Effects of assisted reproductive techniques on offspring cardiovascular health: a systematic review and meta-analysis

Assisted reproductive techniques (ART) are increasingly used worldwide. Concerns persist regarding the long-term cardiovascular health of ART-conceived offspring. To systematically review and meta-analyze cardiovascular, vascular, and echocardiographic outcomes in ART-conceived offspring compared with naturally conceived children. PubMed and Scopus were searched from database inception to January 2025. Reference lists of eligible articles were manually screened. Searches included terms related to assisted reproductive technologies, offspring, and cardiovascular outcomes. Only human studies published in English were included. Observational cohort, cross-sectional, and case-control studies evaluating cardiovascular outcomes in ART-conceived offspring with a naturally conceived comparison group were eligible. Studies without relevant outcomes, lacking a control group, or including populations with genetic conditions affecting cardiovascular health were excluded. Two reviewers independently screened studies, with disagreements resolved by a third investigator. Eighty-one studies met inclusion criteria. Data extraction was independently performed by two reviewers following PRISMA and MOOSE guidelines. Risk of bias and study quality were assessed using the Cambridge Quality Checklist. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity (I² statistic). Meta-regression analyses explored the influence of parental and perinatal factors. Primary outcomes included vascular indices (carotid intima-media thickness [CIMT], flow-mediated dilation [FMD]), risk of congenital heart disease (CHD), echocardiographic measures of cardiac structure and function, and blood pressure. ART conception was associated with increased CIMT in singleton offspring (mean difference, 0.03 mm; 95% CI, 0.01-0.06) and reduced FMD (mean difference, - 2.32%; 95% CI, - 3.05 to - 1.59). ART-conceived children showed a higher risk of CHD, including severe forms, particularly in singleton pregnancies. Echocardiographic analyses revealed subtle alterations in left ventricular function, including reduced shortening fraction and prolonged isovolumetric relaxation time. Systolic blood pressure was slightly higher in ART offspring. Meta-regression indicated that vascular and echocardiographic alterations were largely independent of parental age, body mass index, gestational age, and birth weight. ART conception is associated with early vascular dysfunction, increased CHD risk, and subtle cardiac functional alterations that may precede future cardiovascular disease, supporting the need for long-term cardiovascular follow-up.