Secondhand Tobacco Smoke Exposure and its Effects among Women Undergoing In Vitro Fertilization.

Abstract

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). In one of the only previous studies of early pregnancy that utilized 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 also observed fair reliability (ICC=0.42-0.52) in FF cotinine concentrations from 415 women undergoing multiple IVF cycles. In the second chapter, we report a significant increase in the risk of embryo 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) based on cotinine measures in FF collected during 3,270 IVF cycles from 1,909 nonsmoking women. 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, among 337 of the women in the study, we report a significant increase in circulating prolactin (p=0.03), but no change in circulating TSH, among STS-exposed women. These findings 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 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. 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.