Certain Fertility Treatments Do Not Increase CVD Risk for Mothers, Study Says

Assisted reproductive technology (ART) use is not associated with an increased risk of cardiovascular disease (CVD) for the mother, according to new research published today in JAMA Cardiology.

The global utilization of ART is on the rise, but the effects of these treatments on an individual's long-term well-being—including potential risk of CVD—remain largely uncertain due to the limited number of studies conducted and their relatively short follow-up.

To assess the potential effect of ART on CVD risk, investigators conducted a registry-based cohort study using national data on nearly 2.5 million individuals from Denmark, Finland, Norway, and Sweden. Data from 1984 to 2015 were available, with years slightly varying by country, and the data analysis was conducted in 2022. Of the 2,496,441 women with a registered delivery in the national birth registries during these timeframes, 97,474 (4%) gave birth after using ART.

Information about ART use was pulled from ART quality and medical birth registries, and information on CVD was pulled from patient and cause-of- death registries. In this study, ART included in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) and the use of fresh or frozen embryo transfer.

It’s important to note for generalizability that, although the authors also used the term individuals, the study only included women. Additionally, the study excluded women who gave birth before the start of the registries, women who died or emigrated before follow-up, and women with preexisting CVD. The investigators also did not examine CVD risk among women who used ART and did not have a child.

The median (IQR) follow-up in the study was 11 (5-18) years, and the overall rate of CVD was 153 per 100,000 person-years. The mean (SD) age of women who had not used ART was 29.1 (4.9) years, and the median age of women who had used ART was slightly older, at 33.8 (4.7) years.

Importantly, the investigators did not find an increased risk of CVD for women who gave birth after using ART compared with women who gave birth without using ART (adjusted HR [aHR], 0.97; 95% CI, 0.91-1.02). They also found evidence of heterogeneity between the 4 countries when only looking at the association between ART and deep vein thrombosis (I², 76%; P = .01 for heterogeneity).

“When we further explored the source of heterogeneity in the estimates between countries, by excluding each country in turn, we found that Finland was the main source of this,” they noted.

There were also no significant differences in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis with the use of ART. However, there was a slightly reduced risk of myocardial infarction (aHR, 0.80; 95% CI, 0.65-0.99) among women who used ART, without any notable heterogeneity between countries.

There were also important findings when looking at each ART fertilization method. First, the authors observed a lower CVD risk among women who used ICSI compared with women who used no ART.

“A lower risk among individuals who had used ICSI was also observed for the other outcomes, although the CIs were wide and included the null value,” the authors said.

They also found a weak association between frozen embryo transfers and an increased risk of stroke (HR, 1.59; 95% CI, 1.11-2.26), but not for fresh embryo transfers (HR, 0.91; 95% CI, 0.80-1.05). After further adjusting for pregnancy complications, this association between frozen embryo transfer and stroke risk persisted (aHR, 1.58; 95% CI, 1.10-1.04).

The authors noted that adjusting for multiple gestation and pregnancy complications did not change the study’s results, nor did excluding pulmonary embolism or deep vein thrombosis from the definition of CVD.

“These findings may be reassuring to the increasing number of individuals who require assistance from ART to conceive,” the authors said. “Future studies with longer follow-up may be useful to reexamine differences in the risk of CVD according to ART methods.”

Reference

Magnus MC, Fraser A, Håberg SE, et al. Maternal risk of cardiovascular disease after use of assisted reproductive technologies. JAMA Cardiol. Published online August 9, 2023. doi:10.1001/jamacardio.2023.2324