Abstract

BackgroundCigarette smoking has been associated with worse infertility treatment outcomes, yet some studies have found null or inconsistent results.MethodsWe followed 225 couples who underwent 354 fresh non-donor assisted reproductive technology (ART) cycles between 2006 and 2014. Smoking history was self-reported at study entry. We evaluated the associations between smoking patterns and ART success using multivariable discrete time Cox proportional hazards models with six time periods: cycle initiation to egg retrieval, retrieval to fertilization, fertilization to embryo transfer (ET), ET to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth to estimate hazard ratios (HR) and 95% CIs. Time-dependent interactions between smoking intensity and ART time period were used to identify vulnerable periods.ResultsOverall, 26% of women and 32% of men reported ever smoking. The HR of failing in the ART cycle without attaining live birth for male and female ever smokers was elevated, but non-significant, compared to never smokers regardless of intensity (HR = 1.02 and 1.30, respectively). Female ever smokers were more likely to fail prior to oocyte retrieval (HR: 3.37; 95% CI: 1.00, 12.73). Every one cigarette/day increase in smoking intensity for females was associated with a HR of 1.02 of failing ART (95% CI: 0.97, 1.08), regardless of duration or current smoking status. Women with higher smoking intensities were most likely to fail a cycle prior to oocyte retrieval (HR: 1.07; 95% CI: 1.00, 1.16). Among past smokers, every additional year since a man had quit smoking reduced the risk of failing ART by 4% (HR: 0.96; 95% CI: 0.91, 1.00) particularly between clinical pregnancy and live birth (HR: 0.86; 95% CI: 0.76, 0.96).ConclusionsFemale smoking intensity, regardless of current smoking status, is positively associated with the risk of failing ART cycles between initiation and oocyte retrieval. In men who ever smoked, smoking cessation may reduce the probability of failing ART, particularly between clinical pregnancy and live birth.Trial registrationNCT00011713. Registered: 27 February 2001.

Highlights

  • Cigarette smoking has been associated with worse infertility treatment outcomes, yet some studies have found null or inconsistent results

  • We evaluated the association of pre-treatment smoking patterns and infertility treatment outcomes in a prospective cohort of couples undergoing assisted reproductive technology (ART) at the Massachusetts General Hospital (MGH) Fertility Center, using novel statistical methods to allow for a changing effect of smoking on ART failure across time periods within an ART cycle

  • We found a borderline significant protective effect of smoking cessation in ever-smoker males; for every additional year since a male smoker quit, the risk of failing during an ART cycle decreased by 4% (HR: 0.96; 95% 95% confidence interval (CI): 0.91, 1.00; P-Value

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Summary

Introduction

Cigarette smoking has been associated with worse infertility treatment outcomes, yet some studies have found null or inconsistent results. Tobacco is among the leading causes of death and disability worldwide [1], with over 6 million people dying of tobacco-related causes per year [2]. It is a common exposure in the US, with smoking reported for approximately 25% of reproductive-aged women, 12% of women during pregnancy [3], and 25% of men aged 25 to 44 years [4]. Female smoking has been associated with poorer ovarian response markers, lower oocyte counts, and lower rates of implantation [10] and live birth [11, 12] following assisted reproductive technology (ART). None of the previous studies have utilized methods which allow distinction of smoking effects by stage of the ART cycle, and have not always been able to account for early failures, which may have resulted in contradictory findings [13]

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