Assisted reproductive technology (ART) does not appear to be significantly associated with increased long-term risk of cardiovascular diseases in women, according to a meta-analysis of 10 studies comprised nearly 37 million participants, published in the European Heart Journal.

Carlo Andrea Pivato, MD, et al., conducted a systematic review and meta-analysis of 7,298 articles on randomized, cohort or case-control studies through MEDLINE. Studies were included in the final meta-analysis if they reported on the association between ART and cardiovascular outcomes (adjusted for confounding factors including age), there was a control group and at least one year of follow-up. The study protocol was registered on PROSPERO.

ART was defined as both in vitro fertilization (IVF)-based and non–IVF-based approaches, including ovarian stimulation drugs (gonadotropin-releasing hormone agonist or antagonist), clomiphene citrate and ovulation induction drugs such as letrozole.

In the 10 studies included in the meta-analysis, 500,664 women underwent ART. They were likely to be older, have more ovulatory disorders such as polycystic ovary syndrome, and have more cardiovascular risk factors except for smoking. They were also more likely to have pregnancy-related complications. Women were included in the comparison group regardless of baseline fertility or whether they had ever been pregnant.

Results showed that ART did not appear to be significantly associated with increased risk of cardiovascular diseases in women over a median follow-up of 10 years after adjusting for confounders, including the likelihood of major adverse cardiac events (MACE) (effect size [ES], 1.04), coronary heart disease (ES, 0.88), stroke (ES, 1.21), venous thromboembolism (ES, 0.95), hypertension (ES, 1.08) or diabetes (ES, 1.03).

ART was also associated with a lower risk of heart failure (ES, 0.75), which could be impacted by ART type, lifestyle or socioeconomic factors.

However, studies with shorter follow-up periods reported more elevated risk of cardiovascular and cerebrovascular events following ART.

"Any initial risk signal may become diluted as more events occur due to other causes, rendering the association undetectable at 10 years," write the authors. "This interpretation suggests that ART could indeed increase short-term MACE incidence, an effect we cannot presently exclude."

Keywords: Reproductive Techniques, Assisted, Fertility, Heart Disease Risk Factors