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.

Overnight Melatonin Concentration and Sleep Quality Are Associated with the Clinical Features of Polycystic Ovary Syndrome.

Circulating melatonin is elevated in women with polycystic ovary syndrome (PCOS); whether circadian disruptions coincide with sleep disturbances in women with PCOS or their symptom severity is unclear. The objective of this observational pilot study was to determine whether altered patterns of melatonin excretion are associated with reduced sleep quality in women with versus without PCOS. Participants underwent a clinical assessment, transvaginal ultrasound, and reproductive hormone testing. Morning and evening urine samples were assayed for urinary 6-sulfatoxymelatonin (MEL) as a proxy for melatonin production. The night (morning MEL)-to-day (evening MEL) ratio, or N:D ratio, was determined to approximate the rhythm of MEL production. Sleep quality and duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy. No differences were detected in overnight MEL, daytime MEL, or the N:D ratio in participants with PCOS versus controls. The PCOS group experienced reduced weekend sleep efficiency vs. controls (81% vs. 88% p < 0.05). The number of follicles per ovary (FNPO) was positively associated with overnight MEL (r = 0.359, p < 0.05). Weekend sleep time and overnight MEL concentrations were dependent on PCOS status. Therefore, diagnostic features of PCOS were associated with MEL production and sleep disturbances, suggesting that women with a more severe clinical presentation of PCOS may be more likely to experience altered MEL production or sleep disturbances.

Moderate and increased physical activity is not detrimental to live birth rates among women with unexplained infertility and obesity.

Objective: To determine if moderate physical activity is associated with live birth rates in women with unexplained infertility and obesity. Design: Secondary analysis of the Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial. Setting: US fertility centers, 2015-2019. Patients: A total of 379 women participated in Improving Reproductive Fitness through Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility trial, a lifestyle modification program with increased physical activity (phase I, 16 weeks) and up to three cycles of clomiphene citrate treatment and intrauterine insemination (phase II). Interventions: Participants were instructed to add 500 steps/day weekly until a maximum of 10,000 steps/day was reached and maintained. Participants were stratified as active (top third, N = 125) and less active (lower third, N = 125) on the basis of the average number of steps per day recorded using a FitBit activity tracker. Main Outcome Measures: Live birth rate. Results: Active participants were more physically active at the time of enrollment than less active participants (average baseline steps per day, 8,708 [7,079-10,000] vs. 4,695 [3,844-5,811]; P ≤ 0.001) and were more likely to reach 10,000 steps/day than less active participants (average steps per day, 10,526 [9,481-11,810] vs. 6,442 [4,644-7,747]; P ≤ 0.001), although both groups increased their average steps per day by a similar amount (1,818 vs.1,747; P = 0.57). There was no difference in live birth rates (24/125 [19.2%] vs. 25/125 [20%]; P = 0.87) between active and less active participants nor were there differences in clinical pregnancy rates (P = 0.45) or miscarriage rates (P = 0.49) between the two groups. Conclusions: Active participants were more likely to achieve the physical activity goal, although this was not associated with benefit or harm with respect to live birth. Clinical Trial Registration Number: ClinicalTrials.gov (NCT02432209), first posted: May 4, 2015.

Association between sex steroid hormones and subsequent hyperglycemia during pregnancy.

Objective: Sex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes. Methods: Retrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels. Results: In adjusted models, first trimester total testosterone (ß=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (ß=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (ß=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone. Conclusion: Early-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

Worth the wait? Preconception weight reduction in women and men with obesity and infertility: a narrative review.

Short and long-term weight reduction interventions are considered in the preconception period for women and men with obesity and infertility as obesity is associated with poorer reproductive outcomes. Short-term weight loss achieved with diet, exercise, and medications does not improve per cycle conception or live birth rates in women undergoing ovulation induction, intrauterine insemination, or in vitro fertilization (IVF), but may increase the rate of natural conception. Long-term weight loss achieved through surgical interventions may increase spontaneous conceptions, particularly among women with polycystic ovary syndrome, and may increase the live birth rate from IVF, though these findings are limited by recent evidence. There is a clear need for additional treatment options and well-designed weight loss intervention trials that address the heterogeneous causes of obesity among women and men with infertility and include fertility outcomes and perinatal morbidity as outcome measures.

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial.

BACKGROUND: Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth. METHODS AND FINDINGS: In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful. CONCLUSIONS: A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02432209.

Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location: The ACT or NOT Randomized Clinical Trial.

Importance: Women with an early nonviable pregnancy of unknown location are at high risk of ectopic pregnancy and its inherent morbidity and mortality. Successful and timely resolution of the gestation, while minimizing unscheduled interventions, are important priorities. Objective: To determine if active management is more effective in achieving pregnancy resolution than expectant management and whether the use of empirical methotrexate is noninferior to uterine evacuation followed by methotrexate if needed. Design, Setting, and Participants: This multicenter randomized clinical trial recruited 255 hemodynamically stable women with a diagnosed persisting pregnancy of unknown location between July 25, 2014, and June 4, 2019, in 12 medical centers in the United States (final follow up, August 19, 2019). Interventions: Eligible patients were randomized in a 1:1:1 ratio to expectant management (n = 86), active management with uterine evacuation followed by methotrexate if needed (n = 87), or active management with empirical methotrexate using a 2-dose protocol (n = 82). Main Outcomes and Measures: The primary outcome was successful resolution of the pregnancy without change from initial strategy. The primary hypothesis tested for superiority of the active groups combined vs expectant management, and a secondary hypothesis tested for noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed using a noninferiority margin of -12%. Results: Among 255 patients who were randomized (median age, 31 years; interquartile range, 27-36 years), 253 (99.2%) completed the trial. Ninety-nine patients (39%) declined their randomized allocation (26.7% declined expectant management, 48.3% declined uterine evacuation, and 41.5% declined empirical methotrexate) and crossed over to a different group. Compared with patients randomized to receive expectant management (n = 86), women randomized to receive active management (n = 169) were significantly more likely to experience successful pregnancy resolution without change in their initial management strategy (51.5% vs 36.0%; difference, 15.4% [95% CI, 2.8% to 28.1%]; rate ratio, 1.43 [95% CI, 1.04 to 1.96]). Among active management strategies, empirical methotrexate was noninferior to uterine evacuation followed by methotrexate if needed with regard to successful pregnancy resolution without change in management strategy (54.9% vs 48.3%; difference, 6.6% [1-sided 97.5% CI, -8.4% to ∞]). The most common adverse event was vaginal bleeding for all of the 3 management groups (44.2%-52.9%). Conclusions and Relevance: Among patients with a persisting pregnancy of unknown location, patients randomized to receive active management, compared with those randomized to receive expectant management, more frequently achieved successful pregnancy resolution without change from the initial management strategy. The substantial crossover between groups should be considered when interpreting the results. Trial Registration: ClinicalTrials.gov Identifier: NCT02152696.

Update on PCOS: Consequences, Challenges, and Guiding Treatment.

Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in women and despite this, diagnostic challenges, delayed diagnosis, and less-than-optimal treatment regimens plague the condition. The International PCOS network, consisting of geographically diverse international experts in PCOS as well as consumers, engaged in a multi-year international evidence-based guideline development process that was jointly sponsored by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM). The guideline was published in 2018 and endorsed by more than 40 international societies involved in PCOS. Translation of this evidence-based guideline to medical practice and consumer groups remains a priority. However, there remain many challenges to both understanding the diagnosis and treatment of PCOS. Evidence suggests that both clinicians and consumers are not satisfied with the timeliness of diagnosis and treatment options. This review summarizes the important findings for diagnosis and treatment from the guidelines and expands on recent developments in the literature since its publication. Special attention to diagnosis at the ends of the reproductive spectrum are discussed and remaining areas of controversy are noted. Additionally, the review highlights some of the remaining challenges in the understanding and management of PCOS to help guide clinicians and investigators in this perplexing condition.

Short-term weight change and live birth among women with unexplained infertility and polycystic ovary syndrome undergoing ovulation induction.

OBJECTIVE: To determine if short-term weight change among women with unexplained infertility (UI) and polycystic ovary syndrome (PCOS) undergoing ovulation induction is associated with live birth. DESIGN: Secondary analysis of randomized trials. SETTING: Multicenter fertility trial sites. PATIENT(S): A total of 900 women with UI and 750 women with PCOS. MAIN OUTCOME MEASURE(S): Live birth. INTERVENTION(S): Weight assessment at enrollment and start of up to 4-5 cycles of clomiphene, letrozole, or gonadotropins and intrauterine insemination for women with UI and clomiphene or letrozole with regular intercourse for women with PCOS. RESULT(S): Weight data were available for 856 women with UI and 697 women with PCOS. Mean weight change was -0.2 ± 0.3 kg among women with UI and +2.2 ± 0.2 kg among women with PCOS and did not differ based on treatment allocation. There were 115 women with PCOS (16.4%) who gained ≥3 kg. Increased body mass index and three or more cycles were associated with weight gain in women with PCOS. There was no difference in live birth rate among women with PCOS and ≥3 kg weight gain and women with PCOS who did not gain weight. CONCLUSION(S): Women with PCOS gained an average of 2.2 kg regardless of the medication received, whereas women with UI experienced no short-term weight change during ovulation induction. Weight gain in women with PCOS was not associated with live birth rate.

Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women.

The relationship between diet quality and ovarian morphology has biological plausibility yet remains unclear and was therefore evaluated. In a multicenter cross-sectional analysis, four dietary patterns were scored for 111 consecutive reproductive-aged women (18-45 years) using (1) Healthy Eating Index (HEI-2015); (2) alternative HEI-2010; (3) alternate Mediterranean Diet (aMED); (4) and Dietary Approaches to Stop Hypertension (DASH) indices. Ovarian volume (OV) and follicle number per ovary (FNPO) were evaluated on transvaginal ultrasonography. Relationships between dietary and ovarian morphology indices were evaluated by linear regression and mediation analyses. Associations between aMED and DASH scores and OV/FNPO were completely mediated by obesity, insulin resistance, and hyperandrogenism (All: p < 0.05), unlike direct associations (All: p ≥ 0.89). Namely, a 1-standard deviation [SD] increase in aMED score was associated with decreases in OV (0.09 SD; 0.4 mL) through reducing waist circumference. Likewise, a 1 SD increase in aMED and DASH score was associated with decreases in OV (0.07 SD; 0.3 mL) by reducing glucose response to a 75 g glucose tolerance test. A 1 SD increase in DASH score was associated with decreased FNPO (0.07 SD; 2 follicles) by reducing free androgen index (All: p < 0.05). Adherence to aMED and DASH eating plans was indirectly associated with significant improvements in ovarian form, providing novel mechanistic insights for future interventions about contributions of diet quality on ovarian function.

Osteosarcopenia in Reproductive-Aged Women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study.

CONTEXT: Osteosarcopenia (loss of skeletal muscle and bone mass and/or function usually associated with aging) shares pathophysiological mechanisms with polycystic ovary syndrome (PCOS). However, the relationship between osteosarcopenia and PCOS remains unclear. OBJECTIVE: We evaluated skeletal muscle index% (SMI% = [appendicular muscle mass/weight (kg)] × 100) and bone mineral density (BMD) in PCOS (hyperandrogenism + oligoamenorrhea), and contrasted these musculoskeletal markers against 3 reproductive phenotypes (i): HA (hyperandrogenism + eumenorrhea) (ii); OA (normoandrogenic + oligoamenorrhea) and (iii), controls (normoandrogenic + eumenorrhea). Endocrine predictors of SMI% and BMD were evaluated across the groups. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control study of 203 women (18-48 years old) in New York State. RESULTS: PCOS group exhibited reduced SMI% (mean [95% confidence interval (CI)]; 26.2% [25.1,27.3] vs 28.8% [27.7,29.8]), lower-extremity SMI% (57.6% [56.7,60.0] vs 62.5% [60.3,64.6]), and BMD (1.11 [1.08,1.14] vs 1.17 [1.14,1.20] g/cm2) compared to controls. PCOS group also had decreased upper (0.72 [0.70,0.74] vs 0.77 [0.75,0.79] g/cm2) and lower (1.13 [1.10,1.16] vs 1.19 [1.16,1.22] g/cm2) limb BMD compared to HA. Matsuda index was lower in PCOS vs controls and positively associated with SMI% in all groups (all Ps ≤ 0.05). Only controls showed associations between insulin-like growth factor (IGF) 1 and upper (r = 0.84) and lower (r = 0.72) limb BMD (all Ps < 0.01). Unlike in PCOS, IGF-binding protein 2 was associated with SMI% in controls (r = 0.45) and HA (r = 0.67), and with upper limb BMD (r = 0.98) in HA (all Ps < 0.05). CONCLUSIONS: Women with PCOS exhibit early signs of osteosarcopenia when compared to controls likely attributed to disrupted insulin function. Understanding the degree of musculoskeletal deterioration in PCOS is critical for implementing targeted interventions that prevent and delay osteosarcopenia in this clinical population.

Adolescent polycystic ovary syndrome according to the international evidence-based guideline.

BACKGROUND: Diagnosing polycystic ovary syndrome (PCOS) during adolescence is challenging because features of normal pubertal development overlap with adult diagnostic criteria. The international evidence-based PCOS Guideline aimed to promote accurate and timely diagnosis, to optimise consistent care, and to improve health outcomes for adolescents and women with PCOS. METHODS: International healthcare professionals, evidence synthesis teams and consumers informed the priorities, reviewed published data and synthesised the recommendations for the Guideline. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied to appraise the evidence quality and the feasibility, acceptability, cost, implementation and strength of the recommendations. RESULTS: This paper focuses on the specific adolescent PCOS Guideline recommendations. Specific criteria to improve diagnostic accuracy and avoid over diagnosis include: (1) irregular menstrual cycles defined according to years post-menarche; > 90 days for any one cycle (> 1 year post-menarche), cycles< 21 or > 45 days (> 1 to < 3 years post-menarche); cycles < 21 or > 35 days (> 3 years post-menarche) and primary amenorrhea by age 15 or > 3 years post-thelarche. Irregular menstrual cycles (< 1 year post-menarche) represent normal pubertal transition. (2) Hyperandrogenism defined as hirsutism, severe acne and/or biochemical hyperandrogenaemia confirmed using validated high-quality assays. (3) Pelvic ultrasound not recommended for diagnosis of PCOS within 8 years post menarche. (4) Anti-Müllerian hormone levels not recommended for PCOS diagnosis; and (5) exclusion of other disorders that mimic PCOS. For adolescents who have features of PCOS but do not meet diagnostic criteria an 'at risk' label can be considered with appropriate symptomatic treatment and regular re-evaluations. Menstrual cycle re-evaluation can occur over 3 years post menarche and where only menstrual irregularity or hyperandrogenism are present initially, evaluation with ultrasound can occur after 8 years post menarche. Screening for anxiety and depression is required and assessment of eating disorders warrants consideration. Available data endorse the benefits of healthy lifestyle interventions to prevent excess weight gain and should be recommended. For symptom management, the combined oral contraceptive pill and/or metformin may be beneficial. CONCLUSIONS: Extensive international engagement accompanied by rigorous processes honed both diagnostic criteria and treatment recommendations for PCOS during adolescence.

Dietary and Physical Activity Behaviors in Women with Polycystic Ovary Syndrome per the New International Evidence-Based Guideline.

Lifestyle modifications are recommended as first-line therapy in polycystic ovary syndrome (PCOS). However, usual dietary and physical activity (PA) behaviors of women with PCOS remain uncertain, likely owing to controversy in diagnostic criteria. Our objective was to contrast the usual dietary and PA behaviors of women with PCOS (n = 80) diagnosed by the 2018 International Evidence-based Guideline for the Assessment and Management of PCOS to that of controls (n = 44). Study outcomes were dietary intake, diet quality (Healthy Eating Index-2015), and PA (questionnaire, waist-worn accelerometers). Women with PCOS met the acceptable macronutrient distribution ranges for carbohydrate, fat, and protein, but did not meet the recommended dietary reference intakes for vitamin D (mean (95% confidence interval); 6 (5-7) µg/d), vitamin B9 (275 (252-298) µg/d), total fiber (24 (22-26) g/d), or sodium (4.0 (3.6-4.4) g/d). Women with PCOS also met the US recommendations for PA. No differences were detected in dietary intake, diet quality, or PA levels between groups (p ≥ 0.11). In conclusion, women with and without PCOS have comparable dietary and PA behaviors. A lack of unique targets for dietary or PA interventions supports the position of the new guideline to foster healthy lifestyle recommendations for the management of PCOS.

Impact of right-left differences in ovarian morphology on the ultrasound diagnosis of polycystic ovary syndrome.

OBJECTIVE: To assess right-left differences in ultrasonographic markers of ovarian morphology and determine the impact on the diagnosis of polycystic ovarian morphology (PCOM). DESIGN: A cross-sectional study of data collected from 2006 to 2018. SETTING: Academic clinical research centers. PATIENT(S): Women with polycystic ovary syndrome (PCOS; n = 87) and controls (n = 67). INTERVENTION(S): None. MAIN OUTCOMES MEASURE(S): Follicle number per ovary (FNPO), follicle number per cross-section (FNPS), and ovarian volume (OV) were assessed in both ovaries using transvaginal ultrasonography. PCOM was identified based on recent international consensus guidelines or proposed diagnostic thresholds. RESULT(S): Overall, mean right-left differences were two follicles for FNPO, one follicle for FNPS, and 2 mL for OV. FNPO showed the strongest correlation between ovaries. Its assessment in a single ovary did not impact the diagnosis of PCOM in women with PCOS. However, there were differences in the probability of unilateral versus bilateral PCOM based on FNPS and OV in both groups. CONCLUSION(S): FNPO is the most reliable unilateral marker of PCOM in light of right-left differences in ovarian morphology. Use of FNPS or OV to define PCOM is discouraged when only one ovary is visualized.

Anti-Müllerian Hormone in PCOS: A Review Informing International Guidelines.

Polycystic ovary syndrome (PCOS) affects 8-13% of women. The Rotterdam diagnostic criteria include polycystic ovarian morphology (PCOM) on ultrasound, but given recognized challenges, serum anti-Müllerian hormone (AMH) is proposed as an alternative. To inform international PCOS guidelines, a systematic review was completed. Key identified gaps include large international studies in well-defined populations across the lifespan, clustering of AMH with PCOS features, relationships to long-term health outcomes, and improved quality, assay standardization, and sample handling, all needed to determine cut offs. Here we identify research priorities to address these gaps and enhance AMH utility in PCOS. Once issues are addressed, AMH levels could replace more costly and less accessible ultrasound in PCOS diagnosis.