Frozen embryo transfer outcomes decline with increasing female body mass index in female but not male factor infertility: analysis of 56,564 euploid blastocyst transfers.

OBJECTIVE: To evaluate the association of body mass index (BMI) with cycle outcomes after euploid frozen blastocyst transfer. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 56,564 first single autologous euploid frozen embryo transfers from the 2016-2019 Society for Assisted Reproductive Technology database were analyzed using BMI and using World Health Organization BMI cohorts. Subanalyses were performed on cycles among patients with a sole diagnosis of polycystic ovary syndrome (PCOS) (n = 4,626) and among patients with only a male factor (n = 10,854). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy, pregnancy loss, and live birth (LB). RESULT(S): Success rates and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for all outcomes were most favorable among those with normal BMI and progressively worsened with increasing BMI. These trends persisted among patients with PCOS for clinical pregnancy (aOR, 0.99; 95% CI, 0.98-0.997), pregnancy loss (aOR, 1.02; 95% CI, 1.01-1.04), and LB (aOR, 0.98; 95% CI, 0.97-0.99), but not among patients with a male factor only for clinical pregnancy (aOR, 1.00; 95% CI, 0.99-1.01), pregnancy loss (aOR, 1.01; 95% CI, 0.99-1.03), or LB (aOR, 0.99; 95% CI, 0.98-1.00). CONCLUSION(S): In the largest cohort to date, increasing BMI was associated with decreased pregnancy and LB and increased pregnancy loss after euploid frozen embryo transfers among the entire cohort and among patients with a sole diagnosis of PCOS; however, these results were attenuated among patients with a sole diagnosis of male factor infertility, suggesting that associated female infertility diagnoses and not BMI alone may underlie this trend.

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.

Contemporary Management of the Patient with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex syndrome that affects menstrual regularity, causes hyperandrogenism, increases the risk of metabolic dysfunction and infertility, and is associated with higher rates of mental health disorders. The symptoms of PCOS are unique to each individual and will evolve throughout their reproductive lifespan and beyond. Thus, care should be personalized and provided by an appropriate team of multidisciplinary physicians and clinicians, such as dieticians and psychologists.

A new tissue-agnostic microfluidic device to model physiology and disease: the lattice platform.

To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.

The association of euploid miscarriage with obesity.

OBJECTIVE: To determine whether the frequency of euploid miscarriage is increased in obese women with early pregnancy loss. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: A total of 2,620 women with cytogenetic analysis results from products of conception after a pregnancy loss <20 weeks gestation from 2006-2018. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Frequency of euploid miscarriage was compared in obese (body mass index [BMI] ≥30 kg/m2) versus non-obese (BMI <30 kg/m2) patients. RESULTS: A total of 2,620 women with a mean (± standard deviation) age at time of loss of 34.9 years (± 4.9) and mean (± standard deviation) BMI of 25.3 kg/m2 (±5.5) were included in the final analysis. After adjusting for age and race, obese women were 56% more likely to have a euploid pregnancy loss compared with nonobese women (odds ratio 1.56; 95% confidence interval 1.32-1.92). Within the cohort, 63.8% of the losses were aneuploid, of which 41% were trisomies, 8% were monosomies, and 7% were polyploidies. Of the euploid losses, 50.1% were 46,XX and 49.9% were 46,XY, which suggests that the rate of maternal cell contamination was low. CONCLUSIONS: Obese women have an increased frequency of euploid miscarriage when compared with nonobese women.

Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial.

PURPOSE: Implantation failure is a major limiting factor of successful in vitro fertilization (IVF). The objective of this study was to determine if endometrial mechanical stimulation (EMS) by endometrial biopsy in the luteal phase of the cycle prior to embryo transfer (ET) improves clinical outcomes in an unselected subfertile population. METHODS: Double-blind, randomized controlled trial of EMS versus sham biopsy and odds of clinical pregnancy after IVF and embryo transfer. Secondary outcomes included spontaneous miscarriage and live birth. RESULTS: One hundred women enrolled and were randomized from 2013 to 2017. Enrollment was terminated after futility analysis showed no difference in clinical pregnancy between EMS versus control, 47.2% vs 61.7% (OR 0.55, 95% CI 0.25-1.23, p = 0.15). There were no significant differences between women who underwent EMS and those who did not in terms of positive pregnancy test 54.7% vs 63.8% (OR 0.69, 95% CI 0.31-1.53, p = 0.36), miscarriage 7.5% vs 2.1% (OR 3.76 95% CI 0.41-34.85, p = 0.22), or live birth 43.4% vs 61.7% (OR 0.48 95% CI 0.21-1.06, p = 0.07). CONCLUSIONS: EMS in the luteal phase of the cycle preceding embryo transfer does not improve clinical outcomes in an unselected subfertile population and may result in a lower live birth rate. We caution the routine use of EMS in an unselected population.

Inflammation and Human Ovarian Follicular Dynamics.

Inflammation is a biologic process that mediates tissue effects including vasodilation, hyperemia, edema, collagenolysis, and cell proliferation through complex immunologic pathways. In regard to the ovary, inflammation has key physiologic roles in ovarian folliculogenesis and ovulation. On the other hand, inflammatory processes are subject to underlying pathology and, if pushed, proinflammatory conditions may have a negative impact on ovarian follicular dynamics. Obesity and polycystic ovary syndrome (PCOS) serve as examples of conditions associated with chronic endogenous production of low-grade proinflammatory cytokines. Both conditions negatively impact ovarian folliculogenesis and ovulation. The pages that follow summarize the role of inflammation in normal ovarian follicular dynamics and evidence for its role in mediating the negative effects of obesity and PCOS on ovarian follicular dynamics. The review concludes with a summary supporting a role for lifestyle factors that favorably impact inflammatory process involved in obesity and PCOS to improve ovarian function.