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Fetal development represents a time of potential vulnerability due to rapid cell division, organ development and limited fetal kidney/liver activity for detoxification and metabolism of exposures. Health effects of prenatal toxicant exposure have previously been described, but there is little cohesive evidence surrounding effects on ovarian function. Using bisphenol A (BPA) as a case study, we seek to examine whether a prominent prenatal environmental exposure can pose a real threat to human ovarian function. To do so, we broadly review human oogenesis and menstrual cycle biology. We then present available literature addressing prenatal bisphenol A and diverse outcomes at the level of the ovary. We highlight relevant human cohorts and mammalian models to review the existing data on prenatal exposures and ovarian disruption. Doing so suggests that while current exposures to BPA have not shown marked or consistent results, there is data sufficient to raise concerns regarding ovarian function. Challenges in the examination of this question suggest the need for additional models and pathways by which to expand these examinations in humans. [ABSTRACT FROM AUTHOR]

Low-dose prolactin induces proinflammatory responses and antibody production, whereas high-dose prolactin suppresses these responses. Mechanisms for these opposing effects remain incompletely defined. We have previously demonstrated that T-bet, a key transcription factor directing T helper type 1 inflammatory responses, is regulated by female steroid hormones in human mucosal epithelial cells via Stat1 and 5 pathways. T-bet was also modulated in a CD4+ T cell line by prolactin exposure. Prolactin rapidly induced T-bet transcription through phosphorylation of JAK2 and Stat5, but not Stat1. Phosphorylated Stat5 then bound to the T-bet regulatory region. These effects were weaker with high-dose prolactin exposures. Upon long-term prolactin exposure, low-dose prolactin induced T-bet expression, whereas high-dose prolactin tended to suppress it. Prolactin induced the suppressors of cytokine signaling (SOCS) 1 and 3 in a dose-dependent manner. With high-dose exposure, this was associated with an inhibition of the phosphorylation of T-bet regulatory region-bound Stat5. Further, the dose-dependent prolactin effects on T-bet expression were confirmed in murine primary CD4+ T cells. These data suggest that the divergent immune effects of low- and high-dose prolactin may involve modulation of T-bet and alterations in the balance of the prolactin/JAK2/Stat5 and the prolactin/SOCS1 and 3 pathways.Immunology and Cell Biology (2008) 86, 616–621; doi:10.1038/icb.2008.29; published online 15 April 2008 [ABSTRACT FROM AUTHOR]

To evaluate the association between the urinary benzophenone-3 concentrations and measures of ovarian reserve (OR) among women in the Environment and Reproductive Health study seeking fertility treatment at Massachusetts General Hospital (MGH) in Boston, Massachusetts. Prospective cohort study. MGH infertility clinic in Boston, Massachusetts. Women in the Environment and Reproductive Health cohort seeking fertility treatment. Women contributed spot urine samples prior to assessment of OR outcomes that were analyzed for benzophenone-3 concentrations. Antral follicle count (AFC) and day 3 follicle-stimulating hormone (FSH) levels were evaluated as part of standard infertility workups during unstimulated menstrual cycles. Quasi-Poisson and linear regression models were used to evaluate the association of the specific gravity–adjusted urinary benzophenone-3 concentrations with AFC and FSH, with adjustment for age and physical activity. In the secondary analyses, models were stratified by age. This study included 142 women (mean age ± standard deviation, 36.1 ± 4.6 years; range, 22–45 years) enrolled between 2009 and 2017 with both urinary benzophenone-3 and AFC measurements and 57 women with benzophenone-3 and FSH measurements. Most women were White (78%) and highly educated (49% with a graduate degree). Women contributed a mean of 2.7 urine samples (range, 1–10), with 37% contributing ≥2 samples. Benzophenone-3 was detected in 98% of samples. The geometric mean specific gravity–corrected urinary benzophenone-3 concentration was 85.9 μg/L (geometric standard deviation, 6.2). There were no associations of benzophenone-3 with AFC and day 3 FSH in the full cohort. In stratified models, a 1-unit increase in the log geometric mean benzophenone-3 concentration was associated with a 0.91 (95% confidence interval, 0.86–0.97) times lower AFC among women aged ≤35 years and an increase in the FSH concentration of 0.73 (95% confidence interval, 0.12–1.34) IU/L among women aged >35 years. In the main models, urinary benzophenone-3 was not associated with OR. However, younger patients may be vulnerable to the potential effects of benzophenone-3 on AFC. Further research is warranted. [ABSTRACT FROM AUTHOR]

Background: Multimodal recruitment strategies are a novel way to increase diversity in research populations. However, these methods have not been previously applied to understanding the prevalence of menstrual disorders such as polycystic ovary syndrome. Objective: The purpose of this study was to test the feasibility of recruiting a diverse cohort to complete a web-based survey on ovulation and menstruation health. Methods: We conducted the Ovulation and Menstruation Health Pilot Study using a REDCap web-based survey platform. We recruited 200 women from a clinical population, a community fair, and the internet. Results: We recruited 438 women over 29 weeks between September 2017 and March 2018. After consent and eligibility determination, 345 enrolled, 278 started (clinic: n=43; community fair: n=61; internet: n=174), and 247 completed (clinic: n=28; community fair: n=60; internet: n=159) the survey. Among all participants, the median age was 25.0 (SD 6.0) years, mean BMI was 26.1 kg/m2 (SD 6.6), 79.7% (216/271) had a college degree or higher, and 14.6% (37/254) reported a physician diagnosis of polycystic ovary syndrome. Race and ethnicity distributions were 64.7% (176/272) White, 11.8% (32/272) Black/African American, 7.7% (21/272) Latina/Hispanic, and 5.9% (16/272) Asian individuals; 9.9% (27/272) reported more than one race or ethnicity. The highest enrollment of Black/African American individuals was in clinic (17/42, 40.5%) compared to 1.6% (1/61) in the community fair and 8.3% (14/169) using the internet. Survey completion rates were highest among those who were recruited from the internet (159/174, 91.4%) and community fairs (60/61, 98.4%) compared to those recruited in clinic (28/43, 65.1%). Conclusions: Multimodal recruitment achieved target recruitment in a short time period and established a racially diverse cohort to study ovulation and menstruation health. There were greater enrollment and completion rates among those recruited via the internet and community fair. J Med Internet Res 2021;23(4):e24716 doi:10.2196/24716 [ABSTRACT FROM AUTHOR]

Investigates the reactivity of a series of platinum(IV) anticancer complexes with different reduction potentials toward 5'-guanosine monophosphate (5'-GMP). Cathodic reduction potentials of the platinum complexes; Initial substitution of a platinum ligand by a 5'-GMP molecule; Formation of the intermediate.

Background: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis. Objective: Our goal was to determine the association of air pollution exposures during adulthood, including distance to road, particulate matter < 2.5 μm, between 2.5 and 10 μm, and < 10 μm, (PM2.5, PM10–2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses’ Health Study II. Methods: Proximity to major roadways and outdoor levels of PM2.5, PM10–2.5, and PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk. Results: Among 84,060 women, 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association between endometriosis risk and distance to road or exposure to PM2.5, PM10–2.5, or PM10 averaged over follow-up or during the previous 2- or 4-year period. Conclusions: Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women. Citation: Mahalingaiah S, Hart JE, Laden F, Aschengrau A, Missmer SA. 2014. Air pollution exposures during adulthood and risk of endometriosis in the Nurses’ Health Study II. Environ Health Perspect 122:58–64; http://dx.doi.org/10.1289/ehp.1306627

Background: Bisphenol A (BPA) is used to manufacture polymeric materials, such as polycarbonate plastics, and is found in a variety of consumer products. Recent data show widespread BPA exposure among the U.S. population.Objective Our goal in the present study was to determine the temporal variability and predictors of BPA exposure. Methods: We measured urinary concentrations of BPA among male and female patients from the Massachusetts General Hospital Fertility Center. Results: Between 2004 and 2006, 217 urine samples were collected from 82 subjects: 45 women (145 samples) and 37 men (72 samples). Of these, 24 women and men were partners and contributed 42 pairs of samples collected on the same day. Ten women became pregnant during the follow-up period. Among the 217 urine samples, the median BPA concentration was 1.20 μg/L, ranging from below the limit of detection (0.4 μg/L) to 42.6 μg/L. Age, body mass index, and sex were not significant predictors of urinary BPA concentrations. BPA urinary concentrations among pregnant women were 26% higher (–26%, +115%) than those among the same women when not pregnant (p > 0.05). The urinary BPA concentrations of the female and male partner on the same day were correlated (r = 0.36; p = 0.02). The sensitivity of classifying a subject in the highest tertile using a single urine sample was 0.64. Conclusion: We found a nonsignificant increase in urinary BPA concentrations in women while pregnant compared with nonpregnant samples from the same women. Samples collected from partners on the same day were correlated, suggesting shared sources of exposure. Finally, a single urine sample showed moderate sensitivity for predicting a subject’s tertile categorization.

[Display omitted] The menopausal transition involves significant sex hormone changes. Environmental chemicals, such as urinary phthalate metabolites, are associated with sex hormone levels in cross-sectional studies. Few studies have assessed longitudinal associations between urinary phthalate metabolite concentrations and sex hormone levels during menopausal transition. Pre- and perimenopausal women from the Midlife Women's Health Study (MWHS) (n = 751) contributed data at up to 4 annual study visits. We quantified 9 individual urinary phthalate metabolites and 5 summary measures (e.g., phthalates in plastics (∑Plastic)), using pooled annual urine samples. We measured serum estradiol, testosterone, and progesterone collected at each study visit, unrelated to menstrual cycling. Linear mixed-effects models and hierarchical Bayesian kernel machine regression analyses evaluated adjusted associations between individual and phthalate mixtures with sex steroid hormones longitudinally. We observed associations between increased concentrations of certain phthalate metabolites and lower testosterone and higher sub-ovulatory progesterone levels, e.g., doubling of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), di-2-ethylhexyl phthalate (∑DEHP) metabolites, ∑Plastic, and ∑Phthalates concentrations were associated with lower testosterone (e.g., for ∑DEHP: −4.51%; 95% CI: −6.72%, −2.26%). For each doubling of MEP, certain DEHP metabolites, and summary measures, we observed higher mean sub-ovulatory progesterone (e.g., ∑AA (metabolites with anti-androgenic activity): 6.88%; 95% CI: 1.94%, 12.1%). Higher levels of the overall time-varying phthalate mixture were associated with lower estradiol and higher progesterone levels, especially for 2nd year exposures. Phthalates were longitudinally associated with sex hormone levels during the menopausal transition. Future research should assess such associations and potential health impacts during this understudied period. [ABSTRACT FROM AUTHOR]

[Display omitted] • PFOS was associated with higher parameters of gestational BP trajectories. • Positive associations were stronger in participants with parity ≥ 1. Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters – adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity – compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother. [ABSTRACT FROM AUTHOR]

• Digital cohort of 125,104 menstrual cycles from 17,427 participants within the US. • Modest seasonal variation of menstrual cycle length from June 2020 to July 2022. • Shorter cycles (<1/5 day) in May–Aug and Sept–Dec compared to Jan–April. • Younger participants <35°N and >40°N with PCOS had strongest seasonal trends. • No seasonal patterns in cycle lengths were found for participants above age 40. [ABSTRACT FROM AUTHOR]

Prenatal exposure to endocrine disrupting chemicals (EDCs) from personal care products may be associated with birth outcomes including preterm birth and low birth weight. There is limited research examining the role of personal care product use during pregnancy on birth outcomes. Our pilot study consisted of 164 participants in the Environmental Reproductive and Glucose Outcomes (ERGO) study (Boston, MA), with data on self-reported personal care product use at four study visits throughout pregnancy (product use in the 48 h before a study visit and hair product use in the month before a study visit). We used covariate-adjusted linear regression models to estimate differences in mean gestational age at delivery, birth length, and sex-specific birth weight-for-gestational age (BW-for-GA) Z-score based on personal care product use. Hair product use in the past month prior to certain study visits was associated with decreased mean sex-specific BW-for-GA Z-scores. Notably, hair oil use in the month prior to study visit 1 was associated with a lower mean BW-for-GA Z-score (V1: −0.71, 95% confidence interval: −1.12, −0.29) compared to non-use. Across all study visits (V1–V4), increased mean birth length was observed among nail polish users vs. non-users. In comparison, decreased mean birth length was observed among shave cream users vs. non-users. Liquid soap, shampoo, and conditioner use at certain study visits were significantly associated with higher mean birth length. Suggestive associations were observed across study visits for other products including hair gel/spray with BW-for-GA Z-score and liquid/bar soap with gestational age. Overall, use of a variety of personal care products throughout pregnancy was observed to be associated with our birth outcomes of interest, notably hair oil use during early pregnancy. These findings may help inform future interventions/clinical recommendations to reduce exposures linked to adverse pregnancy outcomes. • Personal care products (PCPs) often contain endocrine disrupting chemicals. • We estimated associations of product use at 4 visits in pregnancy with birth outcomes. • Lower birth weight-for-gestational age (BW-for-GA) was reported among hair product users. • The strongest association with lower BW-for-GA was observed for daily hair oil use. • Use of liquid soaps, shampoos, conditioners were associated with longer infant length. [ABSTRACT FROM AUTHOR]

Purpose of Review: Hypoparathyroidism (hypoPTH) is a rare disease that requires diligent adherence to treatment regimens to prevent hypocalcemia but also treatment-induced hypercalcemia and hypercalciuria. The menstrual cycle, pregnancy, and lactation can all impact calcium homeostasis but there is little known regarding the impact of ovarian stimulation. Furthermore, the limited reports suggest no clear association between menstrual phase and calcium balance among those with hypoPTH. With increasing patient utilization of assisted reproductive technology (ART), there is a need for better understanding the care required for patients with hypoparathyroidism pursuing fertility technology., Recent Findings: There is currently no literature available on patients with hypoparathyroidism and the impact of controlled ovarian stimulation on calcium homeostasis. We present information regarding physiologic changes in pregnancy that impact calcium homeostasis and the first case presentation of a patient with hypoparathyroidism pursuing ART., Summary: This article provides the first insights and guidance when providing fertility care for patients with hypoparathyroidism., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity., Objective: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife., Methods: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR)., Results: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture., Conclusion: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Between 2010 and 2016, elective oocyte cryopreservation (OC) increased in use by 880% in the United States; however, there have been increasing reports of regret among patients after elective OC. There is a growing need for individualized counseling on the timing and number of oocytes to cryopreserve for patients to make informed choices and set realistic expectations, but currently available tools seem to be insufficient. The purpose of this review is to describe the OC calculators currently available online, identify sources of regret, and illustrate the need for unified counseling tools for improved patient care and education. OC calculators were identified via Google search. Only calculators that cite scientific literature were included in the review. Calculators for in vitro fertilization or embryo transfer were excluded. Thirteen OC calculators were found; however, only six cited literature supporting the calculator's design. When entering the same hypothetical patient parameters for age and number of oocytes cryopreserved, the calculators provided drastically different probabilities of live births. The lack of cohesive online educational materials creates confusion and stress for patients considering OC, leading to unrealistic expectations and increased feelings of regret thereafter. Physicians need tools to provide comprehensive guidance to patients seeking to cryopreserve oocytes., Competing Interests: The authors declare no conflict of interest and nothing to disclose., (Thieme. All rights reserved.)

Background: Approximately 13% of women in the United States of reproductive age seek infertility services. Assisted reproductive technology (ART), including in vitro fertilization, is used to help patients achieve pregnancy. Many people are not familiar with these treatments prior to becoming patients and possess knowledge gaps about care., Methods: This study employed qualitative methods to investigate how patients interact with information sources during care. Patients who underwent ART including embryo transfer between January 2017 and April 2022 at a large urban healthcare center were eligible. Semi-structured, in-depth interviews were conducted between August and October 2022. Fifteen females with an average age of 39 years participated. Reflexive thematic analysis was performed., Results: Two main themes emerged. Participants (1) utilized clinic-provided information and then turned to outside sources to fill knowledge gaps; (2) struggled to learn about costs, insurance, and mental health resources to support care. Participants preferred clinic-provided resources and then utilized academic sources, the internet, and social media when they had unfulfilled information needs. Knowledge gaps related to cost, insurance, and mental health support were reported., Conclusion: ART clinics can consider providing more information about cost, insurance, and mental health support to patients., Trial Registration: The Massachusetts General Hospital Institutional Review Board approved this study (#2022P000474) and informed consent was obtained from each participant., (© 2024. The Author(s).)

Importance: Early menarche is associated with adverse health outcomes. Trends toward earlier menarche have been observed in the US, but data remain limited on differences by sociodemographic factors and body mass index (BMI). Time from menarche to cycle regularity is another understudied early-life characteristic with health implications., Objectives: To evaluate the temporal trends and disparities in menarche and time to regularity and explore early-life BMI as a mediator., Design, Setting, and Participants: This ongoing cohort study enrolled participants from an ongoing mobile application-based US cohort from November 14, 2019, to March 20, 2023., Exposures: Birth year (categorized as 1950-1969, 1970-1979, 1980-1989, 1990-1999, and 2000-2005)., Main Outcomes and Measures: Main outcomes were age at menarche and time to regularity, which were self-recalled at enrollment. In addition, early (aged <11 years), very early (aged <9 years), and late (aged ≥16 years) age at menarche was assessed., Results: Among the 71 341 female individuals who were analyzed (mean [SD] age at menarche, 12.2 [1.6] years; 2228 [3.1%] Asian, 3665 [5.1%] non-Hispanic Black, 4918 [6.9%] Hispanic, 49 518 [69.4%] non-Hispanic White, and 8461 [11.9%] other or multiple races or ethnicities), 5223 were born in 1950 to 1969, 12 226 in 1970 to 1979, 22 086 in 1980 to 1989, 23 894 in 1990 to 1999, and 7912 in 2000 to 2005. The mean (SD) age at menarche decreased from 12.5 (1.6) years in 1950 to 1969 to 11.9 (1.5) years in 2000 to 2005. The number of individuals experiencing early menarche increased from 449 (8.6%) to 1223 (15.5%), the number of individuals experiencing very early menarche increased from 31 (0.6%) to 110 (1.4%), and the number of individuals experiencing late menarche decreased from 286 (5.5%) to 137 (1.7%). For 61 932 participants with reported time to regularity, the number reaching regularity within 2 years decreased from 3463 (76.3%) to 4075 (56.0%), and the number not yet in regular cycles increased from 153 (3.4%) to 1375 (18.9%). The magnitude of the trend toward earlier menarche was greater among participants who self-identified as Asian, non-Hispanic Black, or other or multiple races (vs non-Hispanic White) (P = .003 for interaction) and among participants self-rated with low (vs high) socioeconomic status (P < .001 for interaction). Within a subset of 9865 participants with data on BMI at menarche, exploratory mediation analysis estimated that 46% (95% CI, 35%-61%) of the temporal trend in age at menarche was explained by BMI., Conclusions and Relevance: In this cohort study of 71 341 individuals in the US, as birth year increased, mean age at menarche decreased and time to regularity increased. The trends were stronger among racial and ethnic minority groups and individuals of low self-rated socioeconomic status. These trends may contribute to the increase in adverse health outcomes and disparities in the US.

Purpose of Review: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are becoming increasingly popular for the treatment of type II diabetes and obesity. Body mass index (BMI) thresholds at in vitro fertilization (IVF) clinics may further drive the use of these medications before infertility treatment. However, most clinical guidance regarding optimal time to discontinue these medications prior to conception is based on animal data. The purpose of this review was to evaluate the literature for evidence-based guidance regarding the preconception use of GLP-1 RA., Recent Findings: 16 articles were found in our PubMed search, 10 were excluded as they were reviews or reported on animal data. Included were 3 case reports detailing pregnancy outcomes in individual patients that conceived while on a GLP-1 RA and 2 randomized controlled trials (RCTs) and a follow-up study to one of the RCTs that reported on patients randomized to GLP-1 RA or metformin prior to conception. No adverse pregnancy or neonatal outcomes were reported., Summary: There are limited data from human studies to guide decision-making regarding timing of discontinuation of GLP-1 RA before conception. Studies focused on pregnancy and neonatal outcomes would provide additional information regarding a safe washout period. Based on the available literature a 4-week washout period prior to attempting conception may be considered for the agents reviewed in this publication., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Increased fossil fuel usage and extreme climate change events have led to global increases in greenhouse gases and particulate matter with 99% of the world's population now breathing polluted air that exceeds the World Health Organization's recommended limits. Pregnant women and neonates with exposure to high levels of air pollutants are at increased risk of adverse health outcomes such as maternal hypertensive disorders, postpartum depression, placental abruption, low birth weight, preterm birth, infant mortality, and adverse lung and respiratory effects. While the exact mechanism by which air pollution exerts adverse health effects is unknown, oxidative stress as well as epigenetic and immune mechanisms are thought to play roles. Comprehensive, global efforts are urgently required to tackle the health challenges posed by air pollution through policies and action for reducing air pollution as well as finding ways to protect the health of vulnerable populations in the face of increasing air pollution., Competing Interests: Declaration of Competing Interest Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); Stock options from IgGenix, Seed Health, ClostraBio, Cour, Alladapt; Advisor at Cour Pharma; Consultant for Excellergy, Red tree ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; Co-founder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers; patents include, “Mixed allergen com-position and methods for using the same,” “Granulocyte-based methods for detecting and monitoring immune system disorders,” and “Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders”. All other authors indicate no conflict of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Menstrual cycle tracking apps (MCTAs) have potential in epidemiological studies of women's health, facilitating real-time tracking of bleeding days and menstrual-associated signs and symptoms. However, information regarding the characteristics of MCTA users versus cycle nontrackers is limited, which may inform generalizability., Objective: We compared characteristics among individuals using MCTAs (app users), individuals who do not track their cycles (nontrackers), and those who used other forms of menstrual tracking (other trackers)., Methods: The Ovulation and Menstruation Health Pilot Study tested the feasibility of a digitally enabled evaluation of menstrual health. Recruitment occurred between September 2017 and March 2018. Menstrual cycle tracking behavior, demographic, and general and reproductive health history data were collected from eligible individuals (females aged 18-45 years, comfortable communicating in English). Menstrual cycle tracking behavior was categorized in 3 ways: menstrual cycle tracking via app usage, that via other methods, and nontracking. Demographic factors, health conditions, and menstrual cycle characteristics were compared across the menstrual tracking method (app users vs nontrackers, app users vs other trackers, and other trackers vs nontrackers) were assessed using chi-square or Fisher exact tests., Results: In total, 263 participants met the eligibility criteria and completed the digital survey. Most of the cohort (n=191, 72.6%) was 18-29 years old, predominantly White (n=170, 64.6%), had attained 4 years of college education or higher (n= 209, 79.5%), and had a household income below US $50,000 (n=123, 46.8%). Among all participants, 103 (39%) were MCTA users (app users), 97 (37%) did not engage in any tracking (nontrackers), and 63 (24%) used other forms of tracking (other trackers). Across all groups, no meaningful differences existed in race and ethnicity, household income, and education level. The proportion of ever-use of hormonal contraceptives was lower (n=74, 71.8% vs n=87, 90%, P=.001), lifetime smoking status was lower (n=6, 6% vs n=15, 17%, P=.04), and diagnosis rate of gastrointestinal reflux disease (GERD) was higher (n=25, 24.3% vs n=12, 12.4%, P=.04) in app users than in nontrackers. The proportions of hormonal contraceptives ever used and lifetime smoking status were both lower (n=74, 71.8% vs n=56, 88.9%, P=.01; n=6, 6% vs n=11, 17.5%, P=.02) in app users than in other trackers. Other trackers had lower proportions of ever-use of hormonal contraceptives (n=130, 78.3% vs n=87, 89.7%, P=.02) and higher diagnostic rates of heartburn or GERD (n=39, 23.5% vs n=12, 12.4%, P.03) and anxiety or panic disorder (n=64, 38.6% vs n=25, 25.8%, P=.04) than nontrackers. Menstrual cycle characteristics did not differ across all groups., Conclusions: Our results suggest that app users, other trackers, and nontrackers are largely comparable in demographic and menstrual cycle characteristics. Future studies should determine reasons for tracking and tracking-related behaviors to further understand whether individuals who use MCTAs are comparable to nontrackers., (©Tatheer Adnan, Huichu Li, Komal Peer, Elizabeth Peebles, Kaitlyn James, Shruthi Mahalingaiah. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 27.10.2023.)

Background: Previous studies have linked environmental exposures with anti-Müllerian hormone (AMH), a marker of ovarian reserve. However, associations with multiple environment factors has to our knowledge not been addressed., Methods: We included a total of 2,447 premenopausal women in the Nurses' Health Study II (NHSII) who provided blood samples during 1996-1999. We selected environmental exposures linked previously with reproductive outcomes that had measurement data available in NHSII, including greenness, particulate matter, noise, outdoor light at night, ultraviolet radiation, and six hazardous air pollutants (1,3-butadiene, benzene, diesel particulate matter, formaldehyde, methylene chloride, and tetrachloroethylene). For these, we calculated cumulative averages from enrollment (1989) to blood draw and estimated associations with AMH in adjusted single-exposure models, principal component analysis (PCA), and hierarchical Bayesian kernel machine regression (BKMR)., Results: Single-exposure models showed negative associations of AMH with benzene (percentage reduction in AMH per interquartile range [IQR] increase = 5.5%, 95% confidence interval [CI] = 1.0, 9.8) and formaldehyde (6.1%, 95% CI = 1.6, 10). PCA identified four major exposure patterns but only one with high exposure to air pollutants and light at night was associated with lower AMH. Hierarchical BKMR pointed to benzene, formaldehyde, and greenness and suggested an inverse joint association with AMH (percentage reduction comparing all exposures at the 75th percentile to median = 8.2%, 95% CI = 0.7, 15.1). Observed associations were mainly among women above age 40., Conclusions: We found exposure to benzene and formaldehyde to be consistently associated with lower AMH levels. The associations among older women are consistent with the hypothesis that environmental exposures accelerate reproductive aging., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is an endocrine disrupting disorder affecting about 10% of reproductive-aged women. PCOS diagnosis may be delayed several years and may require multiple physicians, resulting in lost time for risk-reducing interventions. Menstrual tracking apps are a potential tool to alert women of their risk while also prompting evaluation from a medical professional., Objective: The primary objective of this study was to develop and pilot test the irregular cycle feature, a predictive model that generated a PCOS risk score, in the menstrual tracking app, Clue. The secondary objectives were to run the model using virtual test subjects, create a quantitative risk score, compare the feature's risk score with that of a physician, and determine the sensitivity and specificity of the model before empirical testing on human subjects., Methods: A literature review was conducted to generate a list of signs and symptoms of PCOS, termed variables. Variables were then assigned a probability and built into a Bayesian network. Questions were created based on these variables. A total of 9 virtual test subjects were identified using self-reported menstrual cycles and answers to the feature's questions. Upon completion of the questionnaire, a Result Screen and Doctor's Report summarizing the probability of having PCOS was displayed. This provided information about PCOS and data to facilitate diagnosis by a medical professional. To assess the accuracy of the feature, the same set of 9 virtual test subjects was assigned probabilities by the feature and the physician, who served as the gold standard. The feature recommended individuals with a score greater than or equal to 25% to follow-up with a physician. Differences between the feature and physician scores were evaluated using a t test and a Pearson correlation coefficient in 8 of the 9 virtual test subjects. A second iteration was conducted to assess the feature's probability capabilities., Results: The irregular cycle feature's first iteration produced 1 false-positive compared with the physician score and had an absolute mean difference of 15.5% (SD 15.1%) among the virtual test subjects. The second iteration had 2 false positives compared with the physician score and had an absolute mean difference of 18.8% (SD 13.6%). The feature overpredicted the virtual test subjects' risk of PCOS compared with the physician. However, a significant positive correlation existed between the feature and physician score (Pearson correlation coefficient=0.82; P=.01). The second iteration performed worse, with a Pearson correlation coefficient of 0.73 (P=.03)., Conclusions: The first iteration of the feature outperformed the second and better predicted the probability of PCOS. Although further research is needed with a more robust sample size, this pilot study indicates the potential value for developing a screening tool to prompt high-risk subjects to seek evaluation by a medical professional., (©Erika Marie Rodriguez, Daniel Thomas, Anna Druet, Marija Vlajic-Wheeler, Kevin James Lane, Shruthi Mahalingaiah. Originally published in JMIR Formative Research (http://formative.jmir.org), 14.05.2020.)

Tetrachloroethylene (PCE) is a common contaminant in both occupational and community settings. High exposure levels in the workplace have been shown to have adverse impacts on reproduction and development but few epidemiological studies have examined these effects at the lower levels commonly seen in community settings. We were presented with a unique opportunity to examine the reproductive and developmental effects of prenatal exposure to PCE-contaminated drinking water resulting from the installation of vinyl-lined water pipes in Massachusetts and Rhode Island from the late 1960s through 1980. This review describes the methods and findings of two community-based epidemiological studies, places their results in the context of the existing literature, and describes the strengths and challenges of conducting epidemiological research on a historical pollution episode. Our studies found that prenatal exposure to PCE-contaminated drinking water is associated with delayed time-to-pregnancy, and increased risks of placental abruption, stillbirths stemming from placental dysfunction, and certain birth defects. No associations were observed with pregnancy loss, birth weight, and gestational duration. Important strengths of this research included the availability of historical data on the affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little opportunity for recall bias and confounding. Challenges arose mainly from the retrospective nature of the exposure assessments. This research highlights the importance of considering pregnant women and their developing fetuses when monitoring, regulating, and remediating drinking water contaminants.