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OBJECTIVE: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility. DESIGN: Cohort study SETTING: Academic fertility center PATIENTS: 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study. INTERVENTION(S): None. Folate intake was measured using a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, BMI, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Non-linearity was assessed with restricted cubic splines. MAIN OUTCOME MEASURES: AFC as measured with transvaginal ultrasonography as part of routine care. RESULTS: Among the 552 women (median age 35.0 years, median folate intake 1,005 μg/day), total and supplemental folate intake had a significant non-linear relationship with AFC (P for non-linearity 0.05 and 0.02, respectively). There was a positive linear association with AFC up to approximately 1200 μg/day for total folate intake and up to 800 μg/day for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of association was modest – for example, the predicted adjusted difference in AFC between a woman consuming 400 versus 800 μg/day of supplemental folate was approximately 1.5 follicles. CONCLUSIONS: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT00011713

Objective To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve. Design Prospective cohort study. Setting Fertility center at an academic hospital in the northeastern United States. Patient(s) 631 women attending the Massachusetts General Hospital Fertility Center (2005–2015) who participated in the Environment and Reproductive Health Study. Intervention(s) Daily temperature at the women’s residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders. Main Outcome Measure(s) Antral follicle count as measured with transvaginal ultrasonography. Result(s) A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated with a −1.6% (95% confidence interval [CI], −2.8, −0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (−0.9%, 95% CI, −1.8, 0.1) and 14 days (−0.8%, 95% CI, −1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research. Conclusion(s) Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women.

Maternal fat intake during pregnancy affects fetal growth, but mechanisms underlying this relationship are unclear. We performed an exploratory study of the associations of fat consumption during pregnancy with cord blood DNA methylation of the insulin-like growth factor 2 (IGF2) and H19 genes. We used data from 96 uncomplicated full-term pregnancies of mothers of whom majority had normal body mass index (BMI) (66%) in Project Viva, a prospective pre-birth cohort. We assessed maternal diet with validated food frequency questionnaires during the first and second trimesters and measured DNA methylation in segments of the IGF2- and H19-differentially methylated regions (DMRs) by pyrosequencing DNA extracted from umbilical cord blood samples. Mean (SD) age was 32.8 (4.1) years and prepregnancy BMI was 24.0 (4.4) kg/m2 . Mean DNA methylation was 56.3% (3.9%) for IGF2-DMR and 44.6% (1.9%) for H19-DMR. Greater first trimester intake of omega-6 polyunsaturated fat (effect per 1% of calories at the expense of carbohydrates) was associated with lower DNA methylation of IGF2-DMR (-1.2%; 95% confidence interval [CI]: -2.2%, -0.2%) and higher DNA methylation at H19-DMR (0.8%; 95% CI: 0.3%, 1.3%). On the other hand, greater first trimester intake of omega-3 polyunsaturated fat was associated with lower DNA methylation of the H19-DMR (-4.3%; 95% CI: -7.9%, -0.8%). We did not find significant associations of IGF2 and H19 methylation with IGF2 cord blood levels. Our findings suggest that early prenatal fat intake (omega-3, omega-6, and saturated fatty acids) may influence DNA methylation at the IGF2 and H19 locus, which could impact fetal development and long-term health.

ObjectivesTo examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses.MethodsOur study included women who enrolled in the Nurses’ Health Study 3 (2010–2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs.ResultsOur study included 2579 nurses with a median of 5.6 years of follow-up (range: 1–9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93).ConclusionsWe observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously.

PURPOSE: Oocyte donor in vitro fertilization (IVF) represents an ideal model to study the effects of embryo stage on reproductive success, as embryos come from young women with high-quality oocytes. Our study aimed to determine if embryo transfer stage affected outcomes in oocyte donor IVF, including the common scenario where only a limited number of quality embryos are available after culture. METHODS: This retrospective cohort analyzed anonymous vitrified donor oocyte cycles at a single clinic between 2008 and 2015. Overall, 983 recipients underwent 1178 warming cycles resulting in fresh transfer of one-to-two embryos. Our primary outcome was live birth; secondary outcomes included multiple birth, birthweight, and gestational age. Log binomial regression with cluster-weighted generalized estimating equations were used to calculate adjusted risk ratios (aRR) accounting for recipient age, race, and transfer year. RESULTS: Among 132 cleavage and 1046 blastocyst transfer cycles, cleavage transfers were associated with lower probability of live birth (aRR 0.72, 95% CI 0.59–0.88). Subgroup analysis focused on cycles with a limited number of quality embryos 3 days post-fertilization (≤2), as clinically these women were most likely to be considered for cleavage transfers. Among these cycles (120 cleavage, 371 blastocyst), cleavage transfers were still associated with lower live birth rates compared to blastocyst (aRR 0.66, 95% CI 0.51–0.87) CONCLUSIONS: Even in a donor oocyte model with high-quality oocytes, there was a benefit to extended culture and blastocyst transfer, including when only one-to-two quality embryos were available after early culture. This is possibly owed to improved uterine synchronicity or decreased contractility.

This review provides a general overview of the literature on B vitamins and fertility, as well as summarizes the evidence concerning B vitamin supplementation and fertility among polycystic ovary syndrome (PCOS) women.Studies among women conceiving with and without medical assistance provide strong evidence for a beneficial effect of B vitamins, particularly folate and vitamin B12, on fecundability and fertility. Moreover, recent work suggests that effects may be even more pronounced among women with menstrual cycle dysfunction (a common symptom of PCOS). Among PCOS women, intervention studies have demonstrated that folic acid supplementation may reduce homocysteine levels, potentially improve women's metabolic profiles, and possibly ameliorate some hallmark features of PCOS. Although none of these intervention studies have included fertility endpoints, it is possible that by reducing homocysteine levels (or other clinical/biochemical features) in PCOS women, there may be a downstream improvement in fertility outcomes.There is growing evidence folate (and possibly vitamin B12) supplementation may be beneficial to fertility in women. Although most studies have not exclusively focused on women with PCOS, there is biological plausibility and some evidence that B vitamin supplementation may be even more important for improving reproductive health outcomes in PCOS women.

Little is understood about physiological and psychological correlates of erectile dysfunction among younger men. We examined prevalence and correlates of erectile dysfunction in a large U.S. sample of 18 to 31-year-old men.Erectile dysfunction prevalence and severity (defined using the International Index of Erectile Function-5 scale) were examined in cross-sectional survey data from 2,660 sexually active men, age 18 to 31 years, from the 2013 Growing Up Today Study. Erectile dysfunction medication and supplement use were self-reported. Multivariable models estimated associations of moderate-to-severe erectile dysfunction with demographic (age, marital status), metabolic (body mass index, waist circumference, history of diabetes, hypertension, hypercholesterolemia) and mental health (depression, anxiety, antidepressant use, tranquilizer use) variables.Among sexually active men 11.3% reported mild erectile dysfunction and 2.9% reported moderate-to-severe erectile dysfunction. Married/partnered men had 65% lower odds of erectile dysfunction compared to single men. Adjusting for history of depression, antidepressant use was associated with more than 3 times the odds of moderate-to-severe erectile dysfunction. Anxiety was associated with greater odds of moderate-to-severe erectile dysfunction, as was tranquilizer use. Few men (2%) reported using erectile dysfunction medication or supplements. However, among them, 29.7% misused prescription erectile dysfunction medication. Limitations include reliance upon cross-sectional data and the sample's limited racial/ethnic and socioeconomic diversity.Erectile dysfunction was common in a large sample of sexually active young adult men from a U.S. cohort and was associated with relationship status and mental health. Health providers should screen for erectile dysfunction in young men, and monitor use of prescription erectile dysfunction medications and supplements for sexual functioning.

To compare the variability in metabolomes between the serum and follicular fluid, as well as across 3 dominant follicles.Prospective cohort study.An academic fertility clinic in the northeastern United States, 2005-2015.One hundred thirty-five women undergoing in vitro fertilization treatment who provided a serum sample during ovarian stimulation and up to 3 follicular fluid samples during oocyte retrieval.None.Samples were analyzed using liquid chromatography with high-resolution mass spectrometry and 2 chromatography columns (C18 hydrophobic negative and hydrophilic interaction chromatography [HILIC] positive). We calculated overall, feature-specific, and subject-specific correlation coefficients to describe how strongly the intensity of overlapping metabolic features were associated between the serum and follicular fluid and between the 1st-2nd, 1st-3rd, and 2nd-3rd follicles. Feature-specific correlations were adjusted for age, body mass index, infertility diagnosis, ovarian stimulation protocol, and year.From the C18-negative column and the high-resolution mass spectrometry, 7,830 serum features and 10,790 follicular fluid features were detected in ≥20% of samples. After screening retention times and checking for 1:1 matching, 1,928 features overlapped between the 2 metabolomes. From the HILIC-positive column and the high-resolution mass spectrometry, after applying the same exclusion criteria, there were 9,074 serum features, 5,542 follicular fluid features, and 1,149 features that overlapped. When comparing the feature intensity of overlapping metabolites in the serum and the follicular fluid, the overall (C18, 0.45; HILIC, 0.63), median feature-specific (C18, 0.35; HILIC, 0.37), and median subject-specific (C18, 0.42; HILIC, 0.59) correlations were low to moderate. In contrast, among the overlapping features across all 3 follicles, the overall (C18, all 0.99; HILIC, all 0.99), median feature-specific (C18, 0.74-0.81; HILIC, 0.79-0.85), and median subject-specific (C18, 0.88-0.89; HILIC, 0.90-0.91) correlations between follicular fluid metabolomics features within a woman were high.We observed minimal overlap and weak-to-moderate correlation between metabolomic features in the serum and follicular fluid but a large overlap and strong correlation between metabolomic features across follicles within a woman. The follicular fluid appears to represent a novel matrix, distinct from serum, which may be a rich source of biologic predictors of female fertility and reproductive outcomes.

ImportancePregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown.ObjectiveTo prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence.Design, Setting, and ParticipantsThis prospective cohort study (the Nurses’ Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years.Main Outcomes and MeasuresPregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence.ResultsA total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up.Conclusions and RelevanceIn this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.

Background Long-term exposure to fine particulate matter (PM2.5) mass has been associated with adverse health effects. However, the health effects of PM2.5 components have been less studied. There is a pressing need to better understand the relative contribution of components of PM2.5, which can lay the scientific basis for designing effective policies and targeted interventions. Methods We conducted a population-based cohort study, comprising all Medicare enrollees aged 65 or older in the southeastern United States from 2000 to 2016, to explore the associations between long-term exposure to PM2.5 major components and all-cause mortality among the elderly. Based on well-validated prediction models, we estimated ZIP code-level annual mean concentrations for five major PM2.5 components, including black carbon (BC), nitrate (NIT), organic matter (OM), sulfate (SO4), and soil particles. Data were analyzed using Cox proportional hazards models, adjusting for potential confounders. Results The cohort comprised 13,590,387 Medicare enrollees and a total of 107,191,652 person-years. In single-component models, all five major PM2.5 components were significantly associated with elevated all-cause mortality. The hazard ratios (HR) per interquartile range (IQR) increase in exposure were 1.027 (95% CI: 1.025–1.030), 1.012 (95% CI: 1.010–1.013), 1.018 (95% CI: 1.017–1.020), 1.021 (95% CI: 1.017–1.024), and 1.004 (95% CI: 1.003–1.006) for BC, NIT, OM, SO4, and soil particles, respectively. While the effect estimate of soil component was statistically significant, it is much smaller than those of combustion-related components. Conclusion Our study provides epidemiological evidence that long-term exposure to major PM2.5 components is significantly associated with elevated mortality.

Aims The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. Methods and results We followed 95 465 ever-gravid women participating in the Nurses’ Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10–1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07–1.35) and stroke (HR 1.23; 95% CI 1.04–1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06–1.31) for 1 and 1.34 (95% CI 1.13–1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21–1.62) for age ≤23 years, 1.25 (95% CI 1.09–1.43) for age 24–29 years, and 1.03 (95% CI 0.88–1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained Conclusion PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders.

Objectives We examined sexual orientation-related differences in various pregnancy outcomes (e.g., teen pregnancy, abortion) across the lifespan. Methods We collected data from 124,710 participants in three U.S. longitudinal cohort studies, the Nurses’ Health Study 2 and 3 and Growing Up Today Study 1, followed from 1989 to 2017. Multivariate regression was used to calculate differences of each outcome—ever had pregnancy, teen pregnancy, ever had abortion, and age at first birth—by sexual orientation groups (e.g., heterosexual, mostly heterosexual, bisexual, lesbian), adjusting for potential confounders of age and race/ethnicity. Results All sexual minority groups—except lesbians—were generally more likely than heterosexual peers to have a pregnancy, a teen pregnancy, and an abortion. For example, Growing Up Today Study 1 bisexual participants were three times as likely as heterosexuals to have had an abortion (risk ratio, 3.21; 95% confident interval, 1.94–5.34). Lesbian women in all of the cohorts were approximately half as likely to have a pregnancy compared with heterosexual women. Few sexual orientation group differences were detected in age at first birth. Conclusions The increased risk of unintended pregnancy among sexual minority women likely reflects structural barriers to sexual and reproductive health services. It is critical that sex education programs become inclusive of sexual minority individuals and medical education train health care providers to care for this population. Health care providers should not make harmful heteronormative assumptions about pregnant patients and providers must learn to take sexual histories as well as offer contraceptive counseling to all patients who want to prevent a pregnancy regardless of sexual orientation.

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

BACKGROUND Personal and indoor air pollution monitors represent two ways to assess acute air pollution exposures; however, few reproductive epidemiology studies have incorporated these tools. OBJECTIVE To provide an overview of the unique challenges and opportunities that arise when measuring acute exposure to air pollution in two ongoing reproductive epidemiology studies. METHODS The Air Pollution, In Vitro Fertilization (IVF), and Reproductive Outcomes (AIR) Study recruits women undergoing IVF to wear a personal particulate matter (PM) air pollution monitor (AirBeam2©) for the 72-hour period following the start of controlled ovarian stimulation. The Reproductive Effects of Chemicals and Air Pollutants (RECAP) Study recruits men across the United States to place an air pollution monitor (emmET) in their home for 3 months, use a smartphone application, and provide a semen sample. We highlight the key issues identified in implementing exposure assessment for both studies. RESULTS The main advantages of using the AirBeam2© personal monitor are as follows: (a) the low cost, (b) the ability to collect multiple size fractions of PM data every second, (c) the portability, (d) its capability to track GPS location, and (e) the ability for the participant to observe their real-time exposure information. The limited battery life, incompatibility with iOS-based smartphones, and frequent connection issues that arise between the AirBeam2© and smartphone are the main disadvantages. The main advantages of the emmET are the ability to measure multiple air pollutants at a high level of accuracy, collect data for a long period of time without burdening the participant, and ship monitors to participants around the country without the need for in-person set-up by trained technicians; however, the monitor only measures the indoor home environment. CONCLUSIONS Novel methods can be utilised to characterise short-term air pollution exposure in reproductive epidemiology studies and represent an exciting area for future research.

STUDY QUESTION Is there an association between air pollution exposures and the risk of spontaneous abortion (SAB)? SUMMARY ANSWER Higher exposure to particulate matter (PM) air pollution above and beyond a woman’s average exposure may be associated with greater risk of SAB, particularly among women experiencing at least one SAB during follow-up. WHAT IS KNOWN ALREADY There is sufficient biologic plausibility to suggest that air pollution adversely affects early pregnancy outcomes, particularly pregnancy loss; however, the evidence is limited. STUDY DESIGN, SIZE, DURATION Our prospective cohort study included 19 309 women in the Nurses’ Health Study II who contributed a total of 35 025 pregnancies between 1990 and 2008. We also conducted a case-crossover analysis among 3585 women (11 212 pregnancies) with at least one SAB and one live birth during follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS Proximity to major roadways and exposure to PM MAIN RESULTS AND THE ROLE OF CHANCE During the 19 years of follow-up, 6599 SABs (18.8% of pregnancies) were reported. In the main analysis, living closer to a major roadway and average exposure to PM10, PM10–2.5 or PM2.5 in the 1 or 2 years prior to pregnancy were not associated with an increased risk of SAB. However, small positive associations between PM exposures and SAB were observed when restricting the analysis to women experiencing at least one SAB during follow-up. In the case-crossover analysis, an increase in PM10 (per 3.9 μg/m3), PM2.5–10 (per 2.3 μg/m3) and PM2.5 (per 2.0 μg/m3) in the year prior to pregnancy was associated with 1.12 (95% CI 1.06, 1.19), 1.09 (95% CI 1.03, 1.14) and 1.10 (95% CI 1.04, 1.17) higher odds of SAB, respectively. LIMITATIONS, REASONS FOR CAUTION We did not have information on the month or day of SAB, which precluded our ability to examine specific windows of susceptibility or acute exposures. We also used ambient air pollution exposures as a proxy for personal exposure, potentially leading to exposure misclassification. WIDER IMPLICATIONS OF THE FINDINGS In our case-crossover analysis (but not in the entire cohort) we observed positive associations between exposure to all size fractions of PM exposure and risk of SAB. This may suggest that changes in PM exposure confer greater risk of SAB or that women with a history of SAB are a particularly vulnerable subgroup. STUDY FUNDING/COMPETING INTEREST(S) The authors are supported by the following NIH grants UM1CA176726, R00ES026648 and P30ES000002. The authors have no actual or potential competing financial interests to disclose.

Background We examined the association between the administration of antineoplastic drugs (AD) and fecundity among female nurses. Methods AD administration and use of exposure controls (EC) such as gloves, gowns, and needleless systems were self-reported at baseline among 2649 participants of the Nurses' Health Study 3, who were actively attempting pregnancy. Every 6 months thereafter, the nurses reported the current duration of their pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% confidence intervals (CI) adjusted for age, race, body mass index, smoking, marital status, hours of work, and other occupational risk factors. Results Mean (standard deviation) age and BMI at baseline were 30.7 years (4.7) and 26.0 kg/m2 (6.4). Forty-one percent of nurses reported ever administering AD; 30% only in the past and 11% currently. The former administration of AD (TR = 1.02, 95% CI, 0.93-1.12) was unrelated to the ongoing duration of pregnancy attempt. Among nurses currently administering AD, those who had administered AD for 6 years and above had a 27% (95% CI, 6%-53%) longer duration of pregnancy attempt than nurses who never handled ADs in unadjusted analyses. This difference disappeared in multivariable analyses (TR = 1.01, 95% CI, 0.85-1.21). 93% (n = 270) of the nurses currently administering ADs reported consistent use of EC. These nurses had a similar median duration of pregnancy attempt to those who never handled AD (TR = 1.00, 95% CI, 0.87-1.15). Conclusions Administration of ADs did not appear to have an impact on fecundity in a cohort of nurses planning for pregnancy with a high prevalence of consistent ECs. Our results may not be generalizable to women who are less compliant with PPE use or with less availability to ECs. Therefore, it is possible that we did not observe an association between occupational exposure to AD and reduced fecundity because of lower exposure due to the more prevalent use of effective ECs.

Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated.This study aimed to examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics.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.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.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.

BACKGROUND AND AIM: Exposure to air pollution has been associated with increased risk of infertility and pregnancy loss; however, the majority of research to date has relied on indirect measurement...

BACKGROUND AND AIM: In recent decades, age of menarche has decreased with some questioning whether environmental factors have played a role. We aimed to examine the association between exposure to ...

Both acute and chronic exposure to fine particulate matter (PMParticipants were women undergoingWe identified 17 pathways related to amino acid, lipid, energy, and nutrient metabolism that were solely associated with acute PMWe identified serum metabolites and metabolic pathways uniquely associated with acute versus chronic PM

ObjectivesOccupational use of disinfectants among healthcare workers has been associated with asthma. However, most studies are cross-sectional, and longitudinal studies are not entirely consistent. To limit the healthy worker effect, it is important to conduct studies among early- to mid-career workers. We investigated the prospective association between use of disinfectants and asthma incidence in a large cohort of early- to mid-career female nurses.MethodsThe Nurses’ Health Study 3 is an ongoing, prospective, internet-based cohort of female nurses in the USA and Canada (2010–present). Analyses included 17 280 participants without a history of asthma at study entry (mean age: 34 years) and who had completed ≥1 follow-up questionnaire (sent every 6 months). Occupational use of high-level disinfectants (HLDs) was evaluated by questionnaire. We examined the association between HLD use and asthma development, adjusted for age, race, ethnicity, smoking status and body mass index.ResultsDuring 67 392 person-years of follow-up, 391 nurses reported incident clinician-diagnosed asthma. Compared with nurses who reported ≤5 years of HLD use (89%), those with >5 years of HLD use (11%) had increased risk of incident asthma (adjusted HR (95% CI), 1.39 (1.04 to 1.86)). The risk of incident asthma was elevated but not statistically significant in those reporting >5 years of HLD use and current use of ≥2 products (1.72 (0.88 to 3.34)); asthma risk was significantly elevated in women with >5 years of HLD use but no current use (1.46 (1.00 to 2.12)).ConclusionsOccupational use of HLDs was prospectively associated with increased asthma incidence in early- to mid-career nurses.

Background Few epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples’ pregnancy outcomes. Objective We investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center. Methods We included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed. Results We identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores. Conclusion Paternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.

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.

Background A growing literature suggests that minority races, particularly Black women, have a lower probability of live birth and higher risk of perinatal complications after autologous assisted reproductive technology. However, questions still remain as to whether these racial disparities have arisen because of associations between race and oocyte/embryo quality, the uterine environment, or a combination of the two. Oocyte donation assisted reproductive technology represents a unique approach to examine this question. Objective This study aimed to evaluate the associations between the race of female oocyte donors and recipients and live birth rates following vitrified donor oocyte assisted reproductive technologies. Study Design This was a retrospective study conducted at a single, private fertility clinic that included 327 oocyte donors and 899 recipients who underwent 1601 embryo transfer cycles (2008–2015). Self-reported race of the donor and recipient were abstracted from medical records. Live birth was defined as the delivery of at least 1 live-born neonate. We used multivariable cluster weighted generalized estimating equations with binomial distribution and log link function to estimate the adjusted risk ratios of live birth, adjusting for donor age and body mass index, recipient age and body mass index, tubal and uterine factor infertility, and year of oocyte retrieval. Results The racial profile of our donors and recipients were similar: 73% white, 13% Black, 4% Hispanic, 8% Asian, and 2% other. Women who received oocytes from Hispanic donors had a significantly higher probability of live birth (adjusted risk ratio, 1.20; 95% confidence interval, 1.05–1.36) than women who received oocytes from white donors. Among Hispanic recipients, however, there was no significant difference in probability of live birth compared with white recipients (adjusted risk ratio, 1.07; 95% confidence interval, 0.90–1.26). Embryo transfer cycles using oocytes from Black donors (adjusted risk ratio, 0.86; 95% confidence interval, 0.72–1.03) and Black recipients (adjusted risk ratio, 0.84; 95% confidence interval, 0.71–0.99) had a lower probability of live birth than white donors and white recipients, respectively. There were no significant differences in the probability of live birth among Hispanic, Asian, and other race recipients compared with white recipients. Conclusion Black female recipients had a lower probability of live birth following assisted reproductive technology, even when using vitrified oocytes from healthy donors. Female recipients who used vitrified oocytes from Hispanic donors had a higher probability of live birth regardless of their own race.

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.

ObjectivesDietary surveys are essential for guiding national efforts to reduce the burden of non-communicable disease, but individual-level dietary data are lacking in many low- and middle-income countries. We aimed to estimate the prevalence of inadequate and excessive intakes of specific nutrients in Bosnia and Herzegovina.MethodsA dietary survey among 853 adults using two 24-h recalls.ResultsThe majority of men (73%) and women (66%) were overweight/obese, and gt 50% of participants had elevated blood pressure. Low intakes of N-3 polyunsaturated fatty acids, specifically alpha-linolenic acid (men: 94.4mg/day among, women: 96.6mg/day) and DHA+EPA (men: 18.2mg/day, women: 16.0mg/day), low fiber intake (women: 21.5g/day), and high sodium (men: 3244mg/day, women: 2291mg/) and saturated fatty acids intakes (men: 29.2g/day) were reported. There was also a suggestion of low intakes of vitamins A, B6, C and D (in both sexes), and of riboflavin, folate, B12 and calcium (in women).ConclusionsOur findings provide initial evidence on the Bosnian population's dietary habits and identify aspects that need attention. As the survey evolves into a continuing surveillance system, it will allow evaluation of dietary changes over time.