Association Between Cigarette Smoking and Ovarian Reserve Among Women Seeking Fertility Care

Abstract Background This study examined the association of smoking with ovarian reserve in a cross-sectional study of 207 women enrolled in the Louisville Tobacco Smoke Exposure, Genetic Susceptibility, and Infertility (LOUSSI) Study and assessed effect modification by NAT2 acetylator phenotype. Methods Information on current smoking status was collected using a structured questionnaire and confirmed by cotinine assay. Serum anti-Müllerian hormone (AMH) levels were used to assess ovarian reserve. Diminished ovarian reserve (DOR) was defined as AMH < 1ng/mL. Single nucleotide polymorphisms in the NAT2 gene, which metabolizes toxins found in cigarette smoke, were analyzed to determine NAT2 acetylator status. Linear and logistic regression were used to determine the effects of smoking on ovarian reserve and evaluate effect modification by NAT2. Regression analyses were stratified by polycystic ovary syndrome (PCOS) status and adjusted for age. Results Current smoking status, either passive or active, was not significantly associated with DOR. For dose-response assessed using self-report, the odds of DOR increased significantly for every additional cigarette currently smoked (odds ratio, OR:1.08; 95% confidence interval, 95%CI:1.01–1.15); additionally, every 1 pack-year increase in lifetime exposure was associated with an increased odds of DOR among women without PCOS (OR: 1.08 95%CI: 0.99–1.18). These trends appear to be driven by the heavy or long-term smokers. Effect modification by NAT2 genotype was not established. Conclusion A history of heavy smoking, but not current smoking status, may indicate increased risk of diminished ovarian reserve.