Endocrine Abstracts

JOINT2776

Objective: Infertility and cardiovascular disease (CVD) are major global health concerns. While some studies suggest infertility may be an early marker of cardiovascular risk, others report no clear association. This meta-analysis (MA) aims to evaluate the relationship between female infertility and the risk of developing CVD later in life, with a focus on the possible impact of assisted reproductive technology (ART) exposure.

Design and Methods: We followed PRISMA guidelines to conduct a MA of 21 studies examining the link between female infertility and CVD outcomes. A total of 178,828 women with a history of infertility and 3,398,781 controls were included. Data on CVD incidence, coronary heart disease (CHD), and cerebrovascular events were extracted. Sensitivity analyses were performed to assess the impact of study design, participants’ age at recruitment and ART exposure on the observed associations.

Results: Women with a history of infertility had a 14% higher risk of developing CVD compared to controls (HR=1.14; 95% CI: 1.12–1.16; I² = 89%). Infertility was also associated with a 17% increased risk of CHD (HR=1.17; 95% CI: 1.12–1.23; I² = 0%) and a 16% higher risk of cerebrovascular events (HR=1.16; 95% CI: 1.11–1.21; I² = 73%). Sensitivity analyses of prospective-only studies confirmed these associations, with a 4% increased risk of CVD (HR=1.04; 95% CI: 1.01–1.08; I² = 0%), a 15% increased risk of CHD (HR=1.15; 95% CI: 1.07–1.24; I² = 54%), and an 11% higher risk of cerebrovascular events (HR=1.11; 95% CI: 1.05–1.17; I² = 54%). Among 392,266 ART-exposed women and 33,630,919 controls, we observed a higher risk of CVD (HR = 1.18; 95% CI: 1.11-1.25; I²=97%), although a woman’s prior exposure to ART did not significantly increase the risk of prevalent or incident CHD, cerebrovascular events, or heart failure. Studies evaluating infertile women aged < 40 years, when compared to controls, found a higher risk of CVD (HR=1.20; I² = 81%). On the contrary, studies evaluating infertile women over 40 years showed a comparable incident risk for CVD to controls (HR=1.04; I² = 29%).

Discussion: This study shows an increased risk of CVD, including CHD and cerebrovascular events, among women with a history of infertility. ART exposure was associated with higher CVD risk. However, the true magnitude of the effect of ART remains uncertain due to significant heterogeneity across studies, likely secondary to differences in study methodologies and ART protocols.