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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

10 Citations (Scopus)

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.

Original language	English
Article number	ehae886
Number of pages	12
Journal	European Heart Journal
Early online date	23 Dec 2024
DOIs	https://doi.org/10.1093/eurheartj/ehae886
Publication status	E-pub ahead of print - 23 Dec 2024

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Pivato, C. A., Inversetti, A., Condorelli, G., Chieffo, A., Levi-Setti, P. E., Latini, A. C., Busnelli, A., Messa, M., Cristodoro, M., Bragato, R. M., Francone, M., Zuccolo, L., Ieva, F., Di angelantonio, E., Stefanini, G., & Di simone, N. (2024). Cardiovascular safety of assisted reproductive technology: a meta-analysis. European Heart Journal, Article ehae886. Advance online publication. https://doi.org/10.1093/eurheartj/ehae886

@article{3cb1805a02ad4ba2941c7255040907e4,

title = "Cardiovascular safety of assisted reproductive technology: a meta-analysis",

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.",

author = "Pivato, \{Carlo Andrea\} and Annalisa Inversetti and Gianluigi Condorelli and Alaide Chieffo and Levi-Setti, \{Paolo emanuele\} and Latini, \{Alessia chiara\} and Andrea Busnelli and Martina Messa and Martina Cristodoro and Bragato, \{Renato maria\} and Marco Francone and Luisa Zuccolo and Francesca Ieva and \{Di angelantonio\}, Emanuele and Giulio Stefanini and \{Di simone\}, Nicoletta",

year = "2024",

month = dec,

day = "23",

doi = "10.1093/eurheartj/ehae886",

language = "English",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

}

TY - JOUR

T1 - Cardiovascular safety of assisted reproductive technology

T2 - a meta-analysis

AU - Pivato, Carlo Andrea

AU - Inversetti, Annalisa

AU - Condorelli, Gianluigi

AU - Chieffo, Alaide

AU - Levi-Setti, Paolo emanuele

AU - Latini, Alessia chiara

AU - Busnelli, Andrea

AU - Messa, Martina

AU - Cristodoro, Martina

AU - Bragato, Renato maria

AU - Francone, Marco

AU - Zuccolo, Luisa

AU - Ieva, Francesca

AU - Di angelantonio, Emanuele

AU - Stefanini, Giulio

AU - Di simone, Nicoletta

PY - 2024/12/23

Y1 - 2024/12/23

N2 - 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.

AB - 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.

U2 - 10.1093/eurheartj/ehae886

DO - 10.1093/eurheartj/ehae886

M3 - Article (Academic Journal)

C2 - 39710934

SN - 0195-668X

JO - European Heart Journal

JF - European Heart Journal

M1 - ehae886

ER -

Cardiovascular safety of assisted reproductive technology: a meta-analysis

Abstract

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