, DM2 and metabolic syndrome in both BMI and non-BMI-matched studies. Few studies have determined IGT/DM2 or metabolic syndrome incidence in women with and without PCOS and further research is required.
Publisher: Oxford University Press (OUP)
Date: 05-1998
DOI: 10.1095/BIOLREPROD58.5.1266
Abstract: Evidence that cytokines have important roles in ovulation is accumulating, with various cytokines having been found to influence the ovulatory cascade. Interleukin (IL)-6 is a pluripotent cytokine involved in inflammatory reactions, and it has been demonstrated in high concentrations in human ovarian follicular fluid and in vitro in secretions from the ovary. We set out to determine the effect this cytokine has on ovulation rate and steroidogenesis in the in vitro-perfused rat ovary. Preovulatory ovaries were taken from eCG-primed animals, and ovulation was induced by LH (100 ng/ml) alone or in combination with cytokine. Ovaries in the IL-6/LH groups (IL-6 concentration of 0.19 nM or 1.9 nM) did not have ovulation rates different from ovaries in the LH-only group. Ovaries in the LH/IL-1beta group ovulated more oocytes than ovaries in the LH-only group (LH/IL-1beta =11+/-1.8 oocytes LH alone=4.9+/-1.1 p=0.015) and the IL-6/LH/IL-1beta group (LH/IL-1beta/IL-6 [0.19 nM]=4+/-1.40 LH/IL-1beta=11+/-1.8 p=0.009). We have found that 1) exogenous IL-6 did not significantly alter the LH-induced ovulation rate but significantly reduced the LH/IL-1beta-induced ovulation rate 2) exogenous IL-6 did not alter LH-induced progesterone levels measured at time points during the perfusion period, but the average increase in progesterone over basal level was stimulated by IL-6 3) exogenous IL-6 did not affect LH-induced estradiol production 4) exogenous IL-6 did not affect LH-induced androstenedione production but increased LH/IL-1beta-induced production 5) exogenous IL-6 did not affect LH-induced prostaglandin E2 production. This study demonstrates that IL-6 does not play a role in regulating ovulation induced by LH in vitro but is capable of reducing LH/IL-1beta-enhanced ovulation rates. In addition, IL-6 may play a role in the regulation of ovarian steroid production.
Publisher: Elsevier BV
Date: 10-2010
Publisher: BMJ
Date: 09-08-2017
DOI: 10.1136/ARCHDISCHILD-2017-312968
Abstract: While ovulation is most likely to occur in adolescent girls with regular menstrual cycles, there are limited data on the incidence of ovulation in girls with irregular menstrual cycles in early postmenarcheal years. The aim of the study was to evaluate the presence of ovulation in healthy postmenarcheal girls with irregular menstrual cycles. Prospective cohort study over 12 weeks including 40 healthy postmenarcheal girls recruited from the population-based cohort of adolescents from Western Australian Pregnancy Cohort (Raine) Study with irregular menstrual cycles defined by either menstrual cycles days or days in duration or cycle length that varied from month to month by days according to menstrual diaries. Ovulation defined by urinary pregnanediol-3α–glucuronide/creatinine measurements higher than three times above minimum value obtained from 12 s les (1 per week). Forty girls (37 Caucasians) with irregular menstrual cycles aged 15.1 (median (IQR) 14.9–15.4) years who were 2.3 (1.9–3.3) years postmenarche were assessed. Urinary pregnanediol-3α–glucuronide/creatinine values identified that 33 girls (82.5%) ovulated during the 3 months of observation and 7 girls had anovulatory cycles. Menstrual diaries collected for a median (IQR) of 159 (137.5–188.2) days showed median minimal and maximum menstrual cycle duration of 24 (11.5–29) and 38.5 (35–48) days, respectively. A large proportion of healthy adolescent girls with irregular menstrual cycles are still ovulating despite irregular and infrequent menses.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.FERTNSTERT.2009.11.002
Abstract: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in adolescents, with potentially significant lifelong consequences. This prospective study set out to determine if the investigators could derive a threshold value of antimullerian hormone (AMH) that would predict its presence according to two internationally recognized definitions using a simple measurement, avoiding more extensive and potentially more invasive investigations. The study failed to demonstrate, in a general adolescent population, that serum AMH is a reliable predictor of PCO morphology or for the presence of PCOS.
Publisher: Elsevier BV
Date: 08-2002
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.BPOBGYN.2016.01.006
Abstract: Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions.
Publisher: Oxford University Press (OUP)
Date: 05-2000
Abstract: Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Leptin and leptin receptor mRNA were first detected in the brain and hypothalamus but now their ubiquitous presence has been demonstrated. Leptin receptor signal transduction involves the activation of signal transducer and activator of transcription (STAT)-3, a member of the transcription family of proteins. Leptin is regulated by hormones and cytokines, interleukin-1, tumour necrosis factor-alpha and transforming growth factor-beta, linking this molecule with the inflammatory response. In addition, emerging evidence has demonstrated that this molecule is related to reproductive function. This small protein is present in the ovary and decidua, in mature oocytes and during embryonic development and trophoblast invasion. Animal models have demonstrated that leptin-deficient ob/ob mice are sterile however, fertility can be restored by exogenous leptin. In addition, embryos implanted in STAT-3-deficient mice degenerate rapidly and are the target disruption of STAT-3-provoked embryonic lethality. Leptin acts as a novel placental hormone participating in the control of fetal growth and development. Leptin could be a modulator for invasive features of cytotrophoblast cells. We postulate that leptin may have an autocrine aracrine role in human implantation and placentation.
Publisher: The Electrochemical Society
Date: 2009
DOI: 10.1149/1.3154513
Publisher: Oxford University Press (OUP)
Date: 2006
DOI: 10.1095/BIOLREPROD.105.043729
Abstract: Peroxisome proliferator-activated receptor-gamma (PPARG) and PPAR-alpha (PPARA) control metabolic processes in many cell types and act as anti-inflammatory regulators in macrophages. PPAR-activating ligands include thiazolidinediones (TZDs), such as troglitazone, once frequently used to treat insulin resistance as well as symptoms of polycystic ovary syndrome (PCOS). Since macrophages within the ovary mediate optimal follicle development, TZD actions to improve PCOS symptoms are likely to be partly mediated through these specifically localized immune cells. In mouse ovary, PPARG protein was expressed in granulosa cells and in isolated cells localized to theca, stroma, and corpora lutea, consistent with EMR1+ macrophages. Isolation of immune cells (EMR1+ or H2+) showed that Pparg and Ppara were expressed in ovarian macrophages at much higher levels than in peritoneal macrophages. Ovulatory human chorionic gonadotropin downregulated expression of Pparg and Ppara in EMR1+ ovarian macrophages, but no hormonal responsiveness was observed in H2+ cells. Downstream anti-inflammatory effects of PPARG activation were analyzed by in vitro treatment of isolated macrophages with troglitazone. Interleukin-1 beta (Il1b) expression was not altered, and tumor necrosis factor-alpha (Tnf) expression was affected in peritoneal macrophages only. In ovarian macrophages, inducible nitric oxide synthase (Nos2), an important proinflammatory enzyme that regulates ovulation, was significantly reduced by troglitazone treatment, an effect that was restricted to cells from the preovulatory ovary. Thus, expression of PPARs within ovarian macrophages is hormonally regulated, reflecting the changing roles of these cells during the ovulatory cycle. Additionally, ovarian macrophages respond directly to troglitazone to downregulate expression of proinflammatory Nos2, providing mechanistic information about ovarian effects of TZD treatment.
Publisher: Oxford University Press (OUP)
Date: 09-2000
DOI: 10.1095/BIOLREPROD63.3.839
Abstract: Cumulus cells and mural granulosa cells (MGC) are phenotypically different and there is now evidence suggesting that the oocyte plays an active role in determining the fate of follicular somatic cells. This study investigates the role of oocyte-secreted factor(s) in the regulation of the growth and differentiation of cumulus and MGC. Bovine cumulus-oocyte complexes (COC) and MGC were cultured with various hormones for 18 h followed by a further 6-h pulse of [(3)H]thymidine as an indicator of follicular cell DNA synthesis. The COC incorporated 11 to 14 times more [(3)H]thymidine than MGC in either the absence or presence of 50 ng/ml insulin-like growth factor (IGF)-I. Purified porcine FSH (450 ng/ml) added together with IGF-I marginally increased (3)H incorporation in MGC relative to IGF-I alone but dramatically decreased incorporation in COC sixfold. Conversely, mean progesterone production in the presence of IGF-I + FSH was 13-fold higher from MGC than from COC, confirming a distinctive phenotype of cumulus cells. However, this phenotype was found to be dependent on the presence of the oocyte, as microsurgical removal of the oocyte (oocytectomy) resulted in an 11-fold decrease in [(3)H]thymidine incorporation in cumulus cells treated with IGF-I, elimination of the inhibitory effect of FSH on IGF-I-stimulated DNA synthesis, and led to a 2-fold increase in progesterone production in medium with IGF-I and FSH. All of these markers were completely restored to COC levels when oocytectomized complexes were cocultured with denuded oocytes (DO) at a concentration of 0.5 oocytes/microl, demonstrating that oocytes secrete a soluble factor(s) that promotes growth and attenuates cumulus cell progesterone secretion. In the presence of IGF-I, [(3)H]thymidine incorporation in MGC increased ninefold above control levels with the addition of DO. The addition of FSH to IGF-I-increased (3)H counts in MGC, however, led to a decrease in counts in MGC + DO as is also observed in COC. Furthermore, progesterone production was halved when DO were added to MGC cultures, most notably in the presence of IGF-I and/or FSH. These results provide further evidence that MGC and cumulus cells have distinctive phenotypes and that the oocyte is responsible for some of the characteristic features of cumulus cells. Bovine oocytes secrete a soluble factor(s) that simultaneously promotes growth and attenuates steroidogenesis in follicular somatic cells.
Publisher: The Endocrine Society
Date: 10-2004
DOI: 10.1210/JC.2004-1658
Publisher: Oxford University Press (OUP)
Date: 04-2002
Abstract: The high incidence of preterm birth (<37 weeks gestation) is a major concern in assisted reproductive technology. The objective of this study was to compare the risk of preterm birth from singleton pregnancies following either low technology treatment (intrauterine insemination and donor insemination) or high technology treatment (IVF, ICSI and gamete intra-Fallopian transfer) with that of naturally conceived pregnancies. Three cohorts of pregnancies resulting from either low or high technology treatment or from natural conception were included in the study. A number of potential risk factors were adjusted for. The incidence of very preterm birth (<32 weeks of gestation) was not significantly increased in the low technology treatment group (1.0 versus 1.3% in controls) but was significantly higher in the high technology treatment group (5.2%, P < 0.001). In spontaneous, elective Caesarean section (CS) and induced delivery onset, the risk of preterm birth increased gradually from the controls to the low technology treatment group to the high technology treatment group, while for an emergency CS the risk of preterm birth was very high in both treatment groups. The overall incidence of preterm birth increased significantly from the controls to the low technology treatment group and to the high technology treatment group. Logistic regression analysis showed that younger and older age, previous perinatal death and emergency CS were associated with an increased risk, while a previous live birth reduced the risk. The length of the infertile period did not seem to affect the risk in any of the treatment groups.
Publisher: Wiley
Date: 06-07-2011
Publisher: Informa UK Limited
Date: 06-12-2018
Publisher: Wiley
Date: 05-09-2017
DOI: 10.1111/AJO.12693
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.FERTNSTERT.2003.10.004
Abstract: Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.FERTNSTERT.2022.04.018
Abstract: Immunology and reproduction are intimately combined in human physiology however, the mechanisms whereby the uterus accepts the fetus and allows it to flourish remain unclear, at least in the human. The introduction of unproven and expensive tests and therapies to alter immune mechanisms around conception has spread throughout reproductive medicine. Specialists in this discipline need to understand more of the immune physiology of reproduction and be more conservative in the use of therapeutics until evidence-based data become available.
Publisher: Elsevier BV
Date: 08-2007
Publisher: Wiley
Date: 09-1988
DOI: 10.1111/J.1471-0528.1988.TB06575.X
Abstract: Oxytocin was measured by a specific and sensitive radioimmunoassay in plasma and amniotic fluid after extraction with Sep-Pak cartridges in patients undergoing elective caesarean sections, normal labour and labour induced with oxytocin infusion or prostaglandins. In maternal plasma, levels of oxytocin correlated with the period of gestation concentrations at term were significantly higher than in the first two trimesters. Maternal plasma levels of oxytocin before the onset of contractions were not significantly different from those at the onset of spontaneous labour or at full cervical dilatation. Levels of oxytocin in patients induced with oxytocin were not statistically different from levels observed in spontaneous labour. Amniotic fluid oxytocin levels were not significantly different between the groups either at the onset of labour or immediately before delivery. Umbilical arterio-venous differences in oxytocin were present in all groups except the prostaglandin-induced group. Increased prostaglandins associated with the onset of normal labour are probably not a consequence of changes in oxytocin concentrations.
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: The Endocrine Society
Date: 07-2006
DOI: 10.1210/JC.2006-0069
Abstract: Context: The cause of polycystic ovary syndrome (PCOS) is unknown, although genetic and environmental influences are clearly implicated. Some genetic studies have suggested the involvement of X-linked genes in PCOS, but the influence of X chromosome inactivation (XCI) on manifestation of this disorder has not previously been examined. Objective: The objective of the study was to test the null hypothesis that XCI has no influence on clinical presentation of PCOS. Design: We examined patterns of XCI between sister pairs with the same genotype at a polymorphic locus on the X chromosome in families with PCOS. Setting: The study was conducted at a private practice. Participants: PCOS was defined as hyperandrogenemia with chronic anovulation. Forty families were studied in which DNA was obtained from at least one parent, the proband, and one sister that could be accurately diagnosed as being affected or unaffected. Main Outcome Measure(s): Relative expression of two X-linked alleles was determined, and the ratio of one to the other represented the pattern of XCI. Results: The statistical odds on a different clinical presentation between sisters was approximately 29 times higher in sister pairs with different patterns of XCI, compared with sister pairs with the same pattern of XCI (odds ratio 28.9 95% confidence interval 4.0–206 P = 0.0008). Conclusions: This study provides evidence to refute the null hypothesis and propose a closer inspection of X-linked genes in PCOS, one in which both genotype and epigenotype are considered. Environmental determinants of PCOS may alter clinical presentation via epigenetic modifications, which currently remain undetected in traditional genetic analyses.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.ECL.2011.08.006
Abstract: Overweight and obesity are significant and increasing health problems associated with increased risks of morbidity, quality of life, and metabolic and reproductive health consequences. In women, being overweight or obese is associated with impaired fertility and decreased chance of conception both in natural and assisted reproductive technology births. During pregnancy, overweight and obesity are associated with increased risk of adverse maternal and infant health outcomes. Attention to weight loss before conception may improve fertility and maternal and infant health outcomes during pregnancy.
Publisher: The Endocrine Society
Date: 12-1985
Abstract: Monoclonal antibodies to intact hCG and free beta-subunit of hCG permit the recognition of different in idual antigenic sites on the hCG molecule. At least seven different epitopes may be recognized on the native molecule and a further two on the free beta-subunit. These antibodies were used in a mouse Leydig cell bioassay system to compare the degree of inhibition of hCG-induced testosterone production. Two antibodies were particularly potent at inhibiting hCG action, suggesting that they bind near to the receptor-recognition site on the hCG molecular. One antibody had little effect on biological action and was presumably binding distant from the biologically active site on the hCG. Combinations of monoclonal antibodies in immunoradiometric assays were used to develop highly sensitive and specific assays to intact hCG, free beta-subunit of hCG, and beta-subunit as part of intact hCG. Using these assays it was possible to detect 0.1 ng/ml hCG in the presence of high levels of LH. In 106 serum s les from pregnant woman free beta-subunit was considerably higher in s les with low concentrations of intact hCG, suggesting that free beta-subunit is not a limiting factor in placental production of intact hCG in early pregnancy. Comparison of urinary to serum ratios of hCG and free beta-subunit using specific immunoradiometric assays showed a good correlation for intact hCG but not for free beta subunit which was present in very high concentrations in urine.
Publisher: Oxford University Press (OUP)
Date: 06-2007
DOI: 10.1016/J.EJCNURSE.2006.06.004
Abstract: Successful adjustment following treatment for coronary artery disease is related to both psychological disposition and risk factor status. Consideration of the interplay between these variables is required to better acknowledge their relationship with health outcome. To determine the salience of self-efficacy and locus of control to both general self-rated health and current cardiac health, relative to risk factor status. To determine whether self-efficacy is a more salient predictor of health status than locus of control. Men (n=248) treated in the previous 3 years for either coronary artery disease alone or a myocardial infarction completed a questionnaire in which clinical, risk factor (knowledge of risk factors, current risk factors, change in risk factors), psychological (self-efficacy, locus of control) and health information were sought. Self-efficacy and internal locus of control had both direct and indirect influences on health in the models in which knowledge of risk factors was treated as the potential mediator. This pattern of results was not evident when either current risk factors or change in risk factors were examined as potential mediators. In the models in which self-efficacy was considered as a potential mediator of locus of control in the prediction of health status, self-efficacy was determined to be the more relevant psychological construct. The consistent positive associations obtained among self-efficacy, cognitive risk factor status and health suggest that health professionals involved in cardiac rehabilitation should be encouraged to tailor interventions that allow patients to both improve their understanding of CAD and also to develop greater self-confidence in their ability to implement the acquired knowledge.
Publisher: Wiley
Date: 03-1985
DOI: 10.1111/J.1471-0528.1985.TB01085.X
Abstract: Amniotic fluid concentrations of immunoreactive oestrogens and progesterone were measured at the time of caesarean section in 32 twin pregnancies 25 women had an elective section and seven were in labour at the time of operation. No significant differences between concentrations in the amniotic fluid of the first and second twin were found in respect of conjugated and unconjugated oestrone, oestradiol, oestriol, oestetrol and unconjugated progesterone either before or during labour. It is unlikely that changes in oestrogens or progesterone in the amniotic fluid are responsible for the selective changes seen in prostaglandins and fetal adrenal steroid during labour in the first twin.
Publisher: Oxford University Press (OUP)
Date: 12-2011
DOI: 10.1530/EJE-11-0482
Abstract: The measurement of serum testosterone in women is challenging due to lack of trueness, precision, and sensitivity of various available testosterone assays. Accurate assessment of testosterone in women is crucial especially in conditions associated with alleged over- or under-production of testosterone, such as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI). The aim of this study was to measure and compare androgen concentrations in women with PCOS, POI, and female controls and to evaluate the performance of extraction RIA and liquid chromatography–tandem mass spectrometry (LC–MS/MS) in these women. Cross-sectional study. Carefully phenotyped women with POI ( n =208) or PCOS ( n =200) and 45 healthy, regularly cyclic female controls were included. Method comparison analyses were performed for total testosterone, androstenedione (AD), and DHEA, as measured by LC–MS/MS and extraction RIA. All androgen levels were significantly elevated in women with PCOS compared with POI patients ( P .05) and controls ( P .05). Women with POI presented with similar androgen concentrations as controls, except for AD. Compared with measurements by extraction RIA, testosterone, DHEA, and AD concentrations measured by LC–MS/MS were systematically lower. However, using extraction RIA and LC–MS/MS, testosterone, DHEA, and AD measurements were shown to have good agreement as assessed by Bland–Altman analysis and intraclass correlation coefficient: 0.95 (95% confidence interval 0.94–0.91), 0.83 (0.79–0.86), and 0.96 (0.95–0.97) respectively. LC–MS/MS, compared with a labor-intensive extraction RIA, shows good precision, sensitivity, and high accuracy for measuring female testosterone, DHEA, and AD concentrations under various clinical conditions. LC–MS/MS, therefore, represents a convenient and reliable assay for both clinical and research purposes, where androgen measurement in women is required.
Publisher: The Endocrine Society
Date: 10-2007
DOI: 10.1210/JC.2007-1188
Abstract: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities, specifically menstrual dysfunction and anovulation in conjunction with elevated pre-antral follicle number and arrested follicular maturation. Although anti-müllerian hormone (AMH), an inhibitor of follicle recruitment and maturation, is increased in women with PCOS, the usefulness of circulating AMH levels as a clinical predictor of menstrual response to weight loss in PCOS is not known. Overweight women with PCOS (n = 26, age 32.9 +/- 5.8 yr, weight 98.9 +/- 20.8 kg, body mass index 36.1 +/- 7.0 kg/m(2), mean +/- sd) followed an 8-wk weight loss and 6-month weight maintenance program. Net reductions in weight (4.6 +/- 4.8 kg), waist circumference (6.0 +/- 5.3 cm), testosterone (0.3 +/- 0.6 nmol/liter), fasting insulin (3.7 +/- 7.6 mU/liter), and the homeostasis model assessment of insulin sensitivity (0.7 +/- 1.3) occurred for all subjects over the entire study duration. Of 26 subjects, 15 (57.7%) responded to the intervention with improvements in menstrual cyclicity (responders). Compared to nonresponders, responders had lower AMH levels at baseline (23.6 +/- 12.0 vs. 37.9 +/- 17.8 pmol/liter P = 0.021). Only responders had reductions in fasting insulin (6.1 +/- 5.9 mU/liter P = 0.001) and homeostasis model assessment (1.3 +/- 5.9 P = 0.002) with acute weight loss (wk 0-8). Baseline AMH was most strongly predicted by baseline ghrelin, free testosterone, and insulin (r(2) = 0.528 P = 0.002). Overweight women with PCOS who respond to weight loss with menstrual improvements have significantly reduced preweight loss AMH and demonstrate improvements in surrogate measures of insulin resistance with weight loss. Pretreatment AMH is a potential clinical predictor of menstrual improvements with weight loss in PCOS.
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: Oxford University Press (OUP)
Date: 21-08-2023
Abstract: What is the recommended management for couples presenting with unexplained infertility (UI), based on the best available evidence in the literature? The evidence-based guideline on UI makes 52 recommendations on the definition, diagnosis, and treatment of UI. UI is diagnosed in the absence of any abnormalities of the female and male reproductive systems after ‘standard’ investigations. However, a consensual standardization of the diagnostic work-up is still lacking. The management of UI is traditionally empirical. The efficacy, safety, costs, and risks of treatment options have not been subjected to robust evaluation. The guideline was developed according to the structured methodology for ESHRE guidelines. Following formulation of key questions by a group of experts, literature searches, and assessments were undertaken. Papers written in English and published up to 24 October 2022 were evaluated. Based on the available evidence, recommendations were formulated and discussed until consensus was reached within the guideline development group (GDG). Following stakeholder review of an initial draft, the final version was approved by the GDG and the ESHRE Executive Committee. This guideline aims to help clinicians provide the best care for couples with UI. As UI is a diagnosis of exclusion, the guideline outlined the basic diagnostic procedures that couples should/could undergo during an infertility work-up, and explored the need for additional tests. The first-line treatment for couples with UI was deemed to be IUI in combination with ovarian stimulation. The place of additional and alternative options for treatment of UI was also evaluated. The GDG made 52 recommendations on diagnosis and treatment for couples with UI. The GDG formulated 40 evidence-based recommendations—of which 29 were formulated as strong recommendations and 11 as weak—10 good practice points and two research only recommendations. Of the evidence-based recommendations, none were supported by high-quality evidence, one by moderate-quality evidence, nine by low-quality evidence, and 31 by very low-quality evidence. To support future research in UI, a list of research recommendations was provided. Most additional diagnostic tests and interventions in couples with UI have not been subjected to robust evaluation. For a large proportion of these tests and treatments, evidence was very limited and of very low quality. More evidence is required, and the results of future studies may result in the current recommendations being revised. The guideline provides clinicians with clear advice on best practice in the care of couples with UI, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. The full guideline and a patient leaflet are available in www.eshre.eu/guideline/UI. The guideline was developed by ESHRE, who funded the guideline meetings, literature searches, and dissemination of the guideline in collaboration with the Monash University led Australian NHMRC Centre of Research Excellence in Women’s Health in Reproductive Life (CREWHIRL). The guideline group members did not receive any financial incentives all work was provided voluntarily. D.R. reports honoraria from IBSA and Novo Nordisk. B.A. reports speakers’ fees from Merck, Gedeon Richter, Organon and Intas Pharma is part of the advisory board for Organon Turkey and president of the Turkish Society of Reproductive Medicine. S.B. reports speakers’ fees from Merck, Organon, Ferring, the Ostetric and Gynaecological Society of Singapore and the Taiwanese Society for Reproductive Medicine editor and contributing author, Reproductive Medicine for the MRCOG, Cambridge University Press is part of the METAFOR and CAPE trials data monitoring committee. E.B. reports research grants from Roche diagnostics, Gedeon Richter and IBSA speaker’s fees from Merck, Ferring, MSD, Roche Diagnostics, Gedeon Richter, IBSA E.B. is also a part of an Advisory Board of Ferring Pharmaceuticals, MSD, Roche Diagnostics, IBSA, Merck, Abbott and Gedeon Richter. M.M. reports consulting fees from Mojo Fertility Ltd. R.J.N. reports research grant from Australian National Health and Medical Research Council (NHMRC) consulting fees from Flinders Fertility Adelaide, VinMec Hospital Hanoi Vietnam speaker’s fees from Merck Australia, Cadilla Pharma India, Ferring Australia chair clinical advisory committee Westmead Fertility and research institute MyDuc Hospital Vietnam. T.P. is a part of the Research Council of Finland and reports research grants from Roche Diagnostics, Novo Nordics and Sigrid Juselius foundation consulting fees from Roche Diagnostics and organon speaker’s fees from Gedeon Richter, Roche, Exeltis, Organon, Ferring and Korento patient organization is a part of NFOG, AE-PCOS society and several Finnish associations. S.S.R. reports research grants from Roche Diagnostics, Organon, Theramex consulting fees from Ferring Pharmaceuticals, MSD and Organon speaker’s fees from Ferring Pharmaceuticals, MSD/Organon, Besins, Theramex, Gedeon Richter travel support from Gedeon Richter S.S.R. is part of the Data Safety Monitoring Board of TTRANSPORT and deputy of the ESHRE Special Interest Group on Safety and Quality in ART stock or stock options from IVI Lisboa, Clínica de Reprodução assistida Lda equipment/medical writing/gifts from Roche Diagnostics and Ferring Pharmaceuticals. S.K.S. reports speakers’ fees from Merck, Ferring, MSD, Pharmasure. HRV reports consulting and travel fees from Ferring Pharmaceuticals. The other authors have nothing to disclose. This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each in idual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.)
Publisher: Oxford University Press (OUP)
Date: 05-2002
DOI: 10.1095/BIOLREPROD66.5.1548
Abstract: Leptin is a product of the ob gene that is produced primarily by adipose tissue. Leptin and its receptors are found within the ovary, but it is unclear what function this hormone has in the ovary. Using immunohistochemistry, we determined that leptin is found in most cell types in the murine ovary, with the highest staining levels observed in the oocyte. Leptin receptor was also expressed in all of the main ovarian cell types, with the thecal cell layer exhibiting the highest staining levels. Leptin administration did not affect spontaneous or induced maturation of either isolated denuded oocytes or cumulus-oocyte complexes, but it did significantly increase the rate of meiotic resumption in preovulatory follicle-enclosed oocytes (P < 0.01). Measurements of cAMP within oocytes cultured with leptin showed that this enhanced ability to resume meiosis does not occur via activation of phosphodiesterase 3B and subsequent cAMP reduction. These results provide evidence that leptin affects oocyte maturation when the oocyte is cultured within its normal follicular environment. It is suggested that leptin may induce the production of another factor, possibly from thecal cells, that directly or indirectly acts on the oocyte to initiate germinal vesicle breakdown in this species.
Publisher: Wiley
Date: 11-1983
DOI: 10.1111/J.1471-0528.1983.TB06441.X
Abstract: Cortisol and prostaglandins were measured in umbilical cord blood obtained from 50 twin pregnancies at caesarean section performed either before or during labour. Umbilical artery cortisol concentrations did not differ between twin I and II before labour or in the latent stage. During active labour cortisol levels were significantly higher in twin I than in twin II. Maternal cortisol levels did not correlate with cord blood cortisol levels in either twin before active labour, nor did the rise in maternal cortisol correlate with the cortisol level in twin I maternal cortisol levels did, however, correlate with cortisol levels in twin II during active labour. Prostaglandins E(PGE), F 2 alpha (PGF 2 alpha), 13,14-dihydro-15-keto F 2 alpha (PGFM) and ACTH were measured in cord vein blood. PGE values did not differ between twin I and II before active labour. During active labour PGE levels were significantly greater in twin I and correlated with raised cortisol levels. No differences were seen at any stage in PGE and PGFM levels between twins I and II although PGFM levels increased in both twins during active labour. ACTH and prolactin levels did not increase during labour and were similar in twins I and II. The rise in fetal cortisol during active labour is primarily of fetal origin and PGE may be involved in stimulating cortisol production in the fetus.
Publisher: Wiley
Date: 10-1981
DOI: 10.1111/J.1365-2265.1981.TB00680.X
Abstract: The thyroid status of twenty-seven African patients with gestational trophoblastic neoplasia (GTN) was studied. Fifteen patients were found to be biochemically hyperthyroid (eight patients with choriocarcinoma seven with hydatidiform mole). Of these fifteen patients, nine were clinically thyrotoxic. The most serious complication of thyrotoxicosis was life-threatening acute pulmonary oedema with associated cardiac failure. It was found that when serum levels of the human chorionic gonadotrophin (hCG) reached a level of about 0.1 X 10(6) iu/1, thirteen of sixteen patients were biochemically hyperthyroid at serum levels of 0.3 X 10(6) iu/1 of hCG most patients were clinically thyrotoxic. A feature of hyperthyroidism associated with GTN is that whereas T4 is invariably raised the T3:T4 ratio tends to be low (0.015 +/- 005) rT3:T3 ratios were high in this group. TSH levels were not increased.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.FERTNSTERT.2009.12.060
Abstract: This prospective study was established to determine the impact of maternal circulating androgen levels during normal pregnancy on ovarian function, as determined by early follicular phase antimüllerian hormone (AMH) levels, inhibin B levels, and antral follicle count (AFC) in 244 female offspring in adolescence. Maternal circulating total testosterone levels at 18 weeks' gestation were statistically significantly correlated with early follicular-phase circulating AMH levels in female adolescent offspring, but no other statistically significant correlations were determined among the maternal androgens at 18 or 34 weeks of gestation and the markers of adolescent ovarian function.
Publisher: Wiley
Date: 08-1984
DOI: 10.1111/J.1471-0528.1984.TB04849.X
Abstract: Umbilical artery concentrations of androstenedione, progesterone, pregnenolone, pregnenolone sulphate and dehydroepiandrosterone sulphate were measured at birth in twin pairs, born by caesarean section. In the group born before the onset of labour, there were no significant differences in concentration of any of the steroids between the leading twin (twin I) and the second twin (twin II). In the group born during the latent phase of labour, levels of umbilical artery progesterone were significantly less in twin I (mean 501, SE 112 nmol/l) than in twin II (mean 887, SE 131) (P less than 0.05), while concentrations of androstenedione were increased in twin I [9.9 (SE 1.7) vs 4.7 (SE 0.7) nmol/l, P less than 0.01]. In patients delivered during active labour, androstenedione levels were consistently increased in twin I compared with twin II [11.7 (SE3.4) vs 4.3 (SE 0.7) nmol/l, P less than 0.01]. It is suggested that the rise in umbilical artery levels of androstenedione is derived from the fetal adrenal gland and may have an important role in the onset of labour.
Publisher: Oxford University Press (OUP)
Date: 05-2006
Abstract: Malnutrition is a major problem in developing countries, and obesity and eating disorders are increasingly common in developing as well as developed countries. The reproductive axis is closely linked to nutritional status, especially undernutrition in the female, and inhibitory pathways involving detectors in the hind brain suppress ovulation in subjects with weight loss. Recovery may occur after minimal reacquisition of weight because energy balance is more important than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women of reproductive age causing amenorrhoea, infertility and, in those who do conceive, an increased likelihood of miscarriage. Obesity can affect reproduction through fat cell metabolism, steroids and secretion of proteins such as leptin and adiponectin and through changes induced at the level of important homeostatic factors such as pancreatic secretion of insulin, androgen synthesis by the ovary and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates that 9 to 25% of women in developed countries are severely obese, and obese mothers are much more likely to have obese children, especially if they have gestational diabetes. Obesity-associated anovulation may lead to infertility and to a higher risk of miscarriage. Management of anovulation with obesity involves diet and exercise as well as standard approaches to ovulation induction. Many obese women conceive without assistance, but pregnancies in obese women have increased rates of pregnancy-associated hypertension, gestational diabetes, large babies, Cesarean section and perinatal mortality and morbidity. Among contraceptors, the fear of weight gain affects uptake and continuation of hormonal contraceptives, although existing trials indicate that any such effects are small. For all methods of hormonal contraception, weight above 70 kg is associated with increased failure rates.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.FERTNSTERT.2018.06.005
Abstract: This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.RBMO.2018.08.024
Abstract: Does delaying IVF for 6 months in couples with unexplained infertility, compared with immediate IVF treatment, decrease the cost of IVF without compromising success rates? Decision modelling was used to evaluate the cost and outcomes of immediate IVF versus delayed IVF for a cohort of women aged <40 years suffering unexplained infertility. Australian data and costs were used in the analysis. For different age groups, three scenarios were tested where 10%, 50% and 90% of couples with unexplained infertility delayed IVF for 6 months if they had a good prognosis for natural conception. The study included a total of 8781 couples aged <40 years, diagnosed with unexplained infertility and who had IVF in 2013. The studied couples underwent 27,648 fresh and frozen embryo transfers, for an estimated total cost of $141 million. Potential out-of-pocket cost savings if 90% of couples delayed IVF ranged from $4.7 to $12.2 million, with Medicare cost savings of up to $15.1 million. The impact on the total pregnancy and live birth rates after 18 months was minimal. In couples with unexplained infertility and a good prognosis for natural conception, delaying IVF for 6 months could substantially decrease out-of-pocket costs without compromising pregnancy and live birth rates over an 18-month period.
Publisher: Oxford University Press (OUP)
Date: 05-1999
Abstract: To evaluate a possible role for colony stimulating factor-1 (CSF-1) in human ovarian function, the peripheral blood CSF-1 concentration throughout the human menstrual cycle and during ovarian stimulation was monitored. Blood was s led across the menstrual cycle (n = 10) and at specific times during ovarian stimulation. In addition, the CSF-1 concentrations in follicular fluid (FF) during the follicular phase and during the luteinizing hormone (LH) surge of natural cycles, as well as 35-37 h after human chorionic gonadotrophin (HCG) during ovarian stimulation, were determined. There was no significant variation in CSF-1 concentrations during the natural menstrual cycle (median 470, range 212-1364 pg/ml). CSF-1 concentrations in FF (n = 11) were about four-fold higher (P < 0. 0001) than those in plasma of the same patients. CSF-1 concentrations in these FF showed some stage dependent variability, with significantly higher values during the ovulatory phase (median of 2017 pg/ml, range 1131-2236 pg/ml), compared to mid-follicular phase (median 961 pg/ml, range 830-1340 pg/ml P = 0.02). During ovarian stimulation (n = 20), the plasma concentrations were similar to a time prior to stimulation up to and including 35-37 h after HCG. On day 9 after HCG, the values (median 644, range 357-1352 pg/ml) were significantly higher compared to pre-stimulation (median 422, range 253-1598 pg/ml P < 0.05) and 35-37 h after HCG (median 458, range 250-658 pg/ml P < 0.01). FF concentrations (n = 27) of CSF-1 at oocyte retrieval (median 3116, range 1824-5883 pg/ml) were about seven-fold higher than blood concentrations (median 472, range 250-1055 pg/ml P < 0.0001). These results suggest that the intra-ovarian CSF-1, possibly induced by LH/HCG, plays an important role during ovulation and luteinization.
Publisher: Oxford University Press (OUP)
Date: 25-03-2004
Publisher: The Endocrine Society
Date: 07-2005
DOI: 10.1210/JC.2004-2401
Abstract: The impact of progestins on exercise performance in women has not been previously studied. The objective of this study was to examine the effect of a synthetic progestin on aspects of exercise status in young women. DESIGN, PATIENTS, SETTING: Twenty-three young, healthy, habitually sedentary women participated in a single-blind, randomized, counterbalanced, cross-over study in a university-based laboratory setting. Two monophasic oral contraceptive pills (OCPs) were administered in which the dose of the synthetic progestin, norethisterone, was 2-fold different but the dose of the synthetic estrogen, ethinyl estradiol, was constant. During each month of OCP aspects of exercise status were assessed during incremental exercise to exhaustion and steady-state submaximal exercise and with a performance test. The main outcome measures were peak oxygen uptake (VO(2peak)), respiratory exchange ratio (RER), time to exhaustion, lactate concentrations, and total work done. Peak heart rates were approximately 95% of age-predicted values with both OCP preparations, whereas VO(2peak) was approximately 30% above age-predicted values. Peak postincremental exercise plasma lactate concentrations exceeded those reported for males and females, whereas the RER was below expected values throughout both incremental and steady-state exercise. The effects on VO(2peak) and RER were increased with the higher dose progestin OCP, as were exercise time to exhaustion and total work done. Synthetic progestins in OCP formulations can have a significant effect on the exercise status of young, sedentary women, possibly through an effect on stroke volume and a shift in the principal energy substrate used during exercise from carbohydrate to lipid.
Publisher: BMJ
Date: 12-2018
DOI: 10.1136/BMJOPEN-2018-023413
Abstract: In vitro maturation (IVM) is a potential alternative to conventional in vitro fertilisation (IVF) to avoid ovarian hyperstimulation syndrome (OHSS). This is particularly relevant in women with a high antral follicle count (AFC) and/or polycystic ovary syndrome (PCOS), who are at increased risk for OHSS. However, no randomised controlled trials of IVM versus IVF in women with high AFC have reported both pregnancy and OHSS rates. The aim of this study is to compare the effectiveness and safety of one IVM cycle and one IVF with segmentation cycle within women with PCOS or high AFC-related subfertility. This randomised controlled trial will be conducted at a specialist IVF centre in Vietnam. Eligible subfertile women with PCOS and/or high AFC will be randomised to undergo either IVM or IVF. The primary outcome is live birth after the first embryo transfer of the started treatment cycle. Cycles in which no embryo is available for transfer will be considered as failures. The study has a non-inferiority design, with a maximal acceptable between-group difference of 5%. Rates of OHSS will also be reported. Ethical approval was obtained from the participating centre, and informed patient consent was obtained before study enrolment. Results of the study will be submitted for publication in a peer-reviewed journal. NCT03405701 Pre-results.
Publisher: The Endocrine Society
Date: 11-1987
Abstract: Mobilization of arachidonic acid from glycerophospholipids and prostaglandin (PG) release from fetal membranes were studied in women with dysfunctional labor in the absence of cephalopelvic disproportion or fetal malposition. Using superfusion of intact amnion and chorion, we found a slight decrease in PGE and a more significant decrease in PGF release by the amniotic side of the fetal membrane obtained from women with dysfunctional labor compared to that in women with normal labor (PGE: normal labor, 2992 pg/cm2.h dysfunctional labor, 1846 pg/cm2.h P less than 0.05 PGF: normal labor, 662 pg/cm2.h dysfunctional labor, 204 pg/cm2.h P less than 0.02). Release of both prostanoids was significantly greater from the amniotic side in tissues obtained after labor compared to that in prelabor tissue. Analysis of arachidonic acid (by gas liquid chromatography) and phospholipid content (by two-dimensional thin layer chromatography) confirmed metabolic disposal of arachidonic acid from the amnion after the onset of labor. However, no difference in either phospholipid or phospholipase A2-releasable arachidonic acid of in idual phospholipid classes was found in amnion tissue from women with normal and dysfunctional labor, suggesting similar activities of phospholipase A2 in these two groups. The finding of decreased free and phospholipase A2-releasable arachidonic acid of the total lipid extract of the amnion of women with dysfunctional labor could suggest further metabolic exhaustion of the substrate or failure of liberation of this fatty acid from glycerophospholipids by enzymes other than phospholipase A2, such as phospholipase C or diacyl and monoacylglycerolipases.
Publisher: JMIR Publications Inc.
Date: 12-03-2020
Abstract: here is increasing information characterizing menstrual cycle length in women, but less information is available on the potential differences across lifestyle variables. his study aimed to describe differences in menstrual cycle length, variability, and menstrual phase across women of different ages and BMI among a global cohort of Flo app users. We have also reported on demographic and lifestyle characteristics across median cycle lengths. he analysis was run based on the aggregated anonymized dataset from a menstrual cycle tracker and ovulation calendar that covers all phases of the reproductive cycle. Self-reported information is documented, including demographics, menstrual flow and cycle length, ovulation information, and reproductive health and diseases. Data from women aged ≥18 years and who had logged at least three cycles (ie, 2 completed cycles and 1 current cycle) in the Flo app were included (1,579,819 women). f the 1.5 million users, approximately half (638,683/1,579,819, 40.42%) were aged between 18 and 24 years. Just over half of those reporting BMIs were in the normal range (18.5-24.9 kg/m sup /sup 202,420/356,598, 56.76%) and one-third were overweight or obese (& kg/m sup /sup 120,983/356,598, 33.93%). A total of 16.32% (257,889/1,579,819) of women had a 28-day median cycle length. There was a higher percentage of women aged ≥40 years who had a 27-day median cycle length than those aged between 18 and 24 years (22,294/120,612, 18.48% vs 60,870/637,601, 9.55%), but a lower percentage with a 29-day median cycle length (10,572/120,612, 8.77% vs 79,626/637,601, 12.49%). There were a higher number of cycles with short luteal phases in younger women, whereas women aged ≥40 years had a higher number of cycles with longer luteal phases. Median menstrual cycle length and the length of the follicular and luteal phases were not remarkably different with increasing BMI, except for the heaviest women at a BMI of ≥50 kg/m sup /sup . n a global scale, we have provided extensive evidence on the characteristics of women and their menstrual cycle length and patterns across different age and BMI groups. This information is necessary to support updates of current clinical guidelines around menstrual cycle length and patterns for clinical use in fertility programs.
Publisher: Cambridge University Press (CUP)
Date: 11-2006
DOI: 10.1017/S0967199406003832
Abstract: Relatively little information is available on the local factors that regulate folliculogenesis in goats. To examine the possibility that the Kit ligand (KL) system is expressed throughout the folliculogenesis, we studied the presence and distribution of KL and its receptor, c-Kit, in goat ovaries. Ovaries of goats were collected and either fixed in paraformaldehyde for immunohistochemical localization of KL and c-Kit proteins, or used for the isolation of follicles, luteal cells, surface epithelium and medullary s les to study mRNA expression for KL and c-Kit, using the reverse transcriptase polymerase chain reaction (RT-PCR). KL protein and mRNA were found in follicles at all stages of development, i.e. primordial, primary, secondary, small and large antral follicles, as well as in corpora lutea, surface epithelium and medullary tissue. Antral follicles expressed both KL-1 and KL-2 mRNAs, while earlier staged follicles expressed KL-1 transcript only. KL protein was demonstrated in granulosa cells from the primordial follicle onward. Its mRNA could be detected in granulosa cells isolated from antral follicles and occasionally in their theca cells. c-Kit mRNA was expressed in all antral follicular compartments and at all stages of follicular development. c-Kit protein was predominantly found in oocytes from the primordial follicle stage onwards, in theca cells of antral follicles, as well as in corpora lutea, surface epithelium and medullary tissue, particularly in the wall of blood vessels, which may indicate these cells as the main sites of action of KL. It is concluded that the KL/c-Kit system, in goat ovaries, is widespread and that it may be involved in the regulation of various local processes, including folliculogenesis and luteal activity.
Publisher: Georg Thieme Verlag KG
Date: 10-1990
Abstract: Clinical parameters, androgen status and lipoprotein lipid profiles were assessed in 10 non-obese and 10 obese patients with polycystic ovarian disease (PCOD) and reference subjects matched for age, height and weight. Both obese and non-obese women with PCOD had significantly higher androgen levels when compared to the reference groups. When comparison of lipoprotein lipid profiles were made between groups, non-obese women with PCOD had significantly higher total cholesterol, triglycerides and LDL-cholesterol levels than non-obese reference subjects. Obese PCOD women manifested significantly higher total cholesterol, LDL-cholesterol, cholesterol/HDL, and LDL/HDL values than did obese reference subjects. Correlations between serum androgens and lipoprotein lipid concentrations in PCOD and normal women were unhelpful. Both non-obese and obese patients with PCOD had significantly higher systolic and diastolic blood pressures (BPs) than the reference groups. Thus, both non-obese and obese women with PCOD manifest hyperandrogenaemia which may result in a male pattern of lipoprotein lipid concentrations.
Publisher: Oxford University Press (OUP)
Date: 25-05-2011
DOI: 10.1095/BIOLREPROD.110.090415
Abstract: Oocyte developmental competence is acquired throughout folliculogenesis and is associated with appropriate differentiation and responsiveness to the luteinizing hormone (LH) surge. The recent development of a novel system for culturing ovarian follicles in a three-dimensional alginate matrix shows promise in phenocopying in vivo folliculogenesis. However, oocytes from follicles grown in vitro have a reduced capacity to complete nuclear maturation and be fertilized compared to oocytes matured in vivo. Oocyte metabolism is closely linked with oocyte quality, and we have recently shown that beta-oxidation of lipids is essential for oocyte developmental competence. Thus we investigated whether upregulation of beta-oxidation by treatment with the fatty acid transport cofactor l-carnitine could improve folliculogenesis and developmental competence of mouse follicles following three-dimensional culture. Ovarian hormones (androstenedione, estradiol, and progesterone) and the induction of cumulus matrix proteins (hyaluronan and ADAMTS1) were similar to in vivo follicles, indicating that appropriate differentiation of follicular cells occurs in cultured follicles after an LH/human chorionic gonadotropin (hCG) stimulus. l-carnitine did not alter survival, growth, or differentiation of follicles. However, l-carnitine supplementation significantly increased beta-oxidation, and markedly improved both fertilization rate and blastocyst development. Together, these results show that appropriate responsiveness of the follicle to the LH/hCG surge occurs following three-dimensional follicle culture but limitations on key metabolic requirements remain. l-carnitine supplementation during in vitro follicle culture increased lipid metabolism and improved oocyte developmental competence.
Publisher: Georg Thieme Verlag KG
Date: 2018
Abstract: Polycystic ovary syndrome (PCOS) affects approximately one in seven women worldwide from early adulthood with heterogeneity in their healthcare needs through the life cycle. PCOS is challenging to diagnose and manage, with one-third of women reporting at least a 2-year delay in diagnosis. Current clinical services do not satisfactorily educate and support women with their erse reproductive, metabolic, and psychological care needs with fragmentation of services across health providers. Women are dissatisfied with the care they received, while the first contact general practitioners often feel ill-equipped to diagnose and manage PCOS. Despite national evidence-based guidelines recommending integrated multidisciplinary services, guideline translation has been limited, with wide practice variation and no optimal models of care. Lifestyle management and psychological support are the cornerstones of care and health providers who most commonly manage PCOS (general practitioners, dermatologists, endocrinologists, and gynecologists) require appropriate resources and multidisciplinary support. An evidence-based patient-centered clinical model of care, codeveloped by consumers and health professionals that provides education and resources and offers multidisciplinary holistic care, is vital to support women with PCOS.
Publisher: IOP Publishing
Date: 17-05-2011
DOI: 10.1088/0957-4484/22/26/265401
Abstract: Spray pyrolysis was used to produce hollow hematite (α-Fe(2)O(3)) nanosphere (HHNS)/carbon nanotube (CNT) composite on a large scale. The method offers simplicity, high productivity, versatility, low cost, and suitability for industry. The structure is composed of hollow nanospheres in a network of CNTs. The possible formation mechanism of hollow α-Fe(2)O(3) nanospheres is due to the rapid evaporation of water and the super-hydrophobicity of the CNT surface. The electrochemical tests show that the HHNS/CNT composite is a promising lithium storage material in terms of high capacity (∼700 mAh g(-1)), good high-rate capability, and good cycle life (up to 150 cycles). The materials improve both lithium ion and electron transport, which are limiting factors on the high-rate capability of lithium-ion batteries. The production method can be easily adapted to produce a wide range of hollow metal oxide nanosphere/CNT composites.
Publisher: Oxford University Press (OUP)
Date: 12-11-2009
Abstract: Polycystic ovary syndrome (PCOS) is considered to be the most common endocrine disorder in women of reproductive age, yet debate over appropriate diagnostic criteria and design limitations with s ling methodology have left some doubt as to the actual prevalence in the community. The objective of this study was to create a representative prevalence estimate of PCOS in the community under the National Institutes of Health (NIH) criteria and the more recent Rotterdam consensus criteria and Androgen Excess Society (AES) criteria. A retrospective birth cohort study was carried out in which 728 women born during 1973-1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27-34 year n = 728). Symptoms of PCOS (hyperandrogenism, menstrual dysfunction and polycystic ovaries) were identified by examination and the presence of polycystic ovaries in those that did not consent to the ultrasound were imputed. The estimated prevalence of PCOS in this birth cohort using the NIH criteria was 8.7 +/- 2.0% (with no need for imputation). Under the Rotterdam criteria, the prevalence was 11.9 +/- 2.4% which increased to 17.8 +/- 2.8% when imputed data were included. Under the AES recommendations, PCOS prevalence was 10.2 +/- 2.2%, and 12.0 +/- 2.4% with the imputed data. Of the women with PCOS, 68-69% did not have a pre-existing diagnosis. The Rotterdam and AES prevalence estimates were up to twice that obtained with the NIH criteria in this, as well other prevalence studies. In addition, this study also draws attention to the issue of many women with PCOS in the community remaining undiagnosed.
Publisher: Oxford University Press (OUP)
Date: 12-2000
DOI: 10.1093/HUMREP/15.12.2653
Abstract: Intercourse during an IVF cycle has the potential to improve pregnancy rates since exposure to semen is reported to promote embryo development and implantation in animals. Conversely, coitus-induced uterine contractions or introduction of infection may have a detrimental effect. A multicentre prospective randomized control trial was conducted to determine if intercourse during the peri-transfer period of an IVF cycle has any influence on pregnancy success. Participants undergoing thawed embryo transfer (Australian centre) or fresh embryo transfers (Spanish centres) were randomized either to abstain or to engage in vaginal intercourse around the time of embryo transfer. The transfer of 1343 embryos during 478 cycles of IVF resulted in 107 pregnancies (22.4%), with 125 viable embryos remaining by 6-8 weeks gestation. There was no significant difference between the intercourse and abstain groups in relation to the pregnancy rate (23.6 and 21.2% respectively), but the proportion of transferred embryos that were viable at 6-8 weeks was significantly higher in women exposed to semen compared to those who abstained (11.01 versus 7.69 viable embryos per 100 transferred embryos, P = 0.036, odds ratio 1.48, 95% confidence interval 1.01-2.19). Hence exposure to semen around the time of embryo transfer increases the likelihood of successful early embryo implantation and development.
Publisher: Wiley
Date: 28-05-2012
Publisher: Wiley
Date: 03-12-2017
DOI: 10.1002/UOG.18933
Abstract: To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles WMD, -1.39 95% CI, -2.27 to -0.51 I In women with WHO group II ovulatory disorders, ovulation induction with CC might result in lower EMT than other ovulation induction regimens. Whether the lower EMT caused the lower pregnancy and live birth rates remains to be elucidated. Letrozole seems to be beneficial for these women. However, our findings should be interpreted with caution as the quality of evidence was very low. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Publisher: BMJ
Date: 19-05-1984
DOI: 10.1136/BMJ.288.6429.1487
Abstract: Concentrations of prostaglandins E, F, and 6-keto-prostaglandin F1 alpha were estimated in central venous blood and amniotic fluid in 21 women with ecl sia and 16 healthy pregnant controls. Central venous blood concentrations of 6-keto-prostaglandin F1 alpha and prostaglandin E were significantly lower in patients than controls before delivery and remained reduced for at least 48 hours after delivery. Low concentrations of prostaglandins E and 6-keto-prostaglandin F1 alpha are probably directly related to the pathogenesis of ecl sia.
Publisher: Georg Thieme Verlag KG
Date: 2008
Abstract: Polycystic ovary syndrome (PCOS) is a common condition in women with reproductive age associated with reproductive and metabolic dysfunction. Treatment has traditionally focused on fertility and hormonal therapy. However, obesity, central obesity, and insulin resistance (IR) are strongly implicated in its etiology, and improving these factors has become a treatment target in PCOS. Lifestyle modification programs with an emphasis on behavioral management and dietary and exercise interventions have been successful in reducing the risk of diabetes and the metabolic syndrome in the general population and improving reproductive and metabolic features in PCOS, although as yet there is limited evidence for specific dietary and exercise approaches and guidelines for use in PCOS and requires further investigation. The use of antiobesity pharmacologic agents and bariatric surgery has been recently studied in PCOS and may offer additional treatment options for the future. Future research should focus on the optimal dietary strategies and exercise regimens for PCOS treatment and the relative efficacy and appropriate use of lifestyle management versus antiobesity pharmacologic agents and surgery.
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.THERIOGENOLOGY.2005.02.010
Abstract: A study was conducted to develop an in vitro culture system for growing sheep oocytes from isolated primordial follicles. Enzymatically isolated neonatal sheep primordial follicles were cultured in Waymouth MB752/1 medium containing BSA (3 mg/ml) + ITS (1%, v/v) over 28 days. In Experiment 1, primordial follicles (average diameter 40.2+/-0.60 microm) were cultured at densities of 20, 50 and 100 follicles per well. Less than 20% of the oocytes survived to day 28 but there was a significant (P < 0.05) increase in median oocyte diameter from day 2 to day 28 for oocytes cultured at the higher densities of 50 and 100 follicles. In Experiment 2, two methods to improve oocyte:granulosa cell associations were tested. Altering the fibronectin coating regime did not improve oocyte survival and growth. In contrast lectin-aggregated primordial follicles cultured on non-coated wells showed significantly (P < 0.05) improved oocyte survival to 50% and increased median oocyte diameter compared to non-aggregated follicles. In Experiment 3, the effect of KIT ligand (KL) at 0 ng/ml, 10 ng/ml and 100 ng/ml, on lectin-aggregated primordial follicles cultured on non-coated wells was tested. KL at 100 ng/ml significantly (P < 0.05) increased median oocyte diameter compared to non-treated controls but had no effect on oocyte survival. In addition, follicles cultured with 100 ng/ml KL expressed mRNA for AMH, a gene expressed only in granulosa cells of growing follicles. In conclusion, culture of lectin-aggregated primordial follicles supported the long-term survival and growth of oocytes from isolated sheep primordial follicles. Culture of lectin-aggregates with 100 ng/ml KL further increased oocyte growth and induced granulosa cell differentiation.
Publisher: SAGE Publications
Date: 05-1990
DOI: 10.1177/000456329002700302
Abstract: The structure of human chorionic gonadotrophin (hCG) is so similar to that of luteinizing hormone (LH) that a variety of assay techniques have been devised to differentiate between these two hormones. The principal indications for measurement of hCG using these methods have not changed greatly over the past decade but the improvements in the sensitivity, specificity and the development of assays for free subunits and metabolic fragments have expanded the use of hCG assays. The review discusses the use of hCG measurement in a routine clinical immunoassay laboratory and emphasizes different requirements for clinical situations.
Publisher: MDPI AG
Date: 26-02-2019
DOI: 10.3390/NU11030492
Abstract: Background/objectives: Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women. Weight management is a first-line treatment for PCOS according to international evidence-based guidelines. However, the factors associated with attrition or success in weight loss interventions are not known for women with PCOS. The objective of this study was to identify characteristics associated with attrition and weight loss success in women with PCOS and overweight or obesity undergoing weight loss interventions. Methods: Four randomised controlled clinical weight loss trials comprising energy restricted diets and/or exercise interventions of 2–8 months duration. The interventions were conducted over 2001–2007 in outpatient clinical research centres with n = 221 premenopausal women with PCOS and overweight/obesity recruited through community advertisement. The main outcome measures were attrition and ≥5% weight loss at 2 months and study completion. Results: Weight loss was 5.7 ± 2.9 kg at 2 months and 7.4 ± 5.3 kg after study completion (p 0.001). Attrition was 47.1% and ≥5% weight loss occurred in 62.5% and 62.7% of women at 2 months and study completion respectively. Baseline depressive symptoms (OR 1.07 95% CI 0.88, 0.96, p = 0.032) and lower appointment attendance by 2 months (OR 0.92 95% CI 0.88, 0.96, p 0.001) were independently associated with attrition. Lower appointment attendance over the whole study was independently associated with not achieving ≥5% weight loss at study completion (OR 0.95 95% CI 0.92, 0.99, p = 0.020). Conclusions: Despite high attrition, successful weight loss was achieved by 63% of women with PCOS in a clinical research setting. Higher baseline depressive symptoms were associated with greater attrition and higher appointment attendance was associated with lower attrition and greater weight loss success. These finding have implications for development of successful weight management programs in PCOS.
Publisher: Oxford University Press (OUP)
Date: 1999
DOI: 10.1093/MOLEHR/5.1.5
Abstract: The tumour necrosis factor (TNF)2 allele appears to be linked with increased insulin resistance and obesity, conditions often found in overweight patients with polycystic ovary syndrome (PCOS). The significance of TNFalpha polymorphism in relation to the clinical and biochemical parameters associated with PCOS was investigated in 122 well-characterized patients with polycystic ovaries (PCO). Of these, 84 had an abnormal menstrual cycle and were classified as having PCOS, while the remaining 38 had a normal menstrual cycle and were classified as having PCO. There were a further 28 in iduals without PCO (non-PCO) and 108 in iduals whose PCO status was undetermined (reference population). The promoter region of the TNFalpha gene was lified by polymerase chain reaction (PCR), and the presence or absence of the polymorphism at -308 was determined by single-strand conformational polymorphism (SSCP) analysis. The less common TNF allele (TNF2) was found as TNF1/2 or TNF2/2 in 11/38 (29%) of PCO subjects, 25/84 (30%) of PCOS subjects, 7/28 (25%) of non-PCO subjects, and 45/108 (42%) of the reference population. There was no significant difference in the incidence of the TNF2 allele between the groups. The relationship of TNF genotype to clinical and biochemical parameters was examined. In both the PCO group and the PCOS group, the presence of the TNF2 allele was significantly associated with lower glucose values obtained from the glucose tolerance testing (P<0.05). The TNF genotype was not significantly associated with any clinical or biochemical parameter measured in the PCO, PCOS or non-PCOS groups. Thus, the TNFalpha -308 polymorphism does not appear to strongly influence genetic susceptibility to polycystic ovaries.
Publisher: Oxford University Press (OUP)
Date: 08-09-2005
Abstract: This editorial comments on two similar reviews of the literature on breast cancer and post-menopausal hormone therapies (HTs), puts the results in clinical perspective and suggests where they direct future research and clinical management. Although epidemiological studies have suggested increased breast cancer risk for all menopausal HT regimens, unopposed oral estrogen regimens have not been associated with any increased risk in recent randomized placebo controlled trials (RCTs). Added progestogen after 5 years of combined HT in RCTs increases the risk of breast cancer by four cases per 10,000 per annum. As yet there is no evidence of different risk by progestogen type, dose or route. Theoretically local intrauterine progestogen may not give the same risk, but long-term trials are required. The commentary addresses the responsibility of the media in presenting levels of risk to the public, moving towards safer regimens, safer therapies, appropriate patient choice and, in particular, correct timing of HT where it is prescribed around menopause. This is in contrast to many of the trials when HT was administered after the potential climacteric window of therapeutic opportunity. The current main indication for HT remains for menopausal symptom control where it improves quality of life. HT may be required for many years. The informed woman should decide on HT based on her personal benefits and risks, which should include all aspects of her health.
Publisher: Oxford University Press (OUP)
Date: 09-2002
Abstract: The female reproductive and immune systems are integrally linked with respect to shared cellular and molecular mediators. Cell adhesion molecules (CAMs) involved in leukocyte-endothelial interactions, e.g. intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, are regulated by sex steroids when expressed by cultured endothelium, while uterine and ovarian CAM expression appears to be cyclically or gonadotrophin-regulated. To determine if these effects translate into changes in soluble CAMs (sICAM-1, sVCAM-1 and sE-selectin) levels in peripheral blood, normally cycling women received regular venous s ling throughout a complete menstrual cycle. Soluble ICAM-1 levels were maximal in the early and mid-follicular stages, progressively decreased throughout the remainder of the cycle and were significantly reduced in the late luteal stage (P < 0.001). Levels of sVCAM-1 fluctuated during the follicular phase and mid-cycle, but also declined in the late luteal phase (P < 0.01), whereas sE-selectin concentration did not vary markedly across the menstrual cycle. Plasma hormone and urinary hormone metabolite levels confirmed precise cycle tracking and revealed an inverse relationship between sICAM-1 and estradiol (r = -0.38, P < 0.005). A negative correlation was also apparent between sVCAM-1 and circulating monocyte cell numbers (r = -0.47, P < 0.001). The normal cyclic variation in peripheral sICAM-1 and sVCAM-1 levels reported here may reflect uterine and/or ovarian tissue remodelling events, and is of particular importance if soluble CAM levels are utilized as biological markers of certain disease states in women of reproductive age.
Publisher: World Scientific Pub Co Pte Ltd
Date: 09-2021
DOI: 10.1142/S2661318221500146
Abstract: Research Question: Does the dose of gonadotropin used for superovulation in IVF affect the proportion of euploid blastocysts obtained after fertilization? Study Design: Multicentre randomized controlled trial recruiting 57 women who were treated with ovarian stimulation using either 150 or 300 IU Menopur per day. Both groups received GnRH antagonist from day 5 of ovarian stimulation and final oocyte maturation was induced using a leuprolide GnRH (gonadotropin releasing hormone) agonist trigger when three or more follicles reached 17 mm diameter. Oocyte collection was scheduled 36–38 hours post trigger. In vitro fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) were performed according to in idual unit protocol and embryos were cultured to blastocyst stage. A trophectoderm biopsy was performed on day 5 of embryo culture and used for preimplantation genetic testing for aneuploidy. Euploid embryos were transferred in subsequent frozen embryo transfer cycles with appropriate endometrial preparation. Results: The number of oocytes obtained from women randomized to 150 IU Menopur was between 3 and 17 (mean = 9), whereas the number of oocytes obtained from women randomized to 300 IU Menopur was between 3 and 24 (mean = 11). There was a positive linear relationship between serum AMH concentration and oocyte yield in both the 150 and 300 IU Menopur groups ([Formula: see text] = 0.3359, [Formula: see text] = 0.1129 and [Formula: see text] = 0.3741, [Formula: see text] = 0.1399). The percentage of euploid to aneuploid embryos in the 150 IU Menopur group was 63% and in the 300 IU Menopur group, the proportion was 75%, which was not significantly different ([Formula: see text] = 0.17). Conclusion: The higher dose ovarian stimulation protocol did not significantly increase the number of oocytes retrieved, nor did the higher dose protocol reduce the proportion of euploid embryos created. This study does not support the hypothesis that use of higher doses of gonadotropin for ovarian stimulation results in a reduction in the proportion of euploid embryos obtained after IVF.
Publisher: Bioscientifica
Date: 11-2005
DOI: 10.1530/REP.1.00521
Abstract: Obesity is associated with a erse set of metabolic disorders, and has reproductive consequences that are complex and not well understood. The adipose tissue-produced leptin has dominated the literature with regards to female fertility complications, but it is pertinent to explore the likely role of other adipokines – adiponectin and resistin – as our understanding of their biological functions emerge. Leptin influences the developing embryo, the functioning of the ovary and the endometrium, interacts with the release and activity of gonadotrophins and the hormones that control their synthesis. In this review such biological actions and potential roles of the adipokines leptin, adiponectin and resistin are explored in relation to female fertility and the complexity of the obese metabolic state.
Publisher: Oxford University Press (OUP)
Date: 02-1996
DOI: 10.1095/BIOLREPROD54.2.436
Abstract: The ovulatory process resembles an inflammatory reaction with an infiltration of leukocytes, production of inflammatory mediators such as cytokines, and a general edema and hyperemia. Nitric oxide (NO), a potent vasodilator and the main mediator of macrophage tumoricidal and bacteriocidal activities, is known to participate in inflammatory reactions and has been shown to mediate the interleukin-1 beta (IL-1 beta)-directed tissue-remodeling events within the ovary. The regulation by NO of ovulation rate, leukocyte distribution, and steroid release in the rat ovary was investigated through use of a combination of in vivo and in vitro models of ovulation and a competitive inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), of the NO synthase (NOS) enzyme. Subcutaneous L-NAME (1.5 x 10(-4) mol/kg) administration significantly reduced the in vivo ovulation rate of eCG/hCG-primed rats (L-NAME-treated: 10.6 +/- 1.8 [mean +/- SEM] oocytes per ovary [O/O], 11.0 +/- 1.2 rupture sites per ovary [RS/O] saline-treated: 18.0 +/- 1.8 O/O, 19.4 +/- 1.1 RS/O p < 0.01) at 20 h post-hCG. These results were reflected in vitro, where addition of L-NAME (3.5 x 10(-5) mol/L) to LH (0.1 microgram/ml)-perfused ovaries decreased ovulation rate from 8.2 +/- 1.6 to 2.7 +/- 1 ovulations per ovary (p < 0.05) and simultaneously decreased nitrite accumulation at the completion of perfusions from 16.5 +/- 1.9 to 4.1 +/- 0.5 nmol/ml (p < 0.001). The addition of L-NAME to LH+IL-1 beta (4 ng/ml)-perfused ovaries decreased ovulation rate from 15.2 +/- 2.4 to 0.8 +/- 0.8 ovulations per ovary (p < 0.001) and simultaneously decreased nitrite accumulation at 22 h from 22.8 +/- 2.2 to 1.9 +/- 0.6 nmol/ml (p < 0.001). Studies analyzing and manipulating perfusion flow rate indicated that the L-NAME effects on ovulation rate are primarily due to a reduction in flow rate resulting from inhibition of NO, which may be a consequence of the known vasoconstrictor effects of NOS inhibitors. The observed reduction of in vivo ovulation rate by NO inhibition at 20 h post-hCG was associated with a significant reduction in thecal MCA149+ neutrophils at 12 h post-hCG, the expected time of ovulation (L-NAME-treated: 98.4 +/- 9.2 cells per thecal area saline-treated: 211.5 +/- 11.5 cells per thecal area p < 0.001), while ED1+ monocytes/macrophages underwent similar but nonsignificant changes. Plasma (20 h post-hCG) and perfusate progesterone were not different with L-NAME treatment, while perfusate estradiol levels were markedly reduced upon addition of L-NAME, suggesting a role for NO in ovulation but not in the process of luteinization. In summary, deprivation of NO by use of the competitive inhibitor, L-NAME, led to fewer ovulations, reduced accumulation of nitrite, a decreased neutrophil count in the theca of preovulatory follicles, and reduced estradiol secretion, while progesterone release remained unaffected. The NO pathway may therefore play an important role in the regulation of ovulation and the mediation of IL-1 beta's pro-ovulatory effects. There are likely to be primarily vascular effects, but also a nonvascular component, to the NO regulation of ovulation, with both components indirectly affecting ovulatory leukocyte distribution and steroid secretion.
Publisher: Oxford University Press (OUP)
Date: 27-10-2006
Abstract: This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol. A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt). In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4 P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively not significant). OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.BPOBGYN.2006.04.006
Abstract: Polycystic ovarian syndrome (PCOS) is a condition that is present in 5-6% of women of reproductive age. It has potentially profound implications for women with regard to anovulatory infertility and symptoms related to elevated androgen levels. In addition, in later life women are prone to significant health problems related to hyperinsulinaemia, with an excess risk for diabetes and cardiovascular risk factors. Evidence suggests that the adverse features of PCOS can be ameliorated with lifestyle intervention, such as diet and exercise, while further short-term benefits related to ovulation and cardiac risk factors may be derived from medication with metformin. Evidence for the long-term use of metformin to protect against adverse cardiovascular outcomes and for the use of metformin throughout pregnancy to reduce the risk of miscarriage, gestational diabetes, pre-ecl sia and fetal macrosomia is still lacking.
Publisher: The Endocrine Society
Date: 22-09-2010
DOI: 10.1210/EN.2010-0551
Abstract: In obesity, accumulation of lipid in nonadipose tissues, or lipotoxicity, is associated with endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and ultimately apoptosis. We have previously shown that obese women have increased triglycerides in follicular fluid thus, the present study examined whether high-fat diet–induced obesity causes lipotoxicity in granulosa cells and the cumulus–oocyte complex (COC). Oocytes of mice fed a high-fat diet had dramatically increased lipid content and reduced mitochondrial membrane potential compared to those of mice fed a control diet. COCs from mice fed a high-fat diet had increased expression of ER stress marker genes ATF4 and GRP78. Apoptosis was increased in granulosa and cumulus cells of mice fed a high-fat diet. Mice fed a high-fat diet also exhibited increased anovulation and decreased in vivo fertilization rates. Thus, lipid accumulation, ER stress, mitochondrial dysfunction, and apoptosis are markedly increased in ovarian cells of mice fed a high-fat diet. ER stress markers were also analyzed in granulosa cells and follicular fluid from women with varying body mass indices (BMI). ATF4 was increased in granulosa cells and [Ca2+] in follicular fluid from obese women compared to nonobese women. These results indicate that lipotoxicity may be occurring in ovarian cells of obese women and may contribute to the reduced pregnancy rates observed in response to obesity.
Publisher: Elsevier BV
Date: 10-1999
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: Springer Science and Business Media LLC
Date: 10-1999
Abstract: To determine whether low birthweight is associated with higher plasma leptin concentrations in adult life and whether leptin contributes to the metabolic alterations in adults that are associated with reduced foetal growth. Measurement of plasma leptin concentrations in a group of 502 men and women, aged 61-73, who were born in Hertfordshire and for whom records of birth and infant weight are available. Glucose tolerance was measured with a standard 75 g oral glucose tolerance test. Leptin concentrations were assayed in fasting plasma s les using a radioimmunoassay. Leptin concentrations ranged from 1.4 to 128.9 (mean 13.4) ng/ml and were higher in the 193 women than the 309 men (23.4 vs. 7.1 ng/ml). In both sexes leptin concentrations correlated positively with body mass index (r=0.65 in both men and women). Leptin concentration also correlated with fasting insulin (r=0.41) and with glucose and insulin concentrations 2 h after a glucose load (r=0.19 and 0.49). Adults with lower birth or infant weight had higher leptin concentrations than those of higher birthweight with similar degrees of obesity (P=0.02 and 0.06, respectively). Although both 2 h glucose and insulin concentrations negatively correlated with birthweight (r=-0.17, P<0.001 and r=-0.18, P<0.001, respectively), regression analysis suggested that the higher levels of leptin in adults who had low birthweight did not explain the association between low birthweight and glucose or insulin concentrations. These results suggest that adults who had had low birthweight had higher plasma concentrations of leptin than would be expected from their degree of obesity. The higher leptin concentrations, however, do not account for the association between birthsize and glucose tolerance. They may be a consequence of the altered body composition, hyperinsulinaemia, and other long-term endocrine changes associated with reduced foetal growth.
Publisher: Elsevier BV
Date: 09-2003
Publisher: Proceedings of the National Academy of Sciences
Date: 06-1991
Abstract: Mice homozygous for the viable Sl allele steel-Dickie (Sld) are sterile, severely anemic, and black-eyed white. The nature of the Sld mutation was investigated at the molecular level and was found to be due to a 4.0-kilobase intragenic deletion in mast cell growth factor (MGF) genomic sequences, providing conclusive evidence that Sl encodes MGF. As a consequence of this deletion, Sld is only capable of encoding a soluble truncated growth factor that lacks both transmembrane and cytoplasmic domains. Northern analysis indicates that Sld mRNA is expressed at approximately wild-type levels in adult tissues, and yeast expression studies suggest that the Sld protein is as biologically active as wild-type soluble MGF. These studies provide a molecular basis for explaining the Sld phenotype, a description of a germ-line mutation in the transmembrane and cytoplasmic domains of a membrane-bound growth factor, and in vivo evidence for the importance of membrane-bound forms of growth factors in mammalian development.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2001
DOI: 10.1097/00001703-200106000-00013
Abstract: Polycystic ovary syndrome remains a mystery with respect to its aetiology, consequences and management. There is an increasing emphasis on its familial origins although the genes involved are unknown. There are significant changes in risk profiles for cardiovascular disease but no clear clinical evidence of morbidity or mortality. There is evidence of improvement in insulin resistance or insulin sensitivity drugs but uncertainty about improvement in pregnancy outcomes. This review looks at the latest advances in understanding polycystic ovary syndrome, particularly in obesity.
Publisher: Oxford University Press (OUP)
Date: 06-2003
Abstract: We report two cases of infertility treatment in couples where males suffered from Kartagener's syndrome (KS) and a total absence of motile sperm in the ejaculate. A total of three ICSI cycles was carried out. In all cycles, viable ejaculated or testicular spermatozoa were selected using the hypo-osmotic swelling (HOS) test. Case 1: In the first ICSI cycle total fertilization failure occurred after using ejaculated spermatozoa. In the following cycle testicular spermatozoa were used for ICSI, resulting in 75% fertilized oocytes and a pregnancy. Case 2: In the same ICSI cycle 50% of the oocytes were injected with ejaculated and 50% with testicular spermatozoa. The fertilization rates were 44 and 56% respectively and high quality embryos were achieved in both groups. One single embryo derived from testicular sperm was transferred with a resulting singleton pregnancy. In conclusion, testicular sperm for ICSI seem to have reliable fertilization capacity in men with KS, while ejaculated sperm, even if tested viable, seem more unpredictable. HOS test for selection of viable sperm for ICSI is recommended when ejaculated as well as testicular sperm are used for ICSI.
Publisher: Elsevier BV
Date: 11-2002
DOI: 10.1016/S1043-2760(02)00691-4
Abstract: Here, we explore the influence of fetal programming and early life exposures on lifelong reproductive health through modification of the hypothalamic-pituitary-gonadal axis. A range of programming issues are considered with ex les from the literature demonstrating that environmental or nutritive exposures have a crucial role in reproductive performance, fetal growth, postnatal development and reproduction-related disease risk. We pay particular attention to recent research on associations between indicators of fetal and postnatal growth and the etiology of polycystic ovary syndrome in women. We conclude that the concept of programming can be applied to reproductive development and related health outcomes, and that the complex potential for interactions between parameters controlling fetal development and postnatal exposures invokes a need to adopt a perspective across the life course of an in idual.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-1982
DOI: 10.1097/00006254-198202000-00001
Abstract: A study of 34 full-thickness Stein-Leventhal ovarian wedges and 30 age-matched control ovaries allowed comparison of the entire ovarian cross-sections and quantification of their features. As compared with controls, Stein-Leventhal ovaries showed on average (i) double the cross-sectional area, (II) the same number of primordial follicles, (iii) double the number of ripening and subsequent atretic follicles from the earliest stages, (iv) a tunica increased by 50 per cent and more collagenized, (v) cortical stromal thickness increased by a third, (vi) subcortical stroma, whether deep cortical or medullary in site, increased five times, (vii) ovarian hilus cell nests four times as frequently. The increased subcortical stroma was derived partly from the regressive conversion into stroma of the over-numerous older follicles, so augmenting steadily with duration, and partly from a concurrent stromal hyperplasia. Stromal smooth muscle and lutein cell nests were each found in four-fifths of cases. So-called "hyperthecosis," in which such nests are combined with marked stromal increase, is arguably just a late stage of Stein-Leventhal morphology. The whole picture may result directly or indirectly from the raised LH output, although androgens possibly promote early follicle ripening.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Informa Healthcare
Date: 31-10-2005
DOI: 10.1517/14656566.6.14.2419
Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine condition with reproductive and metabolic implications. In the current setting there is an evolving, yet inadequate, understanding of the pathophysiology, long-term health implications and ideal therapies for women with PCOS. Insulin resistance, secondary to both genetic and lifestyle factors, is integrally involved in the pathogenesis, the metabolic and clinical features and the long-term sequelae of PCOS in a majority of patients. Therapeutic strategies targeting insulin resistance ameliorate clinical features and may reduce long-term sequelae of PCOS, including diabetes. The main benefit of improved insulin resistance is to improve fertility and potentially to improve clinical features of hyperandrogenism and lower androgen levels. Insulin sensitisers also have the potential to delay the development of diabetes and cardiovascular disease in PCOS. Lifestyle therapy is indicated as the first intervention however, metformin as an insulin sensitising agent has a role in first-line medical therapy in women with PCOS. Further research is needed to define the role of insulin sensitisers in PCOS and to determine the long-term risks and benefits of these therapies.
Publisher: The Endocrine Society
Date: 04-2007
DOI: 10.1210/JC.2006-1123
Abstract: Objective: This study aims to examine the impact of insulin resistance (IR) on the risk of spontaneous abortion in patients who received infertility treatment. Patients and Methods: This is a cohort study of 107 patients who achieved their first pregnancy after infertility treatment in a tertiary medical center. A homeostasis model assessment of IR (HOMA-IR) was carried out. Patient demographic characteristics and pregnancy outcome were also recorded. Statistical comparison was made between patients with and without IR. Logistical regression analysis was used to assess the effect of IR and several other factors simultaneously on the risk of spontaneous abortion. Results: The incidence of spontaneous abortion was 17.8%. The association of IR with the risk of spontaneous abortion was significant after adjusting for other risk factors. The effect of overweight/obesity and polycystic ovarian syndrome was not statistically significant in the multivariate model. Discussion and Conclusion: This study suggested that IR was an independent risk factor for spontaneous abortion. Because of the high prevalence of IR in obese or polycystic ovarian syndrome patients, the risk of spontaneous abortion in these patients can be raised. Patients with IR should be advised to improve their insulin sensitivity through lifestyle change or medical intervention before infertility treatment to reduce their risk of spontaneous abortion.
Publisher: Oxford University Press (OUP)
Date: 22-09-2006
Abstract: Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive-aged women and is commonly associated with anovulatory infertility. Leukocytes, together with granulosa cells, may contribute to the pathogenesis of PCOS via their ability to secrete an array of cytokines implicated in follicle growth. The aim of this study was to examine leukocyte subtypes in follicular phase ovaries and to quantify cytokine and chemokine mRNA expression in follicular fluid cells obtained at the time of oocyte retrieval before IVF in women with and without PCOS. Ovaries were immunostained for various leukocyte markers [CD3, CD4, CD14, CD15, CD45, CD45RA, CD45RO, CD57 and major histocompatibility complex (MHC) class II]. In addition, follicular fluid cells were subjected to quantitative RT-PCR to evaluate colony-stimulating factor-1 (CSF-1), granulocyte-macrophage (GM)-CSF, interleukins (IL-1beta, IL-6, IL-8 and IL-10), monocyte chemotactic protein (MCP-1) and tumour necrosis factor (TNFalpha) mRNA expression relative to beta-actin. CD45RO+ cells (activated/memory T lymphocytes) were reduced by 60% in the theca layer of follicles from PCOS women. The relative abundance of macrophages and neutrophils was unchanged. Cytokine and chemokine mRNA transcripts examined were not affected by PCOS status. There was an association between high BMI and high TNFalpha and low IL-6 mRNA expression in follicular cells. IL-6 expression was higher in women who subsequently achieved pregnancy. T lymphocytes potentially play a role in the local pathological mechanisms of PCOS. Further studies are required to identify their contribution to the aetiology of this common condition.
Publisher: Wiley
Date: 11-2004
Publisher: Elsevier BV
Date: 09-1989
DOI: 10.1016/0952-3278(89)90077-X
Abstract: It has been suggested that dietary supplementation with prostaglandin precursors may enhance the synthesis of PGE which lowers vascular sensitivity to increased levels of angiotensin II in pregnancy. Therefore the effect of dietary supplementation with evening primrose oil (linoleic acid and gamma-linoleic acid) in African primigravidae with established pre-ecl sia was studied. Patients were randomly allocated to one of two groups. Group A (23 patients) received 8 capsules/day of evening primrose oil and group B (24 patients) received 8 capsules of placebo. No significant differences were found between the groups in respect to perinatal outcome, blood pressure lowering effect and haematological indices.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.RBMO.2012.07.013
Abstract: Polycystic ovary syndrome (PCOS) is associated with increased cardiovascular disease risk. The effect of weight loss on the vascular inflammatory markers plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1) and intracellular adhesion molecule-1 (sICAM-1) is unknown. Overweight women with (n=14) and without (n=13) PCOS of comparable age and body mass index undertook an 8-week weight-loss programme. Women with PCOS had elevated PAI-1, sVCAM-1 and sICAM-1 before and after weight loss compared with the controls. For all women, sVCAM-1 (P=0.026) and sICAM-1 (P=0.04) decreased with weight loss. Women with PCOS have elevated inflammatory markers, which are partially reduced by weight loss.
Publisher: Georg Thieme Verlag KG
Date: 09-1989
Abstract: Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.
Publisher: The Endocrine Society
Date: 08-2007
DOI: 10.1210/JC.2006-2336
Abstract: Background: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities. It is unknown whether overweight women with and without PCOS achieve similar benefits from weight loss for cardiovascular risk factors. Method: Overweight body mass index-matched women with (n = 15) and without (n = 17) PCOS (weight, 95.3 ± 17.6 kg body mass index, 35.6 ± 5.3 kg/m2, mean ± sd) followed an 8-wk weight loss regime. Results: All subjects had similar reductions in weight (3.9 ± 3.6 kg, 3.8%, vs. 4.5 ± 4.1 kg, 4.7%, respectively, for PCOS and non-PCOS), waist circumference, fat mass, triglycerides, free testosterone, and fasting and postprandial insulin. At baseline, C-reactive protein (CRP) between groups was not significantly different (5.5 ± 3.1 mg/liter for PCOS vs. 4.9 ± 3.0 mg/liter for non-PCOS). There was a significant interaction between PCOS status and CRP (P = 0.016) such that CRP decreased with weight loss for non-PCOS women (−1.2 ± 1.8 mg/liter P = 0.025) but not for PCOS women. For all women, the change in CRP correlated with the change in weight (r = 0.560 P = 0.003), fat mass (r = 0.477 P = 0.016), and postprandial insulin (r = 0.402 P = 0.046). Adiponectin, IL-6, and TNF-α were not significantly different between groups before or after weight loss. Only subjects with baseline CRP levels below the median (4.52 mg/liter) showed increases in adiponectin (0.98 ± 1.3 μg/liter) (P = 0.015) and greater reductions in triglycerides (P = 0.001) with weight loss. Conclusion: A 4–5% weight loss improved lipid, glucose, and insulin profiles in women with and without PCOS. This degree of weight loss was not effective in lowering CRP concentrations in PCOS women, suggesting that greater weight loss is required in this group to achieve equivalent cardiovascular benefit to non-PCOS women.
Publisher: Oxford University Press (OUP)
Date: 25-03-2004
Publisher: Georg Thieme Verlag KG
Date: 02-12-2004
Abstract: Luteinizing hormone (LH) and chorionic gonadotropin (CG) are heterodimeric glycoprotein hormones acting on the luteinizing hormone receptor (LHR). In the LHR, which is genomically encoded by eleven exons, exon 10 encodes for the hinge region and its elimination impairs LH action, while CG maintains normal activity. The two gonadotropins differ in the carboxyterminal peptide (CTP) present in CG but absent in LH. Since the marmoset monkey (Callithrix jacchus) LHR naturally lacks exon 10 (LHR type II), we generated two recombinant marmoset gonadotropin preparations, one consisting of the wild type CG and one of truncated CG lacking the CTP (CG (-CTP)). After calibration in a mouse Leydig cell bioassay against the WHO LH80/522 standard, the ED (50) of the CG preparation on a COS7 cell line permanently expressing the marmoset LHR was 4.25 +/- 0.21 IU/L (n = 3). Stimulation of the COS7 cell line with equipotent concentrations of CG and CG (-CTP) resulted in significantly different formation of cAMP (two-way ANOVA, p < 0.001). In particular, cAMP production stimulated by CG (-CTP) was 3 - 4 times lower compared to CG at the saturating CG concentration (8 IU/L). We conclude, supplementing one current model of LHR activation, that exon 10 might play a permissive role in releasing the constraint of the receptor upon hormone binding, resulting in receptor activation. We speculate that, when exon 10 is lacking, the CTP can overcome its absence and facilitates the opening of the receptor, resulting in normal activation.
Publisher: BMJ
Date: 25-11-2000
Publisher: Elsevier BV
Date: 08-2018
Publisher: Massachusetts Medical Society
Date: 11-01-2018
Publisher: Elsevier BV
Date: 02-1989
DOI: 10.1016/0952-3278(89)90175-0
Abstract: The growth of the cultured human breast carcinoma cell line NUB 1 as well as that of other cultured malignant cells has been shown to be inhibited by addition of gamma-linolenic acid (GLA) to the culture medium. It has previously been suggested that these findings may be attributed to correction of a GLA deficiency in malignant cells, with supplementation of this fatty acid leading to increased prostaglandin (PG) production and consequent growth inhibition. To test this hypothesis the effect of 50 micrograms/ml concentrations of GLA and its sequential metabolite dihomo-gamma-linolenic acid (DGLA) and cell growth, morphology and prostaglandin (PGE and PGF) production by NUB 1 cells was investigated. GLA increased PGE and PGF production, inhibited cell growth and caused accumulation of lipid containing cytoplasmic granules. While treatment with DGLA increased PG production to a significantly greater extent than GLA administration it had no apparent effect on cell growth of morphology and did not inhibit cell growth. These findings suggest that some action other than the ability to increase PG production may be responsible for the inhibitory effects produced by GLA in malignant cells.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2010
Publisher: Oxford University Press (OUP)
Date: 14-08-2023
Abstract: What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS. The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from six continents it is now used in 196 countries and is widely cited. It was based on best available, but generally very low to low quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, evidence quality was low and evidence-practice gaps persist. The 2023 International Evidence-based Guideline update reengaged the 2018 network across professional societies and consumer organizations, with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation-II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength and ersity and inclusion were considered throughout. This summary should be read in conjunction with the full Guideline for detailed participants and methods. Governance included a six-continent international advisory and management committee, five guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health and other experts, alongside consumers, project management, evidence synthesis, statisticians and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and five face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across five guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council (NHMRC). The evidence in the assessment and management of PCOS has generally improved in the past five years, but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpins 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include: i) further refinement of in idual diagnostic criteria, a simplified diagnostic algorithm and inclusion of anti-Müllerian hormone (AMH) levels as an alternative to ultrasound in adults only ii) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy iii) emphasizing the poorly recognized, erse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care and shared decision making to improve patient experience, alongside greater research iv) maintained emphasis on healthy lifestyle, emotional wellbeing and quality of life, with awareness and consideration of weight stigma and v) emphasizing evidence-based medical therapy and cheaper and safer fertility management. Overall, recommendations are strengthened and evidence is improved, but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided. The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the Guideline with an integrated evaluation program. This effort was primarily funded by the Australian Government via the National Health Medical Research Council (NHMRC) (APP1171592), supported by a partnership with American Society for Reproductive Medicine, Endocrine Society, European Society for Human Reproduction and Embryology, and European Society for Endocrinology. The Commonwealth Government of Australia also supported Guideline translation through the Medical Research Future Fund (MRFCRI000266). HJT and AM are funded by NHMRC fellowships. JT is funded by a Royal Australasian College of Physicians (RACP) fellowship. Guideline development group members were volunteers. Travel expenses were covered by the partnering organizations. Disclosures of interest were strictly managed according to NHMRC policy and are available with the full guideline, technical evidence report, peer review and responses (edicine/mchri cos). Of named authors HJT, CTT, AD, LM, LR, JBoyle, AM have no conflicts of interest to declare. JL declares grant from Ferring and Merck consulting fees from Ferring and Titus Health Care speaker’s fees from Ferring unpaid consultancy for Ferring, Roche Diagnostics and Ansh Labs and sits on advisory boards for Ferring, Roche Diagnostics, Ansh Labs, and Gedeon Richter. TP declares a grant from Roche consulting fees from Gedeon Richter and Organon speaker’s fees from Gedeon Richter and Exeltis travel support from Gedeon Richter and Exeltis unpaid consultancy for Roche Diagnostics and sits on advisory boards for Roche Diagnostics. MC declares travels support from Merck and sits on an advisory board for Merck. JBoivin declares grants from Merck Serono Ltd. consulting fees from Ferring B.V speaker’s fees from Ferring Arzneimittell GmbH travel support from Organon and sits on an advisory board for the Office of Health Economics. RJN has received speaker’s fees from Merck and sits on an advisory board for Ferring. AJoham has received speaker’s fees from Novo Nordisk and Boehringer Ingelheim. The guideline was peer reviewed by special interest groups across our 39 partner and collaborating organizations, was independently methodologically assessed against AGREEII criteria and was approved by all members of the guideline development groups and by the NHMRC.
Publisher: Oxford University Press (OUP)
Date: 2008
DOI: 10.1095/BIOLREPROD.106.058529
Abstract: Oocyte-granulosa cell communication, mediated by paracrine factors, is essential for oocyte development. Kit ligand (KITL) is expressed in granulosa cells as soluble (KITL1) or membrane-associated (KITL2) proteins. However, the relative biopotency of each isoform during oocyte development is unknown. Our initial results showed that Kitl2 was down-regulated in cultured granulosa cells. To determine the effect of the two isoforms of KITL on oocyte growth, Kitl-deficient fibroblasts were transfected with constructs expressing either KITL1 or KITL2, and growing oocytes were isolated from 12-day-old mice and cultured on the transfected fibroblasts for 2 days. At the end of culture, oocyte diameters were measured, the incidence of spontaneous germinal vesicle breakdown (GVBD) was noted, and oocytes were analyzed for KIT receptor expression. Oocyte growth occurred only in the presence of the KITL2-producing fibroblasts, and suppression of KITL2 expression impaired oocyte growth. Up-regulation of KIT expression occurred in the presence of KITL2 but not KITL1. The presence of KITL2 inhibited spontaneous GVBD. Meiosis inhibitors did not attenuate the GVBD that occurred in the absence of KITL2, suggesting that this process reflects oocyte degeneration rather than meiotic progression. These results indicate that KITL2 is the principal KITL isoform required for oocyte growth and survival in vitro.
Publisher: Wiley
Date: 05-2009
DOI: 10.1038/OBY.2008.641
Abstract: This cross-sectional study aimed to examine the association between different body composition measures, menstrual cycle characteristics, and hormonal factors in a population-based s le of young women. The study s le included 726 Australian women aged 26-36 years who were not currently taking hormonal contraceptives and were not currently pregnant or breast feeding. Anthropometric measures included BMI, waist circumference (WC), and waist-hip ratio (WHR). Menstrual cycle characteristics were self-reported and usual cycles defined as short ( or=35 days). Cycles were defined as irregular if there were >or=15 days between the longest and shortest cycle in the past 12 months. Fasting serum levels of sex hormone-binding globulin (SHBG), testosterone, insulin, and glucose were measured and the free androgen index (FAI) derived. Compared with those of normal weight, obese women had at least a twofold greater odds of having an irregular cycle, whether defined by BMI (odds ratio (OR) = 2.61 95% CI = 1.28-5.35), WC (OR 2.28 95% CI = 1.16-4.49), or WHR (OR = 2.27 95% CI = 1.09-4.72). Body composition measures were significantly positively associated with fasting insulin, testosterone, and FAI, and negatively associated with SHBG (P < 0.01). Fasting insulin, SHBG, and FAI had the strongest influence on the associations between obesity and irregular cycles, with statistically significant ORs of having an irregular cycle being attenuated to near null values following adjustment. In conclusion, both overall and central obesity were significantly associated with having an irregular menstrual cycle. This association was substantially influenced by hormonal factors, particularly insulin and SHBG.
Publisher: European Respiratory Society (ERS)
Date: 02-2018
Publisher: The Endocrine Society
Date: 10-2009
DOI: 10.1210/JC.2009-0544
Abstract: The prenatal antecedents of polycystic ovary syndrome (PCOS) are not known, but prenatal androgen exposure is thought to contribute. This has not previously been investigated in large prospective studies of normal human pregnancy. The aim of the study was to establish the prospective relationship between early life androgen exposure and PCOS in adolescence. A prospective cohort study was conducted in the general community. A total of 2900 pregnant women were recruited at 18 wk gestation. Prenatal androgen exposure was measured from maternal blood s les (at 18 and 34-36 wk) and umbilical cord blood. Timed (d 2-5 menstrual cycle) blood s les were collected, clinical hyperandrogenism was assessed, and transabdominal ultrasound examination of ovarian morphology was performed in 244 unselected girls from the Raine cohort aged 14-17 yr. We examined the relationship between early life androgen exposure and PCOS in adolescence. We did not observe a statistically significant relationship between early life androgen exposure and PCOS in adolescence. This is the first prospective study to evaluate the relationship between prenatal androgen exposure and PCOS in adolescence in normal pregnancy. Our findings do not support the hypothesis that maternal androgens, within the normal range for pregnancy, directly program PCOS in the offspring.
Publisher: Wiley
Date: 02-1997
DOI: 10.1046/J.1365-2265.1997.1200936.X
Abstract: To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17-36 years, body mass index (BMI) 29.9 +/- 0.9 kg/m2, mean +/- SD) and 18 control women (25-47 years, BMI 25 +/- 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone (2) elevated serum androstenedione and (3) reduced serum SHBG concentrations. Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood s le from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/ hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 +/- 1.3 vs 12.1 +/- 2.3 micrograms/l, mean +/- SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.
Publisher: Elsevier BV
Date: 12-1996
DOI: 10.1016/S0015-0282(16)58687-7
Abstract: To determine whether disorders of insulin secretion are common in male and female family members of subjects with polycystic ovary syndrome (PCOS). Family study of siblings and parents of PCOS subjects (five families). All proband cases met the criteria of polycystic ovaries (PCO) by ultrasound (US) and hyperandrogenism. University Reproductive Medicine Unit. Family members of PCOS subjects. Oral glucose tolerance testing (OGTT), insulin, and lipids were measured. Clinical examination including assessment of premature baldness in men and US of ovaries in female members. Insulin, lipids, and clinical parameters. Hyperinsulinemia (69%) and hypertriglyceridemia (56%) was common in family members as were PCO in 79% of 24 females and premature baldness in men in 88% of eight subjects. Hyperinsulinemia is a potential metabolic and genetic marker for subjects who may be carriers of a familial tendency for PCO.
Publisher: The Endocrine Society
Date: 05-2010
DOI: 10.1210/JC.2009-2724
Abstract: Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. The Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society created a panel to provide evidence-based reviews of studies assessing PCOS-CVD risk relationships and to develop guidelines for preventing CVD. An expert panel in PCOS and CVD reviewed literature and presented recommendations. Only studies comparing PCOS with control patients were included. All electronic databases were searched reviews included in idual studies/databases, systematic reviews, abstracts, and expert data. Articles were excluded if other hyperandrogenic disorders were not excluded, PCOS diagnosis was unclear, controls were not described, or methodology precluded evaluation. Inclusion/exclusion criteria were confirmed by at least two reviewers and arbitrated by a third. Systematic reviews of CVD risk factors were compiled and submitted for approval to the AE-PCOS Society Board. Women with PCOS with obesity, cigarette smoking, dyslipidemia, hypertension, impaired glucose tolerance, and subclinical vascular disease are at risk, whereas those with metabolic syndrome and/or type 2 diabetes mellitus are at high risk for CVD. Body mass index, waist circumference, serum lipid/glucose, and blood pressure determinations are recommended for all women with PCOS, as is oral glucose tolerance testing in those with obesity, advanced age, personal history of gestational diabetes, or family history of type 2 diabetes mellitus. Mood disorder assessment is suggested in all PCOS patients. Lifestyle management is recommended for primary CVD prevention, targeting low-density and non-high-density lipoprotein cholesterol and adding insulin-sensitizing and other drugs if dyslipidemia or other risk factors persist.
Publisher: Elsevier BV
Date: 02-2009
Publisher: Oxford University Press (OUP)
Date: 22-10-2008
Abstract: Human chorionic gonadotrophin (hCG) is measured in serum and urine for the early detection of ectopic pregnancy, patients with higher risk of miscarriage, embryos or fetuses with chromosome abnormalities, prediction of pre-ecl sia or fetal growth restriction and identification or follow-up of trophoblast neoplasia. This review examines basic knowledge on the heterogeneity of hCG protein core and sugar branches and its relevance to assays used in a clinical setting. The databases Scielo and Medline/Pubmed were consulted for identification of the most relevant published papers. Search terms were gonadotrophin, glycoprotein structure, hCG structure and molecular forms of hCG. The synthesis of alpha (hCGalpha) and beta (hCGbeta) peptide chains and their further glycosylation involve the complex action of different enzymes. After assembly, hCG reaches the cell surface and is secreted as a bioactive heterodimer. The complex cascade of enzymes acting in hCG secretion results in heterogeneous molecular forms. The hCG molecules are differently metabolized by the liver, ovary and kidney, but the majority of hCG forms are excreted in the urine. Intact hCG, hCGalpha, hCGbeta, hyperglycosylated (hCGh), nicked (hCGn) and core fragment of hCGbeta (hCGbetacf) forms have relevant clinical use. The immunogenicity of each hCG variant, their epitopes distribution and the available antibodies are important for the development of specific assays. Depending on the prevalent form or proportion in relation to the intact hCG, the choice of assay for measurement of a specific molecule in a particular clinical setting is paramount. Measurement of hCG and/or its related molecules is useful in clinical practice, but greater awareness is needed worldwide regarding the use of new sensitive and specific assays tailored for different clinical applications.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.FERTNSTERT.2012.10.031
Abstract: To explore knowledge about the effects on fertility of age, obesity, smoking, and timing of intercourse among Australians of reproductive age. Telephone survey of a representative s le of Australians. Not applicable. Australians aged 18 to 45 years who wish to have a child or another child now or in the future. None. Knowledge about the effect on fertility of age, obesity, smoking, and timing of intercourse. A total of 462 interviews were conducted. The majority of respondents underestimated, by about 10 years, the age at which male and female fertility starts to decline. Only one in four correctly identified that female fertility starts to decline before age 35, and one in three identified that male fertility starts to decline before age 45. Most (59%) were aware that female obesity and smoking affect fertility, but fewer recognized that male obesity (30%) and smoking (36%) also influence fertility. Almost 40% of respondents had inadequate knowledge of when in the menstrual cycle a woman is most likely to conceive. Considerable knowledge gaps about modifiable factors that affect fertility were identified. These are targeted in a national education c aign to promote awareness of factors that influence fertility.
Publisher: Bioscientifica
Date: 03-2000
Abstract: The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine s les were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine s les collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.
Publisher: Proceedings of the National Academy of Sciences
Date: 20-07-1999
Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72% χ 2 = 12.97 nominal P = 3.2 × 10 −4 ). After correction for multiple testing (33 tests), the follistatin findings were still highly significant ( P c = 0.01). Although the linkage results for CYP11A were also nominally significant ( P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (χ 2 ≥ 3.84 nominal P 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region ( D19S884 allele 5 χ 2 = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0140-6736(03)14410-8
Abstract: Polycystic ovary syndrome is the most common cause of anovulatory infertility. It has long-term health implications and is an important risk factor for type 2 diabetes. However, little is known about the cause of polycystic ovaries. We have used detailed morphological analysis to assess the hypothesis that there is an intrinsic ovarian abnormality that affects the earliest stages of follicular development. We took small cortical biopsies during routine laparoscopy from 24 women with normal ovaries and regular cycles and from 32 women with polycystic ovaries, 16 of whom had regular, ovulatory cycles and 16 of whom had oligomenorrhoea. We used computerised image analysis to assess the density and developmental stage of small preantral follicles in serial sections of fixed tissue. Median density of small preantral follicles, including those at primordial and primary stages, was six-fold greater in biopsies from polycystic ovaries in anovulatory women than in normal ovaries (p=0.009). In both ovulatory and anovulatory women with polycystic ovaries, we noted a significant increase in the percentage of early growing (primary) follicles and a reciprocal decrease in the proportion of primordial follicles compared with normal ovaries. Our findings indicate that there are fundamental differences between polycystic and normal ovaries in early follicular development, suggesting an intrinsic ovarian abnormality. The increased density of small preantral follicles in polycystic ovaries could result from increased population of the fetal ovary by germ cells, or from decreased rate of loss of oocytes during late gestation, childhood, and puberty.
Publisher: Oxford University Press (OUP)
Date: 04-2000
DOI: 10.1095/BIOLREPROD62.4.1059
Abstract: To investigate the role of the ovarian macrophage population in ovulation, we examined the effect of depleting this population using liposome-encapsulated clodronate. Clodronate liposomes, saline liposomes, or saline alone was injected under the ovarian bursa in gonadotropin-primed adult mice, either 84 h (Day -3) or 36 h (Day -1) before ovulation. Ovulation rates were determined by counting the number of oocytes released. The numbers of graafian follicles and corpora lutea were also counted immediately before and after ovulation. Macrophage distribution within the theca and stroma of preovulatory ovaries was examined by immunohistochemistry with specific monoclonal antibodies to the macrophage antigens macrosialin, major histocompatability complex class II (Ia), and F4/80. Injection of clodronate liposomes on Day -1 did not affect ovulation rates, whereas administration on Day -3 caused a significant reduction in ovulation rate (mean oocytes ovulated = 5. 25 +/- 0.6 from clodronate liposome-treated ovaries and 9.13 +/- 0.9 from saline-treated ovaries, respectively, P < 0.05). The numbers of macrosialin-positive macrophages present in the theca at ovulation were reduced by treatment with clodronate liposomes on Day -1, and treatment on Day -3 reduced the numbers of Ia-positive and macrosialin-positive macrophages present in the theca. When the subsequent ovarian cycles were examined by vaginal smearing, the metestrous-2/diestrous stage was found to be extended in clodronate liposome-treated animals (7.5 +/- 1.3 days vs. 3.4 +/- 0.4 days for saline liposome-treated animals, P < 0.05). These results suggest that thecal macrophages may be involved in the regulation of follicular growth and rupture, as well as being important for the normal progression of the estrous cycle.
Publisher: Springer Science and Business Media LLC
Date: 04-06-2012
Publisher: AMPCo
Date: 2012
DOI: 10.5694/MJA11.10553
Abstract: To document the prevalence of polycystic ovary syndrome (PCOS) and its associated characteristics in a s le of urban Indigenous women. A cross-sectional survey of Indigenous women, including biochemical and anthropometric assessments. PCOS was assessed using the National Institutes of Health 1990 criteria. Indigenous women, aged 15-44 years, living in a defined area in and around Darwin, Northern Territory, Australia, September 2003-March 2005. Proportion of participants with PCOS overall and measures of obesity. Among 248 women eligible for assessment, the proportion who had PCOS was 15.3% (95% CI, 10.8%-19.8%). The proportion with PCOS was similar across age groups, but was significantly higher (P = 0.001) in women with a body mass index (BMI) of ≥ 30.0 kg/m(2) (30.5%) compared with women with a BMI of 25.0-29.9 kg/m(2) (8.2%) or a BMI of < 25.0 kg/m(2) (7.0%). A high proportion of these Indigenous women had PCOS. The significant relationship with obesity gives a strong rationale for screening for PCOS during routine care of Indigenous women who are obese and of reproductive age.
Publisher: Oxford University Press (OUP)
Date: 21-07-2005
Abstract: It has been argued that terminology in reproductive medicine related to reproductive success is ambiguous, confusing and misleading. A proposed solution is the conditional use of the term 'fertility' which is qualified according to statements concerning description, diagnosis and prognosis, and for which a grading system is proposed. We argue that there already exists (from 1989) a well-articulated conceptualization of fertility that does not appear to have been well disseminated within reproductive medicine. Within this conceptualization there is an important place for separate terms that clearly distinguish aetiology from outcome. We therefore see a central role for maintaining and articulating the terms fecundity and fertility. It is also suggested that one source of confusion within reproductive medicine stems from the conflation of interests for clinicians and patients when discussing infertility as both a cause and an outcome. Unpacking the meaning of the term 'infertility' reveals a complex of interdependent concepts that are both social and biological in origin.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.BPOBGYN.2006.09.005
Abstract: As assisted reproductive technology (ART) expanded globally, several countries introduced prescribed requirements for treatment and monitoring of outcomes, as well as a licensing or accreditation requirement. While it is common for ART laboratories to be required to have an effective quality control system, the remainder of the clinic is often under less stringent regulation. Furthermore, when treatment conditions are prescribed, the standards tend to be conservative and clinics may choose to establish their own standards. Total quality management systems are now being used by an increasing number of ART clinics. In Australia and New Zealand, it is now a requirement to have a quality management system in order to be accredited and to help meet customer demand for improved delivery of ART services in these two countries.
Publisher: Elsevier BV
Date: 02-2002
Publisher: Wiley
Date: 14-04-2010
Publisher: Elsevier BV
Date: 2006
Publisher: Humana Press
Date: 2007
Publisher: The Endocrine Society
Date: 04-1999
DOI: 10.1210/JC.84.4.1470
Publisher: Oxford University Press (OUP)
Date: 1996
Abstract: In recent years it has become evident that a leukocyte-cytokine network contributes to the paracrine regulation of ovarian function. The objectives of this study were to examine the presence of a potent lympho-haemopoietic cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), in tissues and fluids from human ovaries. In a prospective study, follicular fluid and plasma were collected from naturally cycling women and women undergoing hyperstimulation for in-vitro fertilization (IVF). Granulosa-lutein cells were collected at the time of oocyte recovery for IVF and corpora lutea were collected at the time of hysterectomy for non-ovarian reasons. Culture supernatants from ovarian cell and tissue cultures were harvested on completion of a 48 h incubation. Immunoactive GM-CSF was measured by enzyme-linked immunosorbent assay, and was found to be present at statistically significantly higher levels in follicular fluid (8.9 +/- 0.7 pg/ml) and plasma (11.3 +/- 0.8 pg/ml) of women undergoing hyperstimulation compared to follicular fluid (5.3 +/- 0.3 pg/ml) and plasma (7.1 +/- 0.5 pg/ml) from naturally cycling women. Immunoactive GM-CSF was also detected in culture supernatants of granulosa-lutein cells (47.6 pg/10(5) cells), early luteal phase corpora lutea (0.52 pg/microgram DNA) and mid-luteal phase corpora lutea (0.98 pg/microgram DNA). Furthermore, transcripts for GM-CSF, and both the alpha and beta subunits of the GM-CSF receptor, were detected by reverse transcription polymerase chain reaction (RT-PCR) in granulosa-lutein cell culture preparations and corpora lutea collected during the early, mid- and late luteal phase of the menstrual cycle. These results show that GM-CSF is expressed and secreted by cells within the human ovary, and, together with the finding of expression of mRNA for GM-CSF receptor, suggest a role for GM-CSF in the local regulation of ovarian events.
Publisher: Wiley
Date: 07-1985
DOI: 10.1111/J.1365-2265.1985.TB00179.X
Abstract: The pattern of secretion of human chorionic gonadotrophin (hCG) and its subunits in male subjects with tumours of the genital tract was examined by gel filtration, radioimmunoassay, immunoradiometric assay, bioassay and binding to Concanavalin A. The predominant form of hCG was the intact molecule but all patients had increased levels of free beta subunit. The intact hCG was active in a mouse Leydig cell bioassay and was normally glycosylated. High concentrations of free alpha subunit were not found and the ratio of alpha subunit: beta subunit was less than that in normal pregnancy. It is concluded that hCG-secreting tumours of the male genital tract are similar to choriocarcinoma in the female in that large quantities of intact hormone are produced with a disproportionate increase in free beta sub-unit.
Publisher: Wiley
Date: 31-10-2013
Publisher: Oxford University Press (OUP)
Date: 06-1998
Abstract: Obesity affects ovulation, response to fertility treatment, pregnancy rates and outcome. In this prospective study, a weight loss programme was assessed to determine whether it could help obese infertile women, irrespective of their infertility diagnosis, to achieve a viable pregnancy, ideally without further medical intervention. The subjects underwent a weekly programme aimed at lifestyle changes in relation to exercise and diet for 6 months those that did not complete the 6 months were treated as a comparison group. Women in the study lost an average of 10.2 kg/m2, with 60 of the 67 anovulatory subjects resuming spontaneous ovulation, 52 achieving a pregnancy (18 spontaneously) and 45 a live birth. The miscarriage rate was 18%, compared to 75% for the same women prior to the programme. Psychometric measurements also improved. None of these changes occurred in the comparison group. The cost savings of the programme were considerable. Prior to the programme, the 67 women had had treatment costing a total of A$550,000 for two live births, a cost of A$275,000 per baby. After the programme, the same women had treatment costing a total of A$210,000 for 45 babies, a cost of A$4600 per baby. Thus weight loss should be considered as a first option for women who are infertile and overweight.
Publisher: Oxford University Press (OUP)
Date: 27-09-2023
Publisher: Springer Science and Business Media LLC
Date: 11-2003
DOI: 10.1007/S00421-003-0889-0
Abstract: The purpose of the present study was to compare exercise status during the follicular (FP) and luteal (LP) phases of the menstrual cycle of a single group of young, sedentary women, where the marked differential in the blood concentrations of 17beta-oestradiol ([E(2)]) and progesterone ([P(4)]) has the potential to alter the metabolic response to exercise. Fourteen females [21.8 (4.0) years, peak oxygen uptake ( VO(2peak)) <45 ml x kg (-1) x min(-1)] performed both incremental exercise to exhaustion and steady-state submaximal cycle ergometer exercise while measurements were made of several metabolic and hormonal variables. With the incremental exercise test, time to exhaustion, maximal power output and total work done were not different between the two phases, nor were the absolute values for VO(2peak) or the corresponding values for ventilation ( VE), respiratory frequency ( f(R)) and heart rate (HR). Resting, end-exercise and peak (post-exercise) plasma lactate concentrations and the lactate threshold were not different between the two phases either. However, as the workloads increased during the incremental protocol, plasma lactate concentration, carbon dioxide output ( VCO(2)) and the respiratory exchange ratio (RER) all were lower during LP, while oxygen uptake ( VO(2)) was higher. With steady-state submaximal exercise, at workloads corresponding to 25% and 75% of menstrual cycle phase-specific VO(2peak), VO(2) and the oxygen pulse ( VO(2)/HR) were higher and RER and plasma lactate concentration lower during LP. Regardless of phase, [E(2)] increased with both incremental and steady-state submaximal exercise, while [P(4)] was unchanged. It is concluded that while exercise capacity, as defined by VO(2peak) and the lactate threshold, is unaffected by cycle phase in young, sedentary women, the metabolic responses in the LP during both incremental and steady-state submaximal exercise suggest a greater dependence on fat as an energy source.
Publisher: Oxford University Press (OUP)
Date: 10-2012
DOI: 10.1095/BIOLREPROD.111.096271
Abstract: While formation of the expanded cumulus matrix and its importance for oocyte maturation and ovulation are well described, its function in these processes remains unknown. The degree of expansion and expression of cumulus matrix genes are positively correlated with oocyte quality, suggesting that this matrix plays a key role in oocyte maturation. Based on recognized filtration properties of analogous matrices, we investigated whether the cumulus matrix acts as a molecular filter by assessing diffusion of fluorescently labeled dextrans (neutral and negatively charged) and hydrophilic (glucose) and hydrophobic (cholesterol) metabolites in cumulus oocyte complexes (COCs). Expanded in vivo-matured COCs resisted absorption of glucose and cholesterol compared to unexpanded COCs. In vitro-matured (IVM) COCs have a pronounced deficiency in cumulus matrix proteins and have poor oocyte quality. Here we demonstrate that IVM cumulus matrix has deficient filtration properties, with dextran and glucose and cholesterol molecules diffusing more readily into IVM than in vivo-matured COCs. Taking the inverse approach, we found that prostaglandin E2 (PGE2), synthesized by cumulus cells, is retained within the matrix of in vivo-matured COCs but IVM COCs have reduced capacity to retain PGE2, secreting significantly more into the medium. This is the first demonstration of a biophysical property of the cumulus matrix. The ability to regulate metabolite supply from the surrounding environment while sequestering vital signaling factors, such as PGE2, is likely to impact oocyte maturation. Thus, IVM may reduce oocyte quality due to dysregulated control of metabolites and signaling molecules.
Publisher: The Endocrine Society
Date: 07-2007
DOI: 10.1210/EN.2006-1383
Abstract: There is increasing evidence that epidermal growth factor (EGF) receptor (EGFR) ligand and Kit ligand (KL) play critical roles in controlling follicular development in mammals. Because little is known about their expressions in the ovary of nonmammalian vertebrate, our study aimed to examine the expression, hormonal regulation, and interaction of HB-EGF and KL in the chicken ovary. Using semiquantitative RT-PCR, we demonstrated that ovarian HB-EGF expression increased dramatically with the posthatching ovarian growth. In line with this finding, HB-EGF was shown to be produced primarily by the growing oocytes and capable of stimulating the proliferation of granulosa cells in prehierarchal (3 mm) and preovulatory follicles (F5 and F1). Although HB-EGF expression is mainly restricted to the oocytes, its expression in cultured granulosa cells could be transiently yet strongly induced by HB-EGF and other EGFR ligands including EGF and TGF-α. And the inducing effect of HB-EGF was completely abolished by AG1478 (10 μm) or PD98059 (100 μm), indicating that the action of HB-EGF is mediated by EGFR and intracellular MAPK/ERK signaling pathway. Unlike mammals, only KL-1, not the other three isoforms identified (KL-2, -3, and -4), was detected to be predominantly expressed in the chicken ovary. Interestingly, KL expression in undifferentiated and differentiated granulosa cells could be transiently down-regulated by HB-EGF, implying an intrafollicular communication between growing oocyte and surrounding granulosa cells through the interplay of EGFR ligand and KL. Collectively, our data suggest that HB-EGF is likely a paracrine signal from the oocyte to regulate granulosa cell proliferation and HB-EGF and KL expression during ovarian follicular development.
Publisher: Oxford University Press (OUP)
Date: 22-10-2008
Abstract: Women of reproductive age, who are overweight or obese, are prone to infertility. Weight loss in these women leads to increased fecundity, higher chances of conception after infertility treatment and improved pregnancy outcome. In spite of the advantages, most patients have difficulty in losing weight and often regain lost weight over time. This review assesses whether treatment with insulin sensitizing drugs contributes to weight loss, compared with diet or a lifestyle modification programme. After a systematic search of the literature, only randomized controlled trials (RCTs), investigating the effect of insulin sensitizing drugs on weight loss compared with placebo and diet and/or a lifestyle modification programme, were included. Subjects were restricted to women of reproductive age. The main outcome measure was change in body mass index (BMI). Only 14 trials, unintentionally all but two on women with polycystic ovary syndrome (PCOS) only, were included in the analysis. Treatment with metformin showed a statistically significant decrease in BMI compared with placebo (weighted mean difference, -0.68 95% CI -1.13 to -0.24). There was some indication of greater effect with high-dose metformin (>1500 mg/day) and longer duration of therapy (>8 weeks). Limitations were power, low use of intention-to-treat analysis and heterogeneity of the studies. A structured lifestyle modification programme to achieve weight loss should still be the first line treatment in obese women with or without PCOS. Adequately powered RCTs are required to confirm the findings of this review and to assess whether the addition of high-dose metformin therapy to a structured lifestyle modification programme might contribute to more weight loss.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.JADA.2009.08.008
Abstract: This study aimed to investigate the effects of prescriptive lifestyle advice with quantifiable dietary and physical goals compared to general lifestyle advice on weight and psychological outcomes in young women with overweight or obesity. A total of 203 women (body mass index 33.3+/-0.3, age 28+/-0.3 years) received either prescriptive or general lifestyle advice for weight loss over 12 weeks. Linear mixed models found that the prescriptive lifestyle advice group had significantly greater weight loss (4.2+/-0.4 kg vs 0.6+/-0.2 kg, P<0.001) compared to the general lifestyle advice group. However, the prescriptive lifestyle advice group also had greater attrition (48% vs 31%, P<0.05) compared to the general lifestyle advice group. Linear mixed models found that the prescriptive lifestyle advice group had greater improvement in psychological distress (-3.0+/-0.04 vs -1.1+/-0.01, P<0.05) and in self-esteem (3.2+/-0.8 vs -0.04+/-0.04, P<0.001) compared to the general lifestyle advice group. Changes in psychological distress and self-esteem remained significantly different between groups after correcting for weight loss. Food cravings decreased significantly over time without group differences (P 0.05). Drop-outs had greater baseline psychological distress (15.1+/-0.7 vs 12.5+/-0.4, P<0.01) and higher food cravings (2.42+/-0.07 vs 2.24+/-0.05, P=0.049) compared to completers. In conclusion, a prescriptive approach is associated with greater weight loss and greater improvements in psychological outcomes in young women compared to general lifestyle advice. However, these quantitative targets should be accompanied with qualitative advice on how they could be met in a variety of circumstances.
Publisher: Elsevier BV
Date: 07-2009
Publisher: BMJ
Date: 09-03-2006
Publisher: Elsevier BV
Date: 08-2023
Publisher: Wiley
Date: 03-1984
DOI: 10.1111/J.1471-0528.1984.TB04760.X
Abstract: A prospective study of 54 primigravid twin pregnancies in Durban showed that pregnancy-induced hypertension occurred in 37%. This was more than twice the expected rate for singleton pregnancies in this Black African population. The babies born in the group of patients with pregnancy-induced hypertension were significantly lighter and had a higher rate of fetal growth retardation than the babies born in a normotensive control group of patients matched for age and parity. Monozygotic twins, identified by HLA typing, occurred significantly more often in the group with pregnancy-induced hypertension than in the control group. A possible immunological explanation for this finding is presented.
Publisher: Informa UK Limited
Date: 1999
DOI: 10.3109/13697139909025578
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine condition of premenopausal women and has significant metabolic abnormalities that could have an impact after the menopause. Diabetes mellitus, hyperlipidemia and hyperinsulinemia could potentially affect health in this era of life. Endometrial cancer, due to unopposed estrogen action, is more common where progestins have not been given for menstrual dysfunction. Preventive management earlier in life will avoid postmenopausal problems in PCOS.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.RBMO.2017.11.009
Abstract: Bisphenol A (BPA) is a ubiquitous chemical suspected to possess oestrogenic hormonal activities. Male population studies suggest a negative impact on testicular function. As Sertoli cell proliferation occurs during fetal or early postnatal life, it is speculated that oestrogenic environmental exposures may influence mature testicular function. Among 705 Western Australian Pregnancy Cohort (Raine) Study men aged 20-22 years, 404 underwent testicular ultrasound examination (149 had maternal serum available), and/or 365 provided semen (136 had maternal serum) and/or 609 serum s les for sex steroids, gonadotrophins and inhibin B analysis (244 had maternal serum). Maternal serum collected at 18 and 34 weeks' gestation was pooled and assayed for concentrations of total BPA (free plus conjugated) as an estimate of antenatal exposure. Testicular volume was calculated by ultrasonography, and semen analysis performed. Serum LH, FSH and inhibin B were measured by immunoassay testosterone, oestradiol, oestrone andBPA were measured by liquid chromatography-mass spectrometry. BPA levels were detectable in most (89%) maternal serum s les. After adjustment for maternal smoking, abstinence and varicocele, sperm concentration and motility were significantly correlated to maternal serum BPA (r = 0.18 P = 0.04 for both). No other associations of maternal serum BPA with testicular function were observed.
Publisher: Oxford University Press (OUP)
Date: 18-12-2012
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.TEM.2012.07.001
Abstract: Though widely used, there is uncertainty about the effectiveness and adverse effects of metformin and clomiphene citrate (CC) for infertility in polycystic ovary syndrome (PCOS). A systematic review (SR) of the best available evidence suggests that both CC and metformin are better than placebo for increasing ovulation and pregnancy rates, but CC is more effective than metformin for ovulation, pregnancy and live-birth rates, in PCOS patients with body mass index (BMI) >30. A combination of CC and metformin is superior to either metformin alone or CC alone, depending on the BMI and CC sensitivity of the patient. This SR provides key messages to guide clinicians and consumers on the use of these interventions in different subgroups of women with PCOS.
Publisher: Oxford University Press (OUP)
Date: 09-2001
Abstract: Cross-sectional studies have shown a high frequency of impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus (NIDDM) in women with polycystic ovarian syndrome (PCOS). However, little is known about the change in glucose tolerance that occurs over a period of several years in women with PCOS. Sixty-seven women with PCOS received a 75 g glucose tolerance test and measurement of lipids at baseline and at follow-up after an average time of 6.2 years. All women followed prospectively had normal glucose tolerance (n = 54) or IGT (n = 13) at the start of the study. Change in glycaemic control from baseline was frequent, with 5/54 (9%) of normoglycaemic women at baseline developing IGT and a further 4/54 (8%) moving directly from normoglycaemic to NIDDM. For women with IGT at baseline, 7/13 (54%) had NIDDM at follow-up. Body mass index (BMI) at baseline was an independent significant predictor of adverse change in glycaemic control. Women with PCOS, particularly those with a high BMI, should be reviewed regularly with respect to IGT or NIDDM, as the frequency of impaired glycaemic control is high, and that the rate of conversion from normal glucose tolerance to IGT or NIDDM, or from IGT to NIDDM is substantial.
Publisher: The Endocrine Society
Date: 09-2008
DOI: 10.1210/JC.2008-0751
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/RD10091
Abstract: Lipid droplet proteins regulate the storage and utilisation of intracellular lipids. Evidence is emerging that oocyte lipid utilisation impacts embryo development, but lipid droplet proteins have not been studied in oocytes. The aim of the present study was to characterise the size and localisation of lipid droplets in mouse oocytes during the periovulatory period and to identify lipid droplet proteins as potential biomarkers of oocyte lipid content. Oocyte lipid droplets, visualised using a novel method of staining cumulus–oocyte complexes (COCs) with BODIPY 493/503, were small and diffuse in oocytes of preovulatory COCs, but larger and more centrally located after maturation in response to ovulatory human chorionic gonadotrophin (hCG) in vivo, or FSH + epidermal growth factor in vitro. Lipid droplet proteins Perilipin, Perilipin-2, cell death-inducing DNA fragmentation factor 45-like effector (CIDE)-A and CIDE-B were detected in the mouse ovary by immunohistochemistry, but only Perilipin-2 was associated with lipid droplets in the oocyte. In COCs, Perilipin-2 mRNA and protein increased in response to ovulatory hCG. IVM failed to induce Perilipin-2 mRNA, yet oocyte lipid content was increased in this context, indicating that Perilipin-2 is not necessarily reflective of relative oocyte lipid content. Thus, Perilipin-2 is a lipid droplet protein in oocytes and its induction in the COC concurrent with dynamic reorganisation of lipid droplets suggests marked changes in lipid utilisation during oocyte maturation.
Publisher: CSIRO Publishing
Date: 1998
DOI: 10.1071/R98010
Abstract: Obesity has significant consequences for the reproductive system, depending upon the amount and distribution of body fat. Epidemiological evidence clearly shows that being overweight contributes to menstrual disorders, infertility, miscarriage, poor pregnancy outcome, impaired fetal well-being and diabetes mellitus. Central adiposity is particularly important in clinical sequelae associated with an increased body mass index. The advent of assisted reproduction highlights the problems of being overweight, and the use of gonadotrophins in ovulation induction and in vitro fertilization is more difficult when the subject is overweight. Weight loss has marked effects on improving the menstrual cycle and promoting spontaneous ovulation and fertility. Results indicate that fertility is improved through exercise and sensible eating patterns when conducted in a group environment. The mechanisms for this are unclear but may be associated with changes in sensitivity to insulin.
Publisher: Rockefeller University Press
Date: 07-1991
DOI: 10.1084/JEM.174.1.63
Abstract: The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.
Publisher: Oxford University Press (OUP)
Date: 03-2008
DOI: 10.1111/J.1743-6109.2007.00726.X
Abstract: There are some data to suggest that tibolone improves sexual function in postmenopausal women. However, evidence about the effects of tibolone on female sexual dysfunction is lacking. To compare the efficacy on sexual function of tibolone 2.5 mg to continuous combined transdermal estradiol (E2)/norethisterone acetate (NETA) (50 microg/140 microg) in naturally postmenopausal women with sexual dysfunction. Differences between treatment groups in the change from baseline for the composite subscore of the arousal, desire, and satisfaction domains of the self-reported Female Sexual Function Index (FSFI). A multicenter, double-blind, randomized, clinical trial was performed. Sexual function was assessed with the FSFI at baseline, week 12, and week 24. The outcomes of the Female Sexual Distress Scale (FSDS) and the frequency of satisfying sexual events (daily diaries) were secondary end points. Four hundred three women, mean age 56, were included. Both therapies improved sexual function assessed by the FSFI. In the per protocol analysis, but not in the intent-to-treat analysis, the increase in FSFI scores was significantly larger in the tibolone group when compared with the E2/NETA patch group at week 24 (P = 0.036 and P = 0.025 for the composite subscore and total FSFI score, respectively). The satisfying sexual event rate increased from three to four times per 28 days at week 24 (P < 0.001 from baseline for both groups), with no difference between groups. The FSDS showed a significant decrease from baseline (P < 0.001), which was comparable for both treatment groups. Both treatments resulted to improved overall sexual function, as determined by scores on the FSFI, an increase in the frequency of sexual events, and a reduction in sexuality-related personal distress. The statistically significant higher FSFI scores in the tibolone group, when compared to the E2/NETA group, may be because of tibolone's combined estrogenic and androgenic properties.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.YDBIO.2007.03.006
Abstract: It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.FERTNSTERT.2008.12.003
Abstract: To determine the effects of weight loss on heart rate recovery (HRR) in overweight women with polycystic ovary syndrome (PCOS). A 10-week prospective clinical intervention. Clinical research unit. Fifty-seven overweight and obese women with PCOS (age: 29.8 +/- 0.8 years body mass index [BMI] 36.2 +/- 0.7 kg/m(2)). A dietary plan of 5-6 MJ/day ( approximately 30% energy restricted). Heart rate recovery (defined as the reduction in heart rate after 1 minute from peak heart rate after a graded treadmill test to exhaustion), weight, waist circumference, blood pressure, glucose, insulin, homeostasis model assessment of insulin resistance, and sex steroids before and after the intervention. The mean percentage of weight loss was (-6.7 +/- 0.4%). There were significant reductions in waist circumference (-6.9 +/- 0.6 cm), blood pressure (-4.9/-2.5 +/- 1.2/1.2 mm Hg), fasting insulin (-3.4 +/- 0.7 mU/L), fasting glucose (-0.17 +/- 0.05 mmol/L), homeostasis model assessment of insulin resistance (-0.43 +/- 0.09), T (-0.38 +/- 0.07 nmol/L), free androgen index (-2.86 +/- 0.58), and an increase in sex hormone-binding globulin [SHBG] (5.86 +/- 1.12 nmol/L). The HRR improved from 30.9 +/- 1.1 to 38.0 +/- 1.1 beats/min and that was related to the reduction in body weight (r = -0.34) and waist circumference (r = -0.27). Weight loss in overweight and obese women with PCOS is associated with improvements in HRR, which suggests improved autonomic function. This highlights the importance of weight loss to reduce the cardiovascular disease risk in these women.
Publisher: Oxford University Press (OUP)
Date: 04-2001
Abstract: Familial polycystic ovarian syndrome (PCOS) has been proposed to be linked to a site near the follistatin gene. We studied the concentrations of circulating follistatin, activin A and inhibin B in well-characterized subjects with PCOS (n = 108) and controls without PCOS (n = 20). Mean (+/- SEM) concentrations of follistatin were higher (P < 0.05) in PCOS (0.27 +/- 0.03 ng/ml) than controls (0.15 +/- 0.02 ng/ml) and activin A were lower (P < 0.05) in PCOS (0.20 +/- 0.01ng/ml) than controls (0.24 +/- 0.02 ng/ml). Inhibin B concentrations were not different between the two groups: PCOS (0.06 +/- 0.01ng/ml), and controls (0.06 +/- 0.01ng/ml). It is proposed that higher concentrations of follistatin with lower concentrations of activin A may relate to follicular development not proceeding beyond 8-10 mm and may be partly responsible for the lack of pre-ovular follicle development in PCOS.
Publisher: Oxford University Press (OUP)
Date: 02-04-2008
Abstract: Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility and menstrual cycle abnormalities, but the factors responsible for failure to select a dominant follicle remain unclear. Source is authors' own studies and search of the relevant literature. Arrest of antral follicle growth is associated with an abnormal endocrine environment involving hypersecretion of luteinizing hormone and insulin (and perhaps hyperandrogenism). The net effect is secondary suppression of FSH, which leads to inhibition of maturation of otherwise healthy follicles in the cohort. There is, however, emerging evidence for an intrinsic abnormality of folliculogenesis in PCOS that affects the very earliest, gonadotrophin independent, stages of follicle development. There is an increased density of small pre-antral follicles and an increased proportion of early growing follicles. These abnormalities in anovulatory PCOS are further defined by abnormal granulosa cell proliferation and disparate growth of oocyte and surrounding granulosa cells. This suggests that the normal 'dialogue' between oocyte and granulosa cells in these early growing follicles is altered. There is evidence that abnormal, local (follicle-to-follicle) signalling of anti-Müllerian hormone may play a part in disordered folliculogenesis, but it is plausible that other local regulators that have been implicated in normal and abnormal pre-antral follicle development-such as insulin-like growth factors and sex steroids-have a role in aberrant folliculogenesis in PCOS. Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.FERTNSTERT.2005.12.041
Abstract: A low-calorie diet in a group of overweight or obese patients for a short period before and during IVF results in variable tolerance to the dietary regime and an unsatisfactory IVF outcome.
Publisher: John Wiley & Sons, Ltd
Date: 20-01-2010
Publisher: Elsevier BV
Date: 03-1981
DOI: 10.1016/0161-4630(81)90154-3
Abstract: Umbilical venous plasma and amniotic fluid concentrations of prostaglandins E2 (PGE), F2 alpha (PGF) and 13,14 dihydro-15-keto-F2 alpha (PGFM) were measured in 31 twin pregnancies by specific radioimmunoassays. There was no significant difference between twins I and II in the same pregnancy but PGE and PGFM were significantly increased during labour in fetal blood. This rise was not manifest in the latent phase. PG concentration in amniotic fluid rose with advancing gestational age but was more pronounced in the case of PGE than for PGF and PGFM. No significant differences between amniotic sac concentrations of PGs of twin I and II were found during the prelabour period, but in all four patients in labour with intact membranes, the PG levels were increased in twin I. The fetal plasma and amniotic fluid levels of PGE and PGFM were significantly correlated in the prelabour group.
Publisher: Informa UK Limited
Date: 1986
Publisher: Wiley
Date: 16-05-2012
Publisher: John Wiley & Sons, Ltd
Date: 08-07-2009
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.ATHEROSCLEROSIS.2008.09.010
Abstract: Platelet hyporesponsiveness to the anti-aggregatory effects of nitric oxide (NO) occurs commonly in association with myocardial ischemia and coronary risk factors, often co-exists with endothelial dysfunction and represents an independent marker of long-term cardiovascular risk. We sought to determine whether polycystic ovary syndrome (PCOS), which has been postulated as a cardiovascular risk factor in women, is independently associated with this phenomenon. Twenty-four young women with PCOS (mean age 32.1+/-1.3) were evaluated in lean (n=12) and obese (n=12) subgroups, and compared with age-matched lean normals (n=12). Platelet aggregation and its inhibition by the nitric oxide donor sodium nitroprusside (SNP) were assessed and compared with vascular endothelial function. Plasma concentrations of malondialdehyde (MDA), N(G),N(G)-dimethyl-L-arginine (ADMA) and hs-CRP were measured as markers of oxidative stress, endothelial dysfunction and inflammation, respectively. Circulating endothelial progenitor cell (EPC) counts were also documented. In both PCOS subgroups, which demonstrated hyperaggregability to ADP, responses to SNP inhibition of aggregation (the principal end-point of the study) were significantly impaired (P<0.01 for both), as were their endothelium-dependent vascular responses to salbutamol (P<0.05 for both). However, vasomotor responses to nitroglycerin and circulating EPC counts did not vary between groups. PCOS subjects also had significantly elevated ADMA, MDA and hs-CRP levels relative to normals (all P<0.05). Impairment of SNP response remained unaltered after mean 30+/-2.4 months follow-up in PCOS subjects. We conclude that in PCOS subjects, independent of obesity and associated insulin resistance, profound and reproducible impairment of platelet responsiveness to NO is an additional component of cardiovascular homeostatic disturbance.
Publisher: John Wiley & Sons, Ltd
Date: 07-10-2009
Publisher: Elsevier BV
Date: 09-2010
Publisher: Wiley
Date: 02-1988
DOI: 10.1111/J.1471-0528.1988.TB06850.X
Abstract: It is generally accepted that in adult type 1 diabetes patients (T1D) continuous subcutaneous insulin infusion (CSII) via a personal pump is more effective than the multiple daily injections (MDI) model. However, it is not clear whether all age groups of adult T1D patients may equally benefit from CSII therapy. We aimed to compare the glycemic control and use of selected pump tools in T1D subjects using CSII over the age of 50 (50+ T1D) with patients younger than 50 years of age. The last available insulin pump/blood glucose meter downloads and last available HbA1c levels of 124 adult T1D subjects using CSII were reviewed. We ided our cohort into two subgroups: 50+ T1D patients (n = 13) and younger patients (n = 111). There were no differences in glycemic control achieved with CSII treatment in 50+ T1D patients vs. younger subjects. HbA1c levels were 7.01 ± 0.67% and 7.34 ± 1.24% (p = 0.46), and the mean glycemia based on glucometer downloads was 141.8 ± 17.7 mg/dl and 150.8 ± 35.7 mg/dl (p = 0.69), respectively. Also, there were no differences with respect to the use of important personal pump options and tools. In conclusion, insulin pump therapy appears to be effective and safe in T1D patients regardless of age.
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.APPET.2007.03.222
Abstract: This study compared the psychological effects of a low-protein high-carbohydrate (LPHC) diet and a high-protein low-carbohydrate (HPLC) diet in women with polycystic ovary syndrome (PCOS). Twenty-five overweight women with PCOS were matched for age, weight, and whether they were trying to conceive. They were randomly allocated to the LPHC or HPLC diet for 16 weeks. All participants attended a weekly exercise, group support and educational program. The Hospital Anxiety and Depression Scale and the Rosenberg Self Esteem Scale were administered at the beginning and end of the study. The HPLC diet was associated with significant reduction in depression and improvement in self-esteem. There was no change in any psychological measures for the LPHC group. There was no difference in weight loss between the groups. Due to enhanced feelings of well-being, it is possible that HPLC diets may be associated with better compliance and hence be more successful in the long term treatment of obesity.
Publisher: Oxford University Press (OUP)
Date: 02-05-2012
Abstract: Women with polycystic ovary syndrome (PCOS) present with vascular abnormalities, including elevated markers of endothelial dysfunction. There is limited evidence for the effect of lifestyle modification and weight loss on these markers. The aim of this study was to determine if 20 weeks of a high-protein energy-restricted diet with or without exercise in women with PCOS could improve endothelial function. This is a secondary analysis of a subset of 50 overweight/obese women with PCOS (age: 30.3 ± 6.3 years BMI: 36.5 ± 5.7 kg/m(2)) from a previous study. Participants were randomly assigned by computer generation to one of three 20-week interventions: diet only (DO n = 14, ≈ 6000 kJ/day), diet and aerobic exercise (DA n = 16, ≈ 6000 kJ/day and five walking sessions/week) and diet and combined aerobic-resistance exercise (DC n = 20, ≈ 6000 kJ/day, three walking and two strength sessions/week). At Weeks 0 and 20, weight, markers of endothelial function [vascular cell adhesion molecule-1 (sVCAM-1), inter-cellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1) and asymmetric dimethylarginine (ADMA)], insulin resistance and hormonal profile were assessed. All three treatments resulted in significant weight loss (DO 7.9 ± 1.2%, DA 11.0 ± 1.6%, DC 8.8 ± 1.1 P < 0.001 for time P = 0.6 time × treatment). sVCAM-1, sICAM-1 and PAI-1 levels decreased with weight loss (P≤ 0.01), with no differences between treatments (P ≥ 0.4). ADMA levels did not change significantly (P = 0.06). Testosterone, sex hormone-binding globulin and the free androgen index (FAI) and insulin resistance also improved (P < 0.001) with no differences between treatments (P ≥ 0.2). Reductions in sVCAM-1 were correlated to reductions in testosterone (r = 0.32, P = 0.03) and FAI (r = 0.33, P = 0.02) as well as weight loss (r= 0.44, P = 0.002). Weight loss was also associated with reductions in sICAM-1 (r= 0.37, P = 0.008). Exercise training provided no additional benefit to following a high-protein, hypocaloric diet on markers of endothelial function in overweight/obese women with PCOS.
Publisher: BMJ
Date: 25-10-2003
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.FERTNSTERT.2018.05.029
Abstract: Most expert opinions and guidelines indicate the necessity for weight loss before in vitro fertilization (IVF) in women who are overweight or obese. This is based on the documented impact of obesity on pregnancy rates and pregnancy complications and the long-term impact on the child in natural conceptions. Some clinicians and authorities refuse to treat patients unless they are below a certain body mass index. In the past this advice has been hindered by a lack of opportunity for patients to join lifestyle programs and the high dropout failure before treatment. However, the ideal has remained in the search for effective methods for weight loss. New clinical trials have evaluated a lifestyle program before IVF treatment and compared the results with those who were merely given advice and allowed to proceed directly to other fertility treatments or IVF. No compelling evidence of the value of lifestyle intervention for weight loss on live-birth rates was gained from these well-conducted studies. The research and medical and ethical opinions may now favor moving to fertility treatment earlier than originally recommended for patients who are overweight or obese.
Publisher: Oxford University Press (OUP)
Date: 26-03-2018
Abstract: Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. CRD42017056524.
Publisher: Informa UK Limited
Date: 10-1986
Publisher: Elsevier BV
Date: 08-2022
Publisher: Bioscientifica
Date: 1997
Abstract: Interleukin-1 (IL-1) is a multifunctional cytokine with profound effects on ovarian function. The effects of IL-1 on ovarian steroidogenesis have been demonstrated in several species. IL-1 mRNA levels are increased in the thecal layer of the ovulating follicle and IL-1β has been shown to induce ovulations in vitro . In this study we have investigated the presence and distribution of the mRNAs for type I IL-1 receptor (IL-1RtI) and for the naturally occurring IL-1 receptor antagonist (IL-1ra) in ovaries of adult cycling rats, to elucidate the target cells for IL-1 action. We have demonstrated the presence of mRNA for both substances by in situ hybridisation and reverse transcription PCR. mRNA for IL-1RtI was not found in primordial follicles but was abundant in the granulosa and thecal layer in developing follicles with stronger signals in the granulosa layer. In the preovulatory and ovulatory follicles, there was a further increase in the signal for IL-1RtI mRNA in the thecal layer compared with the granulosa layer. Corpora lutea were weakly positive at all stages and atretic follicles were largely negative. No mRNA was detected in oocytes of any stage. mRNA for IL-1ra showed a similar distribution to that of IL-1RtI. The changes in distribution suggest an action of IL-1 on rat granulosa cells during follicular development and on thecal cells during ovulation. Journal of Endocrinology (1997) 152, 11–17
Publisher: Wiley
Date: 28-07-2004
Publisher: Elsevier BV
Date: 07-2009
Publisher: Oxford University Press (OUP)
Date: 08-2009
DOI: 10.1373/CLINCHEM.2009.124578
Abstract: Background: The 1st WHO International Reference Reagents (IRRs) for 6 human chorionic gonadotropin (hCG)-related molecular variants, highly purified and calibrated in substance concentrations by the IFCC Working Group for hCG, permit experimental elucidation of what commercially available hCG methods measure in molar terms and enable assessment of their fitness for clinical purposes. Methods: Pools containing known amounts of the IRRs spiked into normal human serum were issued to participants through the UK National External Quality Assessment Service for hCG for a period of 7 years. Among 16 assays used, 4 recognized only hCG, whereas 6 recognized hCG and its free β-subunit (hCGβ), and 6 recognized hCG, hCGβ, and the beta core fragment. Results: Differences in calibration of current hCG assays are moderate. Mean recovery of the current International Standard (IS), hCG IS 75/589, was 107% (range 93% to 126%), whereas that of the IRR 99/688 for hCG was 139% (range 109%–164%). Between-method variation for the latter (CV 12.3%) was also greater than for IS 75/589 (CV 8.8%). Recognition of hCGβ varied markedly (CV 37%). Most assays overestimated it, but 2 RIAs produced results that were slight underestimations. Recognition of the beta core fragment was even more variable (CV 57%) and was closest to equimolarity for the RIAs. Conclusions: Assays for hCG show considerable variation in their recognition of various forms of hCG, and this variablility is the most important cause of method-related differences in hCG results in serum and an even more important cause of method-related differences in urine measurements. Equimolar recognition of the major hCG isoforms is essential if between-method comparability for hCG is to be improved.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/S1472-6483(10)60384-7
Abstract: The aim of this study was to identify factors that inhibit or promote the adoption of single embryo transfer (SET). A cohort of 163 women patients receiving IVF/intracytoplasmic sperm injection treatment, comprising 87 women choosing SET and 63 women choosing double embryo transfer (DET), were interviewed using a structured questionnaire. The data were compared using logistic regression analysis. Confidence in the chance of pregnancy with SET, younger age and first treatment were predictive of a decision for SET. Preference for a healthy and singleton pregnancy was predictive but perceptions of the incidence or risk of multiple gestation were not. Factors such as a sense of time urgency and past experience of treatment were significant and predictive of diminished choice of SET. The clinic doctor was an important influencing factor. The results of this study confirm that improved pregnancy rates in SET coupled with an official clinic policy to promote SET in younger, first cycle patients influenced many women to choose SET. However, repeated treatment, advancing age and urgency to become pregnant are factors that moderate a woman's choice for SET.
Publisher: Elsevier BV
Date: 06-1990
DOI: 10.1016/0090-6980(90)90021-M
Abstract: Prostaglandin E2 (PGE) and F2 alpha (PGF) release by the intact fetal membranes is described using a novel superfusion technique allowing for the independent assessment of prostaglandin release from the amnion and chorio-decidua whilst maintaining the anatomical integrity of the fetal membranes. The effect of labour on prostaglandin release is described. Using this system it was confirmed that the amnion is a major site of prostaglandin release and possibly production. Labour resulted in a significant increase of both PGE and PGF release from the amnion side only (Pre-labour: PGE 918 pg/cm2/3h, PGF 370 pg/cm2/3h Labour: PGE 2993 pg/cm2/3h, PGF 662 pg/cm2/3h). No change in either PGE or PGF release from the chorio-decidual side was observed in relation to labour. In addition a change in the pattern of prostaglandin release from the amnion was observed in tissues obtained after the onset of labour. In 6 of 8 s les obtained after spontaneous labour an intermittent or pulsatile release of both PGE and PGF was observed from the amnion side as compared to the steady state of prostaglandin release from all 10 s les obtained before labour.
Publisher: Oxford University Press (OUP)
Date: 04-2001
DOI: 10.1095/BIOLREPROD64.4.1206
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion from epithelial cells lining the female reproductive tract is induced during early pregnancy by ovarian steroid hormones and constituents of seminal plasma. In this study we have investigated the influence of GM-CSF on development of preimplantation mouse embryos. Blastocyst-stage embryos were found to specifically bind (125)I-GM-CSF and analysis of GM-CSF mRNA receptor expression by reverse transcriptase-polymerase chain reaction indicated expression of the low-affinity alpha subunit of the GM-CSF receptor, but not the affinity-converting beta subunit (beta(c)), or GM-CSF ligand. GM-CSF receptor mRNA was present in the fertilized oocyte and all subsequent stages of development, and in blastocysts it was expressed in both inner cell mass and trophectoderm cells. In vitro culture of eight-cell embryos in recombinant GM-CSF accelerated development of blastocysts to hatching and implantation stages, with a maximum response at a concentration of 2 ng/ml (77 pM). Blastocysts recovered from GM-CSF-null mutant (GM-/-) mice on Day 4 of natural pregnancy or after superovulation showed retarded development, with the total cell number reduced by 14% and 18%, respectively, compared with GM+/+ embryos. Blastocysts generated in vitro from two-cell GM-/- and GM+/+ embryos were larger when recombinant GM-CSF was added to the culture medium (20% and 24% increases in total cell numbers in GM+/+ and GM-/- blastocysts, respectively). Incubation of blastocysts with recombinant GM-CSF elicited a 50% increase in the uptake of the nonmetabolizable glucose analogue, 3-O-methyl glucose. In conclusion, these data indicate that GM-CSF signaling through the low-affinity GM-CSF receptor in blastocysts is associated with increased glucose uptake and enhanced proliferation and/or viability of blastomeres. Together, the findings implicate a physiological role for maternal tract-derived GM-CSF in targeting the preimplantation embryo, and suggest that defective blastocyst development contributes to compromised pregnancy outcome in GM-CSF-null mutant mice.
Publisher: Oxford University Press (OUP)
Date: 10-2004
Publisher: Oxford University Press (OUP)
Date: 05-12-2011
Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females with a high prevalence. The etiology of this heterogeneous condition remains obscure and its phenotype expression varies. Two, widely cited, previous ESHRE/ASRM-sponsored PCOS consensus workshops focused on diagnosis (published in 2004) and infertility management (published in 2008). The present third PCOS consensus paper summarizes current knowledge and identifies knowledge gaps regarding various women's health aspects of PCOS. Relevant topics addressed-all dealt with in a systematic fashion-include adolescence, hirsutism and acne, contraception, menstrual cycle abnormalities, quality of life, ethnicity, pregnancy complications, long-term metabolic and cardiovascular health and finally cancer risk. Additional, comprehensive background information is provided separately in an extended online publication.
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.2165/00003495-200666070-00002
Abstract: Polycystic ovary syndrome (PCOS) is a syndrome, which can be defined as a group of recognisable patterns of symptoms or abnormalities that indicate a particular medical situation. The current definition of PCOS requires the presence of two of the following three conditions: (i) oligo- and/or anovulation (ii) clinical and/or biochemical signs of hyperandrogenism and (iii) polycystic ovaries--and the exclusion of other aetiologies. It is generally accepted that the prevalence of PCOS is approximately 5-10%, and that of polycystic ovaries alone is 21-23%. Other features of PCOS are obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, obstructive sleep apnoea and infertility. An approach to a patient with possible PCOS should be directed towards making a diagnosis and screening for associated endocrine abnormalities. Therapeutic interventions are directed towards addressing the needs of the patient at present and towards preventing long-term complications of the syndrome. Body mass index, which is a primary mediator in the relationship between PCOS and health-related quality of life in obese PCOS adolescents, may play a similar role in other PCOS patients. Any intervention directed at reducing central obesity will not only improve quality of life but also correct hyperinsulinism and improve fertility and lipid and androgen profiles. It is also the only currently available intervention that can have a lifelong impact on reducing possible long-term complications of the syndrome. Lifestyle modification is the cardinal intervention. Pharmacological treatments are available for specific indications. Infertility can be treated with clomifene (clomiphene citrate), metformin, gonadotropins or surgery to the ovaries. Cyproterone (alone or in combination with ethinylestradiol) and spironolactone are the main drugs used in the treatment of hirsutism. Other drugs that can be considered include flutamide, ketoconazole and finasteride. Women with PCOS require ongoing surveillance to detect impaired glucose tolerance, hyperlipidaemia, endometrial hyperplasia and consequent complications. Obese women, in particular, require regular glucose tolerance testing because of the potential for rapid progression from normal to impaired glucose tolerance and diabetes. The focus of this article is the epidemiology, diagnosis and management of this common endocrine disorder. Diagnostic and co-morbid features are discussed separately to facilitate understanding of PCOS. Symptom-directed strategies, as well as short- and long-term goals of treatment, are outlined.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2004
Publisher: Elsevier BV
Date: 10-1989
DOI: 10.1016/0022-4731(89)90038-1
Abstract: The binding characteristics of oestrogen and progesterone in intrauterine tissue were studied in the non-pregnant state and throughout pregnancy using sucrose density gradient centrifugation and titration analyses. High affinity receptors for these steroids which were present in high concentrations in tissue from non-pregnant patients and patients in early pregnancy, decreased with the advance of pregnancy to undetectable levels at term. Non-saturable binding to progesterone detected in term tissue was identified as albumin and cortisol binding globulin.
Publisher: Oxford University Press (OUP)
Date: 04-07-2012
Abstract: BACKGROUND Polycystic ovary syndrome (PCOS) is closely associated with obesity but the prevalence of obesity varies between published studies. The objective of this research was to describe the prevalence of overweight, obesity and central obesity in women with and without PCOS and to assess the confounding effect of ethnicity, geographic regions and the diagnostic criteria of PCOS on the prevalence. METHODS MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL) and PSYCINFO were searched for studies reporting the prevalence of overweight, obesity or central obesity in women with and without PCOS. Data were presented as prevalence (%) and risk ratio (RR) [95% confidence interval (CI)]. Random-effect models were used to calculate pooled RR. RESULTS This systematic review included 106 studies while the meta-analysis included 35 studies (15129 women). Women with PCOS had increased prevalence of overweight [RR (95% CI): 1.95 (1.52, 2.50)], obesity [2.77 (1.88, 4.10)] and central obesity [1.73 (1.31, 2.30)] compared with women without PCOS. The Caucasian women with PCOS had a greater increase in obesity prevalence than the Asian women with PCOS compared with women without PCOS [10.79 (5.36, 21.70) versus 2.31 (1.33, 4.00), P < 0.001 between subgroups). CONCLUSIONS Women with PCOS had a greater risk of overweight, obesity and central obesity. Although our findings support a positive association between obesity and PCOS, our conclusions are limited by the significant heterogeneity between studies and further studies are now required to determine the source of this heterogeneity. Clinical management of PCOS should include the prevention and management of overweight and obesity.
Publisher: American College of Physicians
Date: 10-2023
DOI: 10.7326/M23-0872
Publisher: Oxford University Press (OUP)
Date: 06-09-2013
Abstract: BACKGROUND Recent studies suggest that metformin may be more effective in women with polycystic ovary syndrome (PCOS) who are non-obese. The objective here is to determine and compare the effectiveness of metformin and clomiphene citrate for improving fertility outcomes in women with PCOS and a BMI < 32 kg/m(2) (BMI 32 kg/m(2) was used to allow for international differences in BMI values which determine access to infertility therapy through the public health system). METHODS Databases were searched for English language articles until July 2011. women of any age, ethnicity and weight with PCOS diagnosed by all current criteria, who are infertile at least 1000 mg of any type of metformin at any frequency, including slow release and standard release, compared with any type, dose and frequency of clomiphene citrate. rates of ovulation, live birth, pregnancy, multiple pregnancies, miscarriage, adverse events, quality of life and cost effectiveness. Data were extracted and risk of bias assessed. A random effects model was used for meta-analyses of data, using risk ratios (relative risk). RESULTS The search returned 4981 articles, 580 articles addressed metformin or clomiphene citrate and four randomized controlled trials (RCTs) comparing metformin with clomiphene citrate were included. Upon meta-analysis of the four RCTs, we were unable to detect a statistically significant difference between the two interventions for any outcome in women with PCOS and a BMI < 32 kg/m(2), owing to significant heterogeneity across the RCTs. CONCLUSIONS Owing to conflicting findings and heterogeneity across the included RCTs, there is insufficient evidence to establish a difference between metformin and clomiphene citrate in terms of ovulation, pregnancy, live birth, miscarriage and multiple pregnancy rates in women with PCOS and a BMI < 32 kg/m(2). However, a lack of superiority of one treatment is not evidence for equivalence, and further methodologically rigorous trials are required to determine whether there is a difference in effectiveness between metformin and placebo (or no treatment) or between metformin and clomiphene citrate for ovulation induction in women with PCOS who are non-obese. Until then, caution should be exercised when prescribing metformin as first line pharmacological therapy in this group of women.
Publisher: Oxford University Press (OUP)
Date: 12-2001
DOI: 10.1093/HUMREP/16.12.2606
Abstract: A high proportion of infertile patients have polycystic ovarian syndrome (PCOS) with a reportedly greater risk of spontaneous abortion. Because of the close link between PCOS and obesity and the independent association of obesity with poor pregnancy outcomes, it is important to distinguish the possible confounding effect of body mass index (BMI) or other variables from that of PCOS. This study aims to determine the effect of PCOS status on the risk of spontaneous abortion with adjustment for body mass and several other confounding factors in a large cohort of pregnant infertile women. The patients (n = 1018) were treated in a tertiary infertility centre. Their PCOS status was determined by standard criteria and their BMI had been taken less than 1 year before the pregnancy. Patients whose PCOS status or BMI measurements were not assessed were excluded. Student's t-test or chi2 test were used to test the difference between the PCOS and non-PCOS groups while a multivariate logistical regression model was used to assess the effect of PCOS, BMI and other confounding factors. Overall, the incidence of PCOS was 37% in this cohort. The overall incidence of spontaneous abortion in the study population was 21%. Univariate analysis showed that women with PCOS had a significantly greater risk of spontaneous abortion compared with non-PCOS women (25 versus 18%, P < 0.01). However, using multivariate logistic regression analysis this effect was reduced to a non-significant level [odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.85-1.36] after adjusting for obesity and patients/treatment combination factor, and to nil after adjusting for all confounding factors considered in this study (OR = 0.98, 95% CI 0.75-1.28). The results of this study suggest that the higher risk of spontaneous abortion observed in women with PCOS is likely to be due to their high prevalence of obesity and the type of treatment they receive.
Publisher: Wiley
Date: 25-01-2005
DOI: 10.1111/J.1365-2265.2004.02208.X
Abstract: Women with polycystic ovarian syndrome (PCOS) commonly consult endocrinologists or gynaecologists and it is not known whether these specialty groups differ in their approach to management. To compare the investigation, diagnosis and treatment practices of endocrinologists and gynaecologists who treat PCOS. A mailed questionnaire containing a hypothetical patient's case history with varying presentations--oligomenorrhoea, hirsutism, infertility and obesity--was sent to Australian clinical endocrinologists and gynaecologists in teaching hospitals and private practice. Evaluable responses were obtained from 138 endocrinologists and 172 gynaecologists. The two specialty groups differed in their choice of essential diagnostic criteria and investigations. Endocrinologists regarded androgenization (81%) and menstrual irregularity (70%) as essential diagnostic criteria, whereas gynaecologists required polycystic ovaries (61%), androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio (47%) (all P-values < 0.001). In investigation, gynaecologists were more likely to request ovarian ultrasound (91%vs. 44%, P < 0.001) and endocrinologists more likely to measure adrenal androgens (80%vs. 58%, P < 0.001) and lipids (67%vs. 34%, P < 0.001). Gynaecologists were less likely to assess glucose homeostasis but more likely to use a glucose tolerance test to do so. Diet and exercise were chosen by most respondents as first-line treatment for all presentations. However, endocrinologists were more likely to use insulin sensitizers, particularly metformin, for these indications. In particular, for infertility, endocrinologists favoured metformin treatment whereas gynaecologists recommended clomiphene. There is a lack of consensus between endocrinologists and gynaecologists in the definition, diagnosis and treatment of PCOS. As a consequence, women may receive a different diagnosis or treatment depending on the type of specialist consulted.
Publisher: Elsevier BV
Date: 10-2001
No related grants have been discovered for Robert Norman.