A prospective study of male factors, fertility, and pregnancy outcomes

ABSTRACT The proposed supplement will be based on data from Pregnancy Study Online (PRESTO), an ongoing NIH- funded prospective cohort study that enrolls women trying to conceive and follows them from preconception through 6 months after delivery (R01HD086742). Eligible female participants are aged 21-45 years, residents of North America, trying to conceive, and not using contraception or fertility treatment at enrollment. After enrollment, female participants invite their male partners to complete a baseline questionnaire. During 6/2013- 7/2022, PRESTO has enrolled more than 16,750 female participants and nearly 4,000 of their male partners. All questionnaires are completed online and data collection continued during the COVID-19 pandemic. In April 2020, we added new questions for both partners on COVID-19 infection and stressors related to the pandemic, including changes in lifestyle, behaviors and health care, and in January 2021, we added questions for both partners on SARS-CoV-2 vaccination (ever vaccinated, type of vaccine, and date of each shot). In November 2021, we added questions about booster shots. We also obtained female-reported data on male SARS-CoV-2 vaccination and COVID-19 infection data in the event that the male partner did not enroll. Since the study's inception, participants have reported detailed baseline data about socio-demographics, lifestyle, anthropometrics, and medical history. On each bimonthly questionnaire (administered for up to 12 months), female participants report additional data about their pregnancy status and any changes in their exposures or covariates. We will use the above prospectively-collected data to examine the extent to which SARS-CoV-2 vaccination and COVID-19 infection in both partners are associated with spontaneous abortion (SAB), including early SAB (<8 weeks of gestation). We will consider various windows of possible effects of vaccination and infection, examine the number of vaccine doses (including boosters), and identify differences by other possible effect modifiers (e.g., age). We will control for several confounders, including COVID-19-related stressors, and also present results separately by early and late SAB (<8 vs. ≥8 weeks of gestation). Finally, we will examine the effects of joint exposures in both members of a couple (e.g., both partners vaccinated, female partner vaccinated, male partner vaccinated, vs. neither partner vaccinated). Among at least 1,600 U.S. participants who reported a study-related conception after 12/14/2020, we will estimate the hazard ratio and 95% confidence interval using Cox proportional hazards regression models. Our interdisciplinary research team has published extensively on vaccine-related effects and reproductive outcomes, many of which are based on PRESTO data, and we have the expertise necessary to study these research questions. Given our ongoing prospective data collection throughout the pandemic, our successful recruitment of a large and diverse population of couples, and our prospective collection of pregnancy data, PRESTO is uniquely-positioned to analyze data on vaccination and SAB and provide essential information to the scientific community and the public on vaccine safety.