Infertility, Pregnancy Loss and Adverse Birth Outcomes in Relation to Maternal Secondhand Tobacco Smoke Exposure.

A substantial proportion of the etiology involved in female infertility and adverse pregnancy outcomes remains idiopathic. Recent scientific research has suggested a role for environmental factors in these conditions. Secondhand tobacco smoke (STS) contains a number of known or suspected reproductive toxins, and human exposure to STS is prevalent worldwide. Robust evidence exists for the toxic effects of active smoking on fertility and pregnancy, but studies of passive exposure are much more limited in number. While the association between maternal STS exposure and declined birth weight has been fairly well-documented, only recently have epidemiologic studies begun to provide suggestive evidence for delayed conception, altered menstrual cycling, early pregnancy loss (e.g. spontaneous abortion), preterm delivery, and congenital malformations in relation to STS exposure. There is also new evidence that developmental exposures to tobacco smoke may be associated with reproductive effects in adulthood. To date, most studies have estimated maternal STS exposure through self-report even though exposure biomarkers are less prone to error and recall bias. In addition to utilizing biomarkers of STS exposure, future studies should aim to identify vital windows of STS exposure, important environmental co-exposures, individual susceptibility factors, and specific STS constituents associated with female infertility and adverse pregnancy outcomes. The role of paternal exposures/factors should also be investigated.

Secondhand tobacco smoke exposure is associated with prolactin but not thyroid stimulating hormone among nonsmoking women seeking in vitro fertilization.

Prolactin (PRL) and thyroid stimulating hormone (TSH) serve important roles in the reproductive and other systems. Active smoking is associated with changes in PRL and TSH secretion, but the relationship between secondhand tobacco smoke (STS) exposure and these hormones is unclear. We measured PRL and TSH in serum as well as cotinine in follicular fluid (to estimate STS exposure) among 314 nonsmoking women undergoing in vitro fertilization treatment. We observed a significant increase in PRL concentrations (p=0.03) among STS-exposed nonsmokers compared to unexposed nonsmokers. There was no significant difference in TSH concentration (p>0.4) among those exposed to STS compared to those who were unexposed. STS exposure is associated with an increase in circulating PRL but not TSH levels. Future studies are needed to confirm our results, identify biological mechanisms involved, and better understand the potential clinical and public health implications.

Secondhand tobacco smoke exposure is associated with increased risk of failed implantation and reduced IVF success.

BACKGROUND: Infertility and early pregnancy loss are prevalent as is exposure to secondhand tobacco smoke (STS). Previous research has suggested a relationship between STS exposure and early pregnancy loss, but studies have been limited by small study sizes and/or imprecise methods for exposure estimation. IVF allows for the collection of follicular fluid (FF), the fluid surrounding the pre-ovulatory oocyte, which may be a more biologically relevant sample media than urine or serum in studies of early reproduction. METHODS: In a retrospective analysis of a prospective cohort study, we measured cotinine in FF collected during 3270 IVF treatment cycles from 1909 non-smoking women between 1994 and 2003 to examine the relationship between STS exposure and implantation failure. RESULTS: In adjusted models, we found a significant increase in the risk of implantation failure among women exposed to STS compared with those 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 live birth among STS-exposed women (OR = 0.75; 95% CI = 0.57-0.99; RR = 0.81; 95% CI = 0.66-0.99). CONCLUSIONS: Female STS exposure, estimated through the measurement of cotinine in FF, is associated with an increased risk of implantation failure and reduced odds of a live birth.

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.