Abstract
Introduction: Concerns have been raised regarding potential long-term cardiovascular impacts of fertility treatment, but data available so far are inconsistent. This systematic review and meta-analysis aim to assess the association of fertility treatment with cardiovascular outcomes in women.
Methods: We performed a systematic search of PubMed, Scopus, Web of Science, and Google Scholar through February 2024, without language restrictions. We included observational studies and randomized controlled trials that assessed cardiovascular outcomes in women who received fertility treatment vs. women who did not receive fertility treatment. We used random-effects models to estimate pooled relative risks (RRs) and 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic. The risk of bias of studies was assessed using the Newcastle-Ottawa (NOS) scale.
Results: In total, the analysis included 13 studies with over 107 million women (1.2 million with fertility treatment) and a mean follow-up of 17.7 years. According to pooled estimates, there were no statistically significant associations found between fertility treatment and cardiac events (RR 0.90; 95% CI: 0.68-1.21), cardiovascular disease (RR 0.99; 95% CI: 0.66-1.20), venous thromboembolism (RR 1.10; 95% CI: 0.62-1.97), hypertension (RR 1.00; 95% CI: 0.80-1.25), or diabetes mellitus (RR 0.93; 95% CI: 0.87-1.00). However, we found a statistically significant 39% relative increase in the risk of stroke (RR 1.39; 95% CI: 1.14-1.68; I²=22.2%) with low heterogeneity. The higher rates of stroke persisted, especially in the peripartum period. Other outcomes are high heterogeneity (I² 79.5-97.9%), indicating moderate to great variability in the studies.
Conclusion: Fertility treatment was associated with a higher relative risk of stroke, while no statistically significant associations were observed for other cardiovascular outcomes. It highlights the importance of assessing cardiovascular risk during fertility care, pregnancy, and postpartum. Personal risk and educational materials on cerebrovascular risk should be considered. Future research should focus on cardiovascular assessment, phenotyping, and understanding causal pathways to improve prevention strategies.