Antimüllerian hormone level predicts ovulation in women with polycystic ovary syndrome treated with clomiphene and metformin.

OBJECTIVE: To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin. DESIGN: Secondary analysis of randomized controlled trial. SETTING: Not applicable. PATIENT(S): A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed. RESULT(S): A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1-43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders. CONCLUSION(S): These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction with clomiphene, clomiphene + metformin, and metformin. CLINICAL TRIAL REGISTRATION NUMBER: The original trial from which this analysis is derived was entitled "Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome" and was registered on ClinicalTrials.gov as number NCT00068861. The URL for the trial is https://clinicaltrials.gov/study/NCT00068861. The first subject was enrolled in November 2002.

Changing the "scope" of diagnosing endometriosis: the new frontier of noninvasive markers.

Endometriosis affects 1 in 9 women, and diagnosis is often delayed using conventional laparoscopy. Noninvasive markers of endometriosis have the potential to enable earlier diagnosis, leading to more timely treatment and better surgical planning. This issue's Views and Reviews seek to summarize the current status of noninvasive markers of endometriosis. Experts in reproductive medicine with prior work in this field summarize the key literature on endometrial biomarkers, blood biomarkers, and advanced imaging, including ultrasound and magnetic resonance imaging. At present, there is no single definitive biomarker that can diagnose endometriosis with high sensitivity and specificity. Advancing endometriosis biomarkers beyond the discovery phase is challenging, and more work is needed. Clinicians who have an improved understanding of noninvasive imaging and biomarkers will be able to identify endometriosis earlier and more easily, allowing for prompt consideration of treatment options. We believe that continued research, innovation, and development will lead to improved diagnostic accuracy and guidance toward the best treatments for endometriosis-related pain and infertility.

Do gender differences exist in letters of recommendation for reproductive endocrinology and infertility fellowship?

OBJECTIVE(S): To determine if gender differences exist in letters of recommendation (LORs) for reproductive endocrinology and infertility fellowship. DESIGN: Cohort study. SETTING: Academic medical center. PATIENTS: A cohort of applicants to a reproductive endocrinology and infertility fellowship program at a single Midwestern academic institution in a single year. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Quantitative measures included linguistics inquiry and word count analysis, with 4 summary variables and 25 word categories, to quantify tone and themes present by gender. Performing qualitative analysis in parallel to linguistic analysis allowed for the exploration of themes not conveyed in quantitative methods alone. Qualitative measures included the frequency of code themes in LOR by applicant gender. RESULTS: There were 272 letters from 72 applicants, 54 (76%) of which were women and 17 (24%) were men. One applicant was excluded because gender information was not specified; 269 letters were included in the quantitative linguistics and qualitative coding analysis. One hundred 10 letters (41%) were written by women and 159 (59%) by men. LOR written for men had a higher mean word count than those written for women (537 vs. 474, P=.04). Linguistics Inquiry and Word Count analysis exhibited more risk words used to describe men applicants (P=.01). When comparing word categories by letter writer gender, women letter writers more frequently used communal, affect, and home word categories whereas men writers more frequently used affiliation-related words. Qualitative analysis revealed that letters for men applicants described leadership, altruism, rapport with patients, and strong endorsements more frequently, whereas women applicants' letters more often mentioned doubt raisers and disclosures of personal life. In addition, letters for women applicants more often described candidates as drama free, not easy to "fluster," and not complainers. Furthermore, letters for women more frequently disclosed parenthood status. CONCLUSIONS: Gender differences exist among both letter writers and applicants. Qualitative analysis revealed that women applicants were more likely to be described with doubt raisers and personal life disclosures, whereas men were more likely to be described by their altruism and with a strong endorsement. Increasing bias awareness and implementing mitigation strategies would improve gender equity in LOR.

Associations of reproductive and breastfeeding history with anti-Müllerian hormone concentration among African-American women of reproductive age.

RESEARCH QUESTION: Are gravidity, parity and breastfeeding history associated with anti-Müllerian hormone concentration among African-American women of reproductive age? DESIGN: This study included baseline data from the Study of the Environment, Lifestyle and Fibroids, a 5-year longitudinal study of African-American women. Within this community cohort, data from 1392 women aged 25-35 years were analysed. The primary outcome was serum anti-Müllerian hormone concentration measured using the Ansh Labs picoAMH assay, an enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate mean differences in anti-Müllerian hormone concentration (ß) and 95% CI by self-reported gravidity, parity and breastfeeding history, with adjustment for potential confounders. RESULTS: Of the 1392 participants, 1063 had a history of gravidity (76.4%). Of these, 891 (83.8%) were parous and 564 had breastfed. Multivariable-adjusted regression analyses found no appreciable difference in anti-Müllerian hormone concentration between nulligravid participants and those with a history of gravidity (ß = -0.025, 95% CI -0.145 to 0.094). Among participants with a history of gravidity, there was little difference in anti-Müllerian hormone concentration between parous and nulliparous participants (ß = 0.085, 95% CI -0.062 to 0.232). There was also little association between anti-Müllerian hormone concentration and breastfeeding history (ever versus never: ß = 0.009, 95% CI -0.093 to 0.111) or duration of breastfeeding (per 1-month increase: ß = -0.002, 95% CI -0.010 to 0.006). CONCLUSIONS: Gravidity, parity and breastfeeding history were not meaningfully associated with anti-Müllerian hormone concentration in this large sample of the Study of the Environment, Lifestyle and Fibroids cohort.

Neighborhood disadvantage is associated with decreased ovarian reserve in women with overweight and obesity.

OBJECTIVE(S): To evaluate the association between neighborhood disadvantage and ovarian reserve stratified by body mass index (BMI). DESIGN: Cross-sectional cohort study. SETTING: Single academic medical center. PATIENT(S): A total of 193 healthy reproductive-age women with regular menstrual cycles in the St. Louis, Missouri metropolitan area. INTERVENTION(S): Residence in a disadvantaged neighborhood. MAIN OUTCOME MEASURE(S): Ovarian reserve as assessed by ovarian antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) concentration. RESULT(S): Women (n = 193) ranged from 20 to 44 years. The majority had overweight or obesity (59%, n = 117) with mean BMI of 28±7 kg/m2. Forty-eight women lived in the most disadvantaged neighborhood quartile, of which 75% had overweight or obesity, compared with 54% of the 145 women living in the 3 less disadvantaged neighborhood quartiles. When controlling for age, race, and smoking status, women with overweight or obesity living in the most disadvantaged neighborhoods had significantly lower AMH compared with those living in the less disadvantaged neighborhoods. Antral follicle count did not differ among women with overweight or obesity by neighborhood of residence. Neighborhood disadvantage was not associated with ovarian reserve by AFC or AMH in women with normal weight or underweight status. CONCLUSION(S): Living in a socioeconomically deprived area is associated with lower markers of ovarian reserve among women with an elevated BMI.

A review of disparities in access to infertility care and treatment outcomes among Hispanic women.

Hispanic women have lower rates of use of infertility services than non-Hispanic White women. There are many barriers that impede access to infertility care including economic, geographic, cultural, and societal factors and there are disparities in treatment outcomes. Hispanic women are less likely to seek infertility care than non-Hispanic White women and even after infertility evaluation, Hispanic women are less likely to receive treatment for their infertility. Lower use of infertility treatments among Hispanic women is unlikely to be driven solely by economic factors. There is disappointingly little data on in-vitro fertilization treatment outcomes including the population of Hispanic women, and existing data has yielded conflicting results. Incomplete and variable reporting of race data across clinics raises the potential for misclassification bias and invalid study conclusions. Addressing disparities in access to reproductive medicine in the Hispanic population will required a multifaceted approach including expanded insurance coverage, improved education for both patients and providers, and additional research on barriers to care.

Fertility preservation discussions, referral and follow-up in male-to-female and female-to-male adolescent transgender patients.

The number of patients seeking transgender healthcare is growing, and there is a potential impact of gender-affirming therapies on fertility. The use of fertility preservation (FP), particularly among transgender adolescents, has been limited. We aimed to examine differences in FP counselling, referral and utilisation between male-to-female (MtF) and female-to-male (FtM) transgender adolescents. A retrospective review of the medical records of patients ages 12-17 seen at an academic medical centre between 2012 and 2017 with a diagnosis of gender dysphoria was conducted. A total of 22 MtF and 45 FtM adolescents were included. The counselling on the potential fertility impact of gender-affirming therapy was documented in 55%, and of those counselled, 73% were counselled before receiving medication. There was no significant difference between the timing of counselling for MtF versus FtM adolescents. Of patients with documented reproductive wishes, 77% reported either desire for adopted children or no desire for biological children. Among patients offered FP referral, 2 (22.2%) MtF and 3 (12.5%) FtM patients accepted; both MtF patients cryopreserved sperm. While most adolescents were counselled on the fertility impact of gender-affirming therapy, there is room for improvement as 45% of patients had no documented counselling. The rate of transgender adolescents pursuing FP consultation and gamete cryopreservation was low, consistent with prior studies in this population.