Female infertility and long-term cardiovascular risk: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational cohort and case-control studies.
PubMed 41670932 · doi:10.1007/s12020-025-04543-x
What was done
A systematic review and meta-analysis of 22 observational studies (registered in PROSPERO: CRD42023420300, following PRISMA guidelines) was performed to examine associations between female infertility, assisted reproductive technology (ART) exposure, and subsequent risk of cardiovascular disease (CVD), coronary heart disease (CHD), cerebrovascular disease, and heart failure. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using Mantel-Haenszel and inverse variance methods, with heterogeneity evaluated using I².
What was found
Female infertility was associated with a higher risk of incident CVD (178,828 infertile women vs 3,398,781 controls; HR = 1.14, 95% CI 1.12–1.16; I² = 89%), CHD (HR = 1.17, 95% CI 1.12–1.23; I² = 0%), and cerebrovascular events (HR = 1.16, 95% CI 1.11–1.21; I² = 73%). Exposure to ART was associated with higher risk of overall CVD across 5 studies (HR = 1.17, 95% CI 1.11–1.24; I² = 96%) and incident stroke across 4 studies (HR = 1.12, 95% CI 1.03–1.23; I² = 60%), with no significant association observed for CHD.
Why it matters
A personal history of infertility or ART exposure may identify women at elevated long-term risk for cardiovascular and cerebrovascular events, indicating potential value in earlier cardiovascular monitoring.
Limits
The included literature consists of observational studies, precluding causal inference. Substantial statistical heterogeneity was observed across major outcomes (I² reaching 89% to 96%). Findings for heart failure were mentioned in the objectives but specific effect estimates were not reported in the abstract.
Cited by
- supports Infertility is associated with increased rates of metabolic syndrome, cardiovascular disease, stroke, cancer, and early mortality.