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The article discusses the results of a study on the effects of per- and polyfluoroalkyl substances (PFAS) on the reproductive health of women. Topics mentioned include the relation of PFAS and anti-mullerian hormone (AMH) as a biomarker of ovarian reserve among noncontraceptive women, the use of AMH in predicting the timing of menopause and menstrual cycle, and the routes of exposure to PFAS.

Chemical hair straighteners ("relaxers") are used by millions of North Americans, particularly women of color. Hair relaxers may contain endocrine-disrupting compounds, which can harm fertility. We evaluated the association between hair relaxer use and fecundability among 11,274 participants from Pregnancy Study Online (PRESTO), a North American preconception cohort study. During 2014–2022, participants completed a baseline questionnaire in which they reported their history of relaxer use and completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, whichever came first. We used multivariable-adjusted proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Relative to never use, fecundability was lower among current (FR = 0.81, 95% CI: 0.64, 1.03) and former (FR = 0.89, 95% CI: 0.81, 0.98) users of hair relaxers. FRs for first use of hair relaxers at ages <10, 10–19, and ≥20 years were 0.73 (95% CI: 0.55, 0.96), 0.93 (95% CI: 0.83, 1.04), and 0.85 (95% CI: 0.74, 0.98), respectively. Fecundability was lowest among those with longer durations of use (≥10 years vs. never: FR = 0.71, 95% CI: 0.54, 0.91) and more frequent use (≥5 times/year vs. never: FR = 0.82, 95% CI: 0.60, 1.11), but associations were nonmonotonic. In this preconception cohort study, use of chemical hair straighteners was associated with slightly reduced fecundability. [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 Diet is increasingly recognized as an important determinant of human fertility, with most research focused on specific nutrients or food groups. However, there has been limited assessment of the effect of dietary patterns on fertility. Objectives We evaluated the association between 4 dietary patterns [the alternative Mediterranean Diet (aMed), the Healthy Eating Index-2010 (HEI-2010), the Danish Dietary Guidelines (DDGI), and the Dietary Inflammatory Index (DII)] and fecundability in 2 preconception cohorts of couples trying to conceive: SF (SnartForaeldre.dk) in Denmark and PRESTO (Pregnancy Study Online) in North America. Methods Participants completed a baseline questionnaire on sociodemographic, anthropometric, and lifestyle factors and, 10 d later, a validated cohort-specific FFQ. We used data from these respective FFQs to calculate adherence to each dietary pattern. Participants completed bimonthly follow-up questionnaires for ≤12 mo or until pregnancy, whichever came first. We restricted analyses to 3429 SF and 5803 PRESTO participants attempting pregnancy for ≤6 cycles at enrollment. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusting for potential confounders. Results Greater DII, indicative of a less anti-inflammatory diet (i.e. poorer diet quality), was associated with reduced fecundability in both SF and PRESTO (DII ≥ −1.5 compared with < −3.3: FR: 0.83; 95% CI: 0.71, 0.97 and FR: 0.82; 95% CI: 0.73, 0.93, respectively). In PRESTO, greater adherence to the aMed or to the HEI-2010 was associated with greater fecundability. In SF, there was no appreciable association between the aMed and fecundability, whereas greater adherence to the DDGI was associated with greater fecundability. Conclusions In prospective preconception cohort studies from Denmark and North America, higher-quality diets, including diets lower in inflammatory effects, were associated with greater fecundability. [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]

Study Question: To what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception?Summary Answer: Preconception dietary folate intake was positively associated with fecundability in a monotonic pattern.What Is Known Already: Supplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability.Study Design, Size, Duration: A prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020.Participants/materials, Setting, Methods: We used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders.Main Results and the Role Of Chance: Compared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16).Limitations, Reasons For Caution: It is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet.Wider Implications Of the Findings: Recommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability.Study Funding/competing Interest(s): The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Can we derive adequate models to predict the probability of conception among couples actively trying to conceive?Summary Answer: Leveraging data collected from female participants in a North American preconception cohort study, we developed models to predict pregnancy with performance of ∼70% in the area under the receiver operating characteristic curve (AUC).What Is Known Already: Earlier work has focused primarily on identifying individual risk factors for infertility. Several predictive models have been developed in subfertile populations, with relatively low discrimination (AUC: 59-64%).Study Design, Size, Duration: Study participants were female, aged 21-45 years, residents of the USA or Canada, not using fertility treatment, and actively trying to conceive at enrollment (2013-2019). Participants completed a baseline questionnaire at enrollment and follow-up questionnaires every 2 months for up to 12 months or until conception. We used data from 4133 participants with no more than one menstrual cycle of pregnancy attempt at study entry.Participants/materials, Setting, Methods: On the baseline questionnaire, participants reported data on sociodemographic factors, lifestyle and behavioral factors, diet quality, medical history and selected male partner characteristics. A total of 163 predictors were considered in this study. We implemented regularized logistic regression, support vector machines, neural networks and gradient boosted decision trees to derive models predicting the probability of pregnancy: (i) within fewer than 12 menstrual cycles of pregnancy attempt time (Model I), and (ii) within 6 menstrual cycles of pregnancy attempt time (Model II). Cox models were used to predict the probability of pregnancy within each menstrual cycle for up to 12 cycles of follow-up (Model III). We assessed model performance using the AUC and the weighted-F1 score for Models I and II, and the concordance index for Model III.Main Results and the Role Of Chance: Model I and II AUCs were 70% and 66%, respectively, in parsimonious models, and the concordance index for Model III was 63%. The predictors that were positively associated with pregnancy in all models were: having previously breastfed an infant and using multivitamins or folic acid supplements. The predictors that were inversely associated with pregnancy in all models were: female age, female BMI and history of infertility. Among nulligravid women with no history of infertility, the most important predictors were: female age, female BMI, male BMI, use of a fertility app, attempt time at study entry and perceived stress.Limitations, Reasons For Caution: Reliance on self-reported predictor data could have introduced misclassification, which would likely be non-differential with respect to the pregnancy outcome given the prospective design. In addition, we cannot be certain that all relevant predictor variables were considered. Finally, though we validated the models using split-sample replication techniques, we did not conduct an external validation study.Wider Implications Of the Findings: Given a wide range of predictor data, machine learning algorithms can be leveraged to analyze epidemiologic data and predict the probability of conception with discrimination that exceeds earlier work.Study Funding/competing Interest(s): The research was partially supported by the U.S. National Science Foundation (under grants DMS-1664644, CNS-1645681 and IIS-1914792) and the National Institutes for Health (under grants R01 GM135930 and UL54 TR004130). In the last 3 years, L.A.W. has received in-kind donations for primary data collection in PRESTO from FertilityFriend.com, Kindara.com, Sandstone Diagnostics and Swiss Precision Diagnostics. L.A.W. also serves as a fibroid consultant to AbbVie, Inc. The other authors declare no competing interests.Trial Registration Number: N/A. [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]

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]

We conducted a parallel, nonblinded randomized trial to assess whether offering home pregnancy tests (HPTs) to preconception cohort study participants influenced cohort retention or pregnancy detection. Pregnancy Study Online participants were female, aged 21–45 years, attempting pregnancy, and not using fertility treatment. At enrollment (2017–2018), 1,493 participants with 6 or fewer cycles of attempt time were randomly assigned with 50% probability to receive 12 Clearblue visual HPTs plus the standard protocol (n  = 720) or the standard protocol alone (n  = 773). Women completed bimonthly questionnaires for 12 months or until conception, whichever came first. In intent-to-treat analyses, retention (≥1 follow-up) was higher in the HPT arm (n  = 598; 83%) than the standard protocol arm (n  = 535 (69%); mean difference = 15%, 95% CI: 10, 19). Mean time at first pregnancy testing was identical in both arms (2 days before expected menses), as was mean gestational weeks at first positive pregnancy test (4 weeks). Conception was reported by 78% of women in the HPT arm and 75% in the standard protocol arm. Spontaneous abortion was reported by 21% in the HPT arm (mean gestational weeks = 7) and 21% in the standard protocol arm (mean gestational weeks = 6). Randomization of HPTs was associated with greater cohort retention but had little impact on incidence or timing of pregnancy detection. [ABSTRACT FROM AUTHOR]

Background Glycemic load (GL) reflects the quantity and quality of carbohydrates in the diet; dietary fiber and added sugar are components of GL. Few epidemiologic studies have assessed the association between these dietary factors and fecundability. Objective We prospectively evaluated the associations of GL, total carbohydrates, dietary fiber, and added sugar with fecundability. Methods Snart Foraeldre (SF) and Pregnancy Study Online (PRESTO) are parallel web-based prospective preconception cohorts of couples attempting to conceive in Denmark and North America. At baseline, female participants completed a web-based questionnaire on demographic and lifestyle factors and a validated FFQ. We calculated GL, total carbohydrate intake, total dietary fiber, carbohydrate-to-fiber ratio, and added sugar based on reported frequencies for individual foods, standard recipes for mixed foods, and average serving sizes. The analysis included 2709 SF participants and 4268 PRESTO participants. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% CIs. Results Compared with an average daily GL of ≤100, FRs for an average daily GL of ≥141 were 0.89 (95% CI: 0.73, 1.08) in SF and 0.87 (95% CI: 0.77, 0.98) in PRESTO participants. Compared with consuming ≤16 g/d of dietary fiber, FRs for consuming ≥25 g/d were 0.99 (95% CI: 0.81, 1.22) in SF and 1.06 (95% CI: 0.94, 1.20) in PRESTO. Compared with a carbohydrate-to-fiber ratio of ≤8, FRs for a ratio of ≥13 were 0.86 (95% CI: 0.73, 1.01) in SF and 0.87 (95% CI: 0.78, 0.98) in PRESTO. Compared with ≤27 g/d of added sugar, FRs for ≥72 g/d were 0.87 (95% CI: 0.68, 1.10) in SF and 0.86 (95% CI: 0.75, 0.99) in PRESTO participants. Conclusions Among women attempting to conceive in Denmark and North America, diets high in GL, carbohydrate-to-fiber ratio, and added sugar were associated with modestly reduced fecundability. [ABSTRACT FROM AUTHOR]

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]

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]

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]

Study Question: To what extent is preconception use of pain-relieving medication associated with female fecundability?Summary Answer: Women who used naproxen or opioids had slightly lower fecundability than women who did not use any pain-relieving medications; use of acetaminophen, aspirin and ibuprofen was not appreciably associated with fecundability.What Is Known Already: Over-the-counter pain-relieving medications are commonly used by women of reproductive age in the USA. Studies investigating the effects of pain-relieving medication use on ovulation, implantation and fecundability have shown conflicting results.Study Design, Size, Duration: We analyzed data from an internet-based prospective cohort study of 2573 female pregnancy planners aged 21-45 years from the USA and Canada. Participants were enrolled and followed from June 2013 through September 2015. Participants completed a baseline questionnaire and bimonthly follow-up questionnaires until a reported pregnancy or for 12 months, whichever occurred first. Over 80% of participants completed at least one follow-up questionnaire.Participants/materials, Setting, Methods: Use of pain-relieving medication during the past month was assessed at baseline and on each follow-up questionnaire. Medications were categorized according to type (acetaminophen, aspirin, ibuprofen, naproxen and opioids) and total monthly dose. Self-reported pregnancy was assessed at each follow-up. Multivariable-adjusted fecundability ratios (FRs) and 95% CI were calculated using proportional probabilities regression. Models were adjusted for demographic, lifestyle and anthropometric factors; reproductive history; gynecologic morbidity; and indications for use of pain medications. Models were also run with and without adjustment for parity. After restricting to women with 6 or fewer months of attempt time at study entry, 1763 were included in the analyses.Main Results and the Role Of Chance: At baseline, 1279 (73%) women reported using ≥1 pain-relieving medications in the previous month. When compared with non-use of pain-relieving medications, FRs for use of naproxen and opioids at baseline were 0.78 (95% CI: 0.64-0.97) and 0.81 (95% CI: 0.60-1.10), respectively. A dose-response relation was observed between naproxen use and fecundability; FRs for use of <1500 and ≥1500 mg of naproxen were 0.85 (95% CI: 0.68-1.07) and 0.58 (95% CI: 0.36-0.94), respectively. Small numbers (n = 74) precluded the examination of opioid use by dose. Overall, there was little evidence of an association between fecundability and acetaminophen (FR 1.04, 95% CI: 0.92-1.18), aspirin (FR 1.00, 95% CI: 0.80-1.25), or ibuprofen (FR 1.00, 95% CI: 0.89-1.11). Similar results were observed when exposure information was updated over time.Limitations, Reasons For Caution: Numbers of opioid users were small. Information collected on reason for use of pain medications was not specific to each type of pain medication. Therefore, we cannot rule out confounding by indication as an explanation of these results.Wider Implications Of the Findings: Use of naproxen and opioids was associated with a small reduction in fecundability, but there was little association between other pain-relieving medications and fecundability.Study Funding/competing Interests: This study was supported through funds provided by National Institute of Child Health and Human Development, National Institute of Health (R21 HD072326, T32 HD052458). The authors have no conflicts of interest to disclose.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Animal studies have shown that a high intake of galactose, a breakdown product of lactose, increases ovarian toxicity. Few epidemiologic studies, to our knowledge, have examined the association between dairy intake and fertility, and they have had conflicting findings. Objective: We prospectively evaluated dairy intake in relation to fecundability among women who were planning for pregnancy. Design: Data were derived from preconception cohort studies in Denmark (Snart Foraeldre) and North America [PRESTO (Pregnancy Study Online)] in which women completed a validated food-frequency questionnaire 10 d after enrollment. The dietary intake of dairy foods and their constituents was calculated based on reported frequencies, mean serving sizes, and standard recipes for mixed foods. Outcome data were updated every 8 wk for 12 mo or until reported conception. Analyses were restricted to 2426 women attempting pregnancy for =6 cycles at study entry. Fecundability ratios (FRs) and 95% CIs were estimated with the use of proportional probabilities regression models adjusted for potential confounders. Results: FRs for total dairy intake (=18 compared with <7 servings/wk) were 1.37 (95% CI: 1.05, 1.78) among 1126 Snart Foraeldre participants and 1.04 (95% CI: 0.78, 1.38) among 1300 PRESTO participants (pooled FR: 1.11; 95% CI: 0.94, 1.31). The elevated FR for total dairy intake among Snart Foraeldre participants was limited to milk consumption and found only among women aged <30 y. There was no clear association between low- or high-fat dairy intake and fecundability in either cohort. Although there was little evidence of an association between dietary intake of calcium, potassium, magnesium, or vitamin D and fecundability, a greater consumption of phosphorus and lactose was associated with slightly higher fecundability in both cohorts. Conclusions: Associations between dairy intake and fecundability were generally small and inconsistent across cohorts. Our findings do not support the hypotheses that a greater consumption of high-fat dairy improves fertility or that a greater consumption of lactose or low-fat dairy harms fertility. [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]

• Phthalates widely detected among a cohort of reproductive-aged Black women. • Biomarkers generally showed weak-to-moderate inverse associations with UL incidence. • Inverse associations stronger among women with BMI ≥ 30 kg/m2 for specific phthalates. • Little evidence of effect of the phthalate biomarkers mixture on UL incidence. Numerous studies suggest that some phthalates have adverse reproductive effects. However, literature on the association between phthalates and incidence of uterine leiomyomata (UL) is limited and inconsistent, with no existing prospective studies. We examined the association of urinary concentrations of phthalate and phthalate alternative biomarkers with UL incidence. We conducted a case-cohort analysis within a subgroup of 754 participants in the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort of premenopausal Black women aged 23–35 years who were recruited during 2010–2012. We quantified fourteen phthalates and two phthalate alternative [1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH)] biomarkers in urine collected at baseline, 20 months, and 40 months. Transvaginal ultrasounds identified UL at baseline and every 20 months during 60 months of follow-up. We evaluated the individual biomarkers, molar sum of di(2-ethylhexyl) phthalate [ΣDEHP] and potency-weighted sum of anti-androgenic [WΣAA] biomarkers. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between biomarkers and UL incidence. We then used quantile g-computation to examine joint associations of multiple phthalate biomarkers with UL incidence. Most individual biomarkers showed weak-to-moderate inverse associations with UL incidence. HRs comparing highest vs. lowest quartiles of mono-isobutyl phthalate (MiBP) and mono-hydroxyisobutyl phthalate (MHiBP) concentrations were 0.63 (95% CI: 0.40, 1.01) and 0.61 (95% CI: 0.38, 0.96), respectively. Inverse associations for specific phthalates were stronger among women with BMI ≥ 30 kg/m2. HRs comparing detectable vs. nondetectable concentrations of DINCH biomarkers were 0.92 (95% CI: 0.62, 1.35) for cyclohexane-1,2-dicarboxylic acid mono hydroxyisononyl ester (MHNCH) and 0.68 (95% CI: 0.38, 1.18) for cyclohexane-1,2-dicarboxylic acid mono carboxyisoocytl ester (MCOCH). For the DEHP metabolite of mono(2-ethylhexyl) phthalate (MEHP), we observed weak-to-moderate positive associations. HRs comparing highest vs. lowest quartiles for MEHP and ΣDEHP were 1.29 (95% CI: 0.82, 2.06) and 0.96 (95% CI: 0.61, 1.50), respectively. In the mixtures analysis, the HR for a joint quartile increase in phthalate biomarker concentrations was 0.90 (95% CI: 0.73, 1.08). In this prospective ultrasound study of reproductive-aged Black women, urinary concentrations of phthalate and DINCH biomarkers were not appreciably associated with higher risk of UL, either individually or jointly. [ABSTRACT FROM AUTHOR]