Female infertility and long-term cardiovascular risk: a systematic review and meta-analysis

OBJECTIVE: To investigate the association between a personal history of infertility and the risk for future cardiovascular disease (CVD) and related manifestations like coronary heart disease (CHD), cerebrovascular disease and heart failure in women. We also considered the potential influence of exposure to assisted reproductive technology (ART) on the risk of future CVD. METHODS: This systematic review and meta-analysis of 22 studies, registered in PROSPERO (CRD42023420300), followed PRISMA guidelines. Pooled odds ratios (OR) and hazard ratios (HR) were calculated using Mantel-Haenszel and inverse variance methods, while heterogeneity was evaluated using I². Sensitivity analyses were performed to explore the impact of study design. RESULTS: We observed that women with infertility compared to controls had a higher risk of incident CVD (infertile vs controls: 178,828 vs 3,398,781; 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 a higher risk of overall CVD across five studies (HR = 1.17, 95% CI 1.11–1.24; I² = 96%) and with increased incident stroke across four studies (HR = 1.12, 95% CI 1.03–1.23; I² = 60%), whereas no significant association was observed with CHD. However, some of the estimates were heterogenous, which limits certainty and causal inference. DISCUSSION: Women with infertility compared with controls had higher pooled estimates for incident CVD, CHD and cerebrovascular events. However, these estimates were heterogeneous (I² up to 99%), which limits certainty and precludes causal inference.