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STUDY QUESTION To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence? SUMMARY ANSWER COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage. WHAT IS KNOWN ALREADY Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners. STUDY DESIGN, SIZE, DURATION An Internet-based, prospective preconception cohort study of couples residing in the USA and Canada. We analyzed data from 1815 female participants who conceived during December 2020–November 2022, including 1570 couples with data on male partner vaccination. PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible female participants were aged 21–45 years and were trying to conceive without use of fertility treatment at enrollment. Female participants completed questionnaires at baseline, every 8 weeks until pregnancy, and during early and late pregnancy; they could also invite their male partners to complete a baseline questionnaire. We collected data on COVID-19 vaccination (brand and date of doses), history of SARS-CoV-2 infection (yes/no and date of positive test), potential confounders (demographic, reproductive, and lifestyle characteristics), and pregnancy status on all questionnaires. Vaccination status was categorized as never (0 doses before conception), ever (≥1 dose before conception), having a full primary sequence before conception, and completing the full primary sequence ≤3 months before conception. These categories were not mutually exclusive. Participants were followed up from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss to follow-up, 20 weeks' gestation), whichever occurred first. We estimated incidence rate ratios (IRRs) for miscarriage and corresponding 95% CIs using Cox proportional hazards models with GW as the time scale. We used propensity score fine stratification weights to adjust for confounding. MAIN RESULTS AND THE ROLE OF CHANCE Among 1815 eligible female participants, 75% had received at least one dose of a COVID-19 vaccine by the time of conception. Almost one-quarter of pregnancies resulted in miscarriage, and 75% of miscarriages occurred <8 weeks' gestation. The propensity score-weighted IRR comparing female participants who received at least one dose any time before conception versus those who had not been vaccinated was 0.85 (95% CI: 0.63, 1.14). COVID-19 vaccination was not associated with increased risk of either early miscarriage (GW: <8) or late miscarriage (GW: 8–19). There was no indication of an increased risk of miscarriage associated with male partner vaccination (IRR = 0.90; 95% CI: 0.56, 1.44). LIMITATIONS, REASONS FOR CAUTION The present study relied on self-reported vaccination status and infection history. Thus, there may be some non-differential misclassification of exposure status. While misclassification of miscarriage is also possible, the preconception cohort design and high prevalence of home pregnancy testing in this cohort reduced the potential for under-ascertainment of miscarriage. As in all observational studies, residual or unmeasured confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to evaluate prospectively the relation between preconception COVID-19 vaccination in both partners and miscarriage, with more complete ascertainment of early miscarriages than earlier studies of vaccination. The findings are informative for individuals planning a pregnancy and their healthcare providers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Health [R01-HD086742 (PI: L.A.W.); R01-HD105863S1 (PI: L.A.W. and M.L.E.)], the National Institute of Allergy and Infectious Diseases (R03-AI154544; PI: A.K.R.), and the National Science Foundation (NSF-1914792; PI: L.A.W.). The funders had no role in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. L.A.W. is a fibroid consultant for AbbVie, Inc. She also receives in-kind donations from Swiss Precision Diagnostics (Clearblue home pregnancy tests) and Kindara.com (fertility apps). M.L.E. received consulting fees from Ro, Hannah, Dadi, VSeat, and Underdog, holds stock in Ro, Hannah, Dadi, and Underdog, is a past president of SSMR, and is a board member of SMRU. K.F.H. reports being an investigator on grants to her institution from UCB and Takeda, unrelated to this study. S.H.-D. reports being an investigator on grants to her institution from Takeda, unrelated to this study, and a methods consultant for UCB and Roche for unrelated drugs. The authors report no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the association between seasonal influenza vaccination and miscarriage using data from an ongoing, prospective cohort study. METHODS: We analyzed 2013-2022 data from PRESTO (Pregnancy Study Online), a prospective prepregnancy cohort study of female pregnancy planners and their male partners in the United States and Canada. Female participants completed a baseline questionnaire and then follow-up questionnaires every 8 weeks until pregnancy, during early and late pregnancy, and during the postpartum period. Vaccine information was self-reported on all questionnaires. Miscarriage was identified from self-reported information during follow-up. Male partners were invited to complete a baseline questionnaire only. We used Cox proportional hazard models to estimate the hazard ratio (HR) and 95% CI for the association between vaccination less than 3 months before pregnancy detection through the 19th week of pregnancy and miscarriage, with gestational weeks as the time scale. We modeled vaccination as a time-varying exposure and used propensity-score fine stratification to control for confounding from seasonal and female partner factors. RESULTS: Of 6,946 pregnancies, 23.3% of female partners reported exposure to influenza vaccine before or during pregnancy: 3.2% during pregnancy (gestational age 4-19 weeks) and 20.1% during the 3 months before pregnancy detection. The miscarriage rate was 16.2% in unvaccinated and 17.0% among vaccinated participants. Compared with no vaccine exposure, influenza vaccination was not associated with increased rate of miscarriage when administered before (HR 0.99, 95% CI 0.81-1.20) or during (HR 0.83, 95% CI 0.47-1.47) pregnancy. Of the 1,135 couples with male partner vaccination data available, 10.8% reported vaccination less than 3 months before pregnancy. The HR for the association between male partner vaccination and miscarriage was 1.17 (95% CI 0.73-1.90). CONCLUSION: Influenza vaccination before or during pregnancy was not associated with miscarriage. [ABSTRACT FROM AUTHOR]

STUDY QUESTION To what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWER We observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. WHAT IS KNOWN ALREADY Male fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. STUDY DESIGN, SIZE, DURATION We conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015–2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were residents of the USA or Canada, aged 21–45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. MAIN RESULTS AND THE ROLE OF CHANCE Among 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01–1.71), 1.16 (95% CI 0.88–1.51), and 1.43 (95% CI 1.09–1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94–1.55), 1.16 (95% CI 0.89–1.51), and 1.23 (95% CI 0.94–1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner's intakes of trans- and omega-3 fats. LIMITATIONS, REASONS FOR CAUTION Dietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS Our results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

We prospectively examined the association between COVID-19 vaccination and menstrual cycle characteristics in an internet-based prospective cohort study. We included a sample of 1,137 participants who enrolled in Pregnancy Study Online (PRESTO), a preconception cohort study of couples trying to conceive, during January 2021-August 2022. Eligible participants were aged 21–45 years, United States or Canadian residents, and trying to conceive without fertility treatment. At baseline and every 8 weeks for up to 12 months, participants completed questionnaires on which they provided information on COVID-19 vaccination and menstrual cycle characteristics, including cycle regularity, cycle length, bleed length, heaviness of bleed, and menstrual pain. We fit generalized estimating equation (GEE) models with a log link function and Poisson distribution to estimate the adjusted risk ratio (RR) for irregular cycles associated with COVID-19 vaccination. We used linear regression with GEE to estimate adjusted mean differences in menstrual cycle length associated with COVID-19 vaccination. We adjusted for sociodemographic, lifestyle, medical and reproductive factors. Participants had 1.1 day longer menstrual cycles after receiving the first dose of COVID-19 vaccine (95 % CI: 0.4, 1.9) and 1.3 day longer cycles after receiving the second dose (95 % CI: 0.2, 2.5). Associations were attenuated at the second cycle post-vaccination. We did not observe strong associations between COVID-19 vaccination and cycle regularity, bleed length, heaviness of bleed, or menstrual pain. In conclusion, COVID-19 vaccination was associated with a ∼1 day temporary increase in menstrual cycle length, but was not appreciably associated with other menstrual cycle characteristics. [ABSTRACT FROM AUTHOR]

Background: Migraine is associated with hypertensive disorders of pregnancy through common pathophysiological features. This study evaluates the association between migraine diagnosis and treatment, and risk of hypertensive disorders of pregnancy. Methods: We conducted a prospective cohort study in the Clinical Practice Research Datalink GOLD, a large longitudinal database of patient records in the UK. We analyzed data from liveborn or stillborn singleton deliveries from 1993-2020 with at least 24 months of medical history and no history of cardiovascular disease (n=1,049,839). We ascertained migraine through diagnosis or prescription codes before 20 weeks of gestation and hypertensive disorders of pregnancy through diagnosis codes between 20 weeks of pregnancy and delivery. We used log-binomial regression models to estimate the risk ratio and 95% confidence intervals, comparing risk of hypertensive disorders of pregnancy among individuals with migraine to those without migraine, adjusting for confounders. Conclusions: A history of migraine prior to pregnancy was associated with an increased risk of hypertensive disorders of pregnancy (RR=1.17, 95% CI: 1.09-1.26). The greatest risk was among those with pre-pregnancy migraine that persisted into the first trimester (RR=1.84, 95% CI: 1.35-2.50). Use of migraine medication was associated with a higher risk of hypertensive disorders of pregnancy compared to non-migraineurs (RR=1.50, 95% CI: 1.15-1.97). Results from this study indicate that migraine is a potential risk factor for hypertensive disorders of pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Residential green space can have positive physiological effects on human health through various mechanisms, including reducing stress and/or depression or facilitating physical activity. Although green space has been consistently associated with improved birth outcomes in several studies, there has been limited study of its effect on other reproductive outcomes, including fertility. OBJECTIVE: We examined associations between residential green space and fecundability, the per-cycle probability of conception. METHODS: We analyzed data from 8,563 female participants enrolled between 2013 and 2019 in Pregnancy Study Online (PRESTO), a prospective preconception cohort study of North American couples attempting conception. Participants completed a baseline questionnaire on sociodemographic, behavioral, and reproductive factors, and bimonthly follow-up questionnaires for up to 12 months to ascertain pregnancies. Using geocoded addresses, we calculated residential green space exposure using the Normalized Difference Vegetation Index (NDVI) within 50-, 100-, 250-, and 500-m buffers across multiple temporal scales: annual maximum, seasonal maximum, and seasonal mean. We used proportional probabilities regression models to estimate fecundability ratios (FRs), adjusting for sociodemographic, behavioral, and neighborhood characteristics. We also evaluated the extent to which associations were mediated by reductions in perceived stress or depressive symptoms and increased physical activity. RESULTS: When comparing the highest (=0.8) with the lowest (<0.2) NDVI exposures within 50 m, we observed positive associations in the annual maximum NDVI [FR: 1.33; 95% confidence interval (CI): 1.06, 1.67] and seasonal maximum NDVI (FR: 1.19; 95% CI: 1.00, 1.41) models, but little association in the seasonal mean NDVI models (FR: 0.98; 95% CI: 0.73, 1.30). Restricted cubic splines showed evidence of nonlinearity in this association. Results were similar across buffer distances. Perceived stress, depressive symptoms, and physical activity explained =5:0% of mediation across all NDVI metrics. DISCUSSION: In this cohort, greater residential green space was associated with a modest increase in fecundability. [ABSTRACT FROM AUTHOR]

Background: Migraine is common among females of reproductive age (estimated prevalence:17–24%) and may be associated with reproductive health through underlying central nervous system excitability, autoimmune conditions, and autonomic dysfunction. We evaluated the extent to which pre-pregnancy migraine diagnosis and medication use are associated with risk of spontaneous abortion (SAB). Methods: We analyzed data from a preconception study of pregnancy planners (2013–2021). Eligible participants self-identified as female, were aged 21–45 years, resided in the USA or Canada, and conceived during follow-up (n = 7890). Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever occurred first. Pregnant participants then completed questionnaires during early (~ 8–9 weeks) and late (~ 32 weeks) gestation. We defined migraineurs as participants who reported a migraine diagnosis or use of a medication to treat migraine. Preconception questionnaires elicited migraine medication use during the past 4 weeks, and SAB on follow-up and pregnancy questionnaires. We used Cox regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations among preconception migraine, migraine medication use, and SAB, controlling for potential demographic, medical, and lifestyle confounders. Results: Nineteen percent of study pregnancies ended in SAB. History of migraine before conception was not appreciably associated with SAB risk (HR = 1.03, 95% CI: 0.91–1.06). Use of any migraine medication was associated with a modest increase in SAB risk overall (HR = 1.14, 95% CI: 0.96–1.36). We observed the greatest increase in risk among those taking migraine medications daily (HR = 1.38, 95% CI: 0.81–2.35) and those taking prescription migraine prophylaxis (HR = 1.43, 95% CI: 0.72–2.84) or combination analgesic and caffeine medications (HR = 1.42, 95% CI: 0.99–2.04). Conclusions: Migraine medication use patterns suggesting greater underlying migraine severity were associated with increased risk of SAB. This research adds to the limited information available on the reproductive effects of migraine. [ABSTRACT FROM AUTHOR]

Measurement error is pervasive in epidemiologic research. Epidemiologists often assume that mismeasurement of study variables is nondifferential with respect to other analytical variables and then rely on the heuristic that "nondifferential misclassification will bias estimates towards the null." However, there are many exceptions to the heuristic for which bias towards the null cannot be assumed. In this paper, we compile and characterize 7 exceptions to this rule and encourage analysts to take a more critical and nuanced approach to evaluating and discussing bias from nondifferential mismeasurement. [ABSTRACT FROM AUTHOR]

Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21–45 year residing in the United States or Canada during December 2020–September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e. the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner. [ABSTRACT FROM AUTHOR]

Purpose: Diet quality is increasingly recognized as important for human reproductive capacity. We studied the association between intake of protein-rich foods and risk of spontaneous abortion (SAB). Methods: During 2013–2020, we recruited pregnancy planners from the United States and Canada (Pregnancy Study Online; PRESTO) and Denmark (SnartForaeldre.dk; SF). Participants completed a baseline questionnaire and a validated cohort-specific food frequency questionnaire. We estimated preconception intake of red meat, poultry, processed meat, seafood, eggs, plant-based proteins, and dairy from individual foods and mixed recipes. We included 4,246 PRESTO and 2,953 SF participants who reported a pregnancy during the study. Data on SAB were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI), representing the effect of substituting one type of protein-rich food for another. Results: SAB risk was 23% in PRESTO and 16% in SF. In PRESTO, substitution of seafood with other protein-rich foods was associated with higher SAB risk [for example, the HR for replacing 100 g of seafood/week with 100 g of red meat was 1.10 (95% CI 1.00, 1.20)]. In contrast, in SF, substituting seafood with other protein-rich foods was associated with lower SAB risk [HR for replacing 100 g of seafood/week with 100 g of red meat was 0.89 (95% CI 0.82, 0.98)]. Other protein-rich food substitutions were not meaningfully associated with SAB risk. Conclusions: Preconception intake of protein-rich foods was largely unrelated to SAB risk, with the exception of seafood, which was associated with higher risk of SAB in Denmark, but a lower risk in North America. [ABSTRACT FROM AUTHOR]

Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23–35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence. [Display omitted] • EDCs mixtures and UL incidence examined in a prospective ultrasound study. • EDCs were widely detected among a cohort of reproductive-aged Black women. • Strongest individual EDC contributors for joint associations were identified. • Overall mixture of EDCs showed evidence of inverse associations with UL incidence. • Potential evidence of interactions between specific EDCs. [ABSTRACT FROM AUTHOR]

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013–2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM 2.5), nitrogen dioxide (NO 2), and ozone (O 3) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM 2.5 , NO 2 , and O 3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM 2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO 2 and O 3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM 2.5 , NO 2 , and O 3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM 2.5 with SAB incidence in Canada. • We found a positive association of ambient PM 2.5 concentrations with spontaneous abortion in Canada, but not the USA. • NO 2 and O 3 concentrations were not appreciably associated with rate of SAB. • Results were relatively consistent across season and weeks of gestation. • Protection of pregnant individuals from air pollutionis an important measure to safeguard maternal and fetal health. [ABSTRACT FROM AUTHOR]

Background: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. Epidemiologic studies have been restricted largely to couples undergoing fertility treatment or have retrospectively ascertained time-to-pregnancy among pregnant women.Objectives: We examined the association between residential ambient air pollution and fecundability, the per-cycle probability of conception, in a large preconception cohort of Danish pregnancy planners.Methods: During 2007-2018, we used the Internet to recruit and follow women who were trying to conceive without the use of fertility treatment. Participants completed an online baseline questionnaire eliciting socio-demographic characteristics, lifestyle factors, and medical and reproductive histories and follow-up questionnaires every 8 weeks to ascertain pregnancy status. We determined concentrations of ambient nitrogen oxides (NOx ), nitrogen dioxide (NO2 ), carbon monoxide (CO), ozone (O3 ), particulate matter <2.5 µm (PM2.5 ) and <10 µm (PM10 ), and sulphur dioxide (SO2 ) at each participant's residential address. We calculated average exposure during the year before baseline, during each menstrual cycle over follow-up and during the entire pregnancy attempt time. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders and co-pollutants. The analysis was restricted to the 10,183 participants who were trying to conceive for <12 cycles at study entry whose addresses could be geocoded.Results: During 12 months of follow-up, 73% of participants conceived. Higher concentrations of PM2.5 and PM10 were associated with small reductions in fecundability. For example, the FRs for a one interquartile range (IQR) increase in PM2.5 (IQR = 3.2 µg/m3 ) and PM10 (IQR = 5.3 µg/m3 ) during each menstrual cycle were 0.93 (95% CI: 0.87, 0.99) and 0.91 (95% CI: 0.84, 0.99), respectively. Other air pollutants were not appreciably associated with fecundability.Conclusions: In this preconception cohort study of Danish women, residential exposures to PM2.5 and PM10 were associated with reduced fecundability. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of urinary concentrations of phenols, parabens, and triclocarban with incidence and growth of uterine leiomyomata (UL; fibroids).Design: Case-cohort study, nested within the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study.Setting: Clinic visits at baseline and every 20 months for 60 months.Patient(s): 754 Black women aged 23-35 years residing in the Detroit, Michigan area (enrolled during 2010-2012).Intervention: None.Main Outcome Measure(s): At each study visit, women underwent transvaginal ultrasound for measurement of UL incidence and growth and provided urine specimens in which we quantified concentrations of seven phenols, four parabens, and triclocarban. We used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) characterizing the relation of urinary biomarker concentrations with UL incidence during the 60 months of follow-up. In a subset of UL detected and measured at multiple time points, we used linear regression to assess the associations between biomarker concentrations and UL growth.Result(s): Urinary biomarker concentrations were generally inversely associated with UL incidence, but the associations were weak and nonmonotonic. For example, hazard ratios comparing concentrations ≥90th with <50th percentile were 0.77 (95% CI: 0.46, 1.27) for bisphenol A, 0.72 (95% CI: 0.40, 1.28) for bisphenol S, and 0.76 (95% CI: 0.43, 1.33) for methylparaben. Biomarker concentrations were not strongly associated with UL growth.Conclusion(s): In this study of reproductive-aged Black women, urinary phenols, parabens, and triclocarban biomarkers were neither strongly nor consistently associated with UL incidence and growth. [ABSTRACT FROM AUTHOR]

Study Question: To what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)?Summary Answer: In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL.What Is Known Already: UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women.Study Design, Size, Duration: We conducted a prospective cohort study of 21 998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011.Participants/material, Setting, Methods: Women reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants.Main Results and the Role Of Chance: During 196 685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48).Limitations, Reasons For Caution: Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility.Wider Implications Of the Findings: Inequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL.Study Funding/competing Interest(s): This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

[Display omitted] • Residential ambient concentrations of particulate matter, nitrogen dioxide, and ozone were not strongly associated with fecundability, the per cycle probability of conception. • We examined concentrations during multiple critical windows of exposure. • This is one of the largest studies to examine this association among couples trying to conceive spontaneously. Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. However, the level of evidence is limited and specific pollutants driving the association are inconsistent across studies. We used data from a web-based preconception cohort study of pregnancy planners enrolled during 2013–2019 (Pregnancy Study Online; PRESTO). Eligible participants self-identified as female, were aged 21–45 years, resided in the United States (U.S.) or Canada, and were trying to conceive without fertility treatments. Participants completed a baseline questionnaire and bi-monthly follow-up questionnaires until conception or 12 months. We analyzed data from 8,747 participants (U.S.: 7,304; Canada: 1,443) who had been trying to conceive for < 12 cycles at enrollment. We estimated residential ambient concentrations of particulate matter < 2.5 µm (PM 2.5), nitrogen dioxide (NO 2), and ozone (O 3) using validated spatiotemporal models specific to each country. We fit country-specific proportional probabilities regression models to estimate the association between annual average, menstrual cycle-specific, and preconception average pollutant concentrations with fecundability, the per-cycle probability of conception. We calculated fecundability ratios (FRs) and 95% confidence intervals (CIs) and adjusted for individual- and neighborhood-level confounders. In the U.S., the FRs for a 5-µg/m3 increase in annual average, cycle-specific, and preconception average PM 2.5 concentrations were 0.94 (95% CI: 0.83, 1.08), 1.00 (95% CI: 0.93, 1.07), and 1.00 (95% CI: 0.93, 1.09), respectively. In Canada, the corresponding FRs were 0.92 (95% CI: 0.74, 1.16), 0.97 (95% CI: 0.87, 1.09), and 0.94 (95% CI: 0.80, 1.09), respectively. Likewise, NO 2 and O 3 concentrations were not strongly associated with fecundability in either country. Neither annual average, menstrual cycle-specific, nor preconception average exposure to ambient PM 2.5 , NO 2 , and O 3 were appreciably associated with reduced fecundability in this cohort of pregnancy planners. [ABSTRACT FROM AUTHOR]

Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene was associated with reduced size and incidence of oviduct leiomyoma in the Japanese quail. Two US prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. This study examines the association between dietary intake of carotenoids and UL incidence. Data were derived from the Study of the Environment, Lifestyle, and Fibroids, a prospective cohort study. Women completed self-administered baseline questionnaires on demographic characteristics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids—including alpha carotene, beta carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene—and vitamin A were estimated. One thousand two hundred thirty Black women aged 23 to 35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease were eligible for enrollment (2010-2012). Participants were residents of the Detroit, MI, metropolitan area. Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. Cox regression was used to estimate hazard ratios and 95% CIs, adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. Among 1,230 women without prevalent UL at baseline, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. Hazard ratios comparing quartiles 2 (2,376 to 3,397 μg/day), 3 (3,398 to 4,817 μg/day), and 4 (≥4,818 μg/day) with quartile 1 (<2,376 μg/day) of lycopene intake were 1.03 (95% CI 0.72 to 1.47), 1.22 (95% CI 0.86 to 1.72), and 0.95 (95% CI 0.67 to 1.36), respectively. Study findings do not support the hypothesis that greater carotenoid intake is associated with reduced UL incidence. [ABSTRACT FROM AUTHOR]

Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119–2127) found a 35% reduction in fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with fecundability. [ABSTRACT FROM AUTHOR]

The article reports that human influence has warmed planet at an unprecedented rate, and climate change increases the frequency and severity of extreme weather events across the globe. Topics include considered that it seems that hardly a week goes by without news of ever more severe heat waves, wildfires, droughts or severe storms and heavy rainfall with accompanying landslides.

Background: Phytoestrogens are plant-derived hormonally active compounds found in soy, cruciferous vegetables, nuts, and seeds. Although phytoestrogens have been associated with altered endogenous hormonal activity, luteal phase deficiency, and reduced endometrial decidualization, the literature reporting examinations of phytoestrogen intake and fertility presents mixed findings.Objectives: We sought to evaluate prospectively the association between dietary phytoestrogen intake (isoflavones, lignans, and coumestans) and fecundability, the per-cycle probability of conception, in 2 cohorts of women planning pregnancy.Methods: Pregnancy Study Online (PRESTO) and Snart Foraeldre (SF) are parallel web-based preconception cohort studies of women from North America and Denmark, respectively, who are trying to conceive. Participants complete an online baseline questionnaire on sociodemographic, lifestyle, and medical factors. We ascertained intake of individual phytoestrogens from validated FFQs. We measured fecundability using data on menstruation and pregnancy status from bimonthly follow-up questionnaires. We analyzed data from 4880 PRESTO and 2898 SF female study participants who had been attempting conception for ≤6 cycles at study entry. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs.Results: Phytoestrogen intake varied across cohorts, yet was associated with higher socioeconomic status and healthier behaviors in both cohorts. After adjustment for potential confounders, phytoestrogen intake was not substantially associated with fecundability in either cohort. We observed some evidence of improved fecundability with increasing isoflavone intake among women age ≥30 years in PRESTO (FR: 1.12; 95% CI: 0.94, 1.34, for comparison of ≥90th with <25th percentile intake) and SF (corresponding FR: 1.19; 95% CI: 0.92, 1.55). Lignan intake was associated with slightly increased fecundability in SF (FR for comparison of 75th to 90th with <25th percentile: 1.10; 95% CI: 0.96, 1.26), but decreased fecundability in PRESTO (FR for comparison of ≥90th with <25th percentile: 0.83; 95% CI: 0.72, 0.97).Conclusions: We did not observe strong associations between phytoestrogen intake and prospectively-measured fecundability among North American or Danish pregnancy planners. [ABSTRACT FROM AUTHOR]

Study Question: To what extent does fecundability vary across seasons?Summary Answer: After accounting for seasonal patterns in pregnancy planning, we observed higher fecundability in the fall and lower fecundability in the spring, particularly at lower latitudes.What Is Known Already: In human populations, there are strong seasonal patterns of births that vary across geographic regions and time periods. However, previous studies of seasonality and fecundity are limited because they examine season of birth rather than season of conception and therefore neglect to account for seasonal variation in initiating attempts to conceive or pregnancy loss or differences in gestational length.Study Design, Size, Duration: We conducted a preconception cohort study of 14 331 women residing in North America (June 2013-May 2018: n = 5827) and Denmark (June 2007-May 2018: n = 8504). Participants were attempting to conceive without fertility treatment and had been attempting pregnancy for ≤6 menstrual cycles at enrolment.Participants/material, Setting, Methods: We collected information on season of each pregnancy attempt using last menstrual period dates over the study period. Pregnancy was reported on female bi-monthly follow-up questionnaires. We fit log-binomial models with trigonometric regression to examine periodic variation in fecundability. We accounted for seasonal variation in initiation of pregnancy attempts by including indicator variables for menstrual cycle of attempt in the regression models.Main Results and the Role Of Chance: Initiation of pregnancy attempts peaked in September, with stronger seasonality in North America than in Denmark (48 vs. 16% higher probability initiating attempts in September compared with March). After accounting for seasonal variation in initiation of pregnancy attempts, we observed modest seasonal variation in fecundability, with a peak in the late fall and early winter in both cohorts, but stronger peak/low ratios in North America (1.16; 95% confidence interval [CI]: 1.05, 1.28) than in Denmark (1.08; 95% CI: 1.00, 1.16). When we stratified the North American data by latitude, we observed the strongest seasonal variation in the southern USA (peak/low ratio of 1.45 [95% CI: 1.14, 1.84]), with peak fecundability in late November.Limitations, Reasons For Caution: We estimated menstrual cycle dates between follow-up questionnaires, which may have introduced exposure misclassification, particularly when women skipped follow-up questionnaires. We were unable to measure seasonally varying factors that may have influenced fecundability, including ambient temperature, vitamin D levels or infectious disease.Wider Implications Of the Findings: An understanding of how fecundability varies across seasons could help identify factors that can impair reproductive function. Neglecting to account for seasonal variation in initiation of pregnancy attempts could bias estimates of seasonal patterns in fecundability. This is the first preconception cohort study to examine seasonal variation in fecundability after accounting for seasonality in initiation of pregnancy attempts. Fecundability was highest in the fall and lowest in the spring, with stronger effects in southern latitudes of North America, suggesting that seasonal exposures may affect fecundity.Study Funding/competing Interest(s): This research was funded by the Eunice K. Shriver National Institute of Child Health and Human Development (R21-050264, R01-HD060680, R21-HD072326 and R01-HD086742) and the Danish Medical Research Council (271-07-0338). The authors declare no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements. Objectives The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability. Methods We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n  = 1693) and North America (PRESTO; n  = 2969) during 2013–2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders. Results We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles. Conclusions Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are a class of lipophilic endocrine-disrupting chemicals with wide industrial use in the U.S. from the 1930s through 1977. Due to their environmental and biological persistence, low levels of PCBs remain detected in wildlife and humans. Although U.S. studies have shown higher serum PCB concentrations among Black women compared with White women, studies of correlates of PCB exposure among Black women are scarce. We examined predictors of plasma PCB concentrations in a cross-sectional analysis of baseline data from a prospective cohort study of 1693 premenopausal Black women aged 23-35 years from Detroit, Michigan (2010-2012). We collected demographic, behavioral, dietary, and medical data via self-administered questionnaires, telephone interviews, and in-person clinic visits, as well as non-fasting blood samples. We measured concentrations of 24 PCB congeners in baseline plasma from a subset of 762 participants. We used linear regression for log-transformed lipid-adjusted PCB concentrations to calculate percentage differences across levels of selected predictors. We did this separately for individual PCBs, sum of total PCBs, and sum of PCBs by degree of chlorination and hormonal activity. PCB concentrations were positively associated with age, duration of urban residence, cigarette smoking, heavy alcohol intake, and being breastfed in infancy, and inversely associated with body mass index (BMI) and lactation duration. The strength of some associations varied by degree of chlorination. For example, a 5-kg/m2 higher BMI corresponded to a 2.9% lower summed concentration of tri- and tetra-substituted PCBs (95% CI -4.6%, -1.2%), an 8.3% lower summed concentration of penta- and hexa-substituted PCBs (95% CI -10.0%, -6.5%), and a 12.1% lower summed concentration of hepta-, octa-, nona-, and deca-substituted PCBs (95% CI -13.7%, -10.4%). Likewise, associations for age and being breastfed in infancy were stronger for higher-chlorinated PCBs. Results agree with studies on predictors of PCB body burdens, few of which include large numbers of Black women. [ABSTRACT FROM AUTHOR]

To evaluate associations between low job control (operationalized as job independence and freedom to make decisions) and time to pregnancy. Low job control, a form of workplace stress, is associated with adverse health outcomes ranging from cardiovascular disease to premature mortality; few studies have specifically examined its association with reproductive outcomes. We used data from Pregnancy Study Online, an internet-based preconception cohort study of couples trying to conceive in the United States and Canada. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) via proportional probability regression models, adjusting for sociodemographic and behavioral characteristics. Not applicable (Web-based study). Participants self-identified as female, were aged 21–45 years, and reported ≤6 cycles of pregnancy attempt time at enrollment (2018–2022). We assessed job control by matching participants' baseline self-reported occupation and industry with standardized occupation codes from the National Institute for Occupational Safety and Health's Industry and Occupation Computerized Coding System, then linking codes to O∗NET job exposure scores for job independence and freedom to make decisions. Our main outcome measure was fecundability. Participants completed self-administered questionnaires at baseline and every 8 weeks for up to 12 months or until reported pregnancy, whichever occurred first. Among 3,110 participants, lower job independence was associated with reduced fecundability. Compared with the fourth (highest) quartile, corresponding to the most job independence, FRs (95% CI) for first (lowest), second, and third quartiles were 0.92 (0.82–1.04), 0.84 (0.74–0.95), and 0.99 (0.88, 1.11), respectively. Lower freedom to make decisions was associated with slightly reduced fecundability (first vs. fourth quartile: FR = 0.92; 95% CI: 0.80–1.05). Lower job control, a work-related stressor, may adversely influence time to pregnancy. Because job control is a condition of work (i.e., not modifiable by individuals), these findings may strengthen arguments for improving working conditions as a means of improving worker health, including fertility. [ABSTRACT FROM AUTHOR]

Study Question: To what extent is cigarette smoking associated with reduced fecundability?Summary Answer: Current female smokers, particularly those who had smoked ≥10 cigarettes/day for ≥10 years, had lower fecundability than never smokers, but current male smoking and passive smoking in either partner showed little association with reduced fecundability.What Is Known Already: Female smoking has been identified as a cause of infertility, yet there has been limited characterization of the dose and duration at which an effect is observed. Results for male active smoking and passive smoking in both partners are less consistent.Study Design, Size, Duration: We analyzed data from a North American internet-based preconception cohort study of 5473 female and 1411 male pregnancy planners, enrolled from 2013 to 2018. Participants had been attempting conception for ≤6 menstrual cycles at study entry.Participants/materials, Setting, Methods: We collected information on active and passive smoking history on baseline questionnaires. Pregnancy was reported on female bi-monthly follow-up questionnaires. We calculated fecundability ratios (FR) and 95% CI using proportional probabilities regression models, adjusted for demographic, behavioral, medical, reproductive and dietary variables.Main Results and the Role Of Chance: Female current regular smoking (FR = 0.90, 95% CI: 0.77, 1.07), current occasional smoking (FR = 0.88, 95% CI: 0.73, 1.06), and former smoking (FR = 0.89, 95% CI: 0.81, 0.98) were associated with small reductions in fecundability. Results were stronger among women who smoked ≥10 cigarettes/day for ≥10 years (FR = 0.77, 95% CI: 0.53, 1.10). Male current regular and former smoking, and current passive smoking in either partner were not meaningfully associated with reduced fecundability. In utero exposure to ≥10 cigarettes/day among females was associated with reduced fecundability (FR = 0.75, 95% CI: 0.52, 1.06).Limitations, Reasons For Caution: Numbers of cigarette smokers, particularly within categories of intensity and duration, were small. Under-reporting of smoking may have resulted in non-differential misclassification, and smokers were more likely to be lost to follow-up.Wider Implications Of the Findings: Given the consistency of our findings with results from previous studies and our observation of a dose-response relation in intensity of smoking, this study supports an association between female cigarette smoking and lower fecundability.Study Funding/competing Interest(s): This study was funded by the National Institute of Child Health and Human Development (R01-HD086742, R21-HD072326, R03-HD090315 and T32-HD052458). The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

While some epidemiologic studies support the hypothesis that stress can adversely affect fertility, few prospective studies have assessed the association in couples from the general population. We used data from Pregnancy Study Online, a web-based preconception cohort study of pregnancy planners from the United States and Canada (2013–2018), to examine the association between women's and men's perceived stress levels prior to conception and fecundability. Women (aged 21–45 years) and their male partners (aged ≥21 years) who were attempting conception without fertility treatment were eligible. We measured perceived stress using the 10-item Perceived Stress Scale (PSS). We ascertained pregnancy information using bimonthly follow-up questionnaires of female participants. We followed 4,769 couples until self-reported pregnancy, initiation of fertility treatment, loss to follow-up, or 12 menstrual cycles of attempt time, whichever came first. We used proportional probabilities regression models to estimate fecundability ratios and 95% confidence intervals, adjusting for potential confounders. Higher PSS scores among the women were associated with slight reductions in fecundability (comparing PSS scores of ≥25 vs. <10, fecundability ratio = 0.87, 95% confidence interval: 0.74, 1.02). PSS scores among the men were not substantially associated with fecundability. [ABSTRACT FROM AUTHOR]

Abstract Background The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts. Methods The Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results. Results Any cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76). Conclusions We found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure. Highlights • Cape Cod residents were exposed to PCE through contaminated drinking water. • Cumulative PCE exposure was not associated with increased risk of infertility. • High PCE exposure around the pregnancy attempt may be associated with infertility. [ABSTRACT FROM AUTHOR]

The article responds to comments made on the authors' article about the use of heuristics in epidemiology. Topics mentioned include the reasons for the occurrence of nondifferential misclassification bias, the use of quantitative bias analysis, the estimation of the effect of an exposure on an health outcome, and the role of bias due to nondifferential misclassification in changing the policy making on clinical care.

A growing literature indicates that changes in modifiable factors, including diet, can counteract the toxic developmental and reproductive health effects of chemical exposures. In this issue of the Journal , Gaskins et al. (Am J Epidemiol. 2019;000(000):000–000) present data supporting this hypothesis. Specifically, using data on a cohort of 304 women seeking fertility treatment in Boston, Massachusetts, they found that women with higher exposure to ambient air pollutants had lower fertility treatment success but only when they also consumed <800 μg/day of supplemental folate. No association was observed among women consuming ≥800 μg/day of supplemental folate. The public health importance of this interaction is high: Diet and dietary supplement intake are modifiable factors, whereas exposure to air pollution is less so. While this research question is grounded in a strong biological hypothesis related to epigenetic modifications, oxidative stress, and inflammation, this study raises several key questions. In this commentary, we discuss the inconsistency of the interaction across exposure metrics, the possibility of unmeasured confounding by folate intake, and the importance of examining this association in populations with lower folate intake and/or higher exposure to air pollution. [ABSTRACT FROM AUTHOR]

The association between dietary fat and fertility is not well studied. We evaluated intakes of total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, trans fatty acids (TFA), ω-3 fatty acids, and ω-6 fatty acids in relation to fecundability in Danish and North American preconception cohort studies. Women who were attempting to become pregnant completed a validated food frequency questionnaire at baseline. Pregnancy status was updated bimonthly for 12 months or until pregnancy. Fecundability ratios (FR) and 95% confidence intervals were estimated using multivariable proportional probabilities regression. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and ω-6 fatty acids were not appreciably associated with fecundability. TFA intake was associated with reduced fecundability in North American women (for the fourth quartile vs. the first, FR = 0.86, 95% confidence interval (CI): 0.71, 1.04) but not Danish women (for the fourth quartile vs. the first, FR = 1.04, 95% CI: 0.86, 1.25), though intake among Danish women was low. In North America, ω-3 fatty acid intake was associated with higher fecundability, but there was no dose-response relationship (among persons who did not use fish oil supplements: for the fourth quartile vs. the first, FR = 1.40, 95% CI: 1.13, 1.73); no association was found in Danish women, among whom low intake was rare. In the present study, high TFA intake and low ω-3 fatty acid intake were associated with reduced fecundity. [ABSTRACT FROM AUTHOR]

Caffeine is an adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, or sperm quality. We studied the association between female and male preconception caffeine intake and fecundability in a North American prospective cohort study of 2135 pregnancy planners. Frequency of caffeinated beverage intake was self-reported at baseline. Outcome data were updated every 8 weeks until reported pregnancy; censoring occurred at 12 months. Adjusted fecundability ratios (FR) and 95% confidence intervals (CI) were estimated using proportional probabilities regression. Total caffeine intake among males, but not females, was associated with fecundability (FR for ≥300 vs. <100 mg/day caffeine among males = 0.72, 95% CI = 0.54–0.96), although the association was not monotonic. With respect to individual beverages, caffeinated tea intake was associated with slight reductions in fecundability among females, and caffeinated soda and energy drink intake were associated with reduced fecundability among males. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23–35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010–2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (−34.7; −43.0, −25.1) and PFOA (−33.1; −39.2, −26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (−31.1; −37.8, −23.7), PFHxS (−24.2; −34.5, −12.3), and PFOS (−18.4; −28.3, −7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (−33.1; −39.6, −25.8), PFHxS (−29.3; −39.0, −18.1), PFNA (−25.2; −32.7, −16.8), and PFOS (−18.3; −28.3, −6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (−18.8; −28.3, −8.2), PFOS (−16.4; −24.9, −7.1), PFNA (−10.5; −17.8, −2.6), and PFOA (−10.0; −17.2, −2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4). Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use). [ABSTRACT FROM AUTHOR]

Refusal to participate in studies related to sexual health can compromise the internal and external validity of findings. Research examining non-response to sexual health studies has primarily focused on predictors such as specific sexual attitudes and behaviors. Evaluate predictors of non-response to a supplemental sexual health survey added to a web-based cohort study, focusing on predictors that may be important in epidemiologic studies of sexual health. In March 2021, we added the "Sexual Health and Wellbeing Questionnaire" (SQ), an optional supplemental sexual health survey, to the protocol for Pregnancy Study Online , a web-based North American prospective cohort study. Eligible participants identified as female and were aged 21–45 years, actively trying to conceive, and in a relationship with a male partner. Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 8 weeks. Participants were invited to complete the SQ 30 days after baseline questionnaire completion. The analytic sample included all Pregnancy Study Online participants who enrolled between March 2021 and December 2021 and was divided into 3 mutually-exclusive groups: (i) those who completed the baseline questionnaire only (ie, did not complete a follow-up questionnaire or the SQ), (ii) those who completed at least 1 follow-up questionnaire but not the SQ, and (iii) participants who completed the SQ (with or without a follow-up questionnaire). We compared sociodemographic, medical, lifestyle, and reproductive factors across these groups. Of the 1,491 enrolled participants, 302 (20.3%) completed the baseline questionnaire only, 259 (17.4%) completed a follow-up questionnaire but not the SQ, and 930 (62.4%) completed the SQ. Strong predictors of non-response (absolute difference in response >10% comparing SQ responders to baseline-only responders) included longer pregnancy attempt time at study entry, a history of infertility, and lower income and education. Compared with response to the follow-up questionnaire only, SQ response was lower among Hispanic/Latina participants and participants aged <25 years. The addition of sexual health surveys to established cohort studies may be an effective way to expand epidemiologic sex research efforts. Study strengths include the prospective design, geographic heterogeneity of the cohort, and use of online methods. Our findings may not generalize to clinic-based sex research. We report that in an established North American cohort study, response to the SQ exceeded 60%. We observed few strong predictors for SQ non-response among engaged participants. Bond JC, Abrams J, Wesselink AK, et al. Predictors of Non-Response to a Sexual Health Survey in a North American Preconception Cohort Study. J Sex Med 2022;19:1707–1715. [ABSTRACT FROM AUTHOR]

To use self-reported preconception data to derive models that predict the risk of miscarriage. Prospective preconception cohort study. Not applicable. Study participants were female, aged 21–45 years, residents of the United States or Canada, and attempting spontaneous pregnancy at enrollment during 2013–2022. Participants were followed for up to 12 months of pregnancy attempts; those who conceived were followed through pregnancy and postpartum. We restricted analyses to participants who conceived during the study period. On baseline and follow-up questionnaires completed every 8 weeks until pregnancy, we collected self-reported data on sociodemographic factors, reproductive history, lifestyle, anthropometrics, diet, medical history, and male partner characteristics. We included 160 potential predictor variables in our models. The primary outcome was a miscarriage, defined as pregnancy loss before 20 weeks of gestation. We followed participants from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss of follow-up, or 20 weeks of gestation), whichever occurred first. We fit both survival and static models using Cox proportional hazards models, logistic regression, support vector machines, gradient-boosted trees, and random forest algorithms. We evaluated model performance using the concordance index (survival models) and the weighted F1 score (static models). Among the 8,720 participants who conceived, 20.4% reported miscarriage. In multivariable models, the strongest predictors of miscarriage were female age, history of miscarriage, and male partner age. The weighted F1 score ranged from 73%–89% for static models and the concordance index ranged from 53%–56% for survival models, indicating better discrimination for the static models compared with the survival models (i.e., the ability of the model to discriminate between individuals with and without miscarriage). No appreciable differences were observed across strata of miscarriage history or among models restricted to ≥8 weeks of gestation. Our findings suggest that miscarriage is not easily predicted on the basis of preconception lifestyle characteristics and that advancing age and a history of miscarriage are the most important predictors of incident miscarriage. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate socioeconomic determinants of fecundability.Methods: Among 8654 female pregnancy planners from Pregnancy Study Online, a North American prospective cohort study (2013-2019), we examined associations between socioeconomic status and fecundability (the per-cycle probability of conception). Information on income and education was collected via baseline questionnaires. Bimonthly follow-up questionnaires were used to ascertain pregnancy status. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) using proportional probabilities regression, controlling for potential confounders.Results: Relative to an annual household income of greater than or equal to $150,000, adjusted FRs were 0.91 (95% CI: 0.83-1.01) for less than $50,000, 0.99 (95% CI: 0.92-1.07) for $50,000-$99,000, and 1.09 (95% CI: 1.01-1.18) for $100,000-$149,000. FRs for less than 12, 13-15, and 16 years of education, relative to greater than or equal to 17 years, were 0.90 (95% CI: 0.76-1.08), 0.84 (95% CI: 0.78-0.91), and 0.89 (95% CI: 0.84-0.95), respectively. Slightly stronger associations for income and education were seen among older women.Conclusions: Lower levels of education and income were associated with modestly reduced fecundability. These results demonstrate the presence of socioeconomic disparities in fecundability. [ABSTRACT FROM AUTHOR]

Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). We estimated associations between hair product use and EDC biomarker concentrations. We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23–34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women. [Display omitted] • We assessed associations of hair product use and biomarkers of endocrine disrupting chemicals (EDCs). • Hair product use was associated with higher biomarker concentrations of EDCs. • Hair product use may be an important route of exposure to EDCs among Black women. [ABSTRACT FROM AUTHOR]

• We examined dietary exposure to pesticides and fertility in a preconception cohort. • We used a validated exposure metric based on food frequency questionnaire data. • Total fruit and vegetable intake was associated with improved fecundability. • Fecundability did not differ by intake of high- and low-pesticide produce intake. • Women may change their diets in response to trouble conceiving. Intake of conventionally-grown fruits and vegetables with higher levels of pesticide residue contamination has been associated with poorer semen quality and lower probability of live birth among couples undergoing fertility treatment. We examined the association between dietary intake of pesticide residues and fecundability, the per cycle probability of conception, in a preconception cohort of pregnancy planners. We enrolled women aged 21–45 years who were attempting to conceive without use of fertility treatment into Pregnancy Study Online (PRESTO) from June 2013 through September 2019. Participants completed a baseline questionnaire on demographics, lifestyle factors, and medical and reproductive histories, and bimonthly follow-up questionnaires for up to 12 months or until reported conception. Ten days after baseline, participants completed the National Cancer Institute's Diet History Questionnaire II, a validated food frequency questionnaire. Using data from the USDA Pesticide Data Program, we classified fruits and vegetables as having high or low pesticide residues using a validated method. We examined the relation between greater intake of high- and low-pesticide residue fruits and vegetables with fecundability using proportional probabilities regression models, adjusted for potential confounders and accounting for consumption of organic produce. We restricted our analysis to 5234 women who had been attempting conception for ≤6 cycles at study entry, and further stratified by pregnancy attempt time at study entry (<3 vs. 3–6 cycles) to evaluate potential for reverse causation. Intakes of high- and low-pesticide residue fruits and vegetables were not appreciably related to fecundability in the full sample, or among women trying to conceive for <3 cycles at study entry. However, among women trying to conceive for 3–6 cycles at study entry, both high- and low-pesticide residue fruit and vegetable intakes were strongly inversely related to fecundability, indicating potential reverse causation bias. These results do not support the hypothesis that intake of pesticide residues from conventionally-grown fruits and vegetables is harmful to fertility, although non-differential exposure misclassification may have attenuated our findings. [ABSTRACT FROM AUTHOR]

Organochlorine pesticides (OCPs) are lipophilic persistent organic pollutants associated with adverse health outcomes. Black women have higher body burdens compared with other U.S. populations and research on their correlates is limited. Using baseline data from a prospective cohort study of Black women aged 23–35 years from the Detroit, Michigan metropolitan area (enrolled 2010–2012), we examined correlates of plasma concentrations of the following OCPs: dichlorodiphenyltrichloroethane (p,p ʹ-DDE), hexachlorobenzene (HCB), oxychlordane, and trans-nonachlor. At enrollment, we collected non-fasting blood samples from 742 participants. We also collected data on demographic, behavioral, dietary, occupational, and medical history factors via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent (%) differences across categories of each correlate and 95% confidence intervals (CIs). In models adjusted for all other correlates, a 5-year increase in age was associated with 24% higher oxychlordane (95% CI: 12%, 38%) and 26% higher trans-nonachlor (95% CI: 12%, 42%) plasma concentrations. Heavy alcohol use was associated with 7–9% higher plasma concentrations of p,p ʹ-DDE, oxychlordane, and trans-nonachlor. Current smoking was associated with 10–19% higher plasma concentrations of all four OCPs, and was highest for current smokers of ≥10 cigarettes/day (% differences ranged from 22 to 29%). Compared with having never been breastfed during infancy, having been breastfed for ≥3 months was associated with 15% higher concentrations of p,p ʹ-DDE (95% CI: 6%, 25%), 14% higher oxychlordane (95% CI: 5%, 24%), and 15% higher trans-nonachlor (95% CI: 5%, 27%). Consumption of ≥5 vs. ≤2 glasses/day of tap or bottled water was associated with 8–15% higher plasma concentrations of all four OCPs, and was highest for trans-nonachlor (% difference: 15%; 95% CI: 6%, 26%). No other dietary predictors were appreciably associated with plasma OCP concentrations. Obesity, parity, higher birth order, and longer lactation duration were inversely associated with plasma OCP concentrations. In Black U.S. women of reproductive age, older age was an important correlate of plasma OCP concentrations. Exposure to OCPs earlier in life appears to contribute to current blood concentrations. In addition, tobacco, alcohol, and drinking water may be important sources of exposure. • Older age was associated with higher plasma pesticide concentrations. • Tobacco, alcohol and water may be important sources of pesticides. • Diet was not associated with plasma pesticide concentrations. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs) are brominated flame retardant chemicals detectable in the environment and U.S. population, and are associated with adverse health outcomes over the life course. Correlates of these organic pollutants are understudied among U.S. Black women. Using baseline data from a prospective cohort study of U.S. Black women aged 23–35 years from the Detroit area of Michigan (2010−2012), we examined correlates of PBDEs and PBB-153. Non-fasting blood samples were collected from 742 participants at enrollment, a subset of women selected for a case-cohort study of environmental chemicals. Data on socio-demographics, behaviors, diet, medical history, and early-life exposures were collected via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent differences and 95% confidence intervals in lipid adjusted plasma concentrations of 11 individual PBDE congeners and PBB-153 for each baseline predictor. In models adjusted for all other correlates, a 5-year increase in age was inversely associated with most PBDE congeners (% differences ranged from 6 to 15% lower), and was positively associated with PBB-153 (52% higher). A 5-kg/m2 increase in BMI was inversely associated with PBDE-153 and PBB-153 (16% lower for both), and 6% higher for PBDE-28. Compared with having never been breastfed in infancy, ≥3 months of breastfeeding in infancy was associated with 69% higher PBB-153 concentrations. Lower education, current smoking, and heavy alcohol use were associated with higher plasma concentrations of most flame retardants. Diet was not an important predictor. Important correlates for elevated body burdens of PBB-153 were increasing age and a history of having been breastfed in infancy. Education, smoking, and heavy alcohol use were important predictors of elevated body burdens of most flame retardants. This study fills an important gap in the environmental health literature by focusing on an understudied population. Unlabelled Image • Brominated flame retardants are endocrine disrupting chemicals detectable in humans. • Increasing age was associated with decreases in PBDEs and increases in PBB-153. • Increasing BMI was associated with decreases in PBDE-153 and PBB-153. • Some social determinants of health were associated with higher PBDEs. • A history of breastfeeding in infancy was strongly associated with elevated PBB-153. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions On June 24th, 2022, the United States (US) Supreme Court's ruling in Dobbs v. Jackson, et al. (hereafter, the Dobbs decision) removed federal‐level protections for induced abortion, sparking concerns about reproductive rights and health privacy. Although other pregnancy outcomes (e.g. spontaneous abortion, ectopic pregnancy) are not explicit targets of post‐Dobbs abortion bans, study participants may be worried about how their reproductive health data are used by researchers in the post‐Dobbs era.To evaluate the extent to which the Dobbs decision influenced participant's engagement in a preconception cohort study.We leveraged data spanning 20 weeks before and after the Dobbs decision (4 February 2022, to 11 November 2022) from US participants in Pregnancy Study Online (PRESTO), an internet‐based prospective preconception cohort study of couples attempting conception. We categorised participants' state‐level abortion access by residential location: banned or restricted rights; limited access; and protected rights. We evaluated three participant engagement outcomes: follow‐up questionnaire completion; report of a pregnancy; and clicking on the invitation link for a fertility‐tracking app. We fit separate linear regression models and restricted cubic splines to compare outcome prevalence before and after the Dobbs decision by state‐level abortion category.A total of 585 newly enrolled participants and 1247 already‐enrolled participants received 2802 invitations to complete a follow‐up questionnaire. In states with limited or protected abortion rights, we observed little change in participant engagement. In states with banned or restricted abortion rights, however, we observed a 27.12 percentage point reduction (95% confidence interval −43.68, −10.51) in the prevalence of clicking on the invitation link for the fertility‐tracking app comparing the post‐ versus pre‐Dobbs periods.There was some evidence of reduced participant engagement after the Dobbs decision in states with banned or restricted abortion rights, indicating potentially deleterious effects on the conduct of reproductive health studies. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Dietary factors, including high sugar intake, may have adverse effects on male reproduction. Studies of the association between sugar‐sweetened beverage (SSB) intake and semen quality have reported inconsistent results.We estimated the effects of SSB consumption on semen quality in a North American preconception cohort study.We analyzed baseline data from 690 males (n = 1,247 samples) participating in Pregnancy Study Online (PRESTO) during 2015–2022. Participants aged ≥21 years completed a baseline questionnaire on which they reported information about intake of SSBs, including sodas, energy drinks, sports drinks, and fruit juices. After enrollment, we invited U.S. participants to a semen testing substudy, in which they collected and analyzed two samples using an at‐home semen testing kit. We used linear regression models to estimate adjusted percent differences (%D) and 95% confidence intervals (CI) for associations of SSB intake with semen volume, sperm concentration, total sperm count (TSC), motility, and total motile sperm count (TMSC). We used modified Poisson regression models to estimate adjusted risk ratios (RRs) and 95% CIs for the association of SSB intake with World Health Organization semen parameter cut points.Relative to non‐consumers of SSBs, those who consumed ≥7 SSBs/week had lower semen volume (%D = −6, 95% CI: −13, 0), sperm concentration (%D = −22, 95% CI: −38, 0), TSC (%D = −22, 95% CI: −38, −2), motility (%D = −4, 95% CI: −10, 2), and TMSC (%D = −25, 95% CI: −43, −2). High SSB consumers also had greater risks of low sperm concentration (≤16 million/mL; RR = 1.89, 95% CI: 1.11, 3.21), low TSC (≤39 million; RR = 1.75, 95% CI: 0.92, 3.33), low motility (≤42%; RR = 1.23, 95% CI: 0.87, 1.75) and low TMSC (≤21 million; RR = 1.95, 95% CI: 1.12, 3.38). Associations were stronger among participants with body mass index ≥ 25 kg/m2.Greater SSB consumption was associated with reduced semen quality in a North American preconception cohort. [ABSTRACT FROM AUTHOR]

Background: The accuracy of birth outcome data provided by Internet‐based cohort study participants has not been well studied. Methods: We compared self‐reported data on birth characteristics in Pregnancy Study Online (PRESTO), an Internet‐based prospective cohort study of North American pregnancy planners, with birth certificate data. At enrolment, participants were aged 21‐45 years, attempting conception, and not using fertility treatment. Women completed online questionnaires during preconception, early and late pregnancy, and postpartum. We requested birth certificate data during 2014‐2019 from seven health departments in states with the most participants. After restricting to singleton births, we assessed specificity, sensitivity, and agreement comparing self‐reported data from postpartum questionnaires with birth certificate data for gestational age at delivery (GA) and birthweight (grams). Our primary measure of self‐reported GA (weeks) was calculated as [280‐(due date‐birth date)]/7. We used log‐binomial regression to assess predictors of agreement. Results: We linked 85% (771/909) of women in selected states. Median age of women was 30 years (range: 21‐42), 84% had ≥ 16 years of education, nearly 96% were married, 12% had household incomes <$50 000, 32% were parous, and 85% identified as non‐Hispanic White. Median recall interval was 6 months. Among those with self‐reported data, 89% reported the same GA as the birth certificate and 98% reported GA within 1 week of the birth certificate. Self‐report of preterm birth (GA < 37 weeks) agreed with information from birth certificates for 100% of women; sensitivity was 100%, and specificity was 99%. Self‐reported low birthweight (<2500 grams) agreed with birth certificates for 93% of women; sensitivity and specificity were 93% and ≥99%, respectively. Predictors of poorer agreement included higher parity and longer pregnancy attempt time for GA, and lower education and longer recall interval for birthweight. Conclusion: Self‐reported data on GA and birthweight from an Internet‐based cohort showed high accuracy compared with birth certificates. [ABSTRACT FROM AUTHOR]

Isoflavones are phytoestrogens found in plant-based foods and nutritional supplements. Experimental studies show a positive association between isoflavones and hypothyroidism, but epidemiological findings are conflicting. We used multivariable linear regression to examine the association between urinary isoflavone concentrations and serum thyroid hormone concentrations in the National Health and Nutrition Examination Survey (2007–2010). In this study, we found that Daidzein and O-DMA associations with free T4 were stronger among women: a 10-fold increase in daidzein was associated with a 3.2% (95% CI: 1.9%, 4.5%) increase in women and a 0.6% (95% CI: −1.7%, 0.6%) decrease in men and a 10-fold increase in O-DMA was related to a 2.0% (95% CI: 1.1%, 2.9%) increase in women and a 0.3% (95% CI: −1.2%, 0.5%) decrease in men. In this study, selected urinary isoflavone concentrations were associated with serum thyroid hormone concentration in a sex-dependent fashion. [ABSTRACT FROM AUTHOR]

Background: Little is known about the influence of the post-partum interval-defined as the time between giving birth and attempting to conceive again-on subsequent fecundability.Objectives: We evaluated the association between the post-partum interval and fecundability in Pregnancy Study Online (PRESTO), a web-based prospective preconception cohort of pregnancy planners from the United States and Canada.Methods: Eligible women were aged 21-45 years, attempting pregnancy, and not using fertility treatment. Women completed a baseline questionnaire to ascertain information on demographics, life style factors, and reproductive history, including detailed information on all previous pregnancies. They completed bi-monthly follow-up questionnaires for up to 12 months to update pregnancy status over time. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) adjusted for sociodemographic and reproductive history covariates. Analyses were restricted to multiparous women who had been attempting pregnancy with the same male partner for ≤6 menstrual cycles at enrolment.Results: During 2013-2019, 1489 female participants contributed 959 pregnancies and 5003 cycles. The median post-partum interval was 18 months. Compared with a 12- to 23-month post-partum interval, FRs for post-partum intervals of <12, 24-47, and ≥48 months were 0.89 (95% CI 0.77, 1.04), 1.06 (95% CI 0.91, 1.23), and 0.81 (95% CI 0.62, 1.05), respectively. When restricting to women without a history of subfertility, results were consistent for long post-partum interval and attenuated for short post-partum interval.Conclusions: Among North American pregnancy planners, long post-partum intervals (≥48 months) were associated with slightly reduced fecundability. Short post-partum intervals (<12 months) were weakly associated with reduced fecundability in some subgroups including women with a history of caesarean delivery and planned pregnancies. [ABSTRACT FROM AUTHOR]

Background: Infertility is an important public health problem with few known modifiable risk factors. Dietary factors including folic acid have been associated with improved fertility, but the association between iron and fertility is understudied. One study among US nurses found a 40% lower risk of ovulatory infertility with higher intake of nonheme iron and iron supplements.Objectives: The aim of this study was to determine the extent to which iron intake from diet and supplements reported on structured questionnaires is associated with fecundability.Methods: We conducted parallel analyses that used data from 2 prospective cohort studies of pregnancy planners from Denmark (Snart Foraeldre; n = 1693) and North America (PRESTO; n = 2969) during 2013-2018. Follow-up comprised menstrual cycles at risk until pregnancy or censoring for fertility treatment, stopped trying to conceive, withdrawal, loss to follow-up, or 12 cycles of attempt. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for confounders.Results: We found little association between dietary heme iron intake and fecundability in either cohort. The FR for nonheme iron intake (≥11 mg/d compared with <9 mg/day) was 1.11 for Snart Foraeldre participants (95% CI: 0.92, 1.34) and 1.01 for PRESTO participants (95% CI: 0.89, 1.14). The FR for iron-containing supplements was 1.01 in Snart Foraeldre (95% CI: 0.90, 1.13) and 1.19 in PRESTO (95% CI: 1.03, 1.38). In PRESTO, but not Snart Foraeldre, stronger positive associations were found for nonheme iron intake and iron supplement use among women with heavy menses or short menstrual cycles.Conclusions: Overall, dietary intake of iron was not consistently associated with fecundability, although there was some evidence for a positive association among women with risk factors for iron deficiency. We also found a small positive association between supplemental iron intake and fecundability among North American, but not Danish, pregnancy planners. [ABSTRACT FROM AUTHOR]

Although electronic cigarette (e-cigarette) aerosol contains similar toxicants to combustible cigarettes, few studies have examined their influence on fecundability. We assessed the association between e-cigarette use and fecundability, overall and according to combustible cigarette smoking history, in a cohort of 4,586 North American women (aged 21–45 years) enrolled during 2017–2020 in Pregnancy Study Online, a Web-based prospective preconception study. Women reported current and former e-cigarette use on baseline and follow-up questionnaires, and they completed bimonthly follow-up questionnaires until self-reported pregnancy or censoring. Fecundability ratios and 95% confidence intervals were calculated using proportional probabilities models, controlling for potential confounders. Overall, 17% of women had ever used e-cigarettes and 4% were current users. Compared with never use of e-cigarettes, current e-cigarette use was associated with slightly lower fecundability (fecundability ratio = 0.84, 95% confidence interval (CI): 0.67, 1.06). Compared with current nonusers of e-cigarettes and combustible cigarettes, fecundability ratios were 0.83 (95% CI: 0.54, 1.29) for current dual users of e-cigarettes and combustible cigarettes, 0.91 (95% CI: 0.70, 1.18) for current e-cigarette users who were nonsmokers of combustible cigarettes, and 1.01 (95% CI: 0.85, 1.20) for nonusers of e-cigarettes who were current smokers of combustible cigarettes. Current e-cigarette use was associated with slightly reduced fecundability, but estimates of its independent and joint associations with combustible cigarette smoking were inconsistent and imprecise. [ABSTRACT FROM AUTHOR]

Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced ω-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010–2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and trans -fat were not appreciably associated with UL incidence. Intake of the marine ω-3 polyunsaturated fatty acid, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: hazard ratio = 1.49, 95% confidence interval: 1.04, 2.14; P for trend = 0.01). Intakes of total marine ω-3 polyunsaturated fatty acids were similarly associated with elevated UL incidence (hazard ratio = 1.35, 95% confidence interval: 0.94, 1.93; P for trend = 0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association. [ABSTRACT FROM AUTHOR]

The deficiencies of binary statistical significance testing as a framework for presenting and interpreting research findings have been well recognized. However, some journal editors and reviewers still insist that authors use this framework. This commentary discusses approaches that authors can use to resist such editorial requests. [ABSTRACT FROM AUTHOR]