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Cardiovascular safety of assisted reproductive technology: a meta-analysis
Carlo Andrea Pivato1,2, Annalisa Inversetti1,2, Gianluigi Condorelli1,2
1Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20072, Italy.
Background And Aims:
The increasing use of assisted reproductive technology (ART) has raised concerns regarding its long-term cardiovascular safety due to potential hormonal imbalances and pro-thrombotic states. This study aimed to assess the long-term cardiovascular risk associated with fertility treatments in women.
Methods:
Following PRISMA guidelines, a systematic review and meta-analysis was conducted in MEDLINE (via PubMed) from inception to January 2024. Randomized, cohort, or case-control studies were included if fulfilling the following criteria: the association between ART and the subsequent cardiovascular outcome was reported and adjusted for confounding factors (at least age); the presence of a control group; and minimum 1-year follow-up. Effect size (ES) estimates of the association between fertility therapy and subsequent cardiovascular disease were pooled using the DerSimonian and Laird random-effects model. Heterogeneity was assessed with the I2 index. This study is registered on PROSPERO (CRD42024505605).
Results:
Of the 7298 articles screened, 10 studies were included, encompassing 500 664 women undergoing ART and 36 395 240 controls. The analysis found no significant increase in the long-term risk of major adverse cardiovascular events [ES 1.04, 95% confidence interval (CI) 0.88-1.23, I2 87.61%, P = .63], coronary heart disease (ES 0.88, 95% CI 0.71-1.10, I2 24.36%, P = .26), stroke (ES 1.21, 95% CI 0.92-1.59, I2 70.40%, P = .17), venous thromboembolism (ES 0.95, 95% CI 0.70-1.28, I2 49.13%, P = .73), hypertension (ES 1.08, 95% CI 0.88-1.32, I2 94.63%, P = .46), or diabetes (ES 1.03, 95% CI 0.86-1.22, I2 78.44%, P = .77). Assisted reproductive technology was associated with a lower risk of heart failure (ES 0.75, 95% CI 0.60-0.94, I2 0.00%, P = .01).
Conclusions:
Assisted reproductive technology use does not appear to be significantly associated with an increased long-term risk of cardiovascular diseases in women. While these findings suggest the cardiovascular safety of fertility treatments, further research is warranted.
