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Context: Suboptimal endometrial thickening is associated with lower pregnancy rates and occurs in some infertile women treated with clomiphene., Objective: To examine cellular and molecular differences in the endometrium of women with suboptimal vs optimal endometrial thickening following clomiphene., Methods: Translational prospective cohort study from 2018 to 2020 at a university-affiliated clinic. Reproductive age women with unexplained infertility treated with 100 mg of clomiphene on cycle days 3 to 7 who developed optimal (≥8mm; n = 6, controls) or suboptimal (<6mm; n = 7, subjects) endometrial thickness underwent preovulatory blood and endometrial sampling. The main outcome measures were endometrial tissue architecture, abundance and location of specific proteins, RNA expression, and estrogen receptor (ER) α binding., Results: The endometrium of suboptimal subjects compared with optimal controls was characterized by a reduced volume of glandular epithelium (16% vs 24%, P = .01), decreased immunostaining of markers of proliferation (PCNA, ki67) and angiogenesis (PECAM-1), increased immunostaining of pan-leukocyte marker CD45 and ERβ, but decreased ERα immunostaining (all P < .05). RNA-seq identified 398 differentially expressed genes between groups. Pathway analysis of differentially expressed genes indicated reduced proliferation (Z-score = -2.2, P < .01), decreased angiogenesis (Z-score = -2.87, P < .001), increased inflammation (Z-score = +2.2, P < .01), and ERβ activation (Z-score = +1.6, P < .001) in suboptimal subjects. ChIP-seq identified 6 genes bound by ERα that were differentially expressed between groups (P < .01), some of which may play a role in implantation., Conclusion: Women with suboptimal endometrial thickness after clomiphene exhibit aberrant ER expression patterns, architectural changes, and altered gene and protein expression suggesting reduced proliferation and angiogenesis in the setting of increased inflammation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate whether superovulation improves fecundity in women undergoing therapeutic donor insemination (TDI)., Design: Retrospective cohort study., Setting: University-affiliated fertility clinic., Patient(s): Healthy women aged 23-45 years with no history of or risk factors for infertility who underwent 152 medicated and 104 unmedicated TDI cycles from 2013 to 2018., Intervention: Unmedicated TDI versus use of medication in a TDI cycle (clomiphene citrate or letrozole)., Main Outcome Measure(s): Cumulative probability of pregnancy in six TDI cycles., Result(s): In adjusted all-cycle analysis, medicated TDI cycles were less likely to result in pregnancy compared with unmedicated cycles. The incidence of twins was 23% in the medicated group and 0% in the unmedicated group. Medicated cycles were less likely to result in pregnancy in women younger than 40 years or with an antimüllerian hormone (AMH) level >1.2. After three cycles not resulting in pregnancy, the only women who conceived were those who crossed over from an unmedicated to a medicated cycle (12% vs. 0%)., Conclusion(s): Patients undergoing unmedicated TDI cycles had higher fecundity and no incidence of twin gestations. Older women, those with low AMH, and those who fail to conceive after three unmedicated cycles may benefit from medication., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability., Methods: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling., Results: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%)., Conclusions: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education., (© 2019 American Cancer Society.)

Purpose of Review: Anti-Müllerian hormone (AMH), a marker of ovarian reserve, declines over a woman's reproductive lifespan. AMH is highly correlated with a woman's age and number of primordial ovarian follicles, and has been shown to predict time to menopause in women in their 40s. For these reasons, it was assumed that AMH levels could predict a woman's reproductive potential or serve as a 'fertility test'. Recently, studies have sought to determine the association between AMH and fertility., Recent Findings: Although a small, prospective, time-to-pregnancy study of 98 women suggested that an AMH level less than 0.7 ng/ml was associated with lower day-specific probabilities of conception, the follow-up, larger cohort did not identify an association with AMH and fecundability. Women with AMH values less than 0.7 ng/ml had similar pregnancy rates after 12 cycles of attempting to conceive as women with normal AMH values after adjusting for age. Four additional studies, including a secondary analysis of the NICHD EAGER trial including over 1200 women confirmed these findings., Summary: Although AMH is a marker of ovarian reserve, existing literature does not support the use of AMH as a marker of reproductive potential in the general population.

Background: Although alcohol consumption and cigarette smoking are common behaviors in reproductive-age women, little is known about the impact of consumption patterns on ovarian reserve. Even less is known about the effects of smoking and alcohol use in reproductive-age African-American women., Objective: The objective of the study was to examine the impact of the patterns of alcohol intake and cigarette smoking on anti-Müllerian hormone levels as a marker of ovarian reserve in African-American women., Study Design: This was a cross-sectional analysis from the baseline clinical visit and data collection of the Study of Environment, Lifestyle, and Fibroids performed by the National Institute of Environmental Health Sciences. A total of 1654 volunteers, aged 23-34 years, recruited from the Detroit, Michigan community completed questionnaires on alcohol intake and cigarette smoking and provided serum for anti-Müllerian hormone measurement. Multivariable linear and logistic regressions were used as appropriate to estimate the effect of a range of exposure patterns on anti-Müllerian hormone levels while adjusting for potential confounders including age, body mass index, and hormonal contraception., Results: Most participants were alcohol drinkers (74%). Of those, the majority (74%) engaged in binge drinking at least once in the last year. Women who reported binge drinking twice weekly or more had 26% lower anti-Müllerian hormone levels compared with current drinkers who never binged (95% confidence interval, -44, -2, P < .04). Other alcohol consumption patterns (both past and current) were unrelated to anti-Müllerian hormone. The minority of participants currently (19%) or formerly (7%) smoked, and only 4% of current smokers used a pack a day or more. Neither smoking status nor second-hand smoke exposure in utero, childhood, or adulthood was associated with anti-Müllerian hormone levels., Conclusion: Results suggest that current, frequent binge drinking may have an adverse impact on ovarian reserve. Other drinking and smoking exposures were not associated with anti-Müllerian hormone in this cohort of healthy, young, African-American women. A longitudinal study of how these common lifestyle behaviors have an impact on the variability in age-adjusted anti-Müllerian hormone levels is merited., Competing Interests: Consultant for Allergan (EEM); other authors report no conflict of interest, (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate factors associated with second-trimester pregnancy loss in patients with normal uterine anatomy who conceived through in vitro fertilization., Methods: Women aged 21-44 years with ongoing in vitro fertilization pregnancy (at least one fetus with fetal heart tones at 12 weeks of gestation) at an academic hospital from 2001 to 2012 were eligible for inclusion in this retrospective cohort. Comprehensive uterine evaluation permitted inclusion of only women with anatomically normal uterine cavities. Maternal and clinical characteristics associated with spontaneous second-trimester pregnancy loss (between 12 1/7 and 23 6/7 weeks of gestation) were assessed. Multivariable logistic regression generated adjusted odds ratios (ORs), 95% confidence intervals (CIs), and Wald two-sided P values., Results: Among ongoing second-trimester pregnancies, 60 (2.1%) ended in spontaneous pregnancy loss and 2,841 (97.9%) ended in live birth. Multiple gestations (twins or more) conferred greater odds of pregnancy loss (adjusted OR 1.93, CI 1.15-3.24, P=.01) and were more prevalent among losses (48.3%) than live births (34.1%). Uterine leiomyomas were present in 16.7% of losses and 4.7% of live births and were associated with a nearly fourfold increased odds of second-trimester pregnancy loss (adjusted OR 3.82, CI 1.85-7.89, P<.001). Women with obese body mass index ([BMI] 30 or higher) at cycle start experienced twofold greater odds of pregnancy loss compared with normal-weight women (adjusted OR 2.38, CI 1.05-5.65, P=.04). There were eight obese women (32%) among losses and 209 obese women (16.5%) among live births. In vitro fertilization treatment parameters were not associated with odds of second-trimester loss nor were maternal age, ethnicity, or history of recurrent pregnancy loss., Conclusion: Odds of second-trimester spontaneous pregnancy loss among in vitro fertilization conceived pregnancies were greater with multiple gestations, leiomyomas, and obese maternal BMI., Level of Evidence: II.