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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: 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]

[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]

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]

• 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]

Background: There is a well-documented decline in fertility treatment success with increasing female age; however, there are few preconception cohort studies that have examined female age and natural fertility. In addition, data on male age and fertility are inconsistent. Given the increasing number of couples who are attempting conception at older ages, a more detailed characterization of age-related fecundability in the general population is of great clinical utility.Objective: The purpose of this study was to examine the association between female and male age with fecundability.Study Design: We conducted a web-based preconception cohort study of pregnancy planners from the United States and Canada. Participants were enrolled between June 2013 and July 2017. Eligible participants were 21-45 years old (female) or ≥21 years old (male) and had not been using fertility treatments. Couples were followed until pregnancy or for up to 12 menstrual cycles. We analyzed data from 2962 couples who had been trying to conceive for ≤3 cycles at study entry and reported no history of infertility. We used life-table methods to estimate the unadjusted cumulative pregnancy proportion at 6 and 12 cycles by female and male age. We used proportional probabilities regression models to estimate fecundability ratios, the per-cycle probability of conception for each age category relative to the referent (21-24 years old), and 95% confidence intervals.Results: Among female patients, the unadjusted cumulative pregnancy proportion at 6 cycles of attempt time ranged from 62.0% (age 28-30 years) to 27.6% (age 40-45 years); the cumulative pregnancy proportion at 12 cycles of attempt time ranged from 79.3% (age 25-27 years old) to 55.5% (age 40-45 years old). Similar patterns were observed among male patients, although differences between age groups were smaller. After adjusting for potential confounders, we observed a nearly monotonic decline in fecundability with increasing female age, with the exception of 28-33 years, at which point fecundability was relatively stable. Fecundability ratios were 0.91 (95% confidence interval, 0.74-1.11) for ages 25-27, 0.88 (95% confidence interval, 0.72-1.08) for ages 28-30, 0.87 (95% confidence interval, 0.70-1.08) for ages 31-33, 0.82 (95% confidence interval, 0.64-1.05) for ages 34-36, 0.60 (95% confidence interval, 0.44-0.81) for ages 37-39, and 0.40 (95% confidence interval, 0.22-0.73) for ages 40-45, compared with the reference group (age, 21-24 years). The association was stronger among nulligravid women. Male age was not associated appreciably with fecundability after adjustment for female age, although the number of men >45 years old was small (n=37).Conclusion: In this preconception cohort study of North American pregnancy planners, increasing female age was associated with an approximately linear decline in fecundability. Although we found little association between male age and fecundability, the small number of men in our study >45 years old limited our ability to draw conclusions on fecundability in older men. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively examine the association between time-to-pregnancy (TTP) and postpartum depression (PPD) and determine whether perceived stress during early pregnancy mediated this association.Methods: In Pregnancy Study Online, an internet-based preconception cohort study of pregnancy planners, participants completed questionnaires every 8 weeks for up to 12 months or conception, during pregnancy, and at postpartum. A total of 2643 women provided information on sociodemographic factors, reproductive history, and stress (i.e., Perceived Stress Scale [PSS]) during preconception and early pregnancy (completed at ∼4-12 weeks' gestation) and on postpartum depressive symptoms (i.e., Edinburgh Postnatal Depression Scale [EPDS]) at ∼6 months postpartum. We used multivariable modified Poisson regression models to estimate risk ratios and 95% confidence intervals (CIs) for the association between TTP (<3, 3-5, 6-11, ≥12 menstrual cycles) and PPD (EPDS score ≥13). Causal mediation analyses assessed the mediating role of early pregnancy PSS scores.Results: 10.6% of women had EPDS scores indicating possible PPD (≥13). Compared with women who took less than 3 cycles to conceive, risk ratios for those who took 3-5, 6-11, and greater than or equal to 12 were 1.06 (95% CI: 0.77, 1.45), 1.24 (95% CI: 0.90, 1.70), and 1.31 (95% CI: 0.87, 1.99), respectively. Approximately 30% of the association between infertility (TTP ≥ 12) and PPD was mediated by early pregnancy PSS.Conclusions: There was a modest positive dose-response association between delayed conception and PPD. Perceived stress in early pregnancy explained a small proportion of this association. However, given the width of the CIs, chance cannot be ruled out as an explanation for the observed association. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between adiposity, physical activity (PA), and fecundability.Design: Prospective cohort study.Setting: Not applicable.Patient(s): A total of 2,062 female pregnancy planners from the United States and Canada who were enrolled during the preconception period.Intervention(s): None.Main Outcome Measure(s): Self-reported pregnancy. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were estimated using proportional probabilities models that adjusted for potential confounders.Result(s): Relative to body mass index (BMI) 18.5-24 kg/m(2), FRs for BMI <18.5, 25-29, 30-34, 35-39, 40-44, and ≥45 kg/m(2) were 1.05 (95% CI 0.76-1.46), 1.01 (95% CI 0.89-1.15), 0.98 (95% CI 0.82-1.18), 0.78 (95% CI 0.60-1.02), 0.61 (95% CI 0.42-0.88), and 0.42 (95% CI 0.23-0.76), respectively. Reduced fecundability was observed among women with the largest waist-to-hip ratios (≥0.85 vs. <0.75; FR = 0.87, 95% CI 0.74-1.01) and waist circumferences (≥36 vs. <26 inches [≥90 vs. <66 cm]; FR = 0.80, 95% CI 0.59-1.01). Tendency to gain weight in the chest/shoulders (FR = 0.63, 95% CI 0.36-1.08) and waist/stomach (FR = 0.90, 95% CI 0.79-1.02), relative to hips/thighs, was associated with lower fecundability. Moderate PA was associated with increased fecundability (≥5 vs. <1 h/wk; FR = 1.26, 95% CI 0.96-1.65), but there was no dose-response relation. Among overweight/obese women (BMI ≥25 kg/m(2)), fecundability was 27% higher for vigorous PA of ≥5 versus <1 h/wk (95% CI 1.02-1.57).Conclusion(s): Various measures of overall and central adiposity were associated with decreased fertility among pregnancy planners. Vigorous PA was associated with improved fertility among overweight and obese women only; moderate PA was associated with improved fertility among all women. [ABSTRACT FROM AUTHOR]