Fertility Knowledge and Educational Experiences of Graduating Medical Students: A Multi-Institution Survey.

Objective: Our goal was to assess the fertility knowledge and educational experiences of graduating U.S. medical students to evaluate areas of improvement for future educational interventions. Design: Web-based cross-sectional survey. Subjects: Medical students graduating in 2023 from the University of Miami Miller School of Medicine (SOM), New York University (NYU) Grossman SOM, Wayne State University SOM, Perelman SOM at the University of Pennsylvania, and Mayo Clinic Alix SOM. Main Outcome Measures: Fertility-related knowledge and educational experiences of U.S. medical students in their final year of school. Results: In total, 117 students (14.4%) completed the survey. The average knowledge score was 78%. Twenty-three (22%) overestimated the age of most precipitous fertility decline, and 50 (52%) overestimated the chance of getting pregnant for a 40-year-old person with ovaries. One-third of students (30, 32%) incorrectly believe that physicians have equivalent infertility rates to the general population. Students were less cognizant of male fertility issues, incorrectly believing there was no negative impact on male fertility by age (43, 42%) among other factors. Seventy-five (81%) reported less than 5 hours of fertility-related education in medical school. Only one-third (32%) were satisfied or very satisfied with the fertility education they received. In an open-response question, students expressed interest in additional education on transgender and cancer patient care, fertility preservation, assisted reproductive technologies, and reproductive life planning in medicine. Conclusions: There is a need and an opportunity for medical education programs to enhance fertility education. Giving students and trainees the knowledge required to make informed decisions for their family-building purposes and improving their ability to counsel patients adequately should be a goal of future educational endeavors. The data collected in this study will serve as a guide for the development of fertility-related learning modules for medical students and trainees.

Barriers to Family Building Among Physicians and Medical Students.

Importance: Physicians and medical students who desire to build families face significant barriers due to the structure and culture of medicine. Objective: To understand the barriers and facilitators to family building for all people in medicine-not only individuals who can become pregnant-through an open-ended, qualitative analysis of survey responses. Design, Setting, and Participants: This qualitative study used a survey conducted in April and May 2021 with a broad sample of physicians and medical students. Participants were recruited through social media, targeting physician and medical student communities. Physicians (residents, fellows, and physicians in independent practice) and medical students of all gender identities and sexual orientations were included. Informed by a postpositivist approach, coding reliability thematic analysis was performed on 3 open-ended survey questions on family-building experiences (what they would do differently, what advice they have for others, and anything else they wished to share). Main Outcomes and Measures: Identified themes were mapped to the social-ecological model, a model used in public health to examine how a spectrum of factors is associated with health outcomes. Results: A total of 2025 people (1860 [92%] women; 299 [15%] Asian, 151 [8%] Black, and 1303 [64%] White; 1730 [85%] heterosexual; and 1200 [59%] physicians who had completed training) responded to at least 1 of 3 open-ended questions. Themes mapped to social-ecological model levels included: (1) cultural, eg, medical training being at odds with family building; (2) organizational, eg, lack of institutional support for the range of family-building routes; (3) interpersonal, eg, impact of social support on family building; and (4) individual, eg, socioeconomic status and other individual factors that facilitate or inhibit family building. Recommendations to improve family-building experiences include implementing family-building curricula at medical schools, providing adequate parental leave for all physicians and medical students who become parents, and providing insurance coverage for all family-building routes. Conclusions and Relevance: In this qualitative study of physicians and medical students, self-reported barriers to family building were identified at each level of the social-ecological model. Addressing these barriers is critical to creating a more equitable family-building environment for physicians and medical students.

Racial disparities in uterine fibroids and endometriosis: a systematic review and application of social, structural, and political context.

IMPORTANCE: Uterine fibroids and endometriosis are 2 of the leading causes of morbidity among reproductive-aged women. There are significant racial disparities in disease prevalence, incidence, age of onset, and treatment profile in fibroids. The data on endometriosis are less clear. OBJECTIVE: To conduct a systematic review of racial disparities in prevalence of uterine fibroids and endometriosis in the United States and summarize the literature on these 2 highly prevalent benign gynecologic conditions using a framework that explicitly incorporates and acknowledges the social, structural, and political contexts as a root cause of racial disparities between Black and White women. EVIDENCE REVIEW: A systematic review regarding racial disparities in prevalence of fibroids and endometriosis was conducted separately. Two separate searches were conducted in PubMed to identify relevant original research manuscripts and prior systematic reviews regarding racial disparities in uterine fibroids and endometriosis using standardized search terms. In addition, we conducted a structured literature search to provide social, structural, and political context of the disparities. FINDINGS: A systematic review of the literature indicated that the prevalence of uterine fibroids was consistently higher in Black than in White women with the magnitude of the difference varying depending on population and case definition. Prevalence of endometriosis varied considerably depending on the base population and case definition, but was the same or lower among Black vs. White women. As a result of the social, structural, and political context in the United States, Black women disproportionately experience a range of exposures across the life course that may contribute to their increased uterine fibroid incidence, prevalence, and severity of uterine fibroids. However, data suggest no racial difference in the incidence of endometriosis. Nevertheless, Black women with fibroids or endometriosis experience worse clinical and surgical outcomes than their White counterparts. CONCLUSION AND RELEVANCE: Racial disparities in uterine fibroids and endometriosis can be linked with differential exposures to suspected etiologic agents, lack of adequate access to health care, including highly skilled gynecologic surgeons, and bias and discrimination within the health care system. Eliminating these racial disparities will require solutions that address root causes of health disparities through policy, education and programs to ensure that all patients receive culturally- and structurally-competent care.

Probability of Pregnancy With Mono vs Multiple Folliculogenesis in Women With Unexplained Infertility.

Context: Ovarian stimulation (OS) increases pregnancy rates but can cause multiple folliculogenesis and multiple pregnancy. Objective: To determine whether the probability of pregnancy differs in OS cycles with mono- vs multifolliculogenesis in women with unexplained infertility (UI). Design: Secondary analysis of a multicenter, randomized controlled trial: Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation with 3 treatment arms: gonadotropins, clomiphene, or letrozole, combined with intrauterine insemination. Women were categorized as having either 1 or ≥ 2 mature follicles (≥ 16 mm). Relative risk (RR) and 95% CIs for clinical pregnancy and live birth by number of follicles were estimated using generalized linear models adjusted for age, body mass index, years of infertility, and history of prior live birth. Setting: 12 US-based clinical sites. Participants: Normally cycling women aged 18 to 40 years with a normal uterine cavity and at least 1 patent fallopian tube. Male partners with ≥ 5 million total motile sperm. Interventions: Gonadotropins, clomiphene, or letrozole with insemination. Main Outcome Measures: Clinical pregnancy rates (CPR) and live birth rates (LBR). Results: A single mature follicle > 16 mm resulted in lower CPR (RR, 0.70; 95% CI, 0.54-0.90) and LBR (RR, 0.67; 95% CI, 0.51-0.89) compared with ≥ 2 mature follicles. When stratified by treatment modality, no association of follicle number with CPR or LBR was observed for letrozole or clomiphene, but women using gonadotropins had lower CPR and LBR with monofolliculogenesis. Conclusion: In couples undergoing gonadotropin treatment for UI, monofolliculogenesis following OS is related to a lower rate of live birth.

Getting the word out: Methods of learning about research and motivations for participation in a study focusing on a reproductive-aged Latina/x population.

Background: Although one of the fastest-growing populations in the USA, Latinx individuals remain underrepresented in research. In this study, we aimed to identify how Latina/Latinx participants of the Environment, Leiomyomas, Latinas, and Adiposity Study (ELLAS) learned about the research study and what motivated them to participate. Materials and Methods: Using a standardized survey tool, bilingual staff interviewed participants and asked them, 1) how they heard about ELLAS and 2) to identify and rank their top three reasons for participating in ELLAS. Results: "Word of mouth" through a friend or relative was the most common method of learning about ELLAS (49.0%), followed by a "community outreach event" (29.3%). The three most common reasons for participating in ELLAS were "to learn more about women's health" (83.3%), "to receive a free health assessment" (79.4%), and "to contribute to scientific knowledge" (59.5%). Correlation between demographic and socioeconomic characteristics and participant responses indicated that there are different reasons for participation based on these factors. Conclusions: Community engagement and word of mouth are vital to the successful recruitment of Latina/Latinx participants to research studies. Latinx participants are most motivated to participate by health benefits and health education, as well as altruistic aspects of research studies. Therefore, establishing mutually beneficial relationships within Latinx communities and appealing to motivations for research participation with close attention to the demographics of participants can both expand and allow for targeted recruitment efforts for this underrepresented group in research studies.

The Environment, Leiomyomas, Latinas, and Adiposity Study: rationale and design.

BACKGROUND: Uterine leiomyomas, commonly known as fibroids, are benign tumors in postmenarchal females. By the age of 35 years, approximately 30% of females will have fibroids, and by the age of 50 years, the prevalence approaches 70% with some studies reporting >85% prevalence in African American females. Previous studies evaluating the prevalence of fibroids have largely relied on self-reported fibroid diagnoses, which could have falsely underestimated prevalence because many females with fibroids are asymptomatic. Despite known differences in fibroid prevalence by race, there are very limited data on fibroid prevalence by ethnicity. The Latino population is the largest ethnic minority in the United States, yet there is no large study that utilizes ultrasound to confirm the presence of fibroids in Latina/Latinx females. In addition, fibroids have been associated with obesity and with diabetes mellitus, but the data have been inconsistent and at times conflicting. OBJECTIVE: The Environment, Leiomyomas, Latinas, and Adiposity Study was designed to quantify the prevalence of uterine fibroids among Latina/Latinx females and understand the relationships between obesity, glucose dysregulation, and fibroid prevalence and growth. This article presents the study's design and reports early enrollment data. STUDY DESIGN: The Environment, Leiomyomas, Latinas, and Adiposity Study is a 5-year longitudinal cohort study based in Southeast Michigan with the goal of recruiting 600 Latina/Latinx females between the ages of 21 and 50 years. Given the recruitment goals, developing a respectful, transparent, and trusting relationship between the study investigators and the community was a major priority. Thus, a community-engaged research approach was utilized in the design of the Environment, Leiomyomas, Latinas, and Adiposity Study. A community advisory board containing community leaders, largely from the Latinx community, provided input and direction during the entirety of the Environment, Leiomyomas, Latinas, and Adiposity Study design and rollout process. A minimum of 3 visits (orientation and consent, baseline, follow-up) will be conducted for each participant, with baseline and follow-up visits approximately 18 to 30 months apart. At each visit, interviewer and self-administered surveys will assess sociodemographic factors, health behaviors, health history, and social determinants of health. In addition, participants undergo a pelvic ultrasound examination and biologic samples are collected. RESULTS: Using community-engaged approaches, we have successfully enrolled 633 Latina/Latinx females. The mean participant age is 37.5±7.04 years. The mean body mass index is 30.0±6.54 kg/m2. First study visits have been initiated. CONCLUSION: The objective of the Environment, Leiomyomas, Latinas, and Adiposity Study is to address the knowledge gap regarding uterine fibroids in the Latina/Latinx population. The Environment, Leiomyomas, Latinas, and Adiposity Study will generate ultrasound-confirmed evidence of the prevalence and growth patterns of uterine fibroids in this specific population while also examining the associations between obesity and laboratory-confirmed glucose dysregulation with uterine fibroid prevalence and growth patterns.

Factors contributing to persistent disparate outcomes of in vitro fertilization treatment.

PURPOSE OF REVIEW: Disparate healthcare outcomes are ubiquitous and occur across all fields of medicine, specifically for racial and ethnic minorities. Within reproductive health, minority women face disparate access to care, particularly infertility services, poor outcomes of fertility treatment, alarmingly higher rates of maternal morbidity and mortality as well as higher rates of preterm birth, lower live birth rates when they conceive spontaneously or when they conceive with assisted reproductive technology. The objective of this review is to highlight factors contributing to the persistent racial/ethnic disparities in in vitro fertilization (IVF) outcomes. RECENT FINDINGS: Recent studies document poorer outcomes after IVF treatment. Black women have been shown to have lower live birth rates following IVF treatment for more than 15 years. SUMMARY: In an effort to better understand these negative outcomes, scientists and clinicians have investigated possible biological contributing factors including the vaginal microbiome, differences in oocyte quality, embryo viability, endometrial factors, and hormonal differences. Multiple social/cultural factors also play a role including access to care, particularly for people with low income, patient (mis)education, and medical racism/bias.

Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate.

Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18-40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy.

Preconception leptin levels and pregnancy outcomes: A prospective cohort study.

OBJECTIVE: Obesity has become a major, worldwide public health issue and is associated with a greater risk of adverse pregnancy outcomes. Leptin, a hormone produced by adipocytes, is elevated in individuals with obesity and may mediate the association between obesity and pregnancy outcomes. Though leptin levels during pregnancy have been associated with pregnancy outcomes, less is understood regarding preconception levels. Therefore, the objective of this study was to evaluate associations between preconception leptin levels and adverse pregnancy outcomes. METHODS: This was a prospective cohort study nested within a large randomized controlled trial conducted at four medical centres in the United States. A total of 1078 women completed the parent study; this analysis involved women who became pregnant during that study (n = 776). Patients were healthy women, ages 18 to 40, attempting to conceive, with 1 to 2 prior pregnancy losses. Participants were followed for less than or equal to 6 cycles while trying to conceive and throughout pregnancy if they conceived. Preconception leptin concentrations were measured in serum collected at baseline then categorized by tertiles (using the lowest as reference group). Weighted log-binomial regression estimated risk ratios (RR) and 95% confidence intervals (CIs) for pregnancy loss, preterm delivery (PTD), gestational diabetes (GDM), and hypertensive disorders in pregnancy, adjusting for age, waist-to-hip ratio (WHR), and body mass index (BMI). RESULTS: The mean (SD) BMI in this cohort was 25.4 ± 6.0. GDM (RR 18.37; 95% CI, 2.39-141.55) and hypertensive disorders of pregnancy (RR 2.35; 95% CI, 1.20-4.61) risks were higher among women in the high tertile after adjusting for age and WHR. The associated risk persisted when adjusting for BMI for GDM but was attenuated for hypertensive disorders in pregnancy. Leptin levels were not associated with risk of pregnancy loss or PTD. CONCLUSIONS: Women with higher baseline preconception leptin levels had a higher likelihood of experiencing some adverse pregnancy outcomes including GDM and hypertensive disorders of pregnancy. These findings warrant further evaluation, especially in light of the association between leptin and obesity.

Prediction of pregnancy loss by early first trimester ultrasound characteristics.

BACKGROUND: Pregnancy loss prediction based on routinely measured ultrasound characteristics is generally aimed toward distinguishing nonviability. Physicians also use ultrasound indicators for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. To improve clinical utility, allocation of cut-points should be based on clinical data for multiple sonographic characteristics, be specific to gestational week, and be determined by methods that optimize prediction. OBJECTIVES: To identify routinely measured features of the early first trimester ultrasound and the gestational age-specific cut-points that are most predictive of pregnancy loss. MATERIALS AND METHODS: This was a secondary analysis of 617 pregnant women enrolled in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial; all women had 1-2 previous pregnancy losses and no documented infertility. Each participant had a single ultrasound with a detectable fetal heartbeat between 6 weeks 0 days and 8 weeks 6 days. Cut-points for low fetal heart rate and small crown-rump length were separately defined for gestational weeks 6, 7, and 8 to optimize prediction. Identity and log-binomial regression models were used to estimate absolute and relative risks, respectively, and 95% confidence intervals between jointly categorized low fetal heart rate, small crown-rump length, and clinical pregnancy loss. Adjusted models accounted for gestational age at ultrasound in weeks. Missing data were addressed using multiple imputation. RESULTS: A total of 64 women experienced a clinical pregnancy loss following the first ultrasound (10.4%), 7 were lost to follow-up (1.1%), and 546 women (88.5%) had a live birth. Low fetal heart rate and small crown-rump length (≤122, 123, and 158 bpm; ≤6.0, 8.5, and 10.9 mm for gestational weeks 6, 7, and 8, respectively) were independent predictors of clinical pregnancy loss, with greatest risks observed for pregnancies having both characteristics (relative risk, 2.08; 95% confidence interval, 1.24-2.91). The combination of low fetal heart rate and small crown-rump length was linked to a 16% (95% confidence interval, 9.1-23%) adjusted absolute increase in risk of subsequent loss, from 5.0% (95% confidence interval, 1.5-8.5%) to 21% (95% confidence interval, 15-27%). Abnormal yolk sac diameter or the presence of a subchorionic hemmhorage did not improve prediction of clinical pregnancy loss. CONCLUSION: Identified cut-points can be used by physicians for patient counseling, and in some cases to decide upon the frequency of follow-up sonograms. The specified criteria should not be used to diagnose nonviability.

Dietary Intakes of Vitamin B-2 (Riboflavin), Vitamin B-6, and Vitamin B-12 and Ovarian Cycle Function among Premenopausal Women.

BACKGROUND: Riboflavin, vitamin B-6, and vitamin B-12 are key players in one-carbon metabolism as enzymatic cofactors, and deficiency of these nutrients may influence reproductive outcomes possibly through affecting reproductive hormones. OBJECTIVE: The goal was to investigate associations between dietary intakes of riboflavin, vitamin B-6, and vitamin B-12, and menstrual function among premenopausal women. DESIGN: This was a secondary analysis of a prospective cohort study conducted at the University at Buffalo during 2005 to 2007. PARTICIPANTS/SETTING: Participants were 259 healthy, regularly menstruating women (aged 18 to 44 years) with self-reported menstrual cycles between 21 and 35 days, who were not trying to conceive, and who had not used hormonal contraception during the past 3 months. MAIN OUTCOME MEASURES: Intakes of B vitamins were assessed via 24-hour dietary recalls four times per menstrual cycle for two cycles. Serum reproductive hormones and plasma homocysteine were measured eight and three times, respectively, per cycle for two cycles. Anovulatory cycles were determined by progesterone concentrations ≤5 ng/mL (15.9 nmol/L) and no observed serum luteinizing hormone peak during the mid or late luteal phase visit. STATISTICAL ANALYSIS: Weighted linear mixed regressions were used to evaluate associations between cycle-averaged B vitamin intakes and hormones and homocysteine, and generalized linear regressions for associations with anovulation. Models were adjusted for age, race, body mass index, physical activity, alternate Mediterranean diet score, intakes of total energy, protein, fiber, and folate, and percentage of energy intake from fat. RESULTS: Higher intakes of riboflavin (per 0.1 mg increase in intake) were inversely correlated with estradiol (-0.87%, 95% CI -1.67 to -0.06) and homocysteine levels (-0.61%, 95% CI -1.10 to -0.12). Higher vitamin B-6 intakes were suggestive of higher follicle-stimulating hormone, although the results were not statistically significant (0.63% difference, 95% CI -0.03 to 1.29, per 0.1 mg increase in intake; P=0.06). Small increases in testosterone and decreases in homocysteine were found with vitamin B-12 intake. No associations were observed between intake of B vitamins and a risk of sporadic anovulation. CONCLUSIONS: Higher intakes of riboflavin were associated with a small decrease in serum estradiol among healthy, regularly menstruating women. Higher intakes of riboflavin and vitamin B-12 were associated with lower plasma homocysteine concentrations. Overall, riboflavin, vitamin B-6, and vitamin B-12 that are one-carbon nutrients do not appear to influence the ovarian cycle among premenopausal women.

Associations Between Preconception Plasma Fatty Acids and Pregnancy Outcomes.

BACKGROUND: Although fatty acids are involved in critical reproductive processes, the relationship between specific fatty acids and fertility is uncertain. We investigated the relationship between preconception plasma fatty acids and pregnancy outcomes. METHODS: We included 1,228 women attempting pregnancy with one to two previous pregnancy losses from the EAGeR trial (2007-2011). Plasma fatty acids were measured at baseline. We used log-binomial regression to assess associations between fatty acids and pregnancy, pregnancy loss, and live birth, adjusting for age, race, smoking, BMI, physical activity, income, parity, treatment arm, and cholesterol. RESULTS: Although total saturated fatty acids (SFAs) were not associated with pregnancy outcomes, 14:0 (myristic acid; relative risk [RR] = 1.10, 95% confidence interval [CI] = 1.02, 1.19, per 0.1% increase) and 20:0 (arachidic acid; RR = 1.05, 95% CI = 1.01, 1.08, per 0.1% increase) were positively associated with live birth. Findings suggested a positive association between total monounsaturated fatty acids (MUFAs) and pregnancy and live birth and an inverse association with loss. Total polyunsaturated fatty acids (PUFAs) were associated with lower probability of pregnancy (RR = 0.97, 95% CI = 0.95, 1.00) and live birth (RR = 0.96, 95% CI = 0.94, 0.99), and increased risk of loss (RR = 1.10, 95% CI = 1.00, 1.20), per 1% increase. Trans fatty acids and n-3 fatty acids were not associated with pregnancy outcomes. CONCLUSIONS: Preconception total plasma MUFAs were positively associated with pregnancy and live birth. PUFAs were inversely associated with pregnancy outcomes. Specific SFAs were associated with a higher probability of live birth. Our results suggest that fatty acids may influence pregnancy outcomes.

Preconception Leptin and Fecundability, Pregnancy, and Live Birth Among Women With a History of Pregnancy Loss.

CONTEXT: With the increase of obesity, it is imperative to understand the neuroendocrine mechanisms, including the neuroendocrine hormone leptin, by which obese or overweight women are at increased risk for subfertility and infertility. OBJECTIVE: The objective was to examine associations between preconception serum leptin concentrations, fecundability, pregnancy, and live birth. DESIGN: Secondary analysis of a prospective cohort among women with prior pregnancy losses. SETTING: The study was conducted at four US medical centers (2006 to 2012). INTERVENTION: Not available. MATERIALS AND METHODS: Preconception serum leptin concentrations were measured at baseline, and women were followed for up to six menstrual cycles, and throughout pregnancy if they conceived. Discrete Cox proportional hazard regression models were used to assess fecundability odds ratios (FORs) and log-binomial regression to estimate risk ratios (RRs) for pregnancy and live birth. Models were adjusted for age, physical activity, treatment arm, and adiposity, either by measured waist-to-hip ratio or body mass index (BMI). RESULTS: High leptin concentrations were associated with decreased fecundability (FOR 0.72, 95% CI 0.58, 0.90), reduced risk of pregnancy (RR 0.87, 95% CI 0.78, 0.96) and live birth (RR 0.76, 95% CI 0.65, 0.89) comparing the upper to the lower tertile. However, adjustment for BMI in lieu of waist-to-hip ratio nullified observed associations. CONCLUSIONS: In women with a history of pregnancy loss, relations between higher preconception leptin and fecundability were attenuated after adjustment for BMI, although not after adjustment for other markers of adiposity. Leptin may serve as a complementary marker of adiposity for assessment of obesity and reproductive outcomes.

Pilot randomized trial of short-term changes in inflammation and lipid levels during and after aspirin and pravastatin therapy.

BACKGROUND: Inflammation and elevated blood lipids are associated with infertility. Aspirin and statin therapy may improve infertility treatment outcomes among overweight and obese women with systemic inflammation, but little is known about the short-term effects of statins in this population. We conducted a pilot study of aspirin, pravastatin, or combined treatment among a group of overweight and obese, reproductive-aged women. Our goal was to characterize short-term changes in inflammatory and lipid biomarkers during and after treatment. METHODS: In this open-label trial, women aged 18-40 years with a body mass index ≥25 kg/m2 were randomized to receive either 162 mg aspirin, 40 mg pravastatin, or both. The study medication was taken daily for 2 weeks, and participants were then followed for a two-week washout period. Participants provided blood samples at baseline, after the intervention period, and after the washout period. The outcomes were changes in biomarkers of inflammation and lipids measured in blood components at each timepoint. RESULTS: Nine, 8, and 8 women were randomized to the aspirin, pravastatin, and combined arms, respectively. Analyses were conducted among 8, 7, and 7 women in the aspirin, pravastatin, and combined arms for whom biomarker data was available at baseline. High-sensitivity C-reactive protein (hsCRP) levels were lower after treatment in all arms and continued to decrease after washout in the pravastatin and combined arms. Results were consistent between the whole sample and women with baseline hsCRP between 2 and 10 mg/L. Low-density lipoprotein (LDL) cholesterol was lower after treatment in the pravastatin and combined arms and rose slightly after washout. CONCLUSIONS: Our results provide preliminary evidence that short-term aspirin and pravastatin therapy reduces hsCRP and LDL cholesterol among overweight and obese women of reproductive age, including those with low-grade inflammation. Because of these short-term effects, these drugs may improve infertility treatment outcomes in this population, which we will assess in a future randomized trial.

Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study.

BACKGROUND: Vitamin D deficiency during pregnancy is associated with adverse pregnancy outcomes, although the association between preconception vitamin D concentrations and livebirth is unknown. We aimed to assess the association between preconception vitamin D and pregnancy outcomes among women with proven fecundity. METHODS: We did a secondary analysis of a prospective cohort from the block-randomised, double-blind, placebo-controlled EAGeR trial. Women aged 18-40 years with one to two previous pregnancy losses were recruited from June 15, 2007, to July 15, 2011, at four clinical sites in the USA and followed up for up to six menstrual cycles while attempting pregnancy and throughout pregnancy if they conceived. Serum 25-hydroxyvitamin D was measured at baseline (preconception) and 8 weeks of gestation. Outcomes of interest included clinical pregnancy, time to pregnancy, pregnancy loss, and livebirths. Risk ratios (RRs) and 95% CIs for livebirths, pregnancy, and pregnancy loss were estimated with weighted log-binomial regression. To assess time to pregnancy, we used discrete time Cox proportional hazards models to calculate fecundability odds ratios (FORs) with 95% CIs. EAGeR is registered with ClinicalTrials.gov, number NCT00467363. FINDINGS: 1191 women had available data on preconception 25-hydroxyvitamin D concentrations. 555 (47%) women were classified as having sufficient concentrations (≥75 nmol/L) and 636 (53%) as having insufficient concentrations (<75 nmol/L). Women with sufficient preconception 25-hydroxyvitamin D were more likely to achieve clinical pregnancy (adjusted RR 1·10 [1·01-1·20]) and livebirth (1·15 [95% CI 1·02-1·29]) than were women with insufficient concentrations. Among women who achieved pregnancy, sufficient preconception 25-hydroxyvitamin D, but not that at 8 weeks of gestation, was associated with reduced risk of pregnancy loss (preconception RR per 25 nmol/L 0·88 [95% CI 0·77-0·99]; 8 weeks of gestation 0·98 [0·95-1·01]). No association was observed with fecundability in women with sufficient versus those with insufficient preconception 25-hydroxyvitamin D concentrations (adjusted FOR 1·13 [95% CI 0·95-1·34]). INTERPRETATION: Sufficient preconception 25-hydroxyvitamin D (≥75 nmol/L) was associated with increased likelihood of pregnancy and livebirth. Increased vitamin D concentrations before conception, but not in early pregnancy, were associated with reduced pregnancy loss. FUNDING: National Institutes of Health and Doris Duke Charitable Foundation.

Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles.

Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.

Vitamin D is associated with bioavailability of androgens in eumenorrheic women with prior pregnancy loss.

BACKGROUND: Prior studies have reported mixed results regarding relationships between vitamin D, androgens, and sex hormone-binding globulin in patients with polycystic ovary syndrome. However, less is known regarding these associations in eumenorrheic, premenopausal women. OBJECTIVE: Our objective was to study the relationships between serum vitamin D and androgen biomarkers in eumenorrheic women with a history of pregnancy loss who were attempting pregnancy. STUDY DESIGN: This was an analysis of a cohort of 1191 participants from the Effects of Aspirin in Gestation and Reproduction trial (2006-2012). Participants were attempting to conceive, aged 18-40 years, with 1-2 documented prior pregnancy losses and no history of infertility, and recruited from 4 academic medical centers in the United States. Serum vitamin D (25-hydroxyvitamin D) and hormone concentrations were measured at baseline. RESULTS: Vitamin D concentration was negatively associated with free androgen index (percentage change [95% confidence interval, -5% (-8% to -2%)] per 10 ng/mL increase) and positively associated with sex hormone-binding globulin (95% confidence interval, 4% [2-7%]), although not with total testosterone, free testosterone, or dehydroepiandrosterone sulfate after adjusting for age, body mass index, smoking status, race, income, education, physical activity, and season of blood draw. CONCLUSION: Overall, vitamin D was associated with sex hormone-binding globulin and free androgen index in eumenorrheic women with prior pregnancy loss, suggesting that vitamin D may play a role in the bioavailability of androgens in eumenorrheic women. We are limited in making assessments regarding directionality, given the cross-sectional nature of our study.

Association of testosterone and antimüllerian hormone with time to pregnancy and pregnancy loss in fecund women attempting pregnancy.

OBJECTIVE: To examine whether higher T and/or antimüllerian hormone (AMH) was associated with anovulation, time to pregnancy (TTP), or pregnancy loss risk among healthy, fecund women without diagnosed polycystic ovary syndrome. DESIGN: Prospective cohort study conducted as a secondary analysis from the Effects of Aspirin in Gestation and Reproduction randomized trial. SETTING: University medical centers. PATIENT(S): A total of 1,198 healthy, eumenorrheic women aged 18-40 years attempting spontaneous pregnancy with one to two prior pregnancy losses were included. Women were categorized by baseline antimüllerian hormone (AMH), as a surrogate marker of antral follicle count, and T concentrations; the highest quartile for each was "high," and below the top quartile (i.e., lower 75% of values) was "norm," forming four groups: norm T/norm AMH (n = 742), norm T/high AMH (n = 156), high T/norm AMH (n = 157), and high T/high AMH (n = 143). INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Anovulation, pregnancy incidence, TTP, and pregnancy loss incidence. RESULT(S): Women with high T/high AMH had a greater anovulation risk (risk ratio 1.58, 95% confidence interval 1.13-2.22) compared with women with norm T/norm AMH, but with imprecise differences in incidence of pregnancy, TTP, or pregnancy loss. CONCLUSION(S): Women with higher T and AMH had more frequent anovulatory cycles but with marginal impacts on TTP or pregnancy loss. A continuum of mild inefficiency in reproductive function may be related to higher T and AMH, including in fecund women with normal menstrual cycles and no clinical diagnosis of polycystic ovary syndrome, but with unclear effects on fecundability and pregnancy loss. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.

C-Reactive protein in relation to fecundability and anovulation among eumenorrheic women.

OBJECTIVE: To assess systemic inflammation in relation to fecundability and anovulation. DESIGN: Prospective cohort study among participants in the Effects of Aspirin in Gestation and Reproduction trial who were assigned to the placebo. SETTING: Academic medical centers. PATIENT(S): Healthy eumenorrheic women (n = 572), 18-40 years of age, with one or two pregnancy losses, attempting spontaneous pregnancy. INTERVENTION(S): Baseline serum high-sensitivity C-reactive protein (hsCRP) values <10 mg/L were categorized into tertiles. MAIN OUTCOME MEASURE(S): Discrete Cox proportional hazards models estimated the fecundability odds ratio (FOR) and 95% confidence interval (CI) and adjusted for potential confounders. Log-binomial regression estimated the risk ratio (RR) and 95% CI of anovulation. The algorithm to define anovulation used data on urinary concentrations of hCG, pregnanediol-3-glucuronide, and LH as well as fertility monitor readings. RESULT(S): Higher hsCRP was associated with reduced fecundability but not with an increased risk of anovulation. CONCLUSION(S): Among healthy women attempting pregnancy after one or two pregnancy losses, we found preliminary evidence that systemic inflammation is associated with reduced fecundability, but not independently from adiposity. Sporadic anovulation did not appear to drive this association. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00467363.