Infertility and early pregnancy loss are prevalent in the United States and worldwide, and a large proportion of non-tobacco users are exposed to secondhand tobacco smoke (STS). While the effects of active smoking on these endpoints have been well-documented, studies on STS exposure remain limited. In one of the only previous studies of early pregnancy that utilized exposure biomarkers of STS exposure, no relationship was observed between urinary cotinine and in vitro fertilization (IVF) outcomes. However, we hypothesize that urine may not be the most relevant sample media within which to measure biomarkers for a study of early pregnancy, and that the lack of an association may have been due to a large degree exposure measurement error. In the first chapter of this dissertation we report a weak rank-order relationship (Spearman r <0.2) and poor exposure category agreement between cotinine concentrations measured in urine and the potentially more biologically-relevant follicular fluid (FF) among 255 women undergoing IVF. We observed fair reliability (ICC = 0.42–0.52) in FF cotinine concentrations from 415 women undergoing multiple IVF cycles. In the second chapter, cotinine was measured in FF collected during 3,270 IVF cycles from 1,909 nonsmoking women to investigate the relationship between STS exposure and failed embryo implantation. We observed a significant increase in the risk of implantation failure among women exposed to STS compared to those who were unexposed (Odds Ratio [OR] = 1.52; 95% confidence interval [CI] = 1.20–1.92; Risk Ratio [RR] = 1.17; 95% CI = 1.10–1.25). We also found a significant decrease in the odds for a livebirth among STS-exposed women (OR = 0.75; 95% CI = 0.57–0.99; RR = 0.81; 95% CI = 0.66–0.99). In the third chapter, we explored the relationship between STS exposure and serum levels of prolactin and TSH measured at baseline among 337 of the women in the study. STS exposure was associated with a significant increase in circulating prolactin (p = 0.03) but was not associated with serum TSH. The findings reported here are likely of great public health significance due to continued widespread STS exposure, the rapidly increasing number of couples utilizing IVF, and the potential relationship between elevated prolactin concentrations and a range of potential downstream adverse health effects. In addition, FF cotinine concentrations, if available, may be desired as a biomarker of low-level tobacco smoke exposure over urinary cotinine in studies of early reproduction. Finally, due to only moderate temporal reliability, cotinine measured in FF samples collected at each IVF cycle may be needed to most accurately represent STS exposure in studies utilizing outcome data from multiple cycles.