Cardiovascular safety of assisted reproductive technology: a meta-analysis

Carlo Andrea Pivato; Annalisa Inversetti; Gianluigi Condorelli; Alaide Chieffo; Paolo Emanuele Levi-Setti; Alessia Chiara Latini; Andrea Busnelli; Martina Messa; Martina Cristodoro; Renato Maria Bragato; Marco Francone; Luisa Zuccolo; Francesca Ieva; Emanuele Di Angelantonio; Giulio Stefanini; Nicoletta Di Simone

doi:10.1093/eurheartj/ehae886

Cardiovascular safety of assisted reproductive technology: a meta-analysis

Eur Heart J. 2024 Dec 23:ehae886. doi: 10.1093/eurheartj/ehae886. Online ahead of print.

Authors

Carlo Andrea Pivato^{1

2}, Annalisa Inversetti^{1

2}, Gianluigi Condorelli^{1

2}, Alaide Chieffo³, Paolo Emanuele Levi-Setti^{1

2}, Alessia Chiara Latini^{1

2}, Andrea Busnelli^{1

2}, Martina Messa^{1

2}, Martina Cristodoro^{1

2}, Renato Maria Bragato^{1

2}, Marco Francone^{1

2}, Luisa Zuccolo^{4

5}, Francesca Ieva^{5

6}, Emanuele Di Angelantonio^{5

7

8

9

10

11}, Giulio Stefanini^{1

2}, Nicoletta Di Simone^{1

2}

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, Milan 20072, Italy.
² IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
³ Interventional Cardiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁴ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵ Health Data Science Research Centre, Human Technopole, Milan, Italy.
⁶ MOX Laboratory, Department of Mathematics, Politecnico di Milano, Milan, Italy.
⁷ British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁸ Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
⁹ British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
¹⁰ National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge, Cambridge, UK.
¹¹ Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.

PMID: 39710934
DOI: 10.1093/eurheartj/ehae886

Abstract

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.

Keywords: In vitro fertilization; Assisted reproductive technology; Cardiovascular disease; Meta-analysis; Metabolic disease; Systematic review.

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