Objective: To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females. Design: Cross-sectional analysis Subjects: Between 2017–2023, 7,227 North American female pregnancy planners aged 21-45 years enrolled in PRESTO (Pregnancy Study Online), a preconception cohort study. Participants completed self-administered baseline questionnaires during preconception. Exposure: Infertility history, defined as: 1) self-reported 12-month clinical infertility, 2) history of visiting a clinician for an infertility work-up, and/or 3) clinician-identified cause of infertility (e.g., ovulatory or tubal). Main Outcome Measure: Adherence to specific diets, including vegetarian, vegan, Mediterranean, Paleo, Weight Watchers®, ketogenic, dairy free, gluten free, Atkins®, South Beach®, Zone®, raw foods, or other at baseline. Multivariable log-binomial regression models estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs), adjusted for age, income, and body mass index (BMI). Results: The percentage of participants with a history of infertility was 26% based on the 12-month clinical infertility definition, 30% based on visiting a physician for infertility evaluation, and 26% based on an infertility diagnosis following a physician visit. Overall adherence to any particular diet was low (4.6% vegetarian, 2.8% ketogenic, 1.7% Weight Watchers®, 1.4% Mediterranean, 1.3% vegan, 0.8% Paleo, and all other diets: <0.8%); 86.6% reported not adhering to any particular diet. A history of 12-month clinical infertility was associated with lower adherence to vegetarian (PR=0.78; 95% CI: 0.60-1.03), Paleo (PR=0.43; 95% CI: 0.19-0.98), and Weight Watchers® (PR=0.55; 95% CI: 0.34-0.91) diets. An infertility history involving a medical work-up was associated with a higher prevalence of adherence to a ketogenic diet (PR=1.56; 95% CI: 1.17-2.09). Participants whose infertility was attributed to ovulatory or tubal causes were nearly two times more likely to adhere to a ketogenic diet (PR=2.01; 95% CI: 1.38-2.94; PR=2.22; 95% CI: 1.09-4.49, respectively). Limitations: The cross-sectional design cannot establish temporality or causality. Data on dietary patterns and infertility history were self-reported, which can introduce misclassification. Generalizability may be limited because participants were pregnancy planners not using fertility treatments; participants were also more likely to be non-Hispanic White and of higher socioeconomic status than the general population. Conclusion: The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers® diets were less prevalent. These associations mirror the results of studies evaluating the reverse relationship, suggesting that some patients with infertility seek information for behavioral modifications via evidence-based medicine.

Inflammatory Bowel Disease (IBD) is an immune-mediated disorder characterized by chronic intestinal inflammation. IBD, along with its associated treatments, may have systemic effects including potential implications for female fertility. Anti-Müllerian hormone (AMH) levels are commonly used as a biomarker of ovarian reserve and fertility potential. However, the impact of IBD and its therapies on AMH levels remains unclear. This study aims to evaluate the association between IBD, AMH levels, and fertility. This retrospective study analyzed electronic medical records from a multicenter academic institution from January 2017 to September 2024. Female patients with recorded AMH levels and a diagnosis of IBD were identified and compared to a control group without an IBD diagnosis. Baseline characteristics were compared between the two groups. Fisher’s exact test was used for statistical analysis. A total of 146 patients were included in the study, with 67 patients diagnosed with IBD and 79 control patients. Among patients with IBD, 7.5

OBJECTIVE:Neighborhood disadvantage is associated with adverse reproductive health outcomes, but its association with menstrual disturbances is understudied. Our objective was to estimate the association between neighborhood socioeconomic disadvantage and prevalence of menstrual disturbances (abnormal uterine bleeding and dysmenorrhea). DESIGN:We conducted a cross-sectional analysis of 8,198 participants in Pregnancy Study Online, an internet-based preconception cohort study, enrolled during October 2014-September 2024. SUBJECTS:Participants were aged 21-39 years, US residents, and not using contraceptives or fertility treatment. EXPOSURE:We linked within-state Area Deprivation Index percentiles to residential addresses by block group and year. MAIN OUTCOME MEASURES:We used self-reported data on typical menstrual cycle characteristics to define abnormal uterine bleeding (irregular cycles, duration of flow ≥7 days, heavy bleeding, or cycle length <24 or >38 days) and dysmenorrhea (severe pain requiring medication use and bed rest). We estimated prevalence ratios and 95% confidence intervals (CI) for associations of Area Deprivation Index quartiles with abnormal uterine bleeding and dysmenorrhea using modified Poisson regression models. RESULTS:Neighborhood disadvantage was positively associated with the prevalence of abnormal uterine bleeding (most [Q4] vs. least disadvantaged [Q1] quartile: prevalence ratio = 1.16, 95% CI: 1.05-1.29) and dysmenorrhea (Q4 prevalence ratio = 1.44, 95% CI: 1.12-1.85) in models adjusted for age, year, parent's educational attainment, race, and ethnicity. After further adjustment for participant household income, the association between neighborhood disadvantage and abnormal uterine bleeding prevalence was attenuated (Q4 prevalence ratio = 0.99, 95% CI: 0.89-1.10), whereas neighborhood disadvantage was positively, nonmonotonically associated with dysmenorrhea prevalence (Q2 prevalence ratio = 1.40, 95% CI: 1.13-1.74; Q3 prevalence ratio = 1.42, 95% CI: 1.13-1.77; and Q4 prevalence ratio = 1.21, 95% CI: 0.93-1.56). CONCLUSION:Living in a more disadvantaged neighborhood was associated with a higher prevalence of menstrual disturbances, particularly dysmenorrhea.

STUDY QUESTION:To what extent are there racial and ethnic disparities in fecundability in North America? SUMMARY ANSWER:In a North American preconception cohort study, we observed large differences in fecundability across racial and ethnic groups. WHAT IS KNOWN ALREADY:Several studies in the United States (USA) have shown that Black women tend to wait longer for fertility treatment and are less likely to seek medical care for infertility than White women. Among those who seek infertility treatment, there are large racial disparities in access to treatment and treatment success rates. However, research has been limited and conflicting on the extent to which fertility measures such as fecundability (per-cycle probability of conception) vary by race and ethnicity. STUDY DESIGN, SIZE, DURATION:We examined the associations of race and ethnicity with fecundability in Pregnancy Study Online (PRESTO), a prospective preconception cohort study of US and Canadian residents aged 21-45 years who were actively trying to conceive without the use of fertility treatment at enrollment (2013-2024). We restricted the analysis to 18 573 participants with fewer than 12 cycles of pregnancy attempt time at enrollment. PARTICIPANTS/MATERIALS, SETTING, METHODS:Participants self-reported data on race and ethnicity on a baseline questionnaire and completed bimonthly follow-up questionnaires for up to 12 months to update data on pregnancy status. We estimated fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression models. We stratified by pregnancy attempt time at enrollment, reproductive history, country of residence, age, and educational attainment. In sensitivity analyses, we applied inverse probability of continuation weights to account for differential loss-to-follow-up. We also calculated the cumulative incidence of infertility during 12 cycles of attempt time by race and ethnicity using life-table methods to account for censoring. MAIN RESULTS AND THE ROLE OF CHANCE:Compared with non-Hispanic White participants, fecundability was appreciably lower among participants who identified as non-Hispanic Black (FR = 0.60, 95% CI: 0.52-0.70), non-Hispanic American Indian/Alaskan Native/Indigenous (FR = 0.70, 95% CI: 0.44-1.11), non-Hispanic multiracial (FR = 0.89, 95% CI: 0.81-0.99), or Hispanic other/unknown race (FR = 0.77, 95% CI: 0.65-0.90). Results were similar when we performed various sensitivity analyses including: application of inverse probability of continuation weights to account for differential loss-to-follow-up; stratification by age and educational attainment; and restriction of analyses to (i) participants with <3 cycles of pregnancy attempt time at enrollment, (ii) nulligravid participants without an infertility history, and (iii) US residents. The 12-cycle cumulative incidence of infertility (i.e. clinical definition) among participants with <2 cycles of attempt time at entry also differed meaningfully by race and ethnicity (33.2% among non-Hispanic Black participants and 29.7% among Hispanic other/unknown race participants vs 16.4% among non-Hispanic White participants). LIMITATIONS, REASONS FOR CAUTION:Due to limited numbers, we grouped participants into broad racial and ethnic groups within which there is considerable heterogeneity. Such groupings will obscure any differences in fecundability that exist between subgroups. Differential loss-to-follow-up was an important source of selection bias, though findings did not vary appreciably when we applied inverse probability of continuation weights. PRESTO is an internet-based convenience sample of pregnancy planners of higher-than-average socioeconomic status and is, therefore, not representative of all individuals who conceive, which may limit generalizability. WIDER IMPLICATIONS OF THE FINDINGS:These descriptive data indicate the strong need for additional studies to carefully measure and better understand the mechanisms underlying disparities in fecundability, including the effects of structural racism and discrimination, as well as programs and policies to advance reproductive health equity. As more research is conducted on the drivers of these disparities, greater efforts should be made to increase fertility awareness, enhance preconception health, expand access to fertility treatments, and improve patient care among underserved populations to reduce the burden of subfertility among those affected. STUDY FUNDING/COMPETING INTEREST(S):This work was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development (R01-HD086742; T32-HD052458) and the National Institute on Minority Health and Health Disparities (K01-MD013911). In the past three years, L.A.W. served as a consultant for AbbVie, Inc. and the Gates Foundation. She was also a member of the steering committee for AbbVie on Abnormal Uterine Bleeding and Fibroids, where payments were made to Dr Wise. Her study, PRESTO, received in-kind donations from Kindara.com (fertility apps) and Swiss Precision Diagnostics (home pregnancy tests). C.N. received payments to her institution from the National Institute on Minority Health and Health Disparities K01-MD013911. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER:N/A.

Disclosure: S.A. Pereira: None. A. Kim: None. G.H. Cherfane: None. A. Lofrano-Porto: None. R.S. Carroll: None. W. Kuohung: None. U.B. Kaiser: None. Background: Infertility affects 10% of those seeking pregnancy, and treatment of infertility may reveal recurrent implantation failure (RIF) or result in ectopic pregnancy (EP). Gaps persist in our understanding of the etiology of these disorders, hampering clinical management. We previously characterized a missense mutation in OSR1 identified in a proband and two sisters with impaired Mullerian duct (MD) development, uterine hypoplasia with estrogen-unresponsive endometrium, and EP. We also showed that OSR1/Osr1 is expressed in adult human and mouse endometrium and that Osr1 knockout mouse embryos have MD developmental abnormalities. We hypothesized that Osr1 expression in uteri and oviducts is sex steroid mediated, varying across the mouse estrous cycle and responding to sex steroid treatment.Methods: Adult wild-type C57BL/6 mice were euthanized during three distinct phases of the estrous cycle—proestrus, estrus, and diestrus—and uteri and oviducts were harvested for total RNA extraction and analysis of Osr1 mRNA levels by RT-qPCR. To assess Osr1 expression during endometrial proliferation and differentiation, uteri were collected from four groups: 1) intact females in diestrus, 2) 14 days post-ovariectomy (OVX), 3) 14 days post-OVX plus 3 days of estradiol (E2, 100 ng/day, proliferation phase), and 4) 14 days post-OVX plus 3 days of E2 followed by a 3-day rest and then 8 days of E2 (10 ng/day) and progesterone (P4, 1 mg/day, differentiation phase). Expression of uterine P4-induced genes (Ihh and Gata2) and of oviductal E2-induced genes (Dcpp3 and Igfbp3) were assessed as controls for estrous cycle phases and hormonal replacement. Results: Across the estrous cycle, Osr1 mRNA levels in mouse uteri were higher in diestrus compared to proestrus and estrus, but did not vary in oviducts. Expression of P4-induced genes in uteri was higher in diestrus than in proestrus or estrus. In the oviducts, expression of E2-induced genes was higher in phases with higher E2 levels (i.e., proestrus and estrus) compared to diestrus. In the model of endometrial proliferation and differentiation, uterine Osr1 expression was lower 14 days post-OVX compared to diestrus and recovered after 8 days of E2+P4 treatment, but not after 3 days of E2 alone. Expression of P4-induced genes was higher in diestrus and after E2+P4 treatment compared to both the 14-day post-OVX and E2 only groups.Conclusions: While Osr1 expression in oviducts was stable across the estrous cycle, it varied in the uterus with highest expression in diestrus, the implantation window in mice. Uterine Osr1 expression was reduced in the absence of sex steroids and restored following E2+P4 treatment. Higher Osr1 expression correlated with increased expression of P4-induced genes. Our data suggest that Osr1 may play a role in implantation in mice. Future studies will assess whether OSR1 expression is altered in the endometrium of patients with RIF or EP. Presentation: Monday, July 14, 2025

To identify factors contributing to misdiagnosis of interstitial ectopic pregnancy (IEP). Retrospective chart review identified patients who presented to Boston Medical Center with suspected and/or true IEP from January 1, 2012 to April 30, 2019. Final diagnoses identified two IEP diagnosis groups: correct initial diagnosis and incorrect initial diagnosis. Data collected included age, gravidity, parity, body mass index (BMI), estimated gestational age, anatomic anomalies of the reproductive tract, smoking status, and history of pelvic surgery, sexually transmitted infections, pelvic inflammatory disease, or adnexal lesions. Continuous variables were analyzed using analysis of covariance and unpaired t-tests. Fisher’s exact tests were used for discrete variables. Of 53 patients with suspected and/or true IEP, 15 (28

OBJECTIVE:To compare differences in the management and outcomes of ectopic pregnancy (EP) in an urban population before and after the COVID-19 pandemic. METHODS:A retrospective cohort study of 188 patients aged >18 years who presented with an EP to Boston Medical Center (BMC) between March 2019 and March 2021 was performed. Sociodemographic and clinical data were collected from medical records. Patients were stratified into 'pre-COVID' and 'intra-COVID' groups. Differences in patient characteristics, presentation, and management between the groups were evaluated. RESULTS:There were 95 patients in the pre-COVID group and 93 in the intra-COVID group. Overall, there was little difference in age, socio-demographics, presenting symptoms, management, or outcomes, across groups. However, patients presenting intra-COVID were more likely to have a prior history of STIs (difference in proportion +0.14 (95 % CI 0.02, 0.25), report current alcohol use (+0.14 (95 % CI 0.02, 0.25)), and current recreational drug use (+0.11 (95 % CI 0.01, 0.20)). Time from decision for surgery to start of operation (+49.3 min, (95 % CI -62.5, 161.1)) and estimated blood loss (EBL) (+12.9 mL (95 % CI -13.0, 38.8)) was greater for the intra-COVID group. CONCLUSION:The observed increase in EBL from EPs managed surgically and in "decision-to-incision" time in the intra-COVID group may be explained by cumbersome personal protective equipment protocols and turnaround time for required COVID-19 PCR testing. The higher prevalence of STIs among intra-COVID patients may reflect increased unwanted sexual activity or reduced access to barrier protection among socioeconomically disadvantaged patients.

Preeclampsia is a severe pregnancy complication that disproportionately affects women of Sub-Saharan African ancestry. Genetic variants of apolipoprotein L1 (APOL1), originally evolved in response to Trypanosoma brucei , have been associated with kidney disease; however, their role in preeclampsia remains unclear. Inaxaplin (VX-147), a first-in-class APOL1 inhibitor, is currently in Phase 3 trials for APOL1-mediated kidney disease, but its therapeutic potential for APOL1-mediated preeclampsia has yet to be explored. This study investigates 1) whether APOL1 risk variants cause preeclampsia and 2) whether inaxaplin can mitigates APOL1-mediated preeclampsia. Due to the absence of APOL1 in rodents, transgenic mouse models carrying human APOL1 alleles were used: wild-type (G0/G0) and high-risk (G2/G2). Hallmarks of preeclampsia, including new-onset hypertension, proteinuria, and intrauterine grow restriction (IUGR) were assessed. Blood pressure (BP) was continuously monitored in conscious pregnant mice via implanted telemetry devices throughout gestation and confirmed by invasive transducer-based measurements under anesthesia on gestation day 18 (GD18). Proteinuria was quantified at GD18 using Coomassie blue staining and normalized by urine creatinine. Fetal weight was also recorded at GD18 to evaluate IUGR. Inaxaplin was administered via drinking water throughout the gestational period. We found that pregnant G2/G2 mice at GD18 exhibited higher BP 106.38 ± 5.50 vs. 89.84± 4.42 mmHg; n=9; p<0.01) and elevated urine albumin-creatinine ratio (944.98 ± 138.28 vs. 66.68 ± 43.78 mg/g; n=5-8; p<0.01) than pregnant G0/G0 mice. Additionally, G2/G2 fetuses had lower weights than G0/G0 fetuses (0.607 ± 0.169 vs.0.941 ± 0.138 g; n=51-95; p<0.01). Moreover, pregnancy acted as a “second hit”, increasing renal APOL1 mRNA expression by 68.6 ± 7.2% in G2/G2 and 60.2 ± 13.5% in G0/G0 mice. This was accompanied by elevated circulating IFN-γ, measured using the Proteome Profiler Cytokine Array, with levels rising by 99.2% in G2/G2 and 97.7% in G0/G0 mice (n=5; p<0.01). Furthermore, inaxaplin restored BP (93.49± 6.60 vs. 106.38± 5.50 mmHg; n=7-9; p<0.01) and fetal weight (1.051 ± 0.097 vs. 0.607 ± 0.169 g; n=10; p<0.01) and reduced albuminuria by 57.9±7.5% (n=5; p<0.01) in pregnant G2/G2 mice. These findings demonstrate that humanized APOL1 mice carrying high-risk alleles spontaneously develop preeclampsia, and that inaxaplin treatment mitigates APOL1-mediated preeclampsia.

Background:Neighborhood context is a root cause of health disparities, but few epidemiologic studies have measured the effect of neighborhoods on fertility, a reproductive outcome with known racial disparities. Methods:The Black Women's Health Study is a prospective cohort study of US Black women who enrolled in 1995. Participants completed questionnaires at baseline and every 2 years afterwards. We linked participant addresses to US Census block group data on six variables representing neighborhood disadvantage and used factor analysis to derive a composite neighborhood disadvantage score. In 2011, participants reported how many months it took to conceive each of their planned pregnancies and whether they had ever tried to conceive for 12 or more months without success. We included 2,085 participants who contributed 2,712 pregnancy attempts during 1995-2011. We fit proportional probabilities regression models with generalized estimating equations to estimate fecundability ratios and 95% confidence intervals (CI). We stratified models by individual-level educational attainment. Results:Relative to the lowest quintile of neighborhood disadvantage, fecundability ratios for participants in quintiles 2, 3, 4, and 5 were 0.89 (95% CI = 0.79, 1.01), 0.94 (95% CI = 0.83, 1.06), 0.84 (95% CI = 0.74, 0.96), and 0.89 (95% CI = 0.79, 1.02), respectively. The association persisted only among participants with a college degree or higher. Conclusion:Higher neighborhood disadvantage was associated with reduced fecundability in this cohort of Black women, particularly among those with high educational attainment. These results support the relevance of studying place-based risk factors for subfertility and have important implications for advancing reproductive justice.

BACKGROUND: Fertility success among mixed-sex couples depends on frequency and timing of sexual intercourse, yet little research has evaluated the association between preconception sexual function time-to-pregnancy. OBJECTIVE: To evaluate the effects of female sexual dysfunction, distress related to sexual functioning, and painful intercourse on time pregnancy. STUDY DESIGN: We followed 2500 participants from Pregnancy Study Online, a prospective cohort study of self-identified females attempting pregnancy without the use of fertility treatments. Participants enrolled between 2021 and 2024. Thirty days after enrollment, participants completed a supplemental questionnaire that contained questions about sexual health, including a modified version of the 6-item Female Sexual Function Index (score range 2-30, score <19 defined as sexual dysfunction) and the Female Sexual Distress Scale (score range 0-48, score >= 20 defined as clinically relevant distress), which assess experiences in the previous 4 weeks. Participants completed the supplemental questionnaire no later than 6 months after initiating conception attempts. We estimated time-to-pregnancy based on self-reported pregnancy status on follow-up questionnaires completed every 8 weeks for up to 12 months. We used proportional probabilities regression to calculate fecundability ratios and 95% confidence intervals relating exposure measures time-to-pregnancy, adjusting for a range of prespecified confounders. an exploratory analysis, we evaluated individual domains of sexual function (ie, interest, arousal, orgasm, lubrication, and satisfaction) in relation time-to-pregnancy. RESULTS: The study population was primarily non-Hispanic White, high income, with college or graduate education. Exposure prevalence was 20.1% for female sexual dysfunction, 8.8% for distress, and 29.6% for any pain with intercourse. We observed no association between female sexual dysfunction and time-to-pregnancy (adjusted fecundability ratio 1.00, 95% confidence interval 0.890, 1.13) when female sexual dysfunction was defined using a clinically validated cut point, but observed that those in the first, second, and third quartile of scores had delayed conception compared to those in the fourth (highest function) (adjusted fecundability ratios 0.90, 95% confidence interval 0.76, 1.06; 0.88, 95% confidence interval 0.75, 1.04; and 0.90, 95% confidence interval 0.77, 1.04, respectively). We found 18% reduced fecundability among those with sexual distress as defined by a clinically validated cut point compared to those without (adjusted fecundability ratio 0.82, 95% confidence interval 0.69, 0.98). Participants reporting painful intercourse most or all the time had a longer time-to-pregnancy than those reporting no pain (adjusted fecundability ratio 0.81, 95% confidence interval 0.62, 1.06). In exploratory analyses, lower function in orgasm and lubrication domains, but not interest, desire, and arousal, were associated with longer time-to-pregnancy. CONCLUSION: Preconception sexual dysfunction, specifically distress and frequent painful intercourse, was associated with delayed conception. Preconception clinical assessment of sexual function, including discussion of individual domains of sexual function, may elucidate important modifiable issues.

Review the current literature regarding fertility preservation options for patients with breast cancer receiving gonadotoxic chemotherapy and common barriers to treatment. Oocyte and embryo cryopreservation are considered the gold standard modalities for fertility preservation. Ovarian tissue preservation is no longer considered an experimental treatment option by ASRM, but patient access to this modality is limited. GnRH agonists may reduce the risk of primary ovarian insufficiency and improve pregnancy rates after completion of cancer therapy, but data on its efficacy in fertility preservation is mixed, and there is limited data on long term outcomes. Counseling regarding the potential impacts of cancer treatment on fertility soon after diagnosis and regardless of cancer staging or patient age reduces patient distress. Early referral to a Reproductive Endocrinology and Infertility (REI) specialist soon after diagnosis can streamline access to fertility preservation methods. Insurance coverage impacts access to fertility treatment and differs by state in the U.S.

Background Black women and people with uteri have utilized collectivistic and relational practices to improve health outcomes in the face of medical racism and discrimination for decades. However, there remains a need for interventions to improve outcomes of uterine fibroids, a condition that disproportionately impacts Black people with uteri. Leveraging personalized approaches alongside evidence that demonstrates the positive impact of social and peer support on health outcomes, we adapted from CenteringPregnancy, an evidence based group prenatal care intervention, for the education and empowerment of patients with uterine fibroids. Methods The present report provides an overview of the study design and planned implementation of CPWF in cohorts at Boston Medical Center and Emory University / Grady Memorial Hospital. After receiving training from the Centering Healthcare Institute (CHI), we adapted the 10-session CenteringPregnancy curriculum to an 8-session hybrid group intervention called Centering Patients with Fibroids (CPWF). The study began in 2022 with planned recruitment of six cohorts of 10-12 participants at each institution. We will conduct a mixed methods evaluation of the program using validated survey tools and qualitative methods, including focus groups and 1:1 interviews. Discussion To date, we have successfully recruited 4 cohorts at Boston Medical Center and are actively implementing BMC Cohort 5 and the first cohort at Emory University / Grady Memorial Hospital. Evaluation of the program is forthcoming.