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Background: Significant early life adversities, such as childhood sexual and physical/emotional abuse, are associated with risk of poor health outcomes but are understudied risk factors for post-COVID-19 conditions. In this prospective study, we examined the associations between combined exposure to sexual and physical/emotional abuse during childhood with risk of post-COVID-19 conditions in adulthood. Additionally, we explored the extent to which lifestyle, health-related and psychological factors explain this association., Methods: We used data from three large, ongoing cohorts: Nurses' Health Study (NHS)-II, NHS3, and the Growing Up Today Study. Between April 2020 and November 2021, participants responded to periodic COVID-19 surveys. Participants were included if they responded to a questionnaire about childhood abuse, subsequently tested positive for SARS-CoV-2 infection and responded to questions about post-COVID-19 conditions. Childhood sexual abuse was measured before the COVID-19 pandemic with the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale, and physical/emotional abuse was measured with the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire. Post-COVID-19 conditions, defined as COVID-19-related symptoms lasting 4 weeks or longer (e.g., fatigue, dyspnea), were self-reported in the final COVID-19 questionnaire in November 2021. Sexual abuse and physical/emotional abuse were examined separately and jointly in relation to post-COVID-19 conditions. Data on key lifestyle (e.g., cigarette smoking), health-related (e.g., asthma, diabetes), and psychological factors (e.g., depression and anxiety) were obtained., Results: Of 2851 participants, the mean age (range) was 55.8 (22.0-75.0) years; 2789 (97.8 %) were females, and 2750 (96.5 %) were whites. We observed a dose-dependent relationship between severity of childhood abuse and post-COVID conditions (p-trend:<0.0001); participants with severe versus no childhood abuse had a 42 % higher subsequent risk of post-COVID conditions [relative risk (95 % confidence interval): 1.42 (1.25 to 1.61)]. Key lifestyle, health-related, and psychological factors mediated 25.5 % of this association. Both sexual and physical/emotional abuse, were independently associated with post-COVID conditions., Conclusions: In this prospective study of 2851 participants, childhood abuse was significantly associated with increased risk of post-COVID conditions. Biological pathways connecting childhood abuse with subsequent risk of post-COVID conditions should be investigated., 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 © 2024 Elsevier Inc. All rights reserved.)

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: 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.)

Food and nutrition-related factors, including foods and nutrients consumed, dietary patterns, use of dietary supplements, adiposity, and exposure to food-related environmental contaminants, have the potential to impact semen quality and male and female fertility; obstetric, fetal, and birth outcomes; and the health of future generations, but gaps in evidence remain. On 9 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and the school's Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships between food, nutrition, and fertility. Topics addressed included male fertility, female fertility and gestation, and intergenerational effects. This meeting report summarizes the presentations and deliberations from the meeting. Regarding male fertility, a positive association exists with a healthy dietary pattern, with high-quality evidence for semen quality and lower quality evidence for clinical outcomes. Folic acid and zinc supplementation have been found to not impact male fertility. In females, body weight status and other nutrition-related factors are linked to nearly half of all ovulation disorders, a leading cause of female infertility. Females with obesity have worse fertility treatment, pregnancy-related, and birth outcomes. Environmental contaminants found in food, water, or its packaging, including lead, perfluorinated alkyl substances, phthalates, and phenols, adversely impact female reproductive outcomes. Epigenetic research has found that maternal and paternal dietary-related factors can impact outcomes for future generations. Priority evidence gaps identified by meeting participants relate to the effects of nutrition and dietary patterns on fertility, gaps in communication regarding fertility optimization through changes in nutritional and environmental exposures, and interventions impacting germ cell mechanisms through dietary effects. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and fertility., (Copyright © 2023. Published by Elsevier Inc.)

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.)

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.)

Background: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19., Objective: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19., Study Design: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases)., Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis., Conclusion: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life., Objective: This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM., Methods: We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption., Results: A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003)., Conclusions: Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated., Objective: This study aimed to examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics., Study Design: This study prospectively observed 3858 premenopausal women in the Nurses' Health Study 3 living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021 and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "before COVID-19" were reported at baseline between 2011 and 2016, and current menstrual cycle length and regularity "after COVID-19" were reported in late 2021. Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between SARS-CoV-2 infection and COVID-19 vaccination and change in menstrual cycle characteristics., Results: The median age at baseline and the median age at end of follow-up were 33 years (range, 21-51) and 42 years (range, 27-56), respectively, with a median follow-up time of 9.2 years. This study documented 421 SARS-CoV-2 infections (10.9%) and 3527 vaccinations (91.4%) during follow-up. Vaccinated women had a higher risk of increased cycle length than unvaccinated women (odds ratio, 1.48; 95% confidence interval, 1.00-2.19), after adjusting for sociodemographic and behavioral factors. These associations were similar after in addition accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: odds ratio, 1.67 [95% confidence interval, 1.05-2.64]; 7-9 months: odds ratio, 1.43 [95% confidence interval, 0.96-2.14]; >9 months: odds ratio, 1.41 [95% confidence interval, 0.91-2.18]) and among women whose cycles were short, long, or irregular before vaccination (odds ratio, 2.82 [95% confidence interval, 1.51-5.27]; odds ratio, 1.10 [95% confidence interval, 0.68-1.77] for women with normal length, regular cycles before vaccination). Messenger RNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics., Conclusion: COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination. The results underscored the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association of a history of infertility with long-term weight, body composition, and blood pressure., Methods: We studied 1581 women from the prospective cohort Project Viva. History of infertility was based on self-reported time to pregnancy ≥12 months or use of medical treatment to conceive for the index or any prior pregnancy; a diagnosis of infertility; claims for infertility treatments/prescriptions abstracted from medical records. The outcomes were weight, waist circumference, and body fat assessed through 12 years postpartum; and blood pressure assessed through 3 years postpartum. We used linear mixed-effect models adjusted for age, race/ethnicity, income, education, marital status, parity, and age at menarche., Results: Three hundred forty-two women (21.6%) had a history of infertility. In adjusted models, women with versus without infertility, had higher average weight (3.29 kg, 95% confidence interval [CI]: 1.35-5.24), waist circumference (2.46 cm, 95% CI: 0.78-4.13) and body fat (1.76 kg, 95% CI: 0.09-3.43). Among younger (18-29 years), but not older (≥30 years) women, infertility was associated with higher systolic (4.08 mmHg, 95% CI: 0.93, 7.23) and diastolic blood pressure (2.16 mmHg, 95% CI: 0.11-4.20)., Conclusions: A history of infertility may serve as a marker to identify women at higher cardiometabolic risk., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake, and endometriosis are pervasive in the lay literature., Objectives: We aimed to investigate the associations of carbohydrate quality [glycemic index (GI) and glycemic load (GL)], fiber intake (total, legume, vegetable, cruciferous vegetable, fruit, cereal), and gluten intake with incident laparoscopically confirmed endometriosis., Methods: This was a prospective cohort study using data collected from 81,961 premenopausal women in the Nurses' Health Study II (mean age = 36 y in 1991). Diet was assessed with a validated FFQ every 4 y. Cox proportional hazards models were used to calculate rate ratios (RRs) and 95% CIs., Results: A total of 3810 incident cases of laparoscopically confirmed endometriosis were reported over 24 y of follow-up. Women in the highest quintile of GI had 12% (95% CI: 1.01, 1.23; Ptrend = 0.03) higher risk of endometriosis diagnosis than those in the lowest quintile. Total vegetable and cruciferous vegetable fiber intakes were also associated with higher risk (highest compared with lowest quintile RR: 1.13; 95% CI: 1.02, 1.24; Ptrend = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; Ptrend = 0.02, respectively). Higher intake of fruit fiber was associated with lower risk of endometriosis but the association was not significant after adjusting for the Alternative Healthy Eating Index. Gluten intake was also associated with lower risk (highest compared with lowest quintile RR: 0.91; 95% CI: 0.80, 1.02; Ptrend = 0.01), but these results were not consistent in direction nor statistical significance across sensitivity analyses. No association was observed for GL or total, legume, or cereal fiber intake., Conclusions: Our findings suggest that carbohydrate quality and specific types of fiber-total vegetable and cruciferous vegetable fiber-are associated with endometriosis diagnosis in premenopausal women. These results also indicate it is unlikely that gluten intake is a strong factor in the etiology or symptomatology of endometriosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant., Objectives: We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN)., Methods: We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders., Results: During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05-1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07-2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87-1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00-2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75-1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%-51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33-0.92)., Conclusions: Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The epidemiologic literature on associations between urinary phenol concentrations and lipid profiles during pregnancy is limited. We examined whether urinary concentrations of phenol and phenol replacement biomarkers were associated with serum lipid levels among pregnant women. This cross-sectional study included 175 women attending the Massachusetts General Hospital Fertility Center who enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 and had data available on urinary phenol biomarkers and serum lipids during pregnancy. We used linear regression models to assess the relationship between groups of urinary phenol and phenol replacement biomarkers and serum lipid levels [total cholesterol, high density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, and triglycerides], while adjusting for age at sample collection, pre-pregnancy BMI, education, race, infertility diagnosis, cycle type, number of fetuses, trimester and specific gravity. In adjusted models, pregnant women with urinary propylparaben concentrations in the highest tertile had 10% [22 (95% CI = 5, 40) mg/dL], 12% [19 (95% CI = 2, 36) mg/dL] and 16% [19 (95% CI = 3, 35) mg/dL] higher mean total, non-HDL and LDL cholesterol, respectively, compared to women with concentrations in the lowest tertile. Similar elevations were observed for urinary bisphenol A concentrations. Urinary bisphenol S, benzophenone-3, triclosan, methylparaben, ethylparaben, and butylparaben were unrelated to serum lipids. Among pregnant women, urinary concentrations of bisphenol A and propylparaben were associated with higher serum levels of total, non-HDL and LDL cholesterol., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility., Objective: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies., Study Design: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet., Results: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids., Conclusion: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Male obesity has been related to poor semen quality and may also have a negative effect on assisted reproductive technologies (ART) outcomes. Whether male waist circumference (WC), as a measure of central obesity, impacts a couple's fertility independently of BMI is unclear., Objectives: To examine the associations of male WC with semen quality and couples' outcomes of infertility treatment with ART., Methods: Couples presenting to the Massachusetts General Hospital Fertility Center were invited to participate in the study. Between 2009 and 2019, 269 males provided 671 semen samples and 176 couples underwent 317 ART cycles. Height, weight, and WC were measured on site. We analyzed the association of male WC with semen quality and pregnancy outcomes using cluster-weighted regression models to account for repeated observations while adjusting for potential confounders. Models were also stratified by male BMI (<25 kg/m2 compared with ≥25 kg/m2)., Results: The median male age, WC, and BMI were 36.1 years, 96.0 cm, and 26.8 kg/m2, respectively. A 5-cm increase in WC was associated with a 6.3% (95% CI, 2.1-10.5%) lower sperm concentration after adjustment for potential confounders, including BMI. Male WC was also inversely related to the probability of achieving a live birth. For each 5-cm increase in male WC, the odds of a live birth per initiated cycle decreased by 9.0% (95% CI, 1.1%-16.4%) after accounting for several anthropometric and demographic characteristics of both partners. These associations were stronger among males in the normal BMI category (<25 kg/m2) than among overweight or obese males., Conclusions: A higher male WC may be an additional risk factor for poor outcomes of infertility treatment, even after accounting for male and female partner BMIs, particularly in couples where the male partner has a normal BMI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Children are vulnerable to adverse health effects associated with phthalates, and food is one source of exposure. A comprehensive analysis investigating urinary phthalate metabolite concentrations in relation to food type and source has yet to be undertaken., Objectives: We use reduced rank regression, a dimension reduction method, to identify dietary patterns associated with urinary phthalate metabolites in children in a large US study., Methods: We used data from 2369 participants 6-19 years old from the 2011-2016 National Health and Nutrition Examination Survey who recalled their diet over the 24 h prior to urine collection. We used dietary data to estimate intake and source (i.e., prepared at a restaurant vs. purchased from a grocery store) of 136 food groups. We used reduced rank regression to identify dietary patterns explaining variation in overall urinary concentrations of ∑di-2-ethylhexyl phthalate and seven phthalate metabolites. We also examined pairwise associations between food groups and urinary phthalate metabolites., Results: We identified eight dietary patterns that cumulatively explained 12.1% of variation in urinary phthalate metabolites, including a dietary pattern characterized by certain starchy vegetables (e.g., plantains and lima beans), quick breads, and citrus juice prepared at a restaurant. A one SD increase in this food pattern score was associated with a 37.2% higher monocarboxyoctyl phthalate (MCOP) concentration (95% CI: 30.3, 44.4). We also observed weak associations between certain food groups and urinary phthalate metabolites (e.g., a one SD increase in intake of certain starchy vegetables prepared at a restaurant was associated with a 1.8% [95% CI: 0.7, 2.8] higher MCOP)., Conclusions: Children whose diets were characterized by higher consumption of certain starchy vegetables, quick breads, and citrus juices prepared at a restaurant had higher urinary phthalate metabolites. More detailed information on the specific methods of food processing and details on packaging materials is needed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study is to examine age at menarche across sexual orientation groups., Methods: Data were obtained from 131,090 female participants, born 1947-2001, in 3 longitudinal studies-the Growing Up Today Study and Nurses' Health Study 2 and 3. We estimated the association between sexual orientation and age at menarche using regression models adjusted for age, race/ethnicity, birthweight, height, and body mass index., Results: Compared to heterosexual participants, sexual minorities were younger at menarche. Sexual minorities were more likely to have early menarche (≤11 years) and less likely to have late menarche (≥14 years) compared to heterosexual girls. As an example of this pattern, Nurses' Health Study 3 bisexual participants were >30% more likely than heterosexuals to have early versus average menarche (odds ratio 1.37, 95% confidence interval 1.09-1.72)., Conclusion: Sexual minority girls have a younger age at menarche than heterosexual girls and may benefit from screening for adverse outcomes associated with early menarche., (Copyright © 2021 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown., Objectives: We aimed to examine associations between plant-based diets and GDM in a large prospective study., Methods: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM., Results: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM., Conclusions: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background: Because randomized trials of sustained dietary changes are sometimes impractical for long-term outcomes, the explicit emulation of a (hypothetical) target trial using observational data may be an important tool for nutritional epidemiology., Objectives: We describe a methodological approach that aims to emulate a target trial of dietary interventions sustained over many years using data from observational cohort studies., Methods: We estimated the 20-y risk of all-cause mortality under the sustained implementation of the food-based goals of the American Heart Association (AHA) 2020 using data from 3 prospective observational studies of US men [Health Professionals Follow-up Study (HPFS)] and women [Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II)]. We applied the parametric g-formula to estimate the 20-y mortality risk under a dietary intervention and under no dietary intervention., Results: There were 165,411 participants who met the eligibility criteria. The mean age at baseline was 57.4 y (range, 43-82 y) in the HPFS, 52.4 y (range, 39-66 y) in the NHS, and 40.2 y (range, 30-50 y) in the NHS II. During 20 y of follow-up, 13,241 participants died. The estimated 20-y mortality risks under a dietary intervention versus no intervention were 21.9% compared with 25.8%, respectively, in the HPFS (risk difference, -3.9%; 95% CI: -4.9% to -3.2%); 10.0% compared with 12.6%, respectively, in the NHS (risk difference, -2.6%; 95% CI: -3.1% to -1.8%); and 2.1% compared with 2.5%, respectively, in the NHS II (risk difference, -0.35%; 95% CI: -0.56% to -0.09%). The corresponding risk ratios were 0.85 (95% CI: 0.81-0.88) in the HPFS, 0.79 (95% CI: 0.75-0.85) in the NHS, and 0.86 (95% CI: 0.78-0.96) in the NHS II., Conclusions: We estimated that adherence to the food-based AHA 2020 Dietary Goals starting in midlife may reduce the 20-y risk of mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Overweight and obesity among women have been associated with lower success of assisted reproduction technologies (ARTs). However, the relation of adolescent body weight and adult weight change to ART outcomes is not well understood., Objective: Our objective was to evaluate the associations of female BMI (in kg/m2) at 18 y and weight change from 18 y to current age with ART outcomes., Methods: We included 486 women in a prospective cohort at the Massachusetts General Hospital Fertility Center (2004-2018) who underwent 863 ART cycles. At study entry, height and weight were measured by research personnel. Women recalled their weight at 18 y. Restricted cubic splines were used to evaluate the associations between BMI at 18 y and weight change since 18 y and ART outcomes adjusting for age, race, education, smoking, and height and accounting for the correlated cycles within women., Results: Women had a median (range) BMI of 20.6 (14.8 to 36.4) at 18 y and 23.3 (16.1 to 45.8) at study entry. The median (range) weight change since 18 y was 7.4 kg (-12.1 to 60.1 kg). There was no association between BMI at 18 y and clinical ART outcomes. Long-term weight change had a nonlinear association with live birth such that higher weight gain since 18 y (particularly ≥15 kg) and weight loss were both associated with lower odds of live birth. The negative association between weight change and live birth was stronger in women ≥22.5 kg/m2 at 18 y such that each 10-kg increase was associated with a 30% (6%, 48%) lower odds of live birth., Conclusions: Weight gain in adulthood is negatively associated with ART success, particularly among women who were heavier at 18 y. These results add to the growing literature supporting the benefits of preventing weight gain in adulthood on female fertility., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: To examine contraceptive methods used by adolescent/young adult women of diverse sexual orientations., Study Design: We collected data from 12,902 females, born 1982-1995, from the longitudinal Growing Up Today Study., Results: Compared to heterosexuals, lesbians were half as likely to use contraceptives; other sexual minority subgroups (e.g., bisexuals) were more likely to use contraceptives, particularly long-acting reversible contraceptives., Conclusions: Many sexual minority women use contraception throughout adolescence/young adulthood, though use is low among lesbians., Implications: With limited contraception use, lesbians miss opportunities for care and need to be brought into the healthcare system in other ways., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To examine the association betweenantineoplastic drug (AD) handling and risk of miscarriage., Methods: Nurses' Health Study-3 participants self-reported AD administration and engineering controls (ECs) and personal protective equipment (PPE) use at baseline. We estimated the hazard ratio (HR) of miscarriage in relation to baseline AD handling using multivariable Cox proportional regression., Results: Overall, 2440 nurses reported 3327 pregnancies, with 550 (17%) ended in miscarriages. Twelve percent of nurses self-reported currently handling AD and 28% previously handling AD. Compared with nurses who never handled AD, nurses who handled AD at baseline had an adjusted HR of miscarriage of 1.26 (95% confidence interval [CI], 0.97-1.64). This association was stronger after 12-weeks gestation (HR=2.39 [95% CI, 1.13-5.07]). Nurses who did not always use gloves had HR of 1.51 (95% CI, 0.91-2.51) compared with 1.19 (95% CI, 0.89-1.60) for those always using gloves; nurses who did not always use gowns had HR of 1.32 (95% CI, 0.95-1.83) compared with 1.19 (95% CI, 0.81-1.75) for nurses always using gowns., Conclusions: We observed a suggestive association between AD handling and miscarriage, particularly among nurses who did not consistently use PPE and EC with stronger associations for second trimester losses., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk., Objectives: To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes., Methods: We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989-1090 and 1994-1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013-2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression., Results: Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015], driven by trans 18:1n-9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P = 0.007], trans 18:1n-7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P = 0.023], and trans 18:2n-6t,t [OR (95% CI): 1.26 (1.01, 1.57); P = 0.037]., Conclusions: Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: It is unclear whether adherence to diet recommendations for the prevention of cardiovascular disease (CVD) in the general population is also related to the risk of hypertensive disorders of pregnancy, including pre-eclampsia and gestational hypertension (GHTN)., Objectives: The aim was to evaluate the relation of prepregnancy adherence to the American Heart Association (AHA) diet recommendations and the Dietary Approaches to Stop Hypertension (DASH) with the risk of pre-eclampsia and GHTN., Methods: Between 1991 and 2009, we prospectively followed 16,892 singleton pregnancies among 11,535 women who participated in the Nurses' Health Study II. Prepregnancy diet was assessed every 4 y, from which we calculated dietary pattern scores from the DASH diet (8 components) and the diet recommendations from the AHA 2020 Strategic Impact Goals (primary score: 5 components; secondary score: primary score plus 3 components). Pregnancy outcomes were self-reported, and we estimated the RR (95% CI) of pre-eclampsia and GHTN with log-binomial regression using generalized estimating equations to account for repeat pregnancies and adjusting for potential confounders., Results: Women had a mean (SD) age of 34.4 (34.0) y at pregnancy. Pre-eclampsia was reported in 495 (2.9%) pregnancies and GHTN in 561 (3.3%) pregnancies. The RR (95% CI) of pre-eclampsia for women in the highest quintile of the DASH was 0.65 (0.48, 0.87) compared with women in the lowest score quintile. A similar inverse trend was observed for the AHA primary (0.74; 95% CI: 0.55, 1.00) and secondary (0.81; 95% CI: 0.61, 1.07) scores comparing women in the highest versus the lowest score quintile. Neither the DASH nor the AHA scores were related to GHTN., Conclusions: Women with higher adherence to dietary recommendations for the prevention of CVD in the general population had a lower risk of pre-eclampsia-a common pregnancy complication related to higher CVD risk among women-than women with lower adherence to these recommendations., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Accumulating evidence suggests that air pollution increases pregnancy loss; however, most previous studies have focused on case identification from medical records, which may underrepresent early pregnancy losses. Our objective was to investigate the association between acute and chronic exposure to ambient air pollution and time to pregnancy loss among women undergoing assisted reproductive technologies (ART) who are closely followed throughout early pregnancy. We included 275 women (345 human chorionic gonadotropin (hCG)-confirmed pregnancies) undergoing ART at a New England academic fertility center. We estimated daily nitrogen dioxide (NO 2 ), ozone (O 3 ), fine particulate matter <2.5 μm (PM 2.5 ), and black carbon (BC) exposures using validated spatiotemporal models estimated from first positive hCG test until day of failure or live birth. Air pollution exposures were averaged over the past week and the whole pregnancy. Multivariable Cox proportional hazards models were used to estimate the hazards ratio (HR) for pregnancy loss for an interquartile range (IQR) increase in pollutant exposure. We tested for violation of proportional hazards by considering an interaction between time (in days) since positive hCG (<30 days vs. ≥30 days) and air pollution. The incidence of pregnancy loss was 29 per 100 confirmed pregnancies (n = 99). Among pregnancies not resulting in live birth, the median (IQR) time to loss was 21 (11, 30) days following positive hCG. Average past week exposures to NO 2 , O 3 , PM 2.5 , and BC were not associated with time to pregnancy loss. Exposure throughout pregnancy to NO 2 was not associated with pregnancy loss; however, there was a statistically significant interaction with time (p-for-interaction<0.001). Specifically, an IQR increase in exposure to NO 2 was positively associated with pregnancy loss after 30 days (HR = 1.34, 95% CI: 1.13, 1.58), but not in the first 30 days after positive hCG (HR = 0.83, 95% CI: 0.57, 1.20). Overall pregnancy exposure to O 3 , PM 2.5 , and BC were not associated with pregnancy loss regardless of timing. Models evaluating joint effects of all pollutants yielded similar findings. In conclusion, acute and chronic exposure to NO 2 , O 3 , PM 2.5 , and BC were not associated with risk of pregnancy loss; however, higher exposure to NO 2 throughout pregnancy was associated with increased risk of loss 30 days after positive hCG. In this cohort, later pregnancy losses appeared more susceptible to the detrimental effects of air pollution exposure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Modifiable risk factors such as diet may be important in both the etiology and progression of endometriosis as well as the prevalence of pain symptoms and infertility associated with this condition. In adults, higher intake of dairy has been associated with a lower risk of endometriosis diagnosis. There is currently no literature on whether dairy intake during adolescence, a potentially critical window of exposure, influences endometriosis risk., Objective: The objectige of the study was to evaluate the association between consumption of dairy foods in adolescence and the risk of laparoscopically confirmed endometriosis., Study Design: This was a prospective cohort study, the Nurses' Health Study II, which has prospectively collected data since 1989. In 1998, when participants were aged 34-51 years, they completed a 124 item food frequency questionnaire about their high school diet. Cases were defined as those who self-reported laparoscopically confirmed endometriosis. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for the association between dairy foods and laparoscopically confirmed endometriosis., Results: Among women who completed the questionnaire about their high school diet in 1998, 581 cases of laparoscopically confirmed endometriosis were diagnosed among 32,868 premenopausal women from 1998 to 2013. Women who consumed more than 4 servings per day of dairy foods during adolescence had a 32% lower risk of laparoscopically confirmed endometriosis during adulthood (95% confidence interval, 0.47-0.96; P trend  = .04) compared with women consuming 1 or fewer servings per day. The association was similar for low-fat and high-fat dairy foods. Yogurt and ice cream consumption, specifically, were associated with a lower risk of endometriosis. Those who consumed 2 or more servings of yogurt per week as an adolescent had a 29% lower risk of endometriosis diagnosis (95% confidence interval, 0.52-0.97; P trend  = .02) compared with those consuming less than 1 serving per week. In addition, women who consumed 1 or more servings per day of ice cream per day during adolescence had a 38% lower risk of endometriosis diagnosis (95% confidence interval, 0.40-0.94; P trend  = .20) compared with those consuming less than 1 serving per week., Conclusion: Our findings suggest that dairy consumption, specifically yogurt and ice cream intake, in adolescence may reduce the risk of subsequent endometriosis diagnosis. Future studies in adolescent populations are needed to confirm these results., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The role of diet on hypertensive disorders of pregnancy (HDPs), including preeclampsia and gestational hypertension (GHTN), remains unclear., Objectives: We evaluated whether adherence during pregnancy to dietary recommendations that reduce cardiovascular disease (CVD) in the general population is related to the risk of HDPs., Methods: We followed 66,651 singleton pregnancies from 62,774 women participating in the Danish National Birth Cohort. Diet was assessed during week of gestation 25 with an FFQ from which we created 2 dietary pattern scores: 1) AHA, based on the diet recommendations from the AHA 2020 Strategic Impact Goals; and 2) the Dietary Approaches to Stop Hypertension (DASH) diet. Cases of HDPs were identified through linkage with the Danish National Patient Registry. RRs and 95% CIs of HDPs were estimated by increasing quintiles of adherence to the AHA and DASH scores using log-Poisson regression models with generalized estimating equations-to account for repeated pregnancies per woman-while adjusting for potential confounders., Results: We identified 1809 cases of HDPs: n = 1310 preeclampsia (n = 300 severe preeclampsia) and n = 499 cases of GHTN. Greater adherence to AHA or DASH scores was not related to the risk of HDPs. However, when each component of the scores was separately evaluated, there were positive linear relations of sodium intake with HDPs (P-linearity < 0.01). Women with the highest sodium intake [median 3.70 g/d (range: 3.52, 7.52 g/d)] had 54% (95% CI:16%, 104%) higher risk of GHTN and 20% (95% CI:1%, 42%) higher risk of preeclampsia than women with the lowest intake [median 2.60 g/d (range: 0.83, 2.79 g/d)]. In addition, intake of whole grains was positively related to the risk of GHTN but not to preeclampsia ( P-heterogeneity = 0.002)., Conclusion: Sodium intake during pregnancy, but no other diet recommendations to prevent CVD among nonpregnant adults, is positively related to the occurrence of HDPs among pregnant Danish women., (Copyright © American Society for Nutrition 2019.)

Background: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans., Objective: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men., Method: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F 2α (8-isoPGF 2α ) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers., Results: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF 2α and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF 2α suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10)., Conclusions: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Randomized clinical trials show that men's use of antioxidant supplements during infertility treatment may improve clinical outcomes. However, important limitations in the design of most trials make it difficult to draw firm conclusions on their findings., Objective: We examined whether men's intake of antioxidants and biologically related compounds without direct antioxidant capacity is associated with outcomes of assisted reproductive technologies (ARTs)., Methods: We conducted a prospective cohort study of men in couples who underwent infertility treatment with ART using their own gametes between 2007 and 2017. We followed 171 couples who presented at Massachusetts General Hospital Fertility Center and underwent 294 autologous ART cycles for infertility treatment. Diet was assessed in both partners using an FFQ. The primary study outcome was the probability of achieving a live birth as a result of infertility treatment. Secondary outcomes were fertilization, implantation, and clinical pregnancy rates. Generalized linear mixed models with random intercepts were fitted to account for multiple ART cycles per woman while adjusting for confounding., Results: Men's vitamin C intake was positively associated with fertilization rate. The adjusted fertilization rate (95% CI) for couples in the lowest and highest quartiles of men's vitamin C intake were 69% (61-76%) and 81% (74-86%) (P-trend = 0.02). Men's β-carotene intake was positively associated with fertilization rate in intracytoplasmic sperm injection cycles but not in conventional in vitro fertilization cycles (P-interaction = 0.01). Men's α-carotene intake was inversely related to the probability of live birth. The adjusted probabilities of live birth for men in the lowest and highest quartiles of α-carotene intake were 43% (28-60%) and 22% (12-36%), respectively., Conclusions: Men's intake of vitamin C and β-carotene is positively related to fertilization rate but this does not translate into higher pregnancy or live birth rates in couples undergoing infertility treatment., (Copyright © American Society for Nutrition 2019.)

Animal models suggest a protective role of antioxidants against the adverse effect of di-2-ethylhexyl phthalate (DEHP) on insulin resistance. However, no epidemiologic study has examined the effects observed in the animal model. We conduct a study to examine associations of urinary concentrations of phthalate metabolites (individually and as a mixture) with insulin resistance, along with potential effect modification by serum antioxidant concentrations. This cross-sectional study included 1605 participants (51% males) aged 12-85 from the National Health and Nutrition Examination Surveys (2003-2006). Urinary concentrations of 9 phthalate metabolites were measured from spot urine samples. Antioxidant (vitamin A, C, E, and carotenoids) concentrations were measured from a fasting serum sample. We used Bayesian Kernel Machine Regression (BKMR) to evaluate associations between phthalate metabolite mixtures and insulin resistance, and examined whether serum antioxidant levels modified these associations, while accounting for the correlations of multiple concurrent exposures. A change in urinary ΣDEHP concentrations from the 25th to the 75th percentile was associated with a higher log HOMA-IR of 0.07 (95% CI = 0.01, 0.14) (4.85% increase in HOMA-IR). In contrast, the same change in urinary monoethyl phthalate (MEP) was associated with a lower HOMA-IR of -0.07 (95% CI = -0.14, -0.02) (6.68% decrease in HOMA-IR). The positive association between ΣDEHP and HOMA-IR became weaker at higher concentrations of serum β-carotene. The relationship between MEP and HOMA-IR, however, was not modified by the serum antioxidants examined. The remaining phthalate metabolites were unrelated to HOMA-IR. In this cross-sectional study, the positive association between DEHP exposure and insulin resistance weakened among participants with higher concentrations of serum β-carotene. As this is the first human report on the protective role of serum β-carotene on DEHP induced insulin resistance, future studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Research Question: Studies in rodents have shown that paternal folate intake prior to conception is associated with pregnancy and offspring outcomes. The aim of this study was to assess whether those associations might apply to humans as well., Design: Between 2007 and 2017, the study prospectively analysed data from 108 couples participating in a preconception cohort of couples undergoing fertility treatment using their own gametes, whose treatment resulted in 113 pregnancies during the course of the study. Paternal and maternal preconception folate intake was assessed using a validated food frequency questionnaire. Linear mixed models were used to assess whether paternal preconception folate intake was associated with gestational age at delivery and gestational age-specific birthweight, while accounting for correlated data and potential confounders., Results: In a multivariable-adjusted model, a 400 μg/day increase in preconception paternal folate intake was associated with a 2.6-day longer gestation (95% confidence interval 0.8-4.3) after adjusting for potential confounders, including maternal folate intake. Similar associations were found for folate from food and supplements. Maternal folate intake was not associated with gestational age at delivery. Neither paternal nor maternal folate intake was associated with gestational-age-specific birthweight., Conclusions: Higher paternal preconception folate intake was associated with slightly longer gestation among live births achieved through assisted reproduction. The results suggest that preconception exposures of the father may have an impact on the health of his offspring, and therefore that preconception care should shift from a woman-centric to a couple-based approach., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Mushrooms are good dietary sources of important vitamins, minerals, and bioactive compounds which may be important in the prevention of chronic diseases. However, studies have not prospectively evaluated the potential health effects of mushrooms with respect to major cardiometabolic diseases., Objectives: The aim of this study was to examine the association of mushroom consumption with major cardiometabolic diseases and mediating biomarkers in 2 large prospective US cohorts., Methods: We followed 67,139 women from the Nurses' Health Study (1986-2012) and 43,541 men from the Health Professionals Follow-up Study (1986-2012) who were free of chronic diseases. Mushroom consumption was assessed at baseline through the use of a food-frequency questionnaire. Cardiometabolic biomarkers were collected in subpopulations of the 2 cohorts. Cox proportional hazards models were used to estimate HRs and 95% CIs of cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, and type 2 diabetes (T2D), associated with mushroom consumption., Results: We identified total 11,894 CVD (7,616 CHD; 4,278 stroke), and 10,206 T2D cases in >2 million person-years of follow-up. In the pooled multivariable-adjusted analysis, participants who consumed ≥5 servings of mushrooms per week had no significantly different risk of total CVD (HR: 1.02; 95% CI: 0.91, 1.14), CHD (HR: 1.00; 95% CI: 0.87, 1.16), stroke (HR: 1.05; 95% CI: 0.87, 1.25), or T2D (HR: 1.04; 95% CI: 0.93, 1.16) than participants who consumed mushrooms <1 time/mo. We consistently found no association between mushroom consumption and the aforementioned cardiometabolic diseases, in subgroups of sex, lifestyle factors, and medical conditions. Moreover, mushroom consumption was not associated with plasma biomarkers of lipids, insulin, and inflammation., Conclusions: We found no association of mushroom consumption with biomarkers and risks of CVD and T2D in US adults. More large prospective cohort studies are warranted to investigate this association in other racial/ethnic groups., (Copyright © American Society for Nutrition 2019.)

Objectives: To examine contraceptive methods used across sexual orientation groups., Study Design: We collected data from 118,462 female participants in two longitudinal cohorts-the Nurses' Health Study (NHS) 2 (founded in 1989, participants born 1947-1964) and NHS3 (founded in 2010, born 1965-1995). We used log-binomial models to estimate contraceptive methods ever used across sexual orientation groups and cohorts, adjusting for age and race., Results: Lesbians were the least likely of all sexual orientation groups to use any contraceptive method. Lesbians in NHS2 were 90% less likely than heterosexuals to use long-acting reversible contraceptives (LARCs; adjusted risk ratio [aRR]; 95% confidence interval [CI]: 0.10 [0.04, 0.26]) and results were similar for other contraceptive methods and in the NHS3 cohort. Compared to the reference group of completely heterosexual participants with no same-sex partners, those who identified as completely heterosexual with same-sex partners, mostly heterosexual, or bisexual were generally more likely to use any method of contraception. Use of LARCs was especially striking across sexual minority groups, and, with the exception of lesbians, they were more likely to use LARCs; as one illustration, NHS3 bisexuals were more than twice as likely to use LARCs (aRR [95% CI]: 2.01 [1.67, 2.42])., Conclusions: While certain sexual minority subgroups (e.g., bisexuals) were more likely than heterosexuals to use contraceptive methods such as LARCs, lesbians were less likely to use any method., Implications: Many sexual minority patients need contraceptive counseling and providers should ensure to offer this counseling to patients in need, regardless of sexual orientation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Benzophenone-3 is used in a variety of cosmetic products as a sunscreen, and has shown weak estrogenic and antiandrogenic activity in animal and in vitro studies. Few studies have evaluated whether benzophenone-3 is associated with reproductive outcomes among women. We studied 304 women undergoing infertility treatment (2007-2017) in the prospective Environment and Reproductive Health cohort study and who underwent 449 treatment cycles (n = 788 urines). Generalized linear mixed models were used with random intercepts to account for multiple cycles, and adjusting for confounders including physical activity. Analyses were also stratified by self-reported moderate/heavy outdoor work. The cycle-specific median (IQR) urinary benzophenone-3 concentration was 147 (58, 462) μg/L, and 98% samples had detectable concentrations. Self-reported sunscreen use, physical activity, and time spent on moderate/heavy outdoor work were positively associated with urinary benzophenone-3. Adjusted probabilities of implantation, clinical pregnancy and live birth were higher in increasing quartiles of benzophenone-3, but these associations were restricted to women who reported spending time outdoors performing moderate/heavy work. Specifically, among these women, those in the highest quartile of benzophenone-3 concentrations had 51% higher implantation (p,trend = 0.02), 68% higher clinical pregnancy (p,trend = 0.01) and 75% higher live birth (p,trend = 0.02) adjusted probabilities than women in the lowest quartile. Benzophenone-3 was unrelated to these outcomes among women who did not report doing moderate/heavy work outdoors. These results confirm that sunscreen use is a source of benzophenone-3 exposure, and show positive associations between benzophenone-3 and pregnancy outcomes, especially among women who reported engaging in outdoor work. Since these associations may be subject to important residual confounding by lifestyle factors, further research is needed to confirm these novel results in other populations, and to investigate whether other factors may be affecting the relation of benzophenone-3 with fertility and other health outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: There is growing acceptance that nutrition may be related to fertility and specifically to assisted reproductive technologies success in women; however, there is still no specific dietary guidance., Objective: The objective of the study was to evaluate the relationship between pretreatment adherence to various dietary patterns and outcomes of assisted reproductive technologies., Study Design: We followed up 357 women enrolled in the prospective Environment and Reproductive Health (EARTH) study, who underwent 608 assisted reproductive technologies cycles (2007-2017). Using a validated food frequency questionnaire completed prior to treatment, we assessed adherence to the Mediterranean diet, the alternate Healthy Eating Index 2010, the Fertility Diet (developed based on risk factors for anovulatory infertility), and a profertility diet we developed based on factors previously related to assisted reproductive technologies outcomes (higher intake of supplemental folic acid, vitamin B12, vitamin D, low- rather than high-pesticide residue produce, whole grains, dairy, soy foods, and seafood rather than other meats)., Results: Higher adherence to the alternate Healthy Eating Index 2010 and Fertility Diet was not related to live birth following assisted reproductive technologies. Women in the second through the fourth quartiles of Mediterranean diet adherence had significantly higher probability of live birth (0.44, 95% confidence interval, 0.39-0.49) compared with women in the first quartile (0.31, 95% confidence interval, 0.25-0.39); however, there was no additional benefit of adherence to the Mediterranean diet above the second quartile. Increased adherence to the profertility diet was linearly associated with assisted reproductive technologies outcomes. The adjusted odds (95% confidence interval) of implantation, clinical pregnancy, and live birth were higher by 47% (21%, 77%), 43% (19%, 72%), and 53% (26%, 85%), respectively, per SD increase. The adjusted difference in the proportion of cycles resulting in live birth for women in the fourth vs first quartile of adherence to the profertility diet was 0.28 (95% confidence interval, 0.16-0.38). While the profertility diet was not related to estradiol levels, oocyte counts, or endometrial thickness, it was inversely associated with clinical pregnancy loss (odds ratio, 0.69, 95% confidence interval, 0.53-0.90 per SD increase)., Conclusion: Higher pretreatment adherence to the profertility diet was associated with an increased probability of live birth among women undergoing assisted reproductive technologies. Commonly recommended dietary advice such as adhering to the Mediterranean diet may not provide the most appropriate guidance for women undergoing infertility treatment in the United States., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Many studies have documented a lower likelihood of live birth with increasing body mass index among women undergoing assisted reproductive technology, but few have examined the association with waist circumference, an anthropometric measure that allows assessment of central adiposity., Objective: To examine the relation between baseline waist circumference and infertility treatment outcomes among women undergoing treatment with assisted reproductive technology., Materials and Methods: We followed up 264 women who underwent 445 assisted reproductive technology cycles for infertility treatment at the Massachusetts General Hospital between 2010 and 2017. Waist circumference was assessed at enrollment. We used cluster-weighted generalized estimating equation models to estimate the probability of live birth by tertiles of waist circumference (<77, 77-86, >86 cm), while accounting for multiple treatment cycles per woman and adjusting for age, race, smoking, infertility diagnosis, day 3 follicle-stimulating hormone, body mass index, and height., Results: Mean (standard deviation) waist circumference and body mass index were 83.6 (12.6) cm and 24.1 (4.3) kg/m 2 , respectively. Waist circumference and body mass index were positively correlated (r = 0.69, P < .0001). Waist circumference was inversely related to the probability of live birth after adjusting for BMI and other confounders. The multivariable adjusted probability of live birth (95% confidence interval) for women in increasing tertiles of waist circumference were 53% (42-65%), 42% (32-53%), and 38% (28-50%) (P, trend = .04). When women were classified in joint categories of body mass index and waist circumference, women with a body mass index ≥25 kg/m 2 and a waist circumference ≥77 cm had the lowest live birth rate (38% [27-50%]), whereas women with a body mass index between 18.5 and 25 kg/m 2 and a waist circumference <77 cm had the highest (54% [42-66%]). The results were similar using different waist circumference cut-off values., Conclusion: Waist circumference was inversely related to the probability of live birth among women undergoing assisted reproductive technology independently of body mass index., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Some dietary factors have been linked to outcomes of infertility treatment with assisted reproductive technology (ART), but the role of intake of meats and other protein-rich foods remains unclear., Objective: The aim of this manuscript was to study the relation between preconception intake of meat and other protein-rich foods and outcomes of infertility treatment with ART., Design: A total of 351 women enrolled in a prospective cohort at the Massachusetts General Hospital Fertility Center and underwent 598 ART cycles for infertility treatment. Meat intake was assessed with a validated food-frequency questionnaire, and ART outcomes were abstracted from electronic medical records. We estimated the associations between intake of protein-rich foods (meats, eggs, beans, nuts, and soy) and the outcome of live birth per initiated cycle using generalized linear mixed models., Results: The average total meat intake was 1.2 servings/d, with most coming from poultry (35%), fish (25%), processed meat (22%), and red meat (17%). Fish intake was positively related to the proportion of cycles resulting in live birth. The multivariable-adjusted probabilities of live birth for women in increasing quartiles of fish intake were 34.2% (95% CI: 26.5%, 42.9%), 38.4% (95% CI: 30.3%, 47.3%), 44.7% (95% CI: 36.3%, 53.4%), and 47.7% (95% CI: 38.3%, 57.3%), respectively (P-trend = 0.04). In the estimated substitution analyses, the ORs of live birth associated with increasing fish intake by 2 servings/wk were 1.54 (95% CI: 1.14, 2.07) when fish replaced any other meat, 1.50 (95% CI: 1.13, 1.98) when fish replaced any other protein-rich food, and 1.64 (95% CI: 1.14, 2.35) when fish replaced processed meat., Conclusions: Fish consumption is related to a higher probability of live birth following infertility treatment with ART. This trial was registered at clinicaltrials.gov as NCT00011713.

Background: Only 2 case-control studies have examined the associations between consumption of meat products and endometriosis risk with inconsistent results. Consumption of animal products has the potential to influence endometriosis risk through effects on steroid hormones levels., Objective: We sought to determine whether higher intake of red meat, poultry, fish, and seafood are associated with risk of laparoscopically confirmed endometriosis., Study Design: A total of 81,908 participants of the prospective Nurses' Health Study II were followed up from 1991 through 2013. Diet was assessed via food frequency questionnaire every 4 years. Cox proportional hazards models were used to calculate rate ratios and 95% confidence intervals., Results: During 1,019,294 person-years of follow-up, 3800 cases of incident laparoscopically confirmed endometriosis were reported. Women consuming >2 servings/d of red meat had a 56% higher risk of endometriosis (95% confidence interval, 1.22-1.99; P trend < .0001) compared to those consuming ≤1 serving/wk. This association was strongest for nonprocessed red meats (rate ratio, 1.57; 95% confidence interval, 1.35-1.83 for ≥2 servings/d vs ≤1 servings/wk; P trend < .0001), particularly among women who had not reported infertility (P interaction  = .0004). Women in the highest category of processed red meat intake also had a higher risk of endometriosis (rate ratio, 1.20; 95% confidence interval, 1.06-1.37 for ≥5 servings/wk vs <1 serving/mo; P trend  = .02). Intakes of poultry, fish, shellfish, and eggs were unrelated to endometriosis risk., Conclusion: Our prospective analysis among premenopausal US nurses suggests that red meat consumption may be an important modifiable risk factor for endometriosis, particularly among women with endometriosis who had not reported infertility and thus were more likely to present with pain symptoms. Well-designed dietary intervention studies among women with endometriosis could help confirm this observation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The literature on the relationship between diet and human fertility has greatly expanded over the last decade, resulting in the identification of a few clear patterns. Intake of supplemental folic acid, particularly at doses higher than those recommended for the prevention of neural tube defects, has been consistently related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. On the other hand and despite promising evidence from animal models, vitamin D does not appear to exert an important role in human fertility in the absence of deficiency. Antioxidant supplementation does not appear to offer any benefits to women undergoing infertility treatment, but it appears to be beneficial when it is the male partner who is supplemented. However, the available evidence does not allow discerning which specific antioxidants, or at which doses, are responsible for this benefit. Long-chain omega-3 fatty acids appear to improve female fertility, although it remains unclear to what extent contamination of shared food sources, such as fish with high levels of environmental toxicants, can dampen this benefit. Lastly, adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. The cumulative evidence has also piled against popular hypotheses. Dairy and soy, once proposed as reproductive toxicants, have not been consistently related to poor fertility. In fact, soy and soy supplements appear to exert a beneficial effect among women undergoing infertility treatment. Similarly, because data from large, high-quality studies continue to accumulate, the evidence of a potentially deleterious effect of moderate alcohol and caffeine intake on the ability to become pregnant seems less solid than it once did. While a complete picture of the role of nutrition on fertility is far from complete, much progress has been made. The most salient gaps in the current evidence include jointly considering female and male diets and testing the most consistent findings in randomized trials., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Two indexes exist to describe dietary inflammatory potential: an empirical dietary inflammatory pattern (EDIP) composed of food groups as reported on a food-frequency questionnaire (FFQ) and a literature-derived dietary inflammatory index (DII) composed mainly of nutrients. Objective: We compared the ability of the 2 indexes to predict concentrations of inflammatory markers and hypothesized that the EDIP would be more predictive because it was derived on the basis of circulating inflammatory markers. Methods: Both EDIP and DII scores were calculated from FFQ data reported by 5826 women in the Nurses' Health Study II and 5227 men in the Health Professionals Follow-Up Study. We used multivariable-adjusted linear regression analyses to calculate relative differences in concentrations of 4 plasma inflammatory markers-C-reactive protein (CRP; milligrams per liter), interleukin 6 (IL-6; picograms per milliliter), tumor necrosis factor α receptor 2 (TNFαR2; picograms per milliliter), and adiponectin (nanograms per milliliter)-in quintiles of the dietary indexes. Results: Spearman correlations between the EDIP and DII scores were modest ( r = 0.29 and 0.21 for women and men, respectively; all P < 0.0001). Higher scores on both dietary indexes were associated with higher concentrations of inflammatory markers, although they were associated with lower adiponectin concentrations and there was no association between the DII and adiponectin in men. For example, percentage differences in concentrations of biomarkers in quintile 5 generally were higher (lower for adiponectin) than in quintile 1 (for the EDIP and DII, respectively-women: CRP, +60% and +49%; IL-6, +23% and +21%; TNFαR2, +7% and +4%; adiponectin, -21% and -14%; men: CRP, +38% and +29%; IL-6, +14% and +24%; TNFαR2, +9% and +5%; adiponectin, -16% and -4%.) Conclusion: Despite design differences, the EDIP and DII both assess dietary inflammatory potential in men and women, with the EDIP showing a greater ability to predict concentrations of plasma inflammatory markers., Competing Interests: Author disclosures: FKT, SAS-W, JEC, TTF, FBH, WCW, and ELG, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P -trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with offspring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted., (© 2017 American Society for Nutrition.)

Physical activity could benefit reproductive function through its ability to regulate energy balance and improve insulin sensitivity, but its association with IVF outcomes remains unclear. The aim of this study was to evaluate whether pre-treatment physical and sedentary activity is associated with outcomes of IVF. The Environment and Reproductive Health Study is an ongoing prospective cohort study that enrols subfertile couples at Massachusetts General Hospital Fertility Center. Time spent in physical and sedentary activities in the year before IVF treatment is self-reported using a validated questionnaire. This analysis included 273 women who underwent 427 IVF cycles. Women engaged in a median of 2.8 h per week of moderate-to-vigorous activities. Time spent in moderate-to-vigorous physical activities and total metabolic equivalent task hours before IVF were not associated with probability of implantation, clinical pregnancy or live birth. Of the specific physical activities, only greater time spent in aerobics, rowing, and on the ski or stair machine was associated with higher probability of live birth. Time spent in total and specific sedentary activities were not associated with clinical outcomes of IVF. Physical activity is unlikely to have a deleterious effect on IVF success and certain forms of vigorous activity may be beneficial., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Vitamin D deficiency impairs fertility in animal models, but the role of vitamin D in human fertility or treatment of infertility is less clear., Objective: We examined the association between circulating 25-hydroxyvitamin D [25(OH)D] concentrations and the outcome in women undergoing assisted reproduction technologies (ARTs)., Design: We randomly selected 100 women undergoing infertility treatment with ART enrolled in an ongoing prospective cohort study who underwent 168 treatment cycles. Serum 25(OH)D concentrations were measured in samples collected from women between days 3 and 9 of gonadotropin treatment. Generalized linear mixed models were used to evaluate the association of 25(OH)D concentrations with ART outcomes while adjusting for potential confounders and accounting for repeated treatment cycles per woman., Results: Median (range) serum 25(OH)D concentrations were 86.5 (33.5-155.5) nmol/L. Ninety-one percent of participants consumed multivitamins. Serum 25(OH)D concentrations were positively related to fertilization rate. The adjusted fertilization rate for women in increasing quartiles of serum 25(OH)D were 0.62 (95% CI: 0.51, 0.72), 0.53 (95% CI: 0.43, 0.63), 0.67 (95% CI: 0.56, 0.76), and 0.73 (95% CI: 0.63, 0.80), respectively (P-trend = 0.03). This association persisted when analyses were restricted to women with serum 25(OH)D between 50 and 125 nmol/L when models were further adjusted for season of blood draw and when analyses were restricted to the first treatment cycle. However, 25(OH)D concentrations were unrelated to probability of pregnancy (P-trend = 0.83) or live birth after ART (P-trend = 0.47)., Conclusion: Vitamin D may be associated with higher fertilization rates, but this apparent benefit does not translate into higher probability of pregnancy or live birth. This trial was registered at www.clinicaltrials.gov as NCT00011713., (© 2016 American Society for Nutrition.)

Background: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns., Objective: We developed and validated an empirical dietary inflammatory index (EDII) based on food groups., Methods: We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor α receptor 2 (TNFαR2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFαR2, adiponectin, and an overall inflammatory marker score combining all biomarkers., Results: The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002., Conclusion: The EDII represents, to our knowledge, a novel, hypothesis-driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied., (© 2016 American Society for Nutrition.)