Cardiovascular Risk Following Fertility Therapy: Systematic Review and Meta-Analysis

The longer term cardiovascular effects of fertility therapy are unknown.

The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes.

We systematically searched published reports for studies addressing the question "does fertility therapy increase the risk of longer term cardiovascular outcomes?" We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not.

Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I² = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I² = 0%). Results were not pooled for hypertension (I² = 95.0%) and venous thromboembolism (I² = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I² = 0%).

The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area.