Cardiovascular Safety of Fertility Therapy: A Systematic Review and Meta-Analysis
Abstract Body (Do not enter title and authors here): 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 via MEDLINE (Pubmed) from inception to January 2024. Randomized, cohort or case-control studies were included if fulfilling the following criteria: the association between fertility therapy and the subsequent cardiovascular outcome was reported and conditioned on confounding factors (at least age); the presence of a control group; minimum one-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 with PROSPERO (CRD42024505605). Results: Of 7,298 articles screened, eleven studies were included, encompassing 606,912 women undergoing ART and 70,562,486 controls. The analysis found no increase in the long-term risk of major adverse cardiovascular events (ES=0.97, 95% CI=0.81-1.16, I2=89.55%, p=0.73), coronary heart disease (ES=0.88, 95% CI=0.71-1.10, I2=24.36%, p=0.26), stroke (ES=1.20, 95% CI=0.96-1.49, I2=48.33%, p=0.11), heart failure (ES=0.74, 95% CI=0.60-0.94, I2=0.00%, p=0.01), venous thromboembolism (ES=1.03, 95% CI=0.78-1.34, I2=54.41%, p=0.85), hypertension (ES=1.08, 95% CI=0.88-1.326, I2=94.63%, p=0.46), or diabetes (ES=1.03, 95% CI=0.86-1.22, I2=78.44%, p=0.77). Conclusions: ART does not increase the long-term risk of cardiovascular diseases in women. These results support the cardiovascular safety of fertility treatments, though further research into specific ART techniques and extended follow-up is recommended.
Pivato, Carlo Andrea
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Bragato, Renato
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Francone, Marco
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Zuccolo, Luisa
( Human Technopole
, MILAN
, Italy
)
Ieva, Francesca
( Human Technopole
, MILAN
, Italy
)
Di Angelantonio, Emanuele
( Human Technopole
, MILAN
, Italy
)
Stefanini, Giulio
( Humanitas University
, Milan
, Italy
)
Inversetti, Annalisa
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Condorelli, Gianluigi
( HUMANITAS UNIVERSITY
, Pieve Emanuele Milan
, Italy
)
Chieffo, Alaide
( San Raffaele Scientific Institute
, Milan
, Italy
)
Levi Setti, Paolo
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Latini, Alessia Chiara
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Busnelli, Andrea
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Messa, Martina
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Cristodoro, Martina
( IRCCS Humanitas Research Center
, Rozzano
, Italy
)
Author Disclosures:
Carlo Andrea Pivato:DO NOT have relevant financial relationships
| Renato Bragato:No Answer
| Marco Francone:No Answer
| LUISA ZUCCOLO:No Answer
| FRANCESCA IEVA:No Answer
| EMANUELE DI ANGELANTONIO:No Answer
| Giulio Stefanini:No Answer
| ANNALISA INVERSETTI:No Answer
| Gianluigi Condorelli:No Answer
| Alaide Chieffo:No Answer
| PAOLO LEVI SETTI:No Answer
| Alessia Chiara Latini:DO NOT have relevant financial relationships
| ANDREA BUSNELLI:No Answer
| MARTINA MESSA:DO NOT have relevant financial relationships
| Martina Cristodoro:No Answer