Smoking and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study
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Authors
Hernáez, Álvaro
Wootton, Robyn
Page, Christian
Skåra, Karoline
Fraser, Abigail
Rogne, Tormod
Magnus, Per
Njølstad, Pål
Andreassen, Ole
Lawlor, Deborah
Magnus, Maria Christine
Publication Date
2022-07Journal Title
Fertility and Sterility
ISSN
0015-0282
Publisher
Elsevier
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Hernáez, Á., Wootton, R., Page, C., Skåra, K., Fraser, A., Rogne, T., Magnus, P., et al. (2022). Smoking and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study. Fertility and Sterility https://doi.org/10.1016/j.fertnstert.2022.04.001
Abstract
<h4>ABSTRACT</h4> <h4>Objective</h4> To investigate the association between smoking-related traits and subfertility. <h4>Design</h4> Prospective study. <h4>Setting</h4> Nationwide cohort in Norway. <h4>Patients</h4> 28,606 women (average age 30) and 27,096 men (average age 33) with questionnaire and genotype information from the Norwegian Mother, Father and Child Cohort Study. <h4>Intervention</h4> Self-reported information on smoking (having ever smoked [both sexes], age at smoking initiation [women only], smoking cessation [women only], and cigarettes smoked per week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting the mentioned traits were estimated for Mendelian randomization (MR) analyses. <h4>Main outcome measure</h4> Subfertility, defined as time-to-pregnancy ≥12 months. <h4>Results</h4> A total of 10% of couples were subfertile. In multivariable regression accounting for age, years of education, body mass index, and number of previous pregnancies, having ever smoked was not linked to subfertility in women or men. A higher intensity of tobacco use in women who were current smokers was related to greater odds of subfertility (+ 1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR] 1.12, 95% confidence interval [CI] 1.03 to 1.21), also after adjusting for the partner’s tobacco use. Later smoking initiation (+ 1 SD [3.2 years]: OR 0.89, 95% CI 0.84 to 0.95) and smoking cessation (relative to not quitting: OR 0.83, 95% CI 0.75 to 0.93) were linked to decreased subfertility in women who had ever smoked. Nevertheless, MR results were not directionally consistent for smoking intensity and cessation and were imprecisely estimated in two-sample MR, with wide confidence intervals that overlapped with the multivariable regression results. In men, greater smoking intensity was marginally linked to greater odds of subfertility in multivariable analyses, but this association was attenuated when adjusting for the partner’s smoking intensity (+ 1 SD [54 cigarettes/week]: OR 1.05, 95% CI 0.96 to 1.15). MR estimates were directionally consistent but again imprecisely estimated. <h4>Conclusions</h4> We did not find robust evidence of an effect of smoking on subfertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding. The relevant limitations across all methods highlights the need for larger studies with information on subfertility.
Sponsorship
Medical Research Council (MC_UU_00002/7)
Identifiers
External DOI: https://doi.org/10.1016/j.fertnstert.2022.04.001
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336992
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