Use of ART Did Not Harm Moms’ Long-Term Cardiovascular Health

Women who conceived with assisted reproductive technology (ART) did not have worse long-term cardiovascular outcomes, according to a large Nordic registry-based study.

Between those who gave birth with and without ART, risk of cardiovascular disease (CVD) was similar over a median 11 years of follow-up (adjusted HR 0.97, 95% CI 0.91-1.02), reported researchers led by Maria Magnus, PhD, of the Norwegian Institute of Public Health in Oslo, and colleagues.

Rates of incident ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis were unchanged with ART. Even better, there was a modest reduction in the risk of myocardial infarction (adjusted HR 0.80, 95% CI 0.65-0.99), the authors reported in JAMA Cardiology.

“These findings may be reassuring to the increasing number of individuals who require assistance from ART to conceive,” Magnus and colleagues wrote.

However, one red flag that emerged from the study was a signal suggesting that frozen embryo transfers were associated with increased CVD risk (HR 1.24, 95% CI 1.02-1.51), namely excess strokes (HR 1.59, 95% CI 1.11-2.26).

Furthermore, while there was no increased risk for CVD after use of ART, there was significant evidence of heterogeneity among the participating countries of Denmark, Finland, Norway, and Sweden.

“The results for the different ART methods were imprecise, and larger studies with longer follow-up are needed,” Magnus and team wrote. “Potential explanations for heterogeneity in the estimates between countries include differences in our ability to capture CVD across the countries (particularly outpatient diagnoses) and variation in the predominant ART methods used (no information on ART method was available for Finland to compare with the other countries).”

Things are nevertheless looking up for the use of ART, which as a whole had been linked to a higher maternal risk of cerebrovascular disease in prior smaller observational studies.

“These null findings from a large population-based sample that included all live births from 4 countries during 3 decades provide reassurance about the short-term cardiovascular safety of ART in birthing individuals,” noted JAMA Cardiology associate editor Sadiya Khan, MD, MSc, and colleagues of Northwestern University Feinberg School of Medicine in Chicago, in an accompanying editorial.

“Given the growing exposure to ART among birthing individuals, these longitudinal data on longer-term cardiovascular health are much needed,” they added.

ART’s effects outside maternal cardiovascular health are also under investigation. For instance, there is conflicting evidence on whether children conceived with ART are more prone to developing childhood cancers.

For their study, Magnus and colleagues used nationwide records from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1985-2015) that included nearly 2.5 million people with a registered delivery and no pre-existing CVD.

Of the whole cohort, 4% had given birth after using ART, including in vitro fertilization with or without intracytoplasmic sperm injection or the use of fresh or frozen embryo transfer. Women who gave birth after ART tended to be older, had a lower parity, and were less likely to use tobacco compared with those who gave birth without ART.

Participants were followed starting from 2 years after their first registered delivery. At start of follow-up, mean age was 29.1 years and 33.8 years for the non-ART and ART groups, respectively.

The investigators acknowledged that they could not identify whether someone had given birth as a result of non-ART assistance such as intrauterine insemination or ovulation induction. Women who had undergone ART but remained without a delivery were also excluded.

Khan’s group added that the Nordic populations in the study may not represent the diversity of the U.S. “However, U.S.-based studies may encounter their own unique challenges, given use of ART is often self-pay and may not be documented in electronic health record databases,” they noted.

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