Association between serum 25-hydroxyvitamin D and antimüllerian hormone levels in a cohort of African-American women.

OBJECTIVE: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] levels and ovarian reserve as measured using antimüllerian hormone (AMH) levels. DESIGN: Cross-sectional study. SETTING: Detroit, Michigan area. PATIENTS: Data were obtained from a prospective cohort of self-identified Black or African American women aged 23-35 years at the time of enrollment (N = 1,593), who had no prior diagnosis of polycystic ovary syndrome, were not currently pregnant, and were not missing AMH or 25(OH)D level measures. INTERVENTION: Serum 25(OH)D. MAIN OUTCOME MEASURE(S): The serum AMH level was the main outcome. Linear regression was used to examine the associations between categorical 25(OH)D levels (<12, 12-<20, 20-<30, and ≥30 ng/mL) and continuous natural log-transformed AMH levels. Associations between 25(OH)D and high (upper 10th percentile: >7.8 ng/mL) or low AMH (<0.7 ng/mL) levels were estimated with logistic regression. Models were adjusted for age, age-squared, body mass index (kg/m2), hormonal contraceptive use, smoking, and exercise. RESULTS: The 25(OH)D levels were low; 70% of participants were below 20 ng/mL. In fully adjusted models, compared with 25(OH)D levels <12 ng/mL, those with 25(OH)D levels of 12-<20, 20-<30, and ≥30 ng/mL had an AMH level that was 7% (95% confidence interval [CI]: -4, 20), 7% {95% CI: -6, 22}, or 11% {95% CI: -7, 34} higher, respectively. Moreover, these groups had lower odds of having low AMH levels (odds ratio [95% CI]: 0.63 {0.40, 0.99}, 0.60 {0.34, 1.07}, and 0.76 {0.35, 1.65}, respectively), and the highest category of 25(OH)D levels had higher odds of having high AMH levels (odds ratio [95% CI]: 1.42 {0.74, 2.72}). Exclusion of participants with either irregular cycles or very high AMH (>25 ng/mL) levels did not alter the associations. CONCLUSION: Taken together, these results indicate that higher levels of 25(OH)D are associated with slightly higher AMH levels, lower odds of low AMH levels, and higher odds of high AMH levels. This evidence is weak, however, because only a small percentage of participants had high 25(OH)D levels. Future studies should examine populations with a wide distribution of 25(OH)D levels (both high and low), with a clinical trial design, or with longitudinal measures of both 25(OH)D and AMH levels.

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.

Chronic endometritis: screening, treatment, and pregnancy outcomes in an academic fertility center.

PURPOSE: To identify the prevalence of chronic endometritis (CE), compare the efficacy of antibiotic regimens for CE, and examine pregnancy outcomes after treatment for CE among patients in an academic fertility clinic. METHODS: In this retrospective cohort study, data from patients who underwent endometrial sampling (ES) for CE evaluation at a single academic institution from 2014 to 2020 were collected and analyzed. Rates of CE were compared by indication for ES including recurrent pregnancy loss (RPL), implantation failure (IF), and recent first-trimester pregnancy loss. Treatment and pregnancy outcomes were also evaluated. RESULTS: Six hundred fifty-three individuals underwent ES to evaluate for CE. The overall prevalence of CE was 28.5%; when stratified by indication, the prevalence of CE was 66.2% for recent first-trimester loss, 27.9% for RPL, and 13.1% for IF (p < .001). Of those with CE, 91.9% received antibiotics, most commonly doxycycline (76.0%). CE clearance was not significantly different when doxycycline was compared to all other regimens (71.3% vs. 58.8%, p = .17), and 68.5% of patients cleared CE after one course of antibiotics. Following two antibiotic courses, CE was cleared in 88.3% of patients. Live birth rates (LBRs) were higher for those with cleared CE compared to patients with untreated CE (34.1% vs. 5.6%, p = .014) and similar for those with cleared CE versus those without CE (34.1% vs. 29.3%, p = .297). CONCLUSION: CE is common among patients with infertility, particularly those with a recent first-trimester loss. Treatment and clearance of CE were associated with higher LBRs; however, persistent CE was common despite treatment with antibiotics.

Undergraduate students have low fertility knowledge and high anxiety regarding future fertility: An opportunity for education.

Objectives: To assess childbearing intentions, concerns about future fertility, knowledge about the age-related decline in fertility, and interest in receiving fertility education among undergraduate students. Design: From March to April 2021, a cross-sectional, web-based survey with 42 reproductive and fertility-related questions was administered to and completed by actively enrolled undergraduates at Northwestern University in the United States. Results: The survey was completed by 291 students (mean age 20.2 years). Of all participants, 62.5% plan to have children and 68.3% intend to delay childbearing. Significantly more females than males (70.7% vs 40.9%, P = 0.004) and premedical students compared to non-premedical students (78.2% vs 60.1%, P = 0.002) reported planning to delay childbearing due to educational or career aspirations. Significantly more females than males (43.5% vs 4.5%, P < 0.001) and premedical compared to non-premedical students (50.4% vs 31.5%, P = 0.002) also reported having anxiety about future fertility due to career aspirations.When surveyed about fertility knowledge, 31.1% of participants reported that females are as fertile in their forties as they are in their thirties, and 25.4% stated that female fertility does not dramatically decline until age 40 or later. When asked to estimate the oldest age a woman has conceived using autologous oocytes, 83.3% reported age 48 or older. Of all participants, 72.3% were interested in learning about fertility. Conclusions: The majority of surveyed undergraduates plan to delay childbearing, yet they have concerns about how career goals will impact future fertility. Notably, females and premedical students reported higher rates of anxiety when compared to their male and non-premedical counterparts. Knowledge about the age-related decline in fertility was limited, but students have a strong interest in learning about fertility, highlighting an opportunity for educational intervention at the undergraduate level. With education, students may be empowered to make informed decisions about future reproductive strategy earlier in time, potentially decreasing future anxiety.

Anxiety, attitudes, and education about fertility among medical students in the United States.

BACKGROUND: As delayed family building is common among physicians, the goal of this study was to evaluate childbearing plans, anxiety related to future fertility, and interest in fertility education among medical students. METHODS: Using convenience and snowball sampling methods, an electronic REDCap survey was distributed via social media and group messaging applications to medical students enrolled in medical schools across the United States. Answers were collected, and analysis of the descriptive statistics was performed. RESULTS: The survey was completed by 175 participants, 72% of which were female (assigned at birth). The mean (± SD) age of participants was 24.9 ± 1.9 years. Of all participants, 78.3% desire to have children and 65.1% of these individuals plan to delay childbearing. On average, the planned age of first pregnancy is 31.0 ± 2.3 years. "Lack of time" was the greatest influence on decision regarding timing of childbearing. Of all respondents, 58.9% reported at least some anxiety related to future fertility. When females and males were compared, significantly more females (73.8%) versus males (20.4%) reported worrying about future fertility (p < 0.001). Participants reported that greater knowledge about infertility and potential treatments would help ease fertility related anxiety, and 66.9% of respondents showed interest in learning about how things such as age and lifestyle can impact fertility, preferably through medical curricula, videos, and podcasts. CONCLUSION: A majority of the medical students in this cohort intend to have children and most plan to delay childbearing. A large percentage of female medical students reported anxiety related to future fertility, but many students showed interest in receiving fertility education. This study highlights an opportunity for medical school educators to incorporate targeted fertility education into their curriculum with the intention of decreasing anxiety and improving future reproductive success.

Natural Cycle Frozen Embryo Transfer: Evaluating Optimal Protocols for Preparation and Timing.

Background: While natural cycle frozen embryo transfer (NC-FET) is becoming increasingly common, significant practice variation exists in the use of ovulation induction medications, administration of ovulation trigger, and timing of embryo transfer without consensus as to the optimal protocol. Aims: The objective of this study is to evaluate the association of key aspects of the NC-FET protocol with implantation, pregnancy and live birth. Settings and Design: This was a retrospective cohort study of blastocyst stage NC-FET cycles from October 2019 to July 2021 at a single academic fertility centre. Materials and Methods: Protocols varied between cycles across three key parameters which were evaluated as primary predictors of cycle outcomes: (1) use of letrozole for mild ovarian stimulation/ovulation induction, (2) administration of exogenous ovulation trigger versus spontaneous luteinising hormone surge and (3) transfer timing based on ovulation trigger versus sequential progesterone monitoring. Primary outcomes included implantation rate, clinical pregnancy and ongoing pregnancy. Statistical Analysis Used: Generalised estimating equations were fitted to obtain adjusted odds ratios or rate ratios as appropriate with 95% confidence intervals for each outcome across the three primary predictors. Results: A total of 183 cycles from 170 unique patients were eligible for inclusion. The average implantation rate was 0.58, resulting in an overall clinical pregnancy and ongoing pregnancy rate of 59.0% and 51.4%, respectively. After adjusting for age at embryo freeze and history of a failed embryo transfer, there were no significant associations between any predictor and implantation rate, clinical pregnancy, ongoing pregnancy, or live birth. Conclusion: In NC-FET, a variety of preparation and timing protocols may lead to comparable cycle outcomes, potentially allowing for flexibility on the basis of patient and physician preference. These findings warrant validation in a larger, randomised trial.

Early ß-hCG levels predict live birth after single embryo transfer.

PURPOSE: Specific serum beta human chorionic gonadotropin (ß-hCG) parameters that can predict live birth after an embryo transfer have yet to be defined. METHODS: We performed a retrospective cohort study of 1,028 patients with a detectable ß-hCG who underwent a single embryo transfer between 2002 and 2019 at a large academic center. Two ß-hCG parameters were examined in relation to live birth: 1) "doubling" defined as ß-hCG doubling over 48 h and 2) "reaching 100" defined as a ß-hCG ≥ 100 mIU/mL by 15 days after oocyte retrieval (AOR). RESULTS: One thousand three hundred forty cycles involving a single embryo were analyzed. Two thirds were frozen embryos and 86% were blastocyst transfers. Preimplantation genetic testing was performed in almost 30% of cycles. When ß-hCG levels "doubled," a live birth occurred in 80.7% of cycles and when ß-hCG levels "reached 100" by 15 days AOR, live birth occurred in 81.6% of cycles. When ß-hCG levels both doubled and reached 100 by 15 days, AOR 85.4% cycles resulted in live birth. A multiple logistic regression model to control for patient and cycle level factors revealed a live birth odds ratio (OR) of 8.0 (95% CI 5.7-11.1) when ß-hCG "doubled" and an OR of 21.2 (95% CI 14.3-31.5) when ß-hCG "reached 100." When both these latter parameters were met, the OR was 12.5 (95% CI 8.9-17.8). CONCLUSION: ß-hCG parameters of "doubling" and "reaching 100" by 15 days AOR are robust predictors of live birth and can aid in patient counseling regarding pregnancy outcomes soon after single embryo transfer.

Retained pregnancy tissue after miscarriage is associated with high rate of chronic endometritis.

The objective of this study was to evaluate prevalence of chronic endometritis in a cohort of patients with retained pregnancy tissue (RPT) following miscarriage, with and without a history of recurrent pregnancy loss (RPL). In a cohort of our single academic fertility centre, we evaluated women with unexplained RPL (two or more losses) without evidence of RPT and women undergoing hysteroscopic resection of RPT following miscarriage. Endometrial samples underwent staining with H and E and CD138. A pathologist blinded to patient history recorded the number of plasma cells per 10 high power fields (HPF) and the presence or absence of endometrial stromal changes. Our main outcome measure was to measure the prevalence of chronic endometritis. Endometrial samples from 50 women with RPT following miscarriage and 50 women with unexplained RPL without evidence of RPT were reviewed. The prevalence of chronic endometritis was significantly higher in the RPT cohort (62% versus 30%). A multivariable regression demonstrated significantly higher odds of chronic endometritis in the RPT cohort, aOR 7.3 (95% CI 2.1, 25.5). We conclude that women with RPT following pregnancy loss have a high rate of chronic endometritis, suggesting that RPT is a risk factor for this disorder. Impact StatementWhat is already known on this subject? Known risk factors for chronic endometritis include a history of pelvic inflammatory disease, intrauterine polyps and fibroids. The aetiology for increased chronic endometritis among women with RPL is unknown.What do the results of this study add? The prevalence of chronic endometritis is significantly higher among women with retained pregnancy tissue (RPT) following miscarriage compared to women with RPL. These data presented suggest that RPT is associated with chronic endometritis among women with a history of miscarriage.What are the implications of these findings for clinical practice and/or further research? We suggest a pathologic evaluation for chronic endometritis be performed on all patients who undergo hysteroscopic resection of RPT following miscarriage. Our findings also suggest that a uterine cavity evaluation with hysteroscopy to evaluate for RPT may be reasonable in women with a history of miscarriage who are found to have chronic endometritis on endometrial biopsy. Further research is needed to determine if resection of retained tissue is sufficient to treat RPOC associated chronic endometritis, or if additional antibiotic treatment is necessary.

Oral Hygiene in Adolescence: A Questionnaire-Based Study.

Oral health is fundamental to our well-being, especially in adolescence. The aim of this study is to investigate oral hygiene knowledge through a questionnaire in a sample of adolescents, paying particular attention to those wearing orthodontic braces. The study was designed as a descriptive report of a local survey. An anonymous questionnaire was distributed to individuals born between 2000 and 2005, both on paper and online. Among 213 adolescents answering the questionnaire, 206 went to the dentist at least once (most of them between 5 and 9 years old), and 144 experienced at least one session of professional oral hygiene. Approximately 83% of the sample brushed their teeth at least twice a day, while only 7% used dental floss daily. Only 54% of respondents wearing orthodontic braces were advised to undergo professional oral hygiene during their orthodontic treatment. Education on oral hygiene at home came only from their parents for 61% of the whole sample. Most respondents had their first visit to the dentist apparently too late. Flossing was rare, whether the adolescents wore orthodontic braces or not. In many cases, professional oral hygiene was not common during orthodontic treatment. Adolescents did not learn about oral hygiene from a dental specialist.

Association between uterine fibroids and antimüllerian hormone concentrations among African American women.

OBJECTIVE: To evaluate the extent to which uterine fibroids are associated with antimüllerian hormone (AMH) concentrations. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle, and Fibroids, which is a 5-year longitudinal study of African American women. PATIENT(S): A total of 1,643 women aged 23-35 years without a known history of fibroids. EXPOSURE: Fibroid presence. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was percent difference in the mean AMH concentration between participants with fibroids and those without fibroids. The secondary outcomes were percent differences in the mean AMH concentrations in participants with different numbers, sizes, types, and positions of fibroids and the percent difference in the mean AMH concentration in participants with different uterine volumes. RESULT(S): At least 1 fibroid was identified on ultrasound in 362 (22%) participants. There was a small difference in the mean AMH concentrations in participants with fibroids (age-adjusted model: -4.6%, 95% confidence interval (CI): -14.5% to 6.5%; multivariable model: -4.6%, 95% CI: -14.4% to 6.3%). The mean AMH concentrations were found to decrease with increasing fibroid number. Although differences in AMH concentrations were not statistically significant, compared with no fibroids, the mean percent differences in AMH concentrations for 1, 2-3, and ≥4 fibroids were -1.2% (95% CI: -13.2% to 12.5%), -7.1% (95% CI: -23.3% to 12.5%), and -17.5% (95% CI: -38.2% to 10.0%), respectively. There were no consistent associations between AMH concentrations and fibroid location, size, or uterine volume. CONCLUSION(S): The presence of fibroids was not materially associated with AMH concentrations. Other than a monotonic inverse relationship between fibroid number and AMH concentrations, no other fibroid characteristics were consistently or appreciably associated, although associations were imprecise.

Planned oocyte cryopreservation in women with blepharophimosis-ptosis-epicanthus inversus syndrome: a case series.

OBJECTIVE: To describe the experiences of three women with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) who desired to pursue planned oocyte cryopreservation. DESIGN: Case series. SETTING: An academic institution and a private clinic. PATIENTS: Three nulligravid women aged 23, 25, and 34 years who desired to pursue planned oocyte cryopreservation. Two women had BPES diagnosed when they were infants and one had BPES diagnosed after presenting to discuss oocyte cryopreservation. INTERVENTIONS: All three women underwent ovarian stimulation. One woman underwent three oocyte retrievals. MAIN OUTCOMES MEASURES: Vitrification of metaphase II oocytes. RESULTS: One woman had a total of eight metaphase II oocytes vitrified. In addition, she underwent genetic testing that confirmed type 1 BPES. The other two women, who had BPES diagnosed when they were newborns, each underwent two cycles of ovarian stimulation. Neither of these two women responded to ovarian stimulation and both cycles were cancelled before oocyte retrieval. CONCLUSIONS: BPES is a rare condition that can lead to primary ovarian insufficiency. Early identification of this condition is important to allow for timely reproductive counseling so that oocyte cryopreservation can be offered at a young age before oocyte depletion. Careful counseling is critical for these patients, because this case series demonstrated that not all women with BPES will respond to stimulation. Further, outcomes with cryopreserved oocytes have not yet been described in women with BPES.

Redefining chronic endometritis: the importance of endometrial stromal changes.

OBJECTIVE: To develop diagnostic criteria for chronic endometritis and compare the prevalence of chronic endometritis between women with recurrent pregnancy loss (RPL) and controls. DESIGN: Cohort study. SETTING: Single academic fertility center. PATIENTS: Women with unexplained RPL (two or more pregnancy losses) and prospectively recruited controls without a history of RPL or infertility. INTERVENTIONS: Endometrial samples were stained with hematoxylin and eosin and CD138. A pathologist blinded to patient history recorded the number of plasma cells per 10 high-power fields (HPFs). In addition, the presence or absence of endometrial stromal changes was documented. MAIN OUTCOME MEASURE: Prevalence of chronic endometritis. RESULTS: Endometrial samples from 50 women with unexplained RPL and 26 controls were evaluated. When chronic endometritis was defined as the presence of one or more plasma cells per 10 HPFs, 31% of controls and 56% of women with RPL met the criterion. When both endometrial stromal changes and plasma cells were required for a diagnosis of chronic endometritis, no controls and 30% of women with RPL met the criteria. CONCLUSIONS: Although rare plasma cells were found in biopsy samples from controls, the presence of both plasma cells and endometrial stromal changes was limited to the RPL cohort. We propose that chronic endometritis be defined as the presence of one or more plasma cells per 10 HPFs in the setting of endometrial stromal changes. With the use of these strict diagnostic criteria, women with RPL have a significantly higher rate of chronic endometritis, supporting an association between chronic endometritis and RPL.

Duration, recency, and type of hormonal contraceptive use and antimüllerian hormone levels.

OBJECTIVE: To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimüllerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. DESIGN: Cross-sectional study. SETTING: Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. PATIENT(S): The patients were 1,643 African American women aged 23-35 years at the time of blood drawing (2010-2012). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. RESULT(S): In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: -35.3%, -13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (-4.4%; 95% CI: -16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (-24.0%; 95% CI: -36.6%, -8.9%), vaginal ring (-64.8%; 95% CI: -75.4%, -49.6%), and depot medroxyprogesterone acetate (-26.7%; 95% CI: -41.0%, -8.9%) had lower mean AMH levels than non-users. CONCLUSION(S): The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Can embryo morphokinetic parameters predict euploid pregnancy loss?

OBJECTIVE: To use time-lapse imaging to compare embryo morphokinetic parameters between embryos resulting in euploid pregnancy loss and euploid embryos resulting in live birth. DESIGN: Retrospective cohort study. SETTING: Single academic fertility center. PATIENT(S): All euploid single embryo transfers between October 2015 and January 2018. INTERVENTION(S): Collection and analysis of baseline characteristics, cycle parameters, and outcomes. MAIN OUTCOME MEASURE(S): Embryo morphokinetic measurements assessed with time-lapse imaging for time to syngamy (TPNf), time to two cells, time to three cells, time to four cells, time to eight cells, time to morula, and time to blastocyst. RESULT(S): The study included 192 euploid single-embryo transfers. Of these, the pregnancy rate was 78% (150 of 193) and the live-birth rate was 63% (121 of 193). There were 43 transfers that did not result in pregnancy, 15 biochemical pregnancy losses, 13 clinical losses, and 121 live births. There was no statistically significant difference in age, body mass index, or number of oocytes retrieved between the groups. Unadjusted and adjusted models revealed no differences in the morphokinetics of embryos resulting in euploid miscarriage compared with those resulting in live birth. CONCLUSION(S): Embryos that resulted in a euploid miscarriage did not display evidence of abnormal morphokinetics on time-lapse imaging. Euploid pregnancy loss is likely multifactorial, including both embryo and endometrial factors. Further research is needed to identify factors that can predict and prevent euploid loss.

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.

Knowledge gaps in the understanding of fertility among non-medical graduate students.

OBJECTIVE: To assess knowledge of female and male fertility among students enrolled in a Master of Business Administration (MBA) program. DESIGN: Web-based cross-sectional survey. SETTING: Academic setting. PATIENTS: Not applicable. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Knowledge of how female and male age impacts reproduction, fecundability, and success rates with in vitro fertilization (IVF). RESULTS: A total of 133 female and male MBA students completed the survey. Nearly 10% of participants were not aware that women are born with a fixed number of oocytes and that oocyte quantity and quality decline with age. More than 30% of participants overestimated fecundability in women aged ≥35 years, and >50% overestimated IVF success rates in women older than 40 years. Fifteen percent of participants did not know that men have stem cells in the testes, and >25% were not aware that men experience a decrease in sperm concentration and quality with age. Nearly 30% believed that a man's age never impacts reproductive outcomes. Less than 30% of participants correctly estimated fecundability and IVF success rates based on male age. CONCLUSIONS: These data highlight important knowledge gaps in a highly educated group of MBA students, most whom desire future childbearing. Specifically, there is a lack of understanding of both male and female reproductive aging and an overestimation of treatment success. As delayed childbearing continues, particularly among those with high educational attainment, attention should be focused on introducing broad fertility education at a younger age to improve future reproductive success.

Endometriosis.

Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-ß. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.

The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis.

Endometriotic stromal cells synthesize estradiol via the steroidogenic pathway. Nuclear receptor subfamily 5, group A, member 1 (NR5A1) is critical, but alone not sufficient, in activating this cascade that involves at least 5 genes. To evaluate whether another transcription factor is required for the activation of this pathway, we examined whether GATA Binding Protein 6 (GATA6) can transform a normal endometrial stromal cell (NoEM) into an endometriotic-like cell by conferring an estrogen-producing phenotype. We ectopically expressed GATA6 alone or with NR5A1 in NoEM or silenced these transcription factors in endometriotic stromal cells (OSIS) and assessed the messenger RNAs or proteins encoded by the genes in the steroidogenic cascade. Functionally, we assessed the effects of GATA6 expression or silencing on estradiol formation. In OSIS, GATA6 was necessary for catalyzing the conversion of progesterone to androstenedione (CYP17A1; P < .05). In NoEM, ectopic expression of GATA6 was essential for converting pregnenolone to estrogen (HSD3B2, CYP17A1, and CYP19A1; P < .05). However, simultaneous ectopic expression of both GATA6 and NR5A1 was required and sufficient to confer induction of all 5 genes and their encoded proteins that convert cholesterol to estrogen. Functionally, only simultaneous knockdown of GATA6 and NR5A1 blocked estradiol formation in OSIS ( P < .05). The presence of both transcription factors was required and sufficient to transform endometrial stromal cells into endometriotic-like cells that produced estradiol in large quantities ( P < .05). In summary, GATA6 alone is essential but not sufficient for estrogen formation in endometriosis. However, simultaneous addition of GATA6 and NR5A1 to an endometrial stromal cell is sufficient to transform it into an endometriotic-like cell, manifested by the activation of the estradiol biosynthetic cascade.