Cardiovascular
Infertility Treatment and Offspring Blood Pressure – A Systematic Review & Meta-analysis Edwina Yeung* Edwina Yeung Priscilla Clayton Ian Alicia Livinski Diane Putnick
Studies have inconsistently observed that children conceived by in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI) have higher blood pressure (BP) compared to children not conceived by assisted reproductive technologies (ART). We updated a 2017 meta-analysis and included data from contemporary cohorts and those with long follow-up. The protocol was registered on PROSPERO (CRD42022374232). Three databases and 4 grey literature sources were searched. Two authors screened 2493 records and extracted data from 35 included studies (from 51 publications). Data was analyzed using metafor and robumeta in R, allowing for robust estimation and clustering of effect sizes within cohorts. Unadjusted and covariate-adjusted statistics were analyzed separately as not all studies had adjusted measures. Covariates included maternal demographics (e.g., age, education, smoking), child characteristics (e.g., sex, age), and at times (25%) birth characteristics. Offspring were conceived between 1982 and 2016. Overall, 36 effect sizes from 24 unique cohorts compared BP between ART (N=4,851) and non-ART (N=8,151, reference) groups. No standardized mean difference (SMD) in systolic (β=0.04, 95%CI=-0.09–0.017), or diastolic (β=0.10, 95%CI=-0.05–0.24) BP by treatment was found, but heterogeneity was considerable (I2=77% for SBP; 88% for DBP). Adjusted analyses from 23 unique cohorts (N=2,220 treatment vs. N=39,778 non-treatment) similarly showed no difference for SBP (Figure) and DBP (β=-0.04, 95%CI=-0.17–0.10) but heterogeneity remained high (I2=63% for SBP; 85% for DBP). Removing 7 studies which adjusted for birth characteristics, as these may be mediators, made no material difference. Analyses were further stratified by type of treatment (i.e., IVF vs. ICSI vs. mixed), study quality, and birth year (<2000 vs. ≥ 2000) as potential moderators, but none reduced heterogeneity. In conclusion, conception by ART was not associated with offspring blood pressure in a meta-analysis, although considerable heterogeneity was observed.
