Does ART failure signal CVD risk?

Failure of assisted reproductive therapy (ART) may be a sex-specific risk factor for cardiovascular disease (CVD), according to results of a new study by Canadian researchers. The correlation was particularly striking, say the authors, among women with a prior miscarriage.

Published in CMAJ, the findings are from a population-based cohort analysis of women who received gonadotropin-based ART between April 1, 1993 and March 31, 2011. Multivariable Poisson regression was used to estimate the relative rate of cardiovascular events (nonfatal coronary ischemia, acute stroke, transient ischemic attack, heart failure, or thromboembolism) associated with failure of ART. Adjustments were made for age, year, baseline risk factors, health care history, and number of fertility cycles.

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Among the 28,442 women included in the study, 9,349 (32.9% gave birth and 19,093 (67.1%) did not. The annual rate of cardiovascular events was 19% higher in the women who did not give birth after ART than among those who did (1.08 vs 0.91/100 patient-years, P<0.001), which is equivalent to a 21% relative increase in the annual rate (95% confidence interval 13% to 30%).

Looking at age, number of infertility cycles, type of infertility and history of prior miscarriage, the authors found that only miscarriage accentuated the risk of CVD associated with failed ART (interaction P=0.06). The absolute risk of CVD, the authors said, was modest and the relative risk was mostly confined to the first 5 years after ART. Limitations of the study included an inability to identify less invasive forms of ART and lack of information on clinical factors such as blood pressure, cholesterol levels, and ventricular function.

“A potential increase in cardiovascular events,” the author said, “may become increasingly relevant with broader utilization of fertility therapy and longer follow-up.” They concluded that further research may be warranted on ART as a sex-specific CVD risk factor so that women undergoing infertility treatment who might benefit from CVD risk evaluation can be identified. Commenting on the findings, Editor-in-Chief Dr Charles Lockwood said, ”The link between failed infertility and CVD may reflect the higher rate of obesity and lipid disorders in the failed group, which in turn may reflect higher levels of insulin resistance.”

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