Electronic Cigarettes and Fecundability

Results From a Prospective Preconception Cohort Study

Alyssa F. Harlow; Elizabeth E. Hatch; Amelia K. Wesselink; Kenneth J. Rothman; Lauren A. Wise


Am J Epidemiol. 2021;190(3):353-361. 

In This Article

Abstract and Introduction


Although electronic cigarette (e-cigarette) aerosol contains similar toxicants to combustible cigarettes, few studies have examined their influence on fecundability. We assessed the association between e-cigarette use and fecundability, overall and according to combustible cigarette smoking history, in a cohort of 4,586 North American women (aged 21–45 years) enrolled during 2017–2020 in Pregnancy Study Online, a Web-based prospective preconception study. Women reported current and former e-cigarette use on baseline and follow-up questionnaires, and they completed bimonthly follow-up questionnaires until self-reported pregnancy or censoring. Fecundability ratios and 95% confidence intervals were calculated using proportional probabilities models, controlling for potential confounders. Overall, 17% of women had ever used e-cigarettes and 4% were current users. Compared with never use of e-cigarettes, current e-cigarette use was associated with slightly lower fecundability (fecundability ratio = 0.84, 95% confidence interval (CI): 0.67, 1.06). Compared with current nonusers of e-cigarettes and combustible cigarettes, fecundability ratios were 0.83 (95% CI: 0.54, 1.29) for current dual users of e-cigarettes and combustible cigarettes, 0.91 (95% CI: 0.70, 1.18) for current e-cigarette users who were nonsmokers of combustible cigarettes, and 1.01 (95% CI: 0.85, 1.20) for nonusers of e-cigarettes who were current smokers of combustible cigarettes. Current e-cigarette use was associated with slightly reduced fecundability, but estimates of its independent and joint associations with combustible cigarette smoking were inconsistent and imprecise.


Electronic cigarettes (e-cigarettes) have gained substantial popularity in the United States. Approximately 3.4% of reproductive aged women in the United States currently use e-cigarettes exclusively, and 11.3% use e-cigarettes in combination with combustible cigarettes.[1] A recent analysis of the nationally representative Population Assessment of Tobacco and Health study found that 5% of pregnant women in the United States are current e-cigarette users, and 18% are former e-cigarette users.[2] According to data from the 2015 state-level Pregnancy Risk Assessment Monitoring System survey, approximately 10% of pregnant women in Oklahoma and Texas, the 2 states in which data were available, used e-cigarettes in the 3 months before pregnancy.[3] Women planning to conceive might use e-cigarettes to help quit or reduce smoking, to sustain cigarette cessation, or for recreational use.[4] The extent to which preconceptional use of e-cigarettes affects a woman's ability to conceive is unknown.

E-cigarette aerosol contains toxicants found in combustible cigarettes, including nicotine, ultrafine particles, heavy metals, polycyclic aromatic hydrocarbons, and volatile organic compounds.[5] Combustible cigarette smoking is a risk factor for adverse pregnancy outcomes[6–8] and is associated with reduced fecundability in several studies.[9–14] Fertility-related mechanisms include oocyte damage and alteration of endogenous hormone concentrations from exposure to nicotine, polycyclic aromatic hydrocarbons, and cadmium.[8] We hypothesize a similar effect for women who vape during the period before conception, given that implicated constituents are also found in most e-cigarette products.[15–19] E-cigarette liquids can contain high levels of nicotine; in some cases nicotine delivery by e-cigarettes is comparable with combustible cigarette smoking.[15] Cadmium has been detected in the aerosol of several e-cigarette brands, in addition to other metals including lead, nickel, and chromium.[16,17] Studies of polycyclic aromatic hydrocarbons exposure from e-cigarettes are limited,[16,18,19] although one biomarker study found higher concentrations of polycyclic aromatic hydrocarbons among e-cigarette users compared with never users.[18] In addition, e-cigarette liquid often contains flavoring compounds, humectants, and propellants not found in combustible cigarettes. When heated these constituents convert to toxic and carcinogenic by-products, but any independent effect on reproductive health is unknown.[5,20,21] Importantly, e-cigarette aerosols contain lower levels of toxicants than combustible cigarettes, particularly chemicals such as formaldehyde and metals, and the amount of toxicants in e-cigarette liquid is variable across products.[5,16] In addition, only combustible cigarettes contain carbon monoxide and nitrosamines. To our knowledge, no study has examined the association of e-cigarette exposure with fecundability, either independently or jointly with combustible cigarettes.

Dual use of e-cigarettes and combustible cigarettes might influence health differently from use of e-cigarettes alone. If smokers who use e-cigarettes reduce their combustible cigarette exposure, then dual use of e-cigarettes might be less harmful to fecundity by reducing overall toxicant exposure. However, if dual users do not reduce cigarette exposure, or if there is a synergistic effect of e-cigarettes and combustible cigarettes, dual use could cause more harm to fecundity than use of either product alone.

In a North American prospective cohort study of female pregnancy planners, we evaluated the association between preconceptional e-cigarette use and fecundability, the average per-cycle probability of conception. We additionally assessed the extent to which the association between e-cigarette use and fecundability varies according to cigarette smoking behaviors.