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STUDY QUESTION Is there an association between iron intake and ovarian reserve among women seeking fertility care? SUMMARY ANSWER Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care. WHAT IS KNOWN ALREADY Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects. STUDY DESIGN, SIZE, DURATION This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007–2019) enrolled in the Environment and Reproductive Health (EARTH) Study. PARTICIPANTS/MATERIALS, SETTING, METHODS Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation. MAIN RESULTS AND THE ROLE OF CHANCE Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45–64 mg/day of supplemental iron had a 17% (−35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (−54%, −11%) lower AFC after adjusting for potential confounders (P , linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P , linear trend = 0.02). LIMITATIONS, REASONS FOR CAUTION Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron. WIDER IMPLICATIONS OF THE FINDINGS Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose–response relation of this association across the entire distribution of ovarian reserve and the risk–benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S) The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C. M.M. L.M.-A. E.O.-P. S.W. I.S. and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: Are urinary levels of oxidative stress biomarkers associated with reproductive outcome success following fertility treatments?Summary Answer: Levels of oxidative stress in the middle tertile for women are associated with the highest levels of reproductive success while no associations were noted for men.What Is Known Already: Oxidative stress may contribute to adverse fertility outcomes in the general population, but findings from couples undergoing fertility treatments are sparse.Study Design, Size, Duration: This prospective cohort study included 481 women and 249 of their male partners undergoing fertility treatments from 2007 to 2015, from the Environment and Reproductive Health (EARTH) study in Boston, MA.Participants/materials, Setting, Methods: One urine sample per participant was collected at each cycle and analysed for two oxidative stress markers: 8-isoprostane-PGF2α (8-iso-PGF2α) and 8-isoprostane-PGF2α metabolite (F2-isoP-M). Reproductive outcomes were abstracted from medical records and included the fertilization rate, for IVF (oocytes fertilized/mature oocytes retrieved), and rates of implantation, clinical pregnancy and live birth, for both IVF and IUI. Cluster-weighted generalized estimating equations were used to analyse adjusted associations between exposure tertiles and outcomes.Main Results and the Role Of Chance: Levels of F2-isoP-M in the middle tertile were associated with the most success among women. Women in the upper tertile of F2-isoP-M had an adjusted mean live birth rate after IVF and IUI of 23% (95% CI: 17, 29) compared to 38% (95% CI: 31, 45) for women in the middle tertile and 27% (95% CI: 21, 34) in the lower tertile. The fertilization rate during IVF was higher for women with 8-iso-PGF2α in the middle tertile (0.77 [95% CI: 0.73, 0.80]) compared to women in the lower (0.69 [95% CI: 0.64, 0.73]) or upper tertiles (0.66 [95% CI: 0.61, 0.71]). No significant associations were found for other measured outcomes with 8-iso-PGF2α, or between any oxidative stress biomarker in men and reproductive outcomes in their partners.Limitations, Reasons For Caution: Isoprostanes are short-lived biomarkers and this study may not have captured the most relevant window of susceptibility for oxidative stress on the outcomes of interest. Findings from this study may not be generalizable to couples attempting conception without fertility assistance.Wider Implications Of the Findings: This study suggests that a non-linear association may exist between oxidative stress and reproductive outcomes in a population undergoing fertility treatment, a finding not previously identified in the literature. Oxidative stress may represent the mechanism through which environmental chemicals are associated with adverse reproductive outcomes.Study Funding/competing Interest(s): This research was supported by the Intramural Research Program of the National Institutes of Environmental Health Sciences (NIEHS) (ZIA ES103314) and by NIEHS grants R01ES022955, R01ES009718 and R01ES00002. There are no competing interests to report.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Abstract Background In animals, anogenital distance (AGD) at birth reflects androgen levels during pregnancy and predicts adult AGD. Little is known about AGD in relation to female reproductive characteristics in humans, a question this study was designed to explore. Methods We used multiple linear and logistic regression analyses to model the relationships between adult female reproductive system characteristics (e.g. ovarian morphology, menstrual cycle) and two measures of AGD [anus-fourchette (AGDAF) and anus-clitoris (AGDAC)] in 100 college-age volunteers in Spain. Ovarian morphology was classified as having < 6 or ≥ 6 follicles per ovary. Results Both AGD measures were positively associated with ovarian follicle number, with AGDAF being more strongly associated. Women in the upper tertile of the AGDAF and AGDAC distributions were more likely to have ≥ 6 ovarian follicles [OR: 6.0 (95% CI 2.0, 17.6) and 3.0 (95% CI 1.1, 8.6), respectively] compared to women in the lowest tertile. Conclusions Increased follicular recruitment has been related to excess androgen exposure in utero in toxicological studies. Our results suggest that the androgenic environment during early fetal life may influence reproductive system development, including AGD, in human females.

Background: Epidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment., Objective: We investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior., Methods: We analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6-13 years and their parents. We estimated covariate-adjusted associations of log e -transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g-computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 and Behavior Rating Inventory of Executive Function T-scores (higher scores indicate more problem behaviors)., Results: This analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non-Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T-scores (propyl paraben β $\beta \;$ = 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β $\beta \;$ = 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T-scores (propyl paraben β $\beta \;$ = 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β $\beta \;$ = 1.6; 95% confidence interval: -0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T-scores respectively. Higher paternal preconception ( β $\beta \;$ = 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception ( β $\beta \;$ = 1.1 95% confidence interval: -0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T-scores in children, but the paraben mixtures was not., Conclusion: In this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent-reported child behaviors., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: We previously reported that the intake of fruits and vegetables (FV) known to have high pesticide contamination in the US food supply is related to lower sperm counts. Whether the same is true for ovarian reserve is unknown., Methods: Participants were 633 females, 21-45 years, presenting to an academic fertility center. We combined surveillance data from the US Department of Agriculture and self-reported food intake data to characterize exposure to pesticide residues through FV intake. Poisson and linear regression were used to evaluate associations of high-pesticide residue, low-pesticide residue, and total FV intake with markers of ovarian reserve (antral follicle count [AFC], follicle-stimulating hormone [FSH], anti-Müllerian hormone [AMH]) adjusting for potential confounders., Results: There was no association of FV intake, overall or according to pesticide residue status, with day 3 FSH or AMH concentrations in multivariable-adjusted models. Regardless of pesticide residue status, FV intake was inversely related to AFC in these models. This pattern was magnified among females who had had a fertility evaluation before joining the study (n=508). Among females who had not had a fertility evaluation before joining the study (n=103), however, there were diverging patterns of association for high- and low-pesticide residue FV intake and markers of ovarian reserve. In this group, day-3 FSH was 71.6% (95%CI: 39.5%, 111.2%) higher among females in the highest quintile of high pesticide residue FV intake than among females in the lowest quintile (p-trend<0.001). Low pesticide residue and total FV intake were unrelated to day 3 FSH in this group, with differences between top and bottom quintile of intake of -8.3% (-25.8%, 13.3%) and 7.5% (-13.8%, 34.0%), respectively., Discussion: High pesticide residue FV intake may be related to lower ovarian reserve among females without a history of infertility treatment. Replication in populations with larger sample sizes and less susceptible to reverse causation is important., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jorge Chavarro reports financial support was provided by National Institute of Health (NIH) to conduct this research (R01ES022955, R01ES033651, R01ES009718, P30ES000002, P30DK046200) and additional support from the NIH (U01HL145386, R24ES028521, R01HD093761, R01HD096032) the CDC and the FDA for unrelated research projects. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Although some studies have investigated the relationships between beverage intake and reproductive health these have generated conflicting results., Objectives: To evaluate the associations between men's beverage intake and semen quality parameters and couple outcomes of medically assisted reproduction., Material and Methods: The relationship between preconception beverage intake and semen quality was evaluated in 896 semen samples from 343 men. The relation between beverage intake and medically assisted reproduction outcomes (fertilization, implantation, clinical pregnancy, total/clinical pregnancy loss, and live birth) was evaluated in 296 men and their female partners who underwent 714 medically assisted reproduction cycles: 306 intrauterine insemination cycles and 408 in vitro fertilization. Intake of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages and sub-groups were considered as exposures., Results: Caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverage intake was not associated with semen quality parameters or with fertilization, implantation, clinical pregnancy, or live birth in couples undergoing medically assisted reproduction. When specific types of beverages were explored, there was an inverse association between a greater intake of coffee/tea with caffeine and lower live birth probabilities in couples undergoing in vitro fertilization cycles. The adjusted probabilities (95% confidence interval) of live birth in the lowest and highest tertiles of intake were 0.49 (0.38, 0.61) and 0.33 (0.24, 0.43) for coffee with caffeine, and 0.49 (0.33, 0.51) and 0.31 (0.22, 0.41) for tea with caffeine. A similar trend was detected with liquor intake and live birth probabilities: 0.45 (0.37, 0.53) and 0.32 (0.25, 0.41). We also found an association between a greater beer intake and higher live birth probabilities. The adjusted probabilities (95% confidence interval) in the lowest and highest quartile of intake were 0.32 (0.23, 0.42) and 0.51 (0.39, 0.62)., Conclusion: Male preconception intakes of coffee, tea, and liquor were inversely associated, whereas beer intake was positively associated with the probability of live birth during infertility treatment., (© 2024 American Society of Andrology and European Academy of Andrology.)

Objective: 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., Design: Prospective cohort study., Setting: MGH infertility clinic in Boston, Massachusetts., Patient(s): Women in the Environment and Reproductive Health cohort seeking fertility treatment., Intervention(s): Women contributed spot urine samples prior to assessment of OR outcomes that were analyzed for benzophenone-3 concentrations., Main Outcome Measure(s): 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., Result(s): 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., Conclusion(s): 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., Competing Interests: Declaration of Interests E.L.S. has nothing to disclose. L.M.-A. has nothing to disclose. B.C. reports funding from NIH grant for the submitted work; funding from NIH grant and research funding from Apple, Inc outside the submitted work. J.E.H. reports funding from NIH (R01 ES009718, R01 ES022955, P30 ES000002) for the submitted work. T.J.-T. reports funding from P30 ES000002 for the submitted work. A.M.C. has nothing to disclose. J.B.F. has nothing to disclose. R.H. reports funding from NIH grant for the submitted work. S.M. reports funding from NIEHS - P30ES000002-58 for this research work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic, highly fluorinated aliphatic compounds, commonly utilised in a wide variety of consumer products with diverse applications. Since the genesis of these compounds, a growing body of evidence has demonstrated adverse health effects associated with PFAS exposure. In a racially diverse cohort of 459 pregnant mothers, demographically weighted towards minority representation (black 44.4%, white 38.4%, other 17.2%), across three major populous cities of the US, PFAS profiling was performed. Nine distinct PFAS species were quantified using mass spectrometry in plasma samples collected during the third trimester. Multivariable logistic and linear regression analyses were conducted to interrogate the associations of PFAS with gestational and birth outcomes: gestational diabetes, preeclampsia, gestational age at delivery, low birth weight, birth weight-, birth length- and head circumference-for-gestational-age. Detectable levels for eight out of nine profiled PFAS species were found in the plasma of pregnant mothers with a median range of 0.1-2.70 ng ml -1 . Using a mixtures approach, we observe that increased quantile-based g-computation (Qg-comp) "total" PFAS levels were associated with increased newborn birth-weight-for-gestational-age ( β 1.28; 95% CI 1.07-1.52; FDR p 0.006). In study centre-stratified analyses, we observed a similar trend in Boston pregnant mothers, with Qg-comp total PFAS associated with higher newborn birth-weight-for-gestational-age ( β 1.39; 95% CI 1.01-1.92, FDR p 0.05). We additionally found elevated PFUA concentrations were associated with longer gestational terms in San Diego pregnant mothers ( β 0.60; 95% CI 0.18-1.02, FDR p 0.05). In this multi-city study, we detected lower levels of PFAS than in many previous US environmental studies, concordant with current US trends indicating environmental PFAS levels are falling, and we note geographical variation in the associations between PFAS levels and birth outcomes., Competing Interests: No authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings.

Background: Prepregnancy body mass index (BMI) is a well-established risk factor of adverse pregnancy outcomes (APOs). The associations of long-term and short-term weight trajectories with APOs are less clear., Objectives: This study aimed to determine the associations of weight trajectories during females' reproductive years, before and between pregnancies, with risk of APOs., Methods: We followed 16,241 females (25,386 singleton pregnancies) participating in a prospective cohort, the Nurses' Health Study II. Weight at age 18 y, current weight, and height were assessed at baseline (1989), and weight was updated biennially. Pregnancy history was self-reported in 2009. The primary outcome was a composite of hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm birth, and stillbirth. Secondary outcomes were individual APOs. The associations of weight change with APOs were estimated using log-binomial regression, adjusting for demographic, lifestyle, reproductive factors, and baseline BMI (in kg/m 2 )., Results: The mean (standard deviation [SD]) age at first in-study pregnancy was 33.7 (4.1) y. The mean (SD) time from age 18 y to pregnancy, baseline to pregnancy, and between pregnancies was 16.3 (4.0), 6.1 (3.0), and 2.9 (1.6) y, with a corresponding weight change of 6.4 (9.1), 3.1 (5.8), and 2.3 (4.8) kg, respectively. Of the pregnancies, 4628 (18.2%) were complicated by ≥1 APOs. Absolute weight change since age 18 y was most strongly associated with APOs. Compared with females whose weight remained stable (0-2 kg) since age 18, females who gained >2 kg had higher risk of APO (2.1-9.9 kg, relative risk [RR]: 1.12; 95% confidence interval [CI]: 1.02, 1.23; 10.0-14.9 kg, RR: 1.43; 95% CI: 1.29, 1.60; ≥15 kg, RR: 1.87; 95% CI: 1.69, 2.08), primarily driven by HDP and GDM. The associations of per 1 kg weight gain before and between pregnancies with HDP were nearly identical., Conclusions: Weight trajectories prior to and between pregnancies were associated with the risk of APOs, particularly HDP. Longer periods of weight gain, corresponding to greater absolute weight gain, were most strongly associated with higher risk of APOs., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Eating behaviors are controlled by the neuroendocrine system. Whether endocrine disrupting chemicals have the potential to affect eating behaviors has not been widely studied in humans. We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol-A (BPA) concentrations were associated with children's eating behaviors., Methods: We used data from mother-father-child triads in the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-13 years whose parent(s) previously enrolled in a fertility clinic-based prospective preconception study. We quantified urinary concentrations of 11 phthalate metabolites and BPA in parents' urine samples collected preconceptionally and during pregnancy. Parents rated children's eating behavior using the Child Eating Behavior Questionnaire (CEBQ). Using multivariable linear regression, accounting for correlation among twins, we estimated covariate-adjusted associations of urinary phthalate biomarkers and BPA concentrations with CEBQ subscale scores., Results: This analysis included 195 children (30 sets of twins), 160 mothers and 97 fathers; children were predominantly non-Hispanic white (84%) and 53% were male. Paternal and maternal preconception monobenzyl phthalate (MBzP) concentrations and maternal preconception mono-n-butyl phthalate (MnBP) were positively associated with emotional overeating, food responsiveness, and desire to drink scores in children (β ' s= 0.11 [95% CI: 0.01, 0.20]-0.21 [95% CI: 0.10, 0.31] per log e unit increase in phthalate biomarker concentration). Paternal preconception BPA concentrations were inversely associated with scores on food approaching scales. Maternal pregnancy MnBP, mono-isobutyl phthalate (MiBP) and MBzP concentrations were associated with increased emotional undereating scores. Maternal pregnancy monocarboxy-isononyl phthalate concentrations were related to decreased food avoiding subscale scores., Conclusions: In this cohort, higher maternal and paternal preconception urinary concentrations of some phthalate biomarkers were associated with increased food approaching behavior scores and decreased food avoiding behavior scores, which could lead to increased adiposity in children., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce., Objective: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy., Study Design: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman., Results: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension., Conclusion: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The epidemiologic literature on women's perceived stress in relation to perinatal outcomes has been inconclusive and does not consider the preconception window of exposure., Objective: To evaluate whether women's preconception perceived stress is related to live birth, gestational age, and birthweight in a cohort receiving fertility treatment., Methods: This observational study included women seeking fertility care at the Massachusetts General Hospital (2004-2019). During preconception, women provided information on their psychological stress using the short version of the validated Perceived Stress Scale 4 (PSS-4). We used regression models to evaluate the associations of stress with live birth ( N  = 768 attempting to conceive) and perinatal outcomes ( N  = 413 live births) while adjusting for confounders. Stratified analyses by mode of conception [natural, intrauterine insemination (IUI), and IVF ( in vitro fertilization)] and selected socioeconomic factors (race, education, and income) were also conducted., Results: Higher psychological stress was negatively associated with the overall probability of live birth (adjusted RR = 0.95, 95% CI: 0.92, 0.98), particularly among women conceiving using IVF. However, we found no association between women's psychological stress and gestational age and birth weight in the overall analyses and also stratified by mode of conception. Similarly, we observed no differences in women's psychological stress with any of the measured outcomes by socioeconomic factors., Discussion: These results highlight the importance of considering the preconception window and mode of conception when evaluating the relationship between women's preconception stress and live birth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Minguez-Alarcón, Williams, Souter, Ford, Hauser and Chavarro.)

Context: The association between women's stress and pregnancy glucose levels remain unclear, specifically when considering the preconception period as a sensitive window of exposure., Objective: We investigated whether preconception perceived stress was associated with glucose levels during pregnancy among women attending a fertility center (2004-2019)., Methods: Before conception, women completed a psychological stress survey using the short version of the validated Perceived Stress Scale 4 (PSS-4), and blood glucose was measured using a 50-gram glucose load test during late pregnancy as a part of screening for gestational diabetes. Linear and log-binomial regression models were used to assess associations of total PSS-4 scores with mean glucose levels and abnormal glucose levels ( ≥ 140 mg/dL), adjusting for age, body mass index, race, smoking, education, physical activity, primary infertility diagnosis, number of babies, and mode of conception., Results: Psychological stress was positively associated with mean abnormal glucose levels. The adjusted marginal means (95% CI) of mean glucose levels for women in the first, second, and third tertiles of psychological stress were 115 (110, 119), 119 (115, 123), and 124 (119, 128), and mg/dL, respectively ( P for trend = .007). Also, women in the second and third tertiles of psychological stress had 4% and 13% higher probabilities of having abnormal glucose compared with women in the first tertile of psychological stress ( P trend = .01)., Conclusion: These results highlight the importance of considering preconception when evaluating the relationship between women's stress and pregnancy glucose levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Epidemiologic studies on health effects of parental preconception exposures are limited despite emerging evidence from toxicological studies suggesting that such exposures, including to environmental chemicals, may affect offspring health., Objective: We investigated whether maternal and paternal preconception and maternal pregnancy urinary phthalate metabolite and bisphenol A (BPA) concentrations were associated with child behavior., Methods: We analyzed data from the Preconception Environmental exposure And Childhood health Effects (PEACE) Study, an ongoing prospective cohort study of children aged 6-11 years whose parent(s) previously enrolled in the prospective preconception Environment and Reproductive Health (EARTH) study. Using linear mixed models, we estimated covariate-adjusted associations of 11 urinary phthalate metabolite and BPA concentrations collected prior to conception and during pregnancy with Behavioral Assessment System for Children-3 (BASC-3) T-scores (higher scores indicate more problem behaviors)., Results: This analysis included 134 mothers, 87 fathers and 157 children (24 sets of twins); parents were predominantly non-Hispanic white (mothers and fathers86%). Higher maternal preconception or pregnancy monobenzyl phthalate (MBzP) concentrations were related to higher mean externalizing problems T-scores in their children (β = 1.3 per 1-log e unit increase; 95 % CI: -0.2, 2.4 and β = 2.1, 95 % CI: 0.7, 3.6, respectively). Higher maternal preconception monocarboxyoctyl phthalate (MCOP) was suggested to be related to lower mean externalizing problems T-scores (β = -0.9; 95 % CI: -1.8, 0.0). Higher paternal preconception MCOP was suggestively associated with lower internalizing problems (β = -0.9; 95 %CI:-1.9, 0.1) and lower Behavioral Symptoms Index (BSI) T-scores (β = -1.3; 95 % CI: -2.1, -0.4)., Conclusion: In this cohort, higher maternal preconception and pregnancy MBzP were associated with worse parent-reported child behavior, while higher maternal and paternal preconception MCOP concentrations were related to lower BASC-3 scores., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Modifiable factors, such as environmental exposures, can impact human fertility. The objective of this review is to summarize the potential effects of exposure to important endocrine-disrupting chemicals on male reproductive health. Most experimental and animal data demonstrate strong evidence for the negative effects of exposure to phenols, phthalates, pesticides, and perfluoroalkyl and polyfluoroalkyl substances on male reproductive health. Although evidence of negative associations in humans was overall strong for phthalates and pesticides, limited and inconclusive relationships were found for the other examined chemical biomarkers. Reasons for the discrepancies in results include but are not limited to, differences in study populations, exposure concentrations, number of samples collected, sample sizes, study design, and residual confounding. Additional studies are needed, particularly for newer phenols and perfluoroalkyl and polyfluoroalkyl substances, given the scarce literature on the topic and increasing exposures over time., Competing Interests: Declaration of interests L.M.A. has nothing to disclose. A.J.G. has nothing to disclose. J.D.M. has nothing to disclose. J.M.B. was financially compensated for serving as an expert witness for plaintiffs in litigation related to tobacco smoke exposures and received an honorarium for serving on an advisory board for Quest Diagnostics. J.M.B.’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; these funds were not paid to JMB directly. J.E.C. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endocrine disrupting chemicals (EDCs) can adversely affect human health and are ubiquitously found in everyday products. We examined temporal trends in urinary concentrations of EDCs and their replacements. Urinary concentrations of 11 environmental phenols, 15 phthalate metabolites, phthalate replacements such as two di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) metabolites, and triclocarban were quantified using isotope-dilution tandem mass spectrometry. This ecological study included 996 male and 819 female patients who were predominantly White/Caucasian (83 %) with an average age of 35 years and a BMI of 25.5 kg/m 2 seeking fertility treatment in Boston, MA, USA. Patients provided a total of 6483 urine samples (median = 2, range = 1-30 samples per patient) between 2000 and 2017. Over the study period, we observed significant decreases (% per year) in urinary concentrations of traditional phenols, parabens, and phthalates such as bisphenol A (β: -6.3, 95 % CI: -7.2, -5.4), benzophenone-3 (β: -6.5, 95 % CI: -1.1, -18.9), parabens ((β range:-5.4 to -14.2), triclosan (β: -18.8, 95 % CI: -24, -13.6), dichlorophenols (2.4-dichlorophenol β: -6.6, 95 % CI: -8.8, -4.3); 2,5-dichlorophenol β: -13.6, 95 % CI: -17, -10.3), di(2-ethylhexyl) phthalate metabolites (β range: -11.9 to -22.0), and other phthalate metabolites including mono-ethyl, mono-n-butyl, and mono-methyl phthalate (β range: -0.3 to -11.5). In contrast, we found significant increases in urinary concentrations of environmental phenol replacements including bisphenol S (β: 3.9, 95 % CI: 2.7, 7.6) and bisphenol F (β: 6, 95 % CI: 1.8, 10.3), DINCH metabolites (cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester [MHiNCH] β: 20, 95 % CI: 17.8, 22.2; monocarboxyisooctyl phthalate [MCOCH] β: 16.2, 95 % CI: 14, 18.4), and newer phthalate replacements such as mono-3-carboxypropyl phthalate, monobenzyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate and di-isobutyl phthalate metabolites (β range = 5.3 to 45.1), over time. Urinary MHBP concentrations remained stable over the study period. While the majority of biomarkers measured declined over time, concentrations of several increased, particularly replacement chemicals that are studied., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004-2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = -0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Increasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns., Objective: To investigate whether women's adherence to a priori-defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment., Design, Setting, and Participants: This prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022., Exposures: Women's pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori-defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet., Main Outcomes and Measures: The adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles., Results: This analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women's adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21-0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern., Conclusions and Relevance: Findings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009-2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography-tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols-both individually and as a mixture-and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT 3 (mean difference for a 1 log unit increase in concentration: -0.088; 95% CI [-0.151, -0.025]) and TT 3 (-0.066; 95% CI [-0.112, -0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT 3 concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: -0.19, 95% CI [-0.35, -0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.

Objective: To investigate the association between intake of soy food and isoflavone with ovarian reserve. Previous studies suggest on the relationship between soy intake and human fertility are inconsistent. Some clinical studies suggest that soy and phytoestrogens may not be deleterious to reproduction and may even be beneficial in couples undergoing infertility treatment. However, no studies have evaluated the relationship between soy or isoflavone intake with markers of ovarian reserve other than follicle-stimulating hormone (FSH)., Design: Cross-sectional study., Setting: An academic fertility center., Patient(s): Patients presenting to an academic fertility center between 2007 and 2019 were invited to participate in the Environment and Reproductive Health Study., Intervention(s): Six hundred and sixty seven participants reported their soy food intake and had an antral follicle count (AFC) assessment. Intake of 15 soy-based foods during the previous 3 months was obtained at baseline and intake of isoflavone was estimated. Participants were divided into 5 groups based on soy food and isoflavone intake considering those who did not consume soy as the reference group., Main Outcome Measure(s): Ovarian reserve was assessed using AFC as the primary outcome measure, with antimüllerian hormone (AMH) and FSH as secondary outcome measures. The AFC was measured on the third day of the menstrual cycle. Moreover, FSH and AMH levels were measured in blood samples obtained on the third day and the follicular phase of the menstrual cycle. To evaluate the association between soy intake and ovarian reserve, we used Poisson regression models for AFC and quantile regression models for AMH and day 3 FSH levels by adjusting for confounders., Result(s): Participants had a median age of 35.0 years. The median intake of soy was 0.09 servings/day and isoflavones was 1.78 mg/day. Moreover, AFC, AMH, and FSH were unrelated to soy intake in crude analyses. We found no association between soy food intake with AFC or day 3 FSH level in multivariable models. However, participants in the highest category of soy food intake had significantly low AMH levels (-1.16, 95% confidence interval: -1.92, -0.41). Soy intake had no association with AFC, AMH, or FSH in sensitivity analyses that included using different cutoff points of soy intake, excluding participants in the highest 2.5 percentile of intake, and additional statistical adjustment for dietary patterns., Conclusion(s): The results of this study are not consistent with a strong positive or inverse association of soy or isoflavone intakes within the observed range of intake, which substantially overlaps with that in the general population of the United States as well as the ovarian reserve among individuals presenting to fertility centers., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Research Question: Is self-reported psychological stress associated with markers of ovarian reserve among subfertile women?, Design: Observational study of women (n = 520) seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health study between 2005 and 2019. Women completed the short version of the validated PSS4, which assesses psychological stress. Ovarian reserve markers included AFC and circulating serum levels of day-3 FSH, with AMH assessed in a subset of participants (n = 185)., Results: Higher total PSS4 scores were negatively associated with AFC and serum AMH levels. Analyses adjusted for age, BMI, race, smoking, education, physical activity and type of infertility diagnosis. Women in the second and third tertiles of stress had lower AFC (13.3, 95% CI 12.7 to 13.8; and 13.5, 95% CI 13.0 to 14.1) compared with women in the lowest tertile of psychological stress score (14.3, 95% CI 13.8 to 14.9, both P < 0.05). Women in the second and third tertiles of total PSS4 scores also had lower mean serum AMH compared with women in the lowest tertile (2.99, 95% CI 2.24 to 3.74), and (2.99 95% CI 2.22 to 3.76) versus (3.94 95% CI 3.23 to 4.64). These associations varied by several socioeconomic factors, and were observed among women who were younger, belonging to minority races, with a college degree or with annual household income less than $100,000., Conclusions: Higher perceived stress was negatively associated with AFC and serum AMH levels. These associations varied by several socioeconomic factors., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Exposure to per- and polyfluoroalkyl substances (PFAS) through the environment can lead to harmful health outcomes and the development of disease. However, little is known about how PFAS impact underlying biology that contributes to these adverse health effects. The metabolome represents the end product of cellular processes and has been used previously to understand physiological changes that lead to disease. In this study, we investigated whether exposure to PFAS was associated with the global, untargeted metabolome. In a cohort of 459 pregnant mothers and 401 children, we quantified plasma concentrations of six individual PFAS- PFOA, PFOS, PFHXS, PFDEA, and PFNA- and performed plasma metabolomic profiling by UPLC-MS. In adjusted linear regression analysis, we found associations between plasma PFAS and perturbations in lipid and amino acid metabolites in both mothers and children. In mothers, metabolites of 19 lipid pathways and 8 amino acid pathways were significantly associated with PFAS exposure at an FDR<0.05 threshold; in children, metabolites of 28 lipid pathways and 10 amino acid pathways exhibited significant associations at FDR<0.05 with PFAS exposure. Our investigation found that metabolites of the Sphingomyelin, Lysophospholipid, Long Chain Polyunsaturated Fatty Acid (n3 and n6), Fatty Acid- Dicarboxylate, and Urea Cycle showed the most significant associations with PFAS, suggesting these may be particular pathways of interest in the physiological response to PFAS. To our knowledge, this is the first study to characterize associations between the global metabolome and PFAS across multiple periods in the life course to understand impacts on underlying biology, and the findings presented here are relevant in understanding how PFAS disrupt normal biological function and may ultimately give rise to harmful health effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Study Question: Are occupational factors associated with markers of testicular function among men attending a fertility center?, Summary Answer: Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations., What Is Known Already: Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors., Study Design, Size, Duration: This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019., Participants/materials, Setting, Methods: Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min-max = 1-9) in analyses for semen parameters., Main Results and the Role of Chance: Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P = 0.01) and 44% higher total counts (P = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P = 0.04) and 45% higher estradiol concentrations (P = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations., Limitations, Reasons for Caution: Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns., Wider Implications of the Findings: Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted., Study Funding/competing Interest(s): NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc., which provided funds to perform this analysis. There are no other conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)