Failed Fertility Treatment Tied to Later Cardiac Disease

Jennifer Garcia

March 13, 2017

Women who undergo fertility treatment but fail to give birth may be at increased risk for cardiovascular events years later when compared with women who successfully conceived.

"More informed decision-making around reproductive technology requires an awareness of potential risks and the need for continued long-term clinical care," write Jacob Udell, MD, MPH, from the University of Toronto, Institute for Clinical Evaluative Sciences, and colleagues in an article published online March 13 in CMAJ.

Noting that there are limited data on the long-term effects of fertility treatment, the researchers evaluated data from 28,442 women in Ontario, Canada, who were treated with gonadotropin-based fertility therapy between April 1, 1993, and March 31, 2011. The mean age of the women was 35.2 years (standard deviation, 4.8 years), and the median number of fertility cycles was 3.

Treatment was successful in 9349 (32.9%) women, whereas 19,093 (67.1%) women did not give birth within 1 year of their final treatment.

Cardiovascular events included stroke, nonfatal coronary ischemia, transient ischemic attack, heart failure, or thromboembolism.

The researchers found that during the 8.4-year median follow-up period (interquartile range, 5.3-12.4 years), women who did not give birth had a 19% higher risk for cardiovascular events compared with women who did give birth after fertility therapy (1.08 vs 0.91 events per 100 patient-years; relative rate ratio, 1.19, 95% confidence interval, 1.11 - 1.27).

The authors noted that the increase in events was primarily a result of increases in heart failure and cerebrovascular events specifically, and that the risk appeared to be irrespective of the number of fertility treatment cycles.

The authors emphasize, however, that although the relative risk was higher, the absolute risk was modest, "equal to about 4 additional cardiac events for every 1000 women treated for 10 years of follow-up amongst those who did not deliver a child," Dr Udell explained in an audio interview with the journal.

The study authors acknowledge that the cause for the increase rate of cardiovascular events after fertility failure therapy is complex and likely multifactorial. Proposed mechanisms include direct activation of the renin-angiotensin system with ovarian hyperstimulation and subsequent vascular complications.

Alternatively, Dr Udell theorized that having to undergo fertility therapy may act as a cardiometabolic "stress test," and "may uncover those who are destined for medical troubles."

The authors acknowledge that there are limitations to any study that relies on administrative data, and note that potentially pertinent information regarding blood pressure, ventricular function, and cholesterol levels was lacking. Further, they note, the results should be interpreted with caution, as other risk factors and underlying mechanisms may also affect the risk for cardiovascular disease.

"A potential increase in cardiovascular events may become increasingly relevant with broader utilization of fertility therapy and longer follow-up," the authors write. As more women contemplate fertility treatment, Dr Udell and colleagues conclude that "[f]ertility therapy failure may be another sex-specific cardiovascular risk factor that warrants further research to identify women who may benefit from a cardiovascular risk evaluation."

Funding for this study was provided by the Heart and Stroke Foundation of Canada and the Canada Research Chair in Medical Decision Science. The authors have disclosed no relevant financial relationships.

CMAJ. Published online March 13, 2017. Full text

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