Abstract
Objective: To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes.
Design: Prospective study.
Setting: Population-based cohort.
Subjects: We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study (HUNT).
Exposure: Self-reported subfertility. Men were not directly asked about fertility, so male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners.
Main Outcome Measures: The primary outcomes were risk of stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were risk of myocardial infarction and angina (subgroups of coronary heart disease), and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in HUNT (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models.
Results: A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with increased risk of stroke (age-adjusted hazard ratio [aaHR] 1.19, 95% confidence interval [CI] 1.02-1.39; adjusted hazard ratio [aHR] 1.18, 95% CI 1.01-1.37) and coronary heart disease (aaHR 1.19, 95% CI 1.06-1.33; aHR 1.16, 95% CI 1.03-1.30) compared to fertile women. In men, we observed a weak positive association for stroke (aaHR 1.11, 95% CI 0.91-1.34; aHR 1.10, 95% CI 0.91-1.33), and a weak inverse association for coronary heart disease (aaHR 0.92, 95% CI 0.81-1.05; aHR 0.93, 95% CI 0.81-1.06).
Conclusion: We observed modest increased risks of CVD outcomes in women and some weak associations in men, though with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large
sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences.
Design: Prospective study.
Setting: Population-based cohort.
Subjects: We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study (HUNT).
Exposure: Self-reported subfertility. Men were not directly asked about fertility, so male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners.
Main Outcome Measures: The primary outcomes were risk of stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were risk of myocardial infarction and angina (subgroups of coronary heart disease), and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in HUNT (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models.
Results: A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with increased risk of stroke (age-adjusted hazard ratio [aaHR] 1.19, 95% confidence interval [CI] 1.02-1.39; adjusted hazard ratio [aHR] 1.18, 95% CI 1.01-1.37) and coronary heart disease (aaHR 1.19, 95% CI 1.06-1.33; aHR 1.16, 95% CI 1.03-1.30) compared to fertile women. In men, we observed a weak positive association for stroke (aaHR 1.11, 95% CI 0.91-1.34; aHR 1.10, 95% CI 0.91-1.33), and a weak inverse association for coronary heart disease (aaHR 0.92, 95% CI 0.81-1.05; aHR 0.93, 95% CI 0.81-1.06).
Conclusion: We observed modest increased risks of CVD outcomes in women and some weak associations in men, though with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large
sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences.
Original language | English |
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Number of pages | 11 |
Journal | Fertility and Sterility |
Volume | 118 |
Issue number | 3 |
Early online date | 13 Jul 2022 |
DOIs | |
Publication status | Published - 1 Sept 2022 |
Bibliographical note
Funding Information:K.H.S. has nothing to disclose. B.O.A. has nothing to disclose. A.H. has nothing to disclose. A.F. has nothing to disclose. J.W.R.-E. has nothing to disclose. L.V.F. has nothing to disclose. O.N. has nothing to disclose. D.A.L. reports grants from the European Research Council, UK Medical Research Council, and British Heart Foundation outside the submitted work and grants from Medtronic Ltd and Roche Diagnostics outside the submitted work. B.B. has nothing to disclose. M.C.M. reports grants from the Research Council of Norway and the European Research Council for the submitted work.
Funding Information:
Supported by grants from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreements No 947684 and 101021566 ). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project No 262700), and partly funded by the Research Council of Norway , project: Women’s fertility – an essential component of health and well-being (project No 320656). D.A.L., A.F., and M.C.M. work in or are affiliated with a unit that is supported by the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L.’s contribution to the article is further supported by the British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). None of the funding organizations influenced the study design, reporting, or interpretation of results. The views expressed in the present article are those of the authors and not necessarily any acknowledged funding organization.
Funding Information:
Supported by grants from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreements No 947684 and 101021566). This research was also supported by the Research Council of Norway through its Centres of Excellence funding scheme (project No 262700), and partly funded by the Research Council of Norway, project: Women's fertility – an essential component of health and well-being (project No 320656). D.A.L., A.F., and M.C.M. work in or are affiliated with a unit that is supported by the University of Bristol and the UK Medical Research Council (MC_UU_00011/6). D.A.L.’s contribution to the article is further supported by the British Heart Foundation (CH/F/20/90003 and AA/18/7/34219). None of the funding organizations influenced the study design, reporting, or interpretation of results. The views expressed in the present article are those of the authors and not necessarily any acknowledged funding organization. K.H.S. has nothing to disclose. B.O.A. has nothing to disclose. A.H. has nothing to disclose. A.F. has nothing to disclose. J.W.R.-E. has nothing to disclose. L.V.F. has nothing to disclose. O.N. has nothing to disclose. D.A.L. reports grants from the European Research Council, UK Medical Research Council, and British Heart Foundation outside the submitted work and grants from Medtronic Ltd and Roche Diagnostics outside the submitted work. B.B. has nothing to disclose. M.C.M. reports grants from the Research Council of Norway and the European Research Council for the submitted work.
Publisher Copyright:
© 2022 The Authors
Keywords
- cardiovascular disease
- infertility
- Subfertility
- the HUNT Study