Polycystic ovary syndrome.

Despite affecting ~11-13% of women globally, polycystic ovary syndrome (PCOS) is a substantially understudied condition. PCOS, possibly extending to men's health, imposes a considerable health and economic burden worldwide. Diagnosis in adults follows the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, requiring two out of three criteria - clinical or biochemical hyperandrogenism, ovulatory dysfunction, and/or specific ovarian morphological characteristics or elevated anti-Müllerian hormone. However, diagnosing adolescents omits ovarian morphology and anti-Müllerian hormone considerations. PCOS, marked by insulin resistance and hyperandrogenism, strongly contributes to early-onset type 2 diabetes, with increased odds for cardiovascular diseases. Reproduction-related implications include irregular menstrual cycles, anovulatory infertility, heightened risks of pregnancy complications and endometrial cancer. Beyond physiological manifestations, PCOS is associated with anxiety, depression, eating disorders, psychosexual dysfunction and negative body image, collectively contributing to diminished health-related quality of life in patients. Despite its high prevalence persisting into menopause, diagnosing PCOS often involves extended timelines and multiple health-care visits. Treatment remains ad hoc owing to limited understanding of underlying mechanisms, highlighting the need for research delineating the aetiology and pathophysiology of the syndrome. Identifying factors contributing to PCOS will pave the way for personalized medicine approaches. Additionally, exploring novel biomarkers, refining diagnostic criteria and advancing treatment modalities will be crucial in enhancing the precision and efficacy of interventions that will positively impact the lives of patients.

Depression, Anxiety, and Risk of Metabolic Syndrome in Women With Polycystic Ovary Syndrome: A Longitudinal Study.

CONTEXT: Patients with PCOS are at high risk of depression, anxiety, and metabolic syndrome (MetSyn), a key predictor of cardiovascular disease. The impact of depression and/or anxiety on MetSyn is unknown in this population. OBJECTIVE: To compare the risk of developing MetSyn in patients with PCOS with and without a history of depression and/or anxiety. DESIGN: Retrospective longitudinal cohort study (2008-2022) with median follow-up of 7 years. SETTING: Tertiary care ambulatory practice. PATIENTS OR OTHER PARTICIPANTS: Patients with hyperandrogenic PCOS and at least 2 evaluations for MetSyn ≥3 years apart (n=321). INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): The primary outcome was risk of developing MetSyn. We hypothesized that this risk would be higher with a history of depression and/or anxiety. RESULTS: At the first visit, 33.0% had a history of depression and/or anxiety, with a third prescribed antidepressants or anxiolytics. Depression and/or anxiety increased risk of developing MetSyn during the study period (adjusted hazard ratio [aHR] 1.45, 95% CI 1.02-2.06, p=0.04) with an incidence of MetSyn of 75.3 compared to 47.6 cases per 100 person-years among those without (p=0.002). This was primarily driven by depression (aHR 1.56, 95% CI 1.10-2.20, p=0.01). CONCLUSIONS: Patients with PCOS and depression and/or anxiety have a high risk of developing MetSyn, with a stronger association between depression and MetSyn. Our findings highlight the urgent need for guideline-directed screening for depression and anxiety at time of diagnosis of PCOS as well as screening at subsequent visits to facilitate risk stratification for metabolic monitoring and early intervention in this high-risk group.

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To derive and internally validate a clinical prediction model for live birth (LB) in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Four academic reproductive endocrinology clinics. PATIENTS: A total of 207 women with PCOS confirmed using Rotterdam criteria undergoing their first fresh IVF cycle. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was cumulative LB per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for LB were calculated using the prediction model which included the 90% shrinkage factor for each adjusted odds ratio. RESULTS: The final model, on the basis of maximization of the area under the receiver operating characteristic curve, included age < 35 years, White race, presence of polycystic ovaries on ultrasound (polycystic ovary morphology), normal body mass index (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a nonresponder to ovulation induction agents including letrozole and clomiphene citrate. The area under the receiver operating characteristic curve score for the model was 0.68 (95% confidence interval [CI]: 0.60, 0.77). Predicted probabilities of LB ranged from 8.1% (95% CI: 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. CONCLUSION: Our study demonstrated that, in addition to anovulation, the underlying pathophysiology and associated comorbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it can serve as a tool to personalize prediction estimates for the probability of LB in women with PCOS.

Sexual function in women with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common and distressing endocrine disorder associated with lower quality of life, subfertility, diabetes, cardiovascular disease, depression, anxiety, and eating disorders. PCOS characteristics, its comorbidities, and its treatment can potentially influence sexual function. However, studies on sexual function in women with PCOS are limited and contradictory. OBJECTIVE AND RATIONALE: The aim was to perform a systematic review of the published literature on sexual function in women with PCOS and assess the quality of the research and certainty of outcomes, to inform the 2023 International Guidelines for the Assessment and Management of PCOS. SEARCH METHODS: Eight electronic databases were searched until 1 June 2023. Studies reporting on sexual function using validated sexuality questionnaires or visual analogue scales (VAS) in PCOS populations were included. Random-effects models were used for meta-analysis comparing PCOS and non-PCOS groups with Hedges' g as the standardized mean difference. Study quality and certainty of outcomes were assessed by risk of bias assessments and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method according to Cochrane. Funnel plots were visually inspected for publication bias. OUTCOMES: There were 32 articles included, of which 28 used validated questionnaires and four used VAS. Pooled Female Sexual Function Index (FSFI) scores in random-effects models showed worse sexual function across most subdomains in women with PCOS, including arousal (Hedges's g [Hg] [95% CI] = -0.35 [-0.53, -0.17], I2 = 82%, P < 0.001), lubrication (Hg [95% CI] = -0.54 [-0.79, -0.30], I2 = 90%, P < 0.001), orgasm (Hg [95% CI] = -0.37 [-0.56, -0.19], I2 = 83%, P < 0.001), and pain (Hg [95% CI] = -0.36 [-0.59, -0.13] I2 = 90%, P < 0.001), as well as total sexual function (Hg [95% CI] = -0.75 [-1.37, -0.12], I2 = 98%, P = 0.02) and sexual satisfaction (Hg [95% CI] = -0.31 [-0.45, -0.18], I2 = 68%, P < 0.001). Sensitivity and subgroup analyses based on fertility status and body mass index (BMI) did not alter the direction or significance of the results. Meta-analysis on the VAS studies demonstrated the negative impact of excess body hair on sexuality, lower sexual attractiveness, and lower sexual satisfaction in women with PCOS compared to controls, with no differences in the perceived importance of a satisfying sex life. No studies assessed sexual distress. GRADE assessments showed low certainty across all outcomes. WIDER IMPLICATIONS: Psychosexual function appears to be impaired in those with PCOS, but there is a lack of evidence on the related distress scores, which are required to meet the criteria for psychosexual dysfunction. Health care professionals should discuss sexual function and distress and be aware of the multifactorial influences on sexual function in PCOS. Future research needs to assess both psychosexual function and distress to aid in understanding the degree of psychosexual dysfunction in PCOS. Finally, more diverse populations (e.g. non-heterosexual and more ethnically diverse groups) should be included in future studies and the efficacy of treatments for sexual dysfunction should also be assessed (e.g. lifestyle and pharmacological interventions).

Management of polycystic ovary syndrome must include assessment and treatment of mental health symptoms.

Polycystic ovary syndrome (PCOS) is an endocrine disorder with reproductive and metabolic manifestations affecting millions of women worldwide. The health risks associated with PCOS, however, go beyond physical health. Over the past decade, data have emerged demonstrating a high risk of concurrent mental health conditions, specifically depression and anxiety, but extending into other aspects of psychological health, including body image distress, eating disorders, and sexual dysfunction. International surveys suggest physician knowledge about the mental health associations with PCOS is poor and that patients are often dissatisfied regarding counseling-related psychological issues. We performed a review of mental health comorbidities in individuals with PCOS, including depression, anxiety, body image distress, eating disorders, psychosexual dysfunction, and decreased quality of life, as well as evaluated the impact of common PCOS treatments on these conditions. Most meta-analyses in reproductive age women demonstrate increased risks of these conditions, although data are more limited in adolescents and older adults. In addition, the impact of PCOS treatments on these conditions as well as data on first-line treatments in the PCOS population is limited. All providers involved in the multidimensional care of individuals with PCOS should be aware of these mental health risks to provide appropriate screening, counseling and referral options. Future studies should be designed to evaluate targeted treatment for individuals with PCOS.

Mental health disorders-should we screen all our patients?

Understanding the precise interplay between mental and physical health, as related to specific gynecological diseases, is crucial to providing high-quality, comprehensive, and effective care to our patients. A large body of literature provides evidence for the association of infertility, polycystic ovary syndrome, endometriosis and fibroids with anxiety, depression, eating disorders, sexual dysfunction, and/or reduced health related quality of life. Although the precise etiology of these associations is not clear, chronic pain, hormonal changes, body image distress, feelings of helplessness and high stress levels have all been described as possible mediators. Lack of early diagnosis and management of mental health conditions is known to impact compliance with office visits, diagnostic testing and treatment leading to overall reduced quality of life. As part of a holistic approach, we need to develop evidence-based guidelines for screening high-risk patients and increase collaboration between gynecologists and mental health professionals to offer seamless care. This goal may be aspirational as there are several patient- and provider-related challenges to offering comprehensive care to this patient population. Embracing novel technology-based opportunities and incorporating connected healthcare delivery models will help us meet these growing challenges.

Considerations in the Treatment of Depression and Anxiety in Women with PCOS.

Women with polycystic ovary syndrome (PCOS) are known to be at a greater risk of depression and anxiety. What is less clear is whether existing treatments for PCOS are effective in managing this increased risk and what the optimal approach to treatment is. In this review, currently available interventions are explored including lifestyle modifications, oral contraceptives, insulin sensitizing agents, psychosocial interventions and psychiatric medications. While data are often conflicting, lifestyle interventions, and cognitive behavioral therapy (CBT) appear most promising in reducing depression and anxiety symptoms in this population. There is an urgent need for large prospective studies to fill gaps in the literature.

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.

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.

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 6 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, the evidence quality was low, and evidence-practice gaps persist. STUDY DESIGN, SIZE, AND DURATION: The 2023 International Evidence-based Guideline update re-engaged 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, AND METHODS: This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 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 5 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 5 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. MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) 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; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management. LIMITATIONS AND 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 programme supports the guideline with an integrated evaluation programme.

Elevated antimüllerian hormone levels are not associated with preterm delivery after in vitro fertilization or ovulation induction.

OBJECTIVE: To investigate the association between antimüllerian hormone (AMH) and preterm birth risk in a larger cohort of patients who underwent either in vitro fertilization or ovulation induction with intrauterine insemination at a US academic fertility center. DESIGN: Retrospective cohort study. SETTING: Single academic fertility center. PATIENT(S): Live singleton births from patients who underwent in vitro fertilization or ovulation induction between 2016 and 2020 at a single academic fertility center were included in this study. Patients were excluded if they had a missing prepregnancy AMH level, a pregnancy using donor oocytes or a gestational carrier, multiple gestations, a delivery before 20 weeks gestation, or a cerclage in place. INTERVENTION(S): AMH level. MAIN OUTCOME MEASURE(S): The primary outcome was the proportion of preterm delivery. Secondary outcomes included the rate of pregnancy-induced hypertension, gestational diabetes, and small for gestational age. RESULT(S): In the entire cohort (n = 875), 8.4% of deliveries were preterm. The mean AMH values were similar between those with term and preterm births (3.9 vs. 4.2 ng/mL). Similar proportions of patients with term and preterm deliveries had AMH levels greater than the 75th percentile (25% vs. 21%). The odds of preterm birth were similar by AMH quartile after adjusting for the history of preterm birth. Similarly, in the polycystic ovary syndrome (PCOS) cohort, there was no difference between mean AMH values of term and preterm births (n = 139, 9.6 vs. 10.0 ng/mL). The proportions of patients with PCOS with AMH levels greater than the 75th percentile were similar between those with term and preterm deliveries (25% vs. 22%). The odds of preterm birth were similar by the AMH quartile after adjusting for the history of preterm birth. CONCLUSION(S): Elevated AMH levels were not associated with an increased risk of preterm birth in patients who conceived after in vitro fertilization and ovulation induction, including patients with PCOS. Although studies suggest that AMH levels may help stratify the risk of preterm birth in this population, our findings indicate that further studies are needed before clinical application.

Outcomes of assisted reproductive technology procedures performed on weekdays versus weekends: a retrospective cohort study.

PURPOSE: To evaluate if assisted reproductive technology (ART) outcomes are different based on whether procedures - oocyte retrieval, insemination, embryo biopsy, or embryo transfer - are performed on a weekday versus weekend/holiday. METHODS: Retrospective cohort study of all patients ≥ 18 years old who underwent oocyte retrieval for in vitro fertilization or oocyte banking (n = 3,197 cycles), fresh or natural-cycle frozen embryo transfers (n = 1,739 transfers), or had embryos biopsied for pre-implantation genetic testing (n = 4,568 embryos) in a large academic practice from 2015-2020. The primary outcomes were as follows: oocyte maturity for oocyte retrievals; fertilization rate for insemination; rate of no result on pre-implantation genetic testing for embryo biopsy; and live birth rate for embryo transfers. RESULTS: The average number of procedures performed per embryologist per day was higher on weekends/holidays than weekdays. For oocyte retrievals performed on weekdays vs. weekends/holidays, there was no difference in oocyte maturity rate (88% vs 88%). There was no difference in the fertilization rate (82% vs 80%) in cycles that had intracytoplasmic sperm injection performed on weekdays vs. weekends/holidays. No difference was found in the no result rate for embryos biopsied on weekdays vs. weekends/holidays (2.5% vs 1.8%). Finally, there was no difference by weekday vs. weekend/holiday in the live birth rate per transfer among all transfers (39.6% vs 36.1%), or when stratified by fresh (35.1% vs 34.9%) or frozen embryo transfer (49.7% vs. 39.6%). CONCLUSION: We found no differences in ART outcomes among women who had their oocyte retrievals, inseminations, embryo biopsies, or embryo transfers performed on weekdays versus weekends/holidays.

Genetics in reproductive endocrinology and infertility.

Tremendous advances in genetics have transformed the field of reproductive endocrinology and infertility over the last few decades. One of the most prominent advances is preimplantation genetic testing (PGT), which allows for the screening of embryos obtained during in vitro fertilization before transfer. Moreover, PGT can be performed for aneuploidy screening, detection of monogenic disorders, or exclusion of structural rearrangements. Refinement of biopsy techniques, such as obtaining samples at the blastocyst rather than the cleavage stage, has helped optimize results from PGT, and technological advances, including next-generation sequencing, have made PGT more efficient and accurate. The continued evolution of the approach to PGT has the potential to further enhance the accuracy of results, expand the application to other conditions, and increase access by reducing cost and improving efficiency.

Recognizing racial and ethnic disparities in women's reproductive health is not enough.

This Views and Reviews is a compilation of reports summarizing the published literature describing racial and ethnic disparities in polycystic ovary syndrome, fibroids, endometriosis, assisted reproductive technology, and disorders of mental health in women. The disparities are unique for each of these conditions and encompass disease prevalence and severity, access to care, and the outcomes of treatment.

Risk of severe acute respiratory syndrome coronavirus 2 infection among women with polycystic ovary syndrome.

OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) had a higher incidence of testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than those without PCOS and evaluate whether PCOS diagnosis independently increased the risk of moderate or severe disease in those with positive SARS-CoV-2 test results. DESIGN: Retrospective cohort study using the National COVID Cohort Collaborative (N3C). SETTING: National COVID Cohort Collaborative. PATIENT(S): Adult nonpregnant women (age, 18-65 years) enrolled in the N3C with confirmed SARS-CoV-2 testing for any indication. Sensitivity analyses were conducted in women aged 18-49 years and who were obese (body mass index, ≥30 kg/m2). INTERVENTION(S): The exposure was PCOS as identified by the N3C clinical diagnosis codes and concept sets, which are a compilation of terms, laboratory values, and International Classification of Diseases codes for the diagnosis of PCOS. To further capture patients with the symptoms of PCOS, we also included those who had concept sets for both hirsutism and irregular menses. MAIN OUTCOME MEASURE(S): Odds of testing positive for SARS-CoV-2 and odds of moderate or severe coronavirus disease 2019 (COVID-19) in the PCOS cohort compared with those in the non-PCOS cohort. RESULT(S): Of the 2,089,913 women included in our study, 39,459 had PCOS. In the overall cohort, the adjusted odds ratio (aOR) of SARS-CoV-2 positivity was 0.98 (95% confidence interval [CI], 0.97-0.98) in women with PCOS compared to women without PCOS. The aORs of disease severity were as follows: mild disease, 1.02 (95% CI, 1.01-1.03); moderate disease, 0.99 (95% CI, 0.98-1.00); and severe disease, 0.99 (95% CI, 0.99-1.00). There was no difference in COVID-19-related mortality (aOR, 1.00; 95% CI, 0.99-1.00). These findings were similar in the reproductive-age and obese reproductive-age cohorts. CONCLUSION(S): Women with PCOS had a similar likelihood of testing positive for SARS-CoV-2. Among those who tested positive, they were no more likely to have moderate or severe COVID-19 than the non-PCOS cohort. Polycystic ovary syndrome is a chronic condition associated with several comorbidities, including cardiovascular disease and mental health issues. Although these comorbidities are also associated with COVID-19 morbidity, our findings suggest that the comorbidities themselves, rather than PCOS, drive the risk of disease severity.