TY - JOUR
T1 - Smoking and infertility
T2 - multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study
AU - Hernáez, Álvaro
AU - Wootton, Robyn E.
AU - Page, Christian M.
AU - Skåra, Karoline H.
AU - Fraser, Abigail
AU - Rogne, Tormod
AU - Magnus, Per
AU - Njølstad, Pål R.
AU - Andreassen, Ole A.
AU - Burgess, Stephen
AU - Lawlor, Deborah A.
AU - Magnus, Maria Christine
N1 - Funding Information:
The authors thank all participating families in Norway who take part in this ongoing cohort study, and those who contributed to the recruitment and the infrastructure of the cohort. We also thank the Norwegian Institute of Public Health for generating high-quality genomic data and the NORMENT Centre for providing genotype data, South East Norway Health Authority, and Stiftelsen Kristian Gerhard Jebsen. The authors further thank the Center for Diabetes Research (University of Bergen) for providing genotype information and performing quality control and imputation of the data in research projects funded by the European Research Council Advanced Grant SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, the Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway Health Authority. This work was performed on the Tjeneste for Sensitive Data (TSD) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department ( [email protected] ). This study does not necessarily reflect the position or policy of the Norwegian Research Council.
Funding Information:
The Mother, Father, and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. Supported by funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement No 947684). Supported in part by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700, and the project “Women's fertility–an essential component of health and well-being,” number 320656. Open Access funding was provided by the Folkehelseinstituttet/Norwegian Institute of Public Health. Supported by grant no. R01 DK10324 from the US National Institutes of Health and grant agreement No 669545 from European Research Council Advanced Grant (to D.A.L.). The funders had no role in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.The authors thank all participating families in Norway who take part in this ongoing cohort study, and those who contributed to the recruitment and the infrastructure of the cohort. We also thank the Norwegian Institute of Public Health for generating high-quality genomic data and the NORMENT Centre for providing genotype data, South East Norway Health Authority, and Stiftelsen Kristian Gerhard Jebsen. The authors further thank the Center for Diabetes Research (University of Bergen) for providing genotype information and performing quality control and imputation of the data in research projects funded by the European Research Council Advanced Grant SELECTionPREDISPOSED, Stiftelsen Kristian Gerhard Jebsen, the Trond Mohn Foundation, the Research Council of Norway, the Novo Nordisk Foundation, the University of Bergen, and the Western Norway Health Authority. This work was performed on the Tjeneste for Sensitive Data (TSD) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department ([email protected]). This study does not necessarily reflect the position or policy of the Norwegian Research Council. DIALOG: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/posts/34132
Funding Information:
The Mother, Father, and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. Supported by funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No 947684). Supported in part by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700, and the project “Women’s fertility–an essential component of health and well-being,” number 320656. Open Access funding was provided by the Folkehelseinstituttet/Norwegian Institute of Public Health. Supported by grant no. R01 DK10324 from the US National Institutes of Health and grant agreement No 669545 from European Research Council Advanced Grant (to D.A.L.). The funders had no role in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Publisher Copyright:
© 2022 The Authors
PY - 2022/7
Y1 - 2022/7
N2 - Objective: To investigate the association between smoking and infertility. Design: Prospective study. Setting: Nationwide cohort. Patients: 28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study. Intervention: Self-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization. Main outcome measure: Infertility (time-to-pregnancy ≥12 months). Results: Having ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]crude, 1.19; 95% confidence interval [CI] 1.11–1.28; ORadjusted 1.12; 95% CI, 1.03–1.21), also after adjusting for the partner's tobacco use. Later smoking initiation (+1 SD [3.2 years]: ORcrude, 0.94; 95% CI, 0.88–0.99; ORadjusted 0.89; 95% CI, 0.84–0.95) and smoking cessation (vs. not quitting: ORcrude, 0.83; 95% CI, 0.75–0.91; ORadjusted, 0.83; 95% CI, 0.75–0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization. Conclusions: We did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.
AB - Objective: To investigate the association between smoking and infertility. Design: Prospective study. Setting: Nationwide cohort. Patients: 28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study. Intervention: Self-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization. Main outcome measure: Infertility (time-to-pregnancy ≥12 months). Results: Having ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]crude, 1.19; 95% confidence interval [CI] 1.11–1.28; ORadjusted 1.12; 95% CI, 1.03–1.21), also after adjusting for the partner's tobacco use. Later smoking initiation (+1 SD [3.2 years]: ORcrude, 0.94; 95% CI, 0.88–0.99; ORadjusted 0.89; 95% CI, 0.84–0.95) and smoking cessation (vs. not quitting: ORcrude, 0.83; 95% CI, 0.75–0.91; ORadjusted, 0.83; 95% CI, 0.75–0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization. Conclusions: We did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.
KW - Mendelian randomization
KW - Smoking
KW - infertility
UR - http://www.scopus.com/inward/record.url?scp=85130022567&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2022.04.001
DO - 10.1016/j.fertnstert.2022.04.001
M3 - Article
C2 - 35562204
AN - SCOPUS:85130022567
SN - 0015-0282
VL - 118
SP - 180
EP - 190
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 1
ER -
