Clinical outcomes from ART in predicted hyperresponders: in vitro maturation of oocytes versus conventional ovarian stimulation for IVF/ICSI.

STUDY QUESTION: Do ongoing pregnancy rates (OPRs) differ in predicted hyperresponders undergoing ART after IVM of oocytes compared with conventional ovarian stimulation (OS) for IVF/ICSI? SUMMARY ANSWER: One cycle of IVM is non-inferior to one cycle of OS in women with serum anti-Müllerian hormone (AMH) levels ≥10 ng/ml. WHAT IS KNOWN ALREADY: Women with high antral follicle count and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of OS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to OS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and OS may differ depending on the extent of AMH elevation. STUDY DESIGN, SIZE, DURATION: This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified hMG (HP-hMG) primed, non-hCG-triggered IVM or OS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Predicted hyperresponse was defined as a serum AMH level ≥3.25 ng/ml (Elecsys® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate assessed 10-11 weeks after embryo transfer (ET). The predefined non-inferiority limit was -10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy, defined as the number of ET cycles until ongoing pregnancy was achieved, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Data from 463 IVM cycles were compared with those from 1244 OS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing OS (522/1193, 43.8%), were significantly younger (29.5 years versus 30.5 years, P ≤ 0.001), had a higher BMI (25.7 kg/m2 versus 25.1 kg/m2, P ≤ 0.01) and higher AMH (11.6 ng/ml versus 5.3 ng/ml, P ≤ 0.001). Although IVM cycles yielded more cumulus-oocyte complexes (COCs) (24.5 versus 15.0 COC, P ≤ 0.001), both groups had similar numbers of mature oocytes (metaphase II (MII)) (11.9 MII versus 10.6 MII, P = 0.9). In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to OS (794/1244, 63.8%), P ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to OS from serum AMH levels >10 ng/ml onwards (113/221, 51.1% (IVM); 29/48, 60.4% (OS)). The number of ETs needed to reach an ongoing pregnancy was comparable in both the IVM and the OS group (1.6 versus 1.5 ET's, P = 0.44). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number, and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH >10 ng/ml. LIMITATIONS, REASONS FOR CAUTION: These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Among subfertile women who are eligible for ART, IVM, and OS resulted in comparable reproductive outcomes in a subset of women with a serum AMH ≥10 ng/ml. These findings should be corroborated by a randomised controlled trial (RCT) comparing both treatments in selected patients with elevated AMH. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. P.D. has been consultant to Merck Healthcare KGaA (Darmstadt, Germany) from April 2021 till June 2023 and is a Merck employee (Medical Director, Global Medical Affairs Fertility) with Merck Healthcare KGAaA (Darmstadt, Germany) since July 2023. He declares honoraria for lecturing from Merck KGaA, MSD, Organon, and Ferring. The remaining authors declared no conflict of interest pertaining to this study. TRIAL REGISTRATION NUMBER: N/A.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome†.

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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 diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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). MAIN RESULTS AND THE ROLE OF CHANCE: 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 individual 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, diverse 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): 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 (www.monash.edu/medicine/mchri/pcos). 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.

Homoeopathic Concept of Remedy Relationship And Its Utility in Management of Polycystic Ovarian Syndrome: A Case Report.

Polycystic ovarian syndrome (PCOS) is a common lifestyle disorder that has become a major international public health concern affecting young women of reproductive age. Homeopathy aims to provide an individual with optimal health on all levels-emotional, mental, physical and spiritual. Homeopathy's goal is to promote an individual's overall well-being rather than just treat symptoms. Dr. Boenninghausen's unique contribution to the promotion of scientific prescribing in homeopathic practice is the concept of remedy relationship and its reportorial analysis. Homeopathy takes into account a person's natural environment and lifestyle. Then, a homeopathic physician provides treatment that closely matches individual symptoms and recommends homeopathy remedies for the same. A 22-year-old female came into the homeopathic outpatient department (OPD) with complaints of irregular menses, pustular acne and constipation. An ultrasound of the abdomen and pelvis was done to confirm the diagnosis of POCS. Other investigations were performed, including thyroid function tests and hormonal assays, to rule out the presence of other disorders. The case was managed with homeopathic medicines, which were prescribed per Hahnemannian guidelines after referring relationship of remedies.

Efficacy of Cyclical Prescription in Homoeopathic Management of Polycystic Ovary Disease: A Case Report.

Polycystic ovarian disease is a very common condition affecting women of reproductive age. Homoeopathy believes in a holistic approach and, when prescribed, can correct hormonal imbalances, regulate ovulation, and deal with associated complaints, as well as help to cure the condition from its root cause. A case of a 17-year-old female came into the Homoeopathic outpatient department with complaints of irregular menses and hyperpigmented patches on her back. Hormonal assay and thyroid function tests were done to rule out other disorders, and ultrasound of the abdomen and pelvis was done to confirm the diagnosis of polycystic ovarian disease. In this case Sulphur, Calcarea Carb, and Lycopodium were prescribed in a cyclical manner and proved to be beneficial.

Polycystic Ovarian Syndrome Treated with Individualized Homeopathy: A Case Report.

Introduction: Polycystic ovarian syndrome (PCOS) is a polygenic, multifactorial, syndromic disorder with reproductive, endocrine, and metabolic dysfunction seen in reproductive aged women (12-45 years). The exact cause is not known may involve increased luteinizing hormone, increased insulin levels, and a defect in androgen synthesis. The symptoms include anovulation, irregular menses, and hyperandrogenism. It is clinically manifested by hirsutism, acne, and androgenic alopecia. Health care practitioners continue to seek a cure for PCOS as it is increasing in frequency and is one of the major causes of anovulatory infertility. Methods: The case was recorded in the gynaecological department at the Homoeopathic Medical College and Research Centre. An 18- year-old female patient with PCOS was treated with individualised homeopathy (iHOM) medicine between 26th September 2019 and 26th November 2020. During the follow-up visits, treatment outcomes were assessed. To assess whether the changes were due to homoeopathic medicine, an assessment using the modified Naranjo criteria was performed. Results: Over an observational period of 1 year, beneficial result from iHOM medicine was seen. This treatment method can be used by the physicians in the treatment of PCOS as a complementary health practice. Conclusion: Considering the multi-factorial aetiology of PCOS, iHOM medicine with lifestyle modification is helpful in treating PCOS.

Comparative risk reduction of complications pertaining to polycystic ovarian syndrome by multiple treatment options.

The aim of study was to find effective treatment option which reduces the risk of complications among patients of polycystic-ovarian-syndrome. A cross-sectional study was conducted from January-2019 to December-2019. Data was collected from 200 patients that have visited hospitals and clinics located in Karachi. A questionnaire was used in the survey. Collected data was analyzed with SPSS-22. Hormonal-imbalance (p=0.0001), polycystic-ovaries (p=0.008), irregular-menstruation (p=0.0001), obesity (p=0.0001), diabetes (p=0.0001) and infertility (p=0.014) significantly treated by allopathic-medications. Hormonal-imbalance (p=0.025), polycystic-ovaries (p=0.0001), irregular-menstruation (p=0.0001), obesity (p=0.046), diabetes (p=0.001), acne (p=0.046), anxiety (p=0.014), depression (p=0.014) and eating disorder (p=0.046) significantly treated by homeopathic-medications. Polycystic-ovaries (p=0.0001), irregular-menstruation (p=0.0001), obesity (p=0.014), diabetes (p=0.0001) and acne (p=0.014) significantly treated by herbal-medications. Allopathic treatment was found effective in reducing risk of complication associated with PCOS; hormonal-imbalance (59%), hirsutism (42%), obesity (89%), diabetes (90%), hypertension (17%), infertility (60%) and anxiety (75%). Risk reduction of complications by Homeopathic treatment; polycystic-ovaries (54%), irregular menstruation (91%) and depression (43%). Combination treatment was found effective in reducing the risk of acne (43%) and eating disorder (100%). Allopathic treatment is effective in reducing the majority of risks of complications and the complications of polycystic-ovaries-syndrome can be significantly controlled with the homeopathic mode of treatment.

Homeopathic Treatment in Patients with Polycystic Ovarian Syndrome: A Case Series.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder in women of reproductive age. It is characterized by various clinical presentations such as ovulatory dysfunction, polycystic ovaries, and hyperandrogenism. Considering the side effects associated with conventional treatment and the patients who fail to respond to these measures, there is a demand for a complementary therapy that would alleviate symptoms of PCOS without side effects. Homeopathy is a complementary system of medicine that has been successfully used in different disease conditions, including PCOS. A case series of PCOS is hereby presented, to demonstrate some positive results of individualized homeopathic treatment. METHODS: Seven cases of young women with PCOS were treated with individualized homeopathic medicines. Each case was followed up with clinical and ultrasonographic evidence and was reported according to the criteria set out in the HOM-CASE guidelines. The assessment of causal attribution of homeopathic treatment effect was carried out using the Modified Naranjo Criteria. RESULTS: Marked improvement was observed in all seven cases of PCOS. The irregular menstrual cycles and other associated symptoms became normal, along with a resolution of cysts in ovaries as evidenced by ultrasonography. All cases improved within 4 to 12 months of treatment. The Modified Naranjo Criteria total score was +9/13 for each case, which indicates a positive causal attribution of homeopathy in relieving the symptoms of PCOS. CONCLUSION: This case series suggests a significant role of individualized homeopathic medicines in PCOS by regularizing the menstrual cycle along with the resolution of cysts and associated symptoms.

Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis.

STUDY QUESTION: Can cluster analysis be used to differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with polycystic ovarian morphology (PCOM) in a non-subjective manner? SUMMARY ANSWER: Cluster analysis can be used to accurately and non-subjectively differentiate between normo-ovulatory women with normal ovaries and normo-ovulatory women with PCOM. WHAT IS KNOWN ALREADY: Currently, PCOM is diagnosed using a fixed threshold level, i.e. 12 or more follicles per ovary, and is one of the diagnostic criteria of polycystic ovary syndrome (PCOS). However, PCOM is also encountered in normo-ovulatory women, suggesting that it could just represent a normal variant. On the other hand, recent studies have shown subtle endocrine abnormalities in women with isolated PCOM that resemble those found in women with PCOS. Because of the strong correlation between anti-Müllerian hormone (AMH) and follicle number, a high serum AMH level has been proposed as a surrogate marker for PCOM and could, therefore, be integrated in the diagnostic classifications for PCOS. STUDY DESIGN, SIZE, DURATION: This was a retrospective observational cohort study. Original cohorts had been recruited for previous studies between 1998 and 2010. Two hundred ninety-seven regularly cycling women and 700 women with PCOS were eligible for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cluster analysis was performed in 297 regularly cycling women. After exclusion of 'PCOM' clusters, each 'non-PCOM' cluster (young, n = 118 and old, n = 100) was included in the construction of a receiver operating characteristics curve to test the diagnostic performance of follicle number per ovary (FNPO) and serum AMH in discriminating similarly aged full-blown PCOS patients (n = 411 and 237, respectively) from normal regularly cycling non-PCOM women. MAIN RESULTS AND ROLE OF CHANCE: The optimal number of clusters was four; age was the most important classifying variable, followed by the FNPO and serum AMH. Two distinct clusters of normo-ovulatory women with PCOM were isolated and differed solely by age, i.e. 'young' and 'old'. Both 'PCOM' clusters had their similarly aged counterpart of 'non-PCOM' clusters. Likewise, two clusters comprised women younger than 30 years, with (n = 28, 'PCOM regularly cycling women') or without (n = 118, 'normal regularly cycling women') features of PCOM (increased FNPO and/or serum AMH). The two other clusters in older women could be labelled 'normal regularly cycling women' or 'PCOM regularly cycling women' (n = 100 and 51, respectively). The prevalence of PCOM was significantly greater in old than in young regularly cycling women controls. In the young population, after exclusion of the 'PCOM regularly cycling women', the diagnostic performance of AMH, expressed by area under the curve (AUC) (AUC = 0.903; CI (0.876-0.930)) to differentiate PCOS women from normal regularly cycling women was similar to that using the FNPO (AUC = 0.915, CI (0.891-0.940)) (P = 0.25), confirming results from earlier studies. In the old population, the diagnostic performance of AMH was greater than that of FNPO (AUCs = 0.948 (0.927-0.970) vs 0.874 (0.836-0.912), respectively, P = 0.00035). Cut-off levels of AMH and antral follicle count distinguishing regularly cycling non-PCOM women from PCOS women were higher in young women than in older women. LIMITATIONS, REASONS FOR CAUTION: Data of normal women were obtained from earlier studies, aiming to measure normal endocrine values. Apparently, the strong effect of age in cluster analysis revealed a dichotomy in the age distribution among the cohort of regularly cycling women included. This was involuntary since in none of the original studies, eligibility was limited by age and there was considerable overlap in age ranges of the cohorts. Transvaginal ultrasound was performed using a 6.5-8 mHz probe and our data confirm that this threshold level for FNPO is still valid if using such probe frequencies, although the use of devices with a maximum frequency lower than 8 mHz has become obsolete. Obviously, newer ultrasound scanner using higher transducer frequency will facilitate the detection of more follicles. WIDER IMPLICATIONS OF THE FINDINGS: Our data support the use of AMH as a surrogate for ultrasound to define PCOM, which is one of the three items of the Rotterdam classification. They also show that age should be taken into account to define the optimal threshold. The fact that the prevalence of PCOM was increased in the older regularly cycling women, may be due to 'attenuated' PCOS, a phenomenon that has been described in ageing women with PCOS. These women might have had anovulatory cycles in the past and have become ovulatory with increasing age, and were, therefore, eligible for this study. However, since most women included at older age have had spontaneous pregnancies in the past, PCOM at older age may be associated with a subclinical form of PCOS, which may also be present in young regularly cycling women. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. J.S.E.L. has received grants and support from Ferring, MSD, Organon, Merck-Serono, Schering Plough and Serono during recruitment and analysis of data for this study. S.L.F., A.D. and D.D. do not have any conflict of interest.

Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

STUDY QUESTION: Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER: Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. WHAT IS KNOWN ALREADY: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1-2.8)], after adjustment for age, ethnicity, smoking and BMI (P < 0.001). After adjustment for age, there were no significant differences in androgens between POI and NM (P = 0.15) women and between NM and RC (P = 0.27) women, the latter indicating that chronological aging rather than ovarian aging influences the differences between pre- and post-menopausal women. A high FAI was associated with elevated triglycerides (ß log FAI for PCOS: 0.45, P < 0.001, POI: 0.25, P < 0.001, NM: 0.20, P = 0.002), insulin (ß log FAI for PCOS: 0.77, POI: 0.44, NM: 0.40, all P < 0.001), HOMA-IR (ß log FAI for PCOS: 0.82, POI: 0.46, NM: 0.47, all P < 0.001) and mean arterial pressure (ß log FAI for PCOS: 0.05, P = 0.002, POI: 0.07, P < 0.001, NM: 0.04, P = 0.04) in all women; with increased glucose (ß log FAI for PCOS: 0.05, P = 0.003, NM: 0.07, P < 0.001) and decreased high-density lipoprotein (ß log FAI for PCOS: -0.23, P < 0.001, NM: -0.09, P = 0.03) in PCOS and NM women; and with increased low-density lipoprotein (ß log FAI for POI: 0.083, P = 0.041) in POI women. Adjustment for BMI attenuated the observed associations. Associations between FAI and cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. LIMITATIONS, REASONS FOR CAUTION: Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research regarding the role of androgens in the development of CVD and potential modulatory effects of BMI is required. STUDY FUNDING/COMPETING INTERESTS: N.M.P.D. is supported by the Dutch Heart Foundation (grant number 2013T083). L.J. and O.H.F. work in ErasmusAGE, a center for aging research across the life course, funded by Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA. M.K. is supported by the AXA Research Fund. Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, Merck Sharpe & Dome, Organon, Schering Plough and Serono. In the last 5 years, B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Actavis, COGI, Euroscreen, Ferring, Finox, Genovum, Gedeon-Richter, Merck-Serono, OvaScience, Pantharei Bioscience, PregLem, Roche, Uteron and Watson laboratories. With regard to potential conflicts of interest, there is nothing further to disclose.

Preconception predictors of gestational diabetes: a multicentre prospective cohort study on the predominant complication of pregnancy in polycystic ovary syndrome.

STUDY QUESTION: Can we develop an adequate preconception prediction model to identify those women with polycystic ovary syndrome (PCOS) who have an increased risk of developing gestational diabetes mellitus (GDM) during subsequent pregnancy? STUDY ANSWER: The risk of developing GDM in women with PCOS can be adequately predicted prior to conception by a prediction model. WHAT IS KNOWN ALREADY: Women with PCOS are at increased risk of pregnancy complications, especially GDM. GDM has serious short-term and long-term effects on mother and baby. STUDY DESIGN, SIZE, DURATION: This study is a part of a multicentre prospective cohort study, which was conducted between April 2008 and April 2012. A total of 326 women with PCOS were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS and a wish to conceive were included prior to conception and followed until 6 weeks after delivery. Maternal, neonatal and birth complications were reported. A multivariate model was developed to predict the most common pregnancy complication, GDM, by using univariate and multivariate logistic regression of preconception patient characteristics. The area under the curve (AUC) of the receiver-operating characteristic was used to test the performance of the model. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 189 women (58%) achieved an ongoing pregnancy (8% multiples) and delivered a live-born neonate. One or two maternal complications occurred in 62 (33%) pregnant women, mainly GDM (n = 41; 22%) and pregnancy-induced hypertension (n = 14; 7%). In children, one or two complications were observed in 49 (26%) of 206 children born, e.g. premature delivery (n = 23; 12%) and small for gestational age (n = 15; 8%). The preconception prediction model for GDM performed well (AUC 0.87, 95% CI 0.81-0.93). First-degree relatives with type 2 diabetes mellitus, serum levels of fasting glucose, fasting insulin, androstenedione and sex hormone-binding globulin before conception were identified as predictors. LIMITATIONS, REASONS FOR CAUTIONS: The prediction model has not yet been externally validated in another group of patients. Also, there were missing data for some of the determinants, which were accounted for by multiple imputation. WIDER IMPLICATIONS OF THE FINDINGS: Women with PCOS who achieve a pregnancy have an increased risk of GDM. The prediction model can be used to identify women particularly at risk for GDM who should be monitored closely to enable preventative measures that may reduce the risk of developing GDM and its adverse consequences. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for the study. M.A.W., S.M.V.V., A.J.G., A.F. and M.P.H.K. have nothing to disclose. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, European Society of Human Reproduction and Embryology and MSD. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, Merck-Serono, MSD, Organon, Schering Plough, Sharp & Dome and Serono. M.J.C. has received grant support from the following companies (in alphabetic order): Illumina and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Ferring, Ova-Science, PregLem SA, Roche and Watson Laboratories. TRIAL REGISTRATION NUMBER: NCT00821379 [Clinicaltrials.gov].

Excess mortality in mothers of patients with polycystic ovary syndrome.

STUDY QUESTION: Do diabetic parents of patients with polycystic ovary syndrome (PCOS) encounter excess mortality compared with the mortality of men and women with type 2 diabetes, recruited without selection for PCOS? SUMMARY ANSWER: Type 2 diabetes among mothers of PCOS patients results in excess mortality compared with women with diabetes from the general population. WHAT IS KNOWN ALREADY: Insulin resistance is a prominent feature of PCOS. Because of the heritable nature of PCOS, parents of these patients are also prone to develop type 2 diabetes mellitus, which might influence their life expectancy. STUDY DESIGN, SIZE, DURATION: This reverse parent-offspring study included 946 mothers and 902 fathers of patients with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The medical history of the parents was primarily obtained during the initial screening of each patient and updated via questionnaires. Mortality data of these parents were compared with the mortality rates of the general Dutch population and with mortality rates of a control population consisting of 1353 men and women diagnosed with type 2 diabetes mellitus. The standardized mortality ratio (SMR) was calculated as the ratio of the observed mortality of the parents to the expected mortality in the general Dutch population. The mortality of parents with type 2 diabetes mellitus relative to controls with diabetes but not related to anyone with PCOS was standardized for age, gender and calendar period using Poisson regression. MAIN RESULTS AND ROLE OF CHANCE: In total, 302 parents were deceased in 62 693 person-years. Mothers above age 60 had a significant excess mortality of 1.50 (95% CI 1.15-1.92) compared with the general Dutch population. Moreover, mothers with diabetes had two-times higher mortality risk compared with control women with diabetes (RR 2.0, 95% CI 1.19-3.41). No excess mortality among fathers of PCOS patients was observed. LIMITATIONS, REASON FOR CAUTION: Although recall bias for family history was previously demonstrated to be minimal for long-term chronic diseases, the prevalence of diabetes in the parents was based on their daughter's self-report and was not clinically confirmed. Also, no other additional clinical data regarding the parent population were available. Prospective long-term follow-up studies should be conducted to confirm this excess mortality. WIDER IMPLICATIONS OF THE FINDINGS: Our findings justify screening for type 2 diabetes mellitus among the mothers with a daughter suffering from PCOS to ensure that timely preventive and therapeutic measures according to the appropriate guidelines can be taken. STUDY FUNDING/COMPETING INTERESTS: No particular funding was received for this study. Y.V.L., M.E.R.-S., N.K., J.R.v.L., M.v.d.B., H.J.G.B. and E.J.G.S. do not have any conflict of interest. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Genovum, Merck-Serono, Organon, Schering Plough and Serono. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono, and Wyeth. These companies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Fasting glucose measurement as a potential first step screening for glucose metabolism abnormalities in women with anovulatory polycystic ovary syndrome.

STUDY QUESTION: Is routine screening by oral glucose tolerance test (OGTT) needed for all women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Screening for glucose metabolism abnormalities of PCOS patients by an OGTT could potentially be limited to patients who present with a fasting glucose concentration between 6.1 and 7.0 mmol/l only. WHAT IS KNOWN ALREADY: Women with PCOS are at increased risk of developing diabetes. This study proposes a stepwise screening strategy for (pre)diabetes for PCOS patients based on risk stratification by fasting plasma glucose. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 226 women diagnosed with anovulatory PCOS. PARTICIPANTS AND SETTING: A consecutive series of 226 patients, diagnosed with PCOS at the University Medical Centre Utrecht, the Netherlands, were screened for glucose metabolism abnormalities by OGTT (75 g glucose load). MAIN RESULTS AND ROLE OF CHANCE: The majority of the 226 women (mean age: 29.6 ± 4.3 years; BMI: 27.3 ± 6.7 kg/m(2); 81% Caucasian) presented with a normal OGTT (169 women (75%)). Of the 57 (25%) women presenting with mild to moderate glucose abnormalities, 53 (93%) could be identified by fasting glucose concentrations only. Diabetes was diagnosed in a total of eight women (3.5%). In six women, the diagnosis was based on fasting glucose >7.0 mmol/l. The other two cases of diabetes initially presented with fasting glucose between 6.1 and 7.0 mmol/l and were diagnosed by OGTT assessment. No women diagnosed with diabetes presented with fasting glucose levels below 6.1 mmol/l. We therefore conclude that all diabetes patients could potentially be found by initial fasting glucose assessment followed by OGTT only in patients with fasting glucose between 6.1 and 7.0 mmol/l. LIMITATIONS, REASONS FOR CAUTION: Before general implementation can be advised, this screening algorithm should be validated in a prospective study of a similar or greater number of PCOS women. WIDER IMPLICATIONS OF THE FINDINGS: Our study comprised of a mostly Caucasian (81%) population, therefore generalization to other ethnic populations should be done with caution. STUDY FUNDING/COMPETING INTEREST(S): No external finance was involved in this study. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. A.J.G. has received fees from Abbott, Bayer Schering and IBSA. T.W.H. has received fees from Merck, Sharpe & Dohme, GlaxoSmithKline, NovoNordisk and Eli Lilly. The authors declare complete independence from funders. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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 diversity and inclusion were considered throughout. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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). MAIN RESULTS AND THE ROLE OF CHANCE: 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 individual 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, diverse 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. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remain 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. WIDER IMPLICATIONS OF THE FINDINGS: 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 programme supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): 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 the 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 sponsoring 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 (www.monash.edu/medicine/mchri/pcos). 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.

Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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 diversity and inclusion were considered throughout. PARTICIPANTS/ MATERIALS, SETTING, METHODS: 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). MAIN RESULTS AND THE ROLE OF CHANCE: 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 individual 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, diverse 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. LIMITATIONS, REASONS FOR CAUTION: Overall, recommendations are strengthened and evidence is improved, but remain 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. WIDER IMPLICATIONS OF THE FINDINGS: 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 programme supports the Guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): 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 the 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 sponsoring 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 (www.monash.edu/medicine/mchri/pcos). 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.

Homoeopathy a system of holistic healing as an alternative treatment for PCOS: a review

Polycystic ovarian syndrome (PCOS) is a complex hormonal and metabolic disorder characterized by oligomenorrhea or amenorrhea, hyperandrogenism and infertility. Global prevalence of PCOS is estimated to be between 06% and 26%. Homoeopathy, being a system of holistic healing can be accepted as one of the alternative treatments for PCOS. Aim & Objective: The aim of the study is to review clinical data, where the intervention was aimed to treat PCOS through Homoeopathy. The objective of the study is to identify the therapeutic approach, assessment criteria, treatment outcomes through an alternative therapy i.e., Homoeopathy in cases of PCOS. Methods: A systematic literature search was conducted in the month of June2021 following International/National search databases for all clinical studies published in the period from 2000 to 2021. This search was aimed to target the entire literature of randomized trials or controlled trials, observational studies case studies/reports on PCOS in homoeopathy. Result:28 articles related to Homoeopathy on PCOS were identified. Out of these 28studies, 22 studies (01 RCT, 02 NRCT,06 observational studies,04 case series and 09 case reports) were included in this review. All studies were published in peer reviewed journals.Conclusions:To establish the evidence-based efficacy of the homoeopathic treatment in cases of RCT more pragmatic studies need to be planned in the future based on proper diagnostic criteria.

Induction of ovulation with the use of a starting dose of 50 units of recombinant human follicle-stimulating hormone (Puregon).

OBJECTIVE: To determine whether a starting dose of 50 units of recombinant FSH (follitropin beta, Puregon; Organon Laboratories Limited, Cambridge, United Kingdom) produces a follicular response in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective observational study. SETTING: Routine clinical practice in a teaching hospital fertility unit. PATIENT(S): Patients with clomiphene citrate-resistant PCOS who wanted to become pregnant. INTERVENTION(S): Low-dose step-up protocol of SC recombinant FSH administration, monitored prospectively by transvaginal ultrasonography and retrospectively by serum endocrine assays taken at each monitoring visit. MAIN OUTCOME MEASURE(S): Rate and size of follicular growth, recombinant FSH requirement, E2 response, ovulation, cycle cancellation, and pregnancy. RESULT(S): All patients exhibited a follicular response: Six patients ovulated, of whom two conceived and four had their cycles cancelled because of overstimulation. One patient did not ovulate despite the development of a follicle. CONCLUSION(S): Recombinant FSH can be used successfully to stimulate follicular growth at a starting dose of 50 IU.

Treatment of hirsutism with flutamide and a low-dosage oral contraceptive in polycystic ovarian disease patients.

OBJECTIVE: To evaluate the clinical and hormonal response of the antiandrogen flutamide (Eulexin, Schering Plough, Milan, SA, Italy) associated with a low dosage oral contraceptive (OC) in a group of hirsute women who were unresponsive to OC treatment. DESIGN: Twenty-two polycystic ovarian disease (PCOD) patients with hirsutism were treated with flutamide (250 mg twice/d) in association with ethinyl-E2 (0.030 mg/d) plus desogestrel (0.150 mg/d) (Practil 21; Organon, Rome, Italy) for 21 d/mo. SETTING: Patients were recruited in the Institute of Obstetrical and Gynaecological Pathology, St. Bambino Hospital, University of Catania, Italy. Hormonal assays were performed in the Hormone Laboratories of St. Bambino Hospital, University of Catania, Catania, Italy. MAIN OUTCOME MEASURE: Every 2 months the hirsutism score was evaluated using the Ferriman-Gallwey hair density index. Mean plasma concentrations of LH, FSH, E2, total T, dihydrotestosterone (DHT), androstenedione (A), sex hormone-binding globulin, DHEAS were determined. RESULTS: After 8 months treatment with flutamide and low dosage OC, the Ferriman-Gallwey score improved in all patients, mean values decreasing from 25.4 +/- 3.96 to 14.6 +/- 1.92. Plasma levels of total T and E2 were unchanged, whereas LH, FSH, A, and DHT values decreased significantly. Sex hormone-binding globulin levels showed a marked increase. CONCLUSION: Flutamide, associated with low dosage OC, favorably influence the hirsutism in PCOD women who are unresponsive to OC treatment alone.

Recombinant FSH versus urinary gonadotrophins or recombinant FSH for ovulation induction in subfertility associated with polycystic ovary syndrome.

BACKGROUND: Over the last four decades, various urinary FSH (uFSH) products of different purity have been developed. In 1988 recombinant FSH (rFSH ) was prepared by transfecting Chinese hamster ovary cell lines with both FSH subunit genes. Both rFSH and uFSH are known to be effective in inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome. Ovulation induction with FSH bears the risk of multiple follicle development, multiple pregnancies and ovarian hyperstimulation syndrome. The dose regimen used can affect the incidence of these complications. OBJECTIVES: To compare in women with clomiphene-resistant polycystic ovary syndrome (PCOS) the safety and effectiveness in terms of ovulation, pregnancy, miscarriage, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) of 1) rFSH with uFSH and 2) different dose regimens of rFSH. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility review group was used to identify all relevant trials. Please see Review Group details. SELECTION CRITERIA: All relevant published RCT's were selected. Randomised controlled trials were eligible for inclusion if treatment consisted of recombinant FSH versus urinary FSH or recombinant FSH in different dose regimens, to induce ovulation in subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: A computerised MEDLINE and EMBASE search was used to identify randomised and non randomised controlled trials. The reference lists of all studies found were checked for relevant articles. Handsearching of bibliographies of relevant publications and reviews and abstracts of scientific meetings was performed. Serono Benelux BV and NV Organon, the manufacturers of follitropin alpha (Gonal F(R)) and follitropin beta (Puregon(R)) respectively, were asked for unpublished data and ongoing studies. Relevant data were extracted independently by two reviewers (NB, MW). Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of cross-over and co-intervention. All trials were screened and analysed according to predetermined quality criteria. DATA SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. MAIN RESULTS: Four randomised trials comparing rFSH versus uFSH were identified. No significant differences were demonstrated for the relevant outcomes. The odds ratio for ovulation rate was 1.19 (95% CI 0.78,1.80), for pregnancy rate 0.95 (95% CI 0.64,1.41), for miscarriage rate 1.26 (95% CI 0.59,2.70), for multiple pregnancy rate 0.44 (95% CI 0.16,1.21) and for OHSS 1.55 (95% CI 0.50,4.84). Similarly, in the only randomised trial that compared chronic low dose versus conventional regimen with rFSH no significant differences were found. REVIEWER'S CONCLUSIONS: At this moment there are not sufficient data to determine which of rFSH or uFSH is preferable for ovulation induction in women with PCOS.

[Changes in plasma levels of androgens and SHBG in patients with polycystic ovary syndrome (PCOs) treated with oral contraceptives containing desogestrel]. / Modificazione dei livelli plasmatici degli androgeni e della SHBG in pazienti con sindrome dell'ovaio policistico (PCOs) trattate con contraccettivi orali contenenti desogestrel.

PIP: 8 women, aged 17-25, with polycystic ovary syndrome (PCO) were treated with Practil 21 (Organon) containing 30 mcg of ethinyl estradiol and 150 mcg of desogestrel, or with Planum (Menarini). Checkups were conducted 3 and 6 months later to measure hormone levels. The average level of testosterone dropped significantly from 121.5 (+ or - 50.9) ng/dl to 23.1 (+ or - 10.6) ng/dl after 3 months. The level of androstenedione also decreased significantly from 265.2 (+ or - 101.4) ng.dl to 96.7 (+ or - 22.5) ng/dl. Similarly, the level of 17-hydroxyprogesterone declined from 120.5 (+ or - 69.8) ng/dl to 24.5 (+ or - 10.7) ng/dl . On the other hand, the level of sex hormone binding globulin rose from 1.3 (+ or - .6) mcg/100 ml to 3.9 (+ or - 1.8) mcg/100 ml. Cortisone level increased significantly from 15 (+ or - 3.2) mcg/100 ml to 30.6 (+ or - 10.4) mcg/100 ml after 3 months, but the normal range (5-20 mcg/100 ml) was attained at the end. Ecographic evaluation of the size of the ovaries indicated a 18.2-66.5% reduction after 3 months. In 3 cases, the number and dimension of follicles also diminished conspicuously. Acne, hirsutism, and other symptoms of hyperandrogenism also declined. Side effects were minor and included slight weight gain, spotting and headache; treatment was suspended in only 1 case because of a grand mal seizure. The administration of this new monophasic OC proved to be a valid alternative therapy for PCO.^ieng

Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome.

BACKGROUND: This randomized study's aim was to compare the effect of four oral contraceptives (OCs) containing 30 mcg of ethinylestradiol (EE) and different progestogens [drospirenone, (DRSP), chlormadinone acetate (CMA), desogestrel (DSG), gestodene (GSD)] on biochemical and hormonal parameters of hyperandrogenism and sex hormone-binding globulin (SHBG) in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Forty women with PCOS (age 16-35 years) were recruited and randomly assigned to one of four treatment groups of 10 women each, treated, respectively, with 3 mg DRSP/30 mcg EE (Yasmin, Bayer Shering), 2 mg CMA/30 mcg EE (Belara, Grunenthal), 75 mcg GSD/30 mcg EE (Minulet, Wyeth Lederle) and 150 mcg DSG/30 mcg EE (Practil 21, Organon Italia). Blood samples were obtained on day 6-8 of the control cycle and day 6-8 of the third treatment cycle for assay of the following hormones: androsteredione (A), total testosterone (T), free T, SHBG, dehydroepiandrosterone sulphate (DHEAS). RESULTS: In all groups, mean concentrations of free T, total T and A dropped by 40-60%, and concentrations of DHEAS dropped by 20-50%. Formulations with DRSP and CMA caused a greater reduction of androgens and a progressive increase in serum concentrations of SHBG than those with DSG and GSD. CONCLUSIONS: Clinical studies need to be performed to determine effects of these OCs upon clinical signs of hyperandrogenism.