Failure of fertility therapy and subsequent adverse cardiovascular events

Abstract

Background: Infertility may indicate an underlying predisposition toward premature cardiovascular disease, yet little is known about potential long-term cardiovascular events following fertility therapy. We investigated whether failure of fertility therapy is associated with subsequent adverse cardiovascular events.

Methods: We performed a population-based cohort analysis of women who received gonadotropin-based fertility therapy between Apr. 1, 1993, and Mar. 31, 2011, distinguishing those who subsequently gave birth and those who did not. Using multivariable Poisson regression models, we estimated the relative rate ratio of adverse cardiovascular events associated with fertility therapy failure, accounting for age, year, baseline risk factors, health care history and number of fertility cycles. The primary outcome was subsequent treatment for nonfatal coronary ischemia, stroke, transient ischemic attack, heart failure or thromboembolism.

Results: Of 28 442 women who received fertility therapy, 9349 (32.9%) subsequently gave birth and 19 093 (67.1%) did not. The median number of fertility treatments was 3 (interquartile range 1-5). We identified 2686 cardiovascular events over a median 8.4 years of follow-up. The annual rate of cardiovascular events was 19% higher among women who did not give birth after fertility therapy than among those who did (1.08 v. 0.91 per 100 patient-years, p < 0.001), equivalent to a 21% relative increase in the annual rate (95% confidence interval 13%-30%). We observed no association between event rates and number of treatment cycles.

Interpretation: Fertility therapy failure was associated with an increased risk of long-term adverse cardiovascular events. These women merit surveillance for subsequent cardiovascular events.

Figure 1:

Cumulative incidence of major cardiovascular events or death per 1000 patient-years following fertility therapy failure or success.

Figure 2:

Risk of cardiovascular events or death following fertility therapy failure versus fertility therapy success, stratified by baseline risk factors. Adjusted rate ratios greater than 1.0 indicate an increased risk following fertility therapy failure. Error bars = 95% confidence intervals, CI = confidence interval.

Figure 3:

Cumulative incidence of major cardiovascular events or death per 1000 patient-years following fertility therapy failure or success, stratified by number of treatment cycles.