Association between cigarette smoking and ovarian reserve among women seeking fertility treatment with effect modification by race and NAT2 genotype.

Abstract

Cigarette smoking in women has been associated with adverse reproductive outcomes such as reduced ovarian reserve, poorer in vitro fertilization (IVF) outcomes and increased adverse pregnancy outcomes. This study examined the association of smoking with ovarian reserve in a cross-sectional study of women seeking fertility treatment, and potential effect modification by race and NAT2 acetylator phenotype. Data from 265 women from the Louisville Tobacco Smoke, Genetic Susceptibility, and Infertility (LOUSSI) Study were analyzed. A total of 265 women were recruited through a single infertility clinic between September 2016 and June 2018. Information on current smoking status was assessed using a structured questionnaire and confirmed by cotinine assay. Single nucleotide polymorphisms in NAT2 were genotyped to determine acetylator status and serum anti-Mullerian hormone (AMH) level was used to assess ovarian reserve. The association of smoking with ovarian reserve was assessed using linear and logistic regression models with adjustment for potential confounders. Effect modification by race and NAT2 phenotype were assessed by including interaction terms in the regression models. Overall, smoking was not significantly associated with ovarian reserve. Results suggest that heavy smoking and higher pack-years of exposure may decrease ovarian reserve. Although most associations were not statistically significant, the effect of smoking on ovarian reserve was more pronounced among non-Hispanic Black women and slow NAT2 acetylators. These results are based on a small clinical population and require replication in a larger and more representative study population.