1. In a large cohort study, fertility therapy was not associated with increased risk of maternal cardiovascular events.
2. Fertility therapy was associated with an increased risk of maternal metabolic syndromes during pregnancy, including gestational diabetes, pre-eclampsia and eclampsia.
Evidence Rating Level: 2 (Good)
Study Rundown: This study found that although fertility therapy was associated with increased risk of maternal metabolic syndromes during pregnancy, it was not associated with increased risk of long-term maternal cardiovascular events. These findings are especially pertinent given the increasing use of fertility treatments (from 0.25% incidence in 1993 to 1.25% in 2010 in this study population).
This is the first large-scale, population-based study to look at the long-term cardiovascular effects of fertility treatment. However, findings are limited by the use of an exposure proxy whereby the monitoring of iatrogenic ovulation was used as a surrogate for fertility therapy and inclusion of only those women whose fertility treatment resulted in live birth. Future investigations might prospectively assess outcomes in women following fertility treatments (regardless of cycle outcome) compared to age-matched controls and might also stratify by number of treatment cycles to evaluate dose-response.
In-Depth [population-based cohort study]: This study used information from the Ontario Health Insurance Plan to compare outcomes following 1,186,753 deliveries between 1993 and 2010 in women who received fertility treatment (n=6,979) within 2 years of delivery compared to those who did not (n=1,179,774). The primary outcome was a composite of cardiovascular events including death, MI, stroke, TIA, thromboembolism, and heart failure.
Over a median long-term follow-up of 9.7 years, women in the fertility cohort had fewer cardiovascular events than controls (HR=.96, 95% CI-.72-1.29). The cardiovascular event hazard ratio was further reduced after adjusting for age, income, prior medical history, and prenatal/antenatal care (aHR=0.55, 0.41-0.74). During pregnancy, women in the fertility group were significantly more likely to develop gestational diabetes (8% vs 3%, p<.001), pre-eclampsia/eclampsia (7% vs 3%, p<.001), and preterm labor (16% vs 8%, p<.001). Women in the fertility cohort were more likely to be older, of a higher socioeconomic class, and have more prenatal care than controls.
By Maren Shapiro and Leah Hawkins, MD, MPH
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