Background We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an internet-based preconception cohort study in the U.S. and Canada. Methods We recruited female participants age 21–45 and their male partners through internet advertisements, word of mouth, and flyers. Female participants were randomized with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based program that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively-reported date of last menstrual period (LMP) against FF data. Results After 99 weeks of recruitment (2013–2015), 2,421 women enrolled; 1,384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomization groups. Cohort retention was similar among those randomized vs. not randomized to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for <3, 3–5, and ≥6 months, respectively. The cost per subject enrolled was $146 (2013 $US), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, >97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. Conclusions Use of the internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective.
In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. We examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010). We found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.0, 6.3; for p,p'-DDT, adjusted OR = 2.1, 95% CI: 1.0, 4.5; and for p,p'-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios for girls were nonsignificant. Results were similar for body mass index z score, waist circumference z score, and odds of increased waist circumference but were less consistent for percentage of body fat. The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis.
Some reproductive-aged individuals remain unvaccinated against COVID-19 due to concerns about potential adverse effects on fertility. We examined the associations of COVID-19 vaccination and SARS-CoV-2 infection with fertility among couples trying to conceive spontaneously using data from an internet-based preconception cohort study. We enrolled 2,126 self-identified females residing in the U.S. 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, the per-cycle probability of conception, adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female FR=1.08, 95% 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 (FR=0.82, 95% CI: 0.47, 1.45 for infection within 60 days; FR=1.16, 95% CI: 0.92, 1.47 for infection >60 days). 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.
Background: In animal studies, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters glucose transport and increases serum lipid levels and blood pressure. Epidemiologic evidence suggests an association between TCDD and metabolic disease.Objectives: On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. Using data from the Seveso Women’s Health Study (SWHS), a cohort study of the health of the women, we examined the relation of serum TCDD to diabetes, metabolic syndrome, and obesity > 30 years later.Methods: In 1996, we enrolled 981 women who were newborn to 40 years of age in 1976 and resided in the most contaminated areas. Individual TCDD concentration was measured in archived serum that had been collected soon after the explosion. In 2008, 833 women participated in a follow-up study. Diabetes was classified based on self-report or fasting serum glucose and glycated hemoglobin levels. Metabolic syndrome was defined by International Diabetes Federation criteria. Obesity was defined as body mass index ≥ 30 kg/m2.Results: A 10-fold increase in serum TCDD (log10TCDD) was not associated with diabetes (adjusted hazard ratio = 0.76; 95% CI: 0.45, 1.28) or obesity [adjusted odds ratio (OR) = 0.80; 95% CI: 0.58, 1.10]. Log10TCDD was associated with metabolic syndrome, but only among women who were ≤ 12 years of age at the time of the explosion (adjusted OR = 2.03; 95% CI: 1.25, 3.29; pinteraction = 0.01).Conclusions: We found an increased prevalence of metabolic syndrome associated with TCDD, but only among women who were the youngest at the time of the explosion. Continued follow-up of the SWHS cohort will be informative.
Background There is a well-documented decline in fertility treatment success with increasing female age; however, there are few preconception cohort studies examining female age and natural fertility. In addition, data on male age and fertility is inconsistent. Given the increasing number of couples attempting conception at older ages, a more detailed characterization of age-related fecundability in the general population is of great clinical utility. Objective 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 enrolled between June 2013 and July 2017. Eligible participants were aged 21–45 years (females) or ≥21 years (males), and not using fertility treatments. Couples were followed until pregnancy or for up to 12 menstrual cycles. We analyzed data from 2,962 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), and 95% confidence intervals. Results Among females, 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) to 55.5% (age 40–45 years). Similar patterns were observed among males, 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, where 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 (ages 21–24 years). The association was stronger among nulligravid women. Male age was not appreciably associated with fecundability after adjustment for female age, although the number of men over age 45 years 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. While we found little association between male age and fecundability, the small number of men in our study over age 45 years limited our ability to draw conclusions on fecundability in older men.
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 2,135 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.
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