ABSTRACT About 15% of American couples experience infertility (time-to-pregnancy >12 months) and more than 20% of couples experience spontaneous abortion (SAB, pregnancy loss <20 weeks of gestation). Fertility treatment is costly and inaccessible to most Americans, particularly people of color and low-income individuals. Among those with access to treatment, fertility treatment has relatively low success rates and is associated with adverse perinatal outcomes. There are also large racial/ethnic disparities in treatment success rates. As infertility and SAB exact an emotional and financial toll on affected couples, identifying modifiable risk factors for these outcomes in both partners is an important public health goal. With previous support from the NICHD, we designed a web-based prospective cohort study to recruit, follow, and collect comprehensive data on couples attempting pregnancy. Some of our strongest findings to date pertain to poor sleep quality and stress in both partners. To build on this work, we are submitting a renewal application (R01-HD086742) to evaluate the influence of understudied sleep- and stress-related exposures on subfertility and SAB risk, explore putative mechanisms of effect, and examine the extent to which these factors explain existing race/ethnic disparities in subfertility and SAB. Pregnancy Study Online (PRESTO) is a web-based preconception cohort study in North America that has enrolled more than 16,000 females and nearly 4,000 male partners during the preconception period, with 20% of PRESTO participants identifying as Black, Indigenous, or People of Color (BIPOC). In this renewal application, we propose to enroll an additional 8,000 females to enhance power for more detailed analyses of sleep using the Pittsburgh Sleep Quality Index, selected stressors (e.g., childhood adversity, discrimination, financial hardship, COVID-related factors), and risk of subfertility and SAB. We also propose to collect and analyze more objective exposure data using sleep actigraphy (Fitbit Inspire 2) and stress biomarkers (hair cortisol and salivary alpha-amylase) in a subset of new participants. We will enroll an additional 2,000 male partners to enhance power for examining male exposures and joint effects in both partners. To ensure power for key hypotheses (e.g., reproductive effects of racial discrimination), we will oversample BIPOC participants. This renewal application builds on our previous work indicating that stress and sleep quality are important determinants of reproductive health. Our expanded focus on understudied stressors—in populations that are underrepresented in reproductive and perinatal research (e.g., males and BIPOC)—is novel and of high public health importance. Preconception enrollment minimizes misclassification, selection bias, and reverse causation, and captures early SABs (<8 weeks of gestation), a priority area for NICHD. The cohort’s prospective design, cost-efficient web- based infrastructure for pa...