Cotinine concentrations in follicular fluid as a measure of secondhand tobacco smoke exposure in women undergoing in vitro fertilization: inter-matrix comparisons with urine and temporal variability

We examined the relationship between cotinine measures in follicular fluid (FF) and urine to inform our exposure assessment strategy for an ongoing epidemiological study of secondhand tobacco smoke (STS) exposure and early pregnancy loss. Among subjects undergoing in vitro fertilization (IVF), we compared cotinine levels in paired urine and FF samples from the same women and examined FF cotinine levels over time. We found a weak rank-order relationship (Spearman r<0.2) and poor agreement for classifying nonsmoking individuals as exposed to STS (sensitivity=0.29-0.71; specificity=0.35-0.72) between cotinine concentrations in FF and urine. We observed fair reliability (ICC=0.42-0.52) in FF cotinine concentrations from women undergoing multiple IVF cycles. If available, FF cotinine concentrations may be desired as a biomarker of low-level tobacco smoke exposure over urinary cotinine in studies of early reproduction. Collection of multiple FF samples for cotinine analysis may be needed to accurately represent long-term STS exposure.