Study Finds Increased Risk of CVD Among Women With History of Infertilty

Women who experience infertility are more likely to develop heart and blood vessel conditions later in life, with younger women and those who undergo fertility treatments at greater risk, according to study results that were presented at the European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) 2025 Joint Congress. Despite the findings, the authors noted that the true magnitude of these effects is still uncertain because of significant heterogeneity across research.¹

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About 1 in 6 people of reproductive age worldwide are estimated to experience infertility at some point in their lifetime. For those struggling with infertility, treatment often involves in-vitro fertilization (IVF) and other types of assisted reproductive technology (ART). Both infertility and cardiovascular disease (CVD) are major global health concerns, and with some research suggesting infertility may be an early marker of cardiovascular risks, the data have been conflicting, with no comprehensive review providing a broad assessment of the potential effects of medically assisted reproduction.^1,2

“Recognizing infertility as a potential early marker for CVD could help doctors identify women who may need closer monitoring or preventive strategies earlier in life. It also raises important questions about the long-term effects of fertility treatments like ART,” lead research and study author Elena Armeni, MD, PgDipl, MSc, PhD, explained in a news release. ²

For these reasons, the study authors conducted a meta-analysis to evaluate the relationship between female infertility and the risk of developing CVD later in life, with a focus on the possible impact of ART exposure. The investigators followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, conducting a meta-analysis that included 178,828 women with a history of infertility and nearly 3.4 million controls across 21 studies that examined the possible link between female infertility and CVD outcomes.¹

“This is the largest meta-analysis to not only examine the potential link between a history of infertility in women and cardiovascular risk but also the impact of ARTs on their likelihood of developing future cardiovascular events,” Armeni said. “By gathering data from many studies, our work adds strong evidence to a growing field and suggests that infertility could be an early warning sign for future heart health issues.”²

The data showed that women with a history of infertility had a 14% higher risk of developing CVD compared with the controls (HR = 1.14; 95% CI, 1.12–1.16; I² = 89%). In addition, infertility was also associated with a 17% and 16% increased risk of coronary heart disease (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%), respectively.¹

Sensitivity analyses of prospective-only studies had confirmed these associations, with increased risks of about 4%, 15%, and 11% of CVD (HR = 1.04; 95% CI, 1.01–1.08; I² = 0%), CHD (HR = 1.15; 95% CI, 1.07–1.24; I² = 54%), and cerebrovascular events (HR = 1.11; 95% CI, 1.05–1.17; I² = 54%). Among the 392,266 women who were exposed to ART and 33,630,919 controls, the investigators had observed a higher risk of CVD (HR = 1.18; 95% CI, 1.11-1.25; I2%); however, prior exposure to ART was not shown to significantly increase the risk of prevalent or incident CHD, cerebrovascular events, or heart failure.¹

Of note, studies that evaluated women aged below 40 years with infertility found a higher risk of CVD (HR = 1.20; I² = 81%) when compared with controls. Conversely, studies evaluating women with infertility over the age of 40 demonstrated a comparable incident risk for CVD to controls (HR = 1.04; I² = 29%).¹

“Some earlier studies did not find a strong association between infertility and heart disease, so in our meta-analysis we addressed this by including only high-quality studies and performing sensitivity analyses based on study design and participant age. We hope to clarify the biological mechanisms behind these associations and identify which groups are at greatest risk. Ultimately, this will help shape future guidelines for early prevention strategies and improve cardiovascular care for women with a history of infertility,” Armeni concluded.²

REFERENCES

1. Armeni E, Mili N, Polymeropoulou C, Siliogka E, Augoulea A, Lambrinoudaki I. Abstract P1033 — Long-Term Cardiovascular Risk in Women with Subfertility: Systematic Review and Meta-Analysis. Presented at: European Society of Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) 2025 Joint Congress. Copenhagen, Denmark. May 10-13, 2025.

2. European Society of Endocrinology. Women with infertility history at greater risk of cardiovascular disease after assisted conception. News release. May 9, 2025. Accessed May 20, 2025. https://www.eurekalert.org/news-releases/1083209