Infertility Treatments Raise Risk for Stroke After Childbirth

Brittany Vargas

August 31, 2023

Infertility treatments may increase the risk for hemorrhagic and ischemic stroke among new mothers by 66%, according to new research published this week in the Journal of the American Medical Association.

The retrospective cohort study found that infertility treatments — defined broadly and including intrauterine insemination (IUI), assisted reproductive technology (ART), fertility preservation procedures, and the use of a gestational carrier — increased the risk for stroke-related hospitalization up to 12 months after delivery, with the risk being evident a month after delivery. The study did not examine risk rates associated with individual treatments.

"Our findings suggest that we should be more cautious in how we treat patients for infertility care," said lead author Cande V. Ananth, PhD, MPH, vice chair for academic affairs and chief of the Division of Epidemiology and Biostatistics at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

Dr Cande Ananth

Ananth and colleagues drew data from the Nationwide Readmissions Database, which stores information from 28 states, between 2010 and 2018. They looked at rates of hospitalization from nonfatal hemorrhagic and ischemic strokes among 31.34 million US patients aged 15-54 years. Of those, 287,813 (0.9%) underwent infertility treatments and 31.05 million (99.1%) delivered after spontaneous conception.

Ananth's group identified 37 stroke hospitalizations per 100,000 people in the infertility group compared with 29 hospitalizations per 100,000 people in the group that conceived spontaneously, with the risk for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 - 3.61) being higher than for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 - 2.39). The risk increased as time passed, especially in the case of hemorrhagic strokes.

The 66% increase in stroke risk — 41% higher within 30 days — for patients in the infertility group is what's so striking about the data, Ananth said. Still, "the absolute number of hospitalizations is low in the population, as one would expect. Very few people develop strokes."

Dr Zain Al-Safi

"This study may point to a possible association rather than causation," said Zain A. Al-Safi, MD, a reproductive endocrinologist and infertility specialist at UCLA Health in Los Angeles. "Generally, those with obesity, diabetes/prediabetes, hypertension, and other metabolic abnormalities can have associated infertility, such as ovulatory disorders. Treating the fertility problem would have those patients conceiving, and those pregnancies can have higher risks for cerebrovascular disorders."

However, infertility treatments themselves may affect stroke risk, Ananth said.

First, "any infertility treatment predisposes patients to develop vascular complications in pregnancy itself. Studies have shown that women who receive infertility treatment carry increased risks for preeclampsia  and placental abruption, which have vascular origins."

Infertility treatments also can damage endothelial cells and cause thrombosis, he said, both of which are associated with cardiovascular disease and stroke risk later in life.

Ananth also cited traditional epidemiologic factors like alcohol use, obesity, genetics, and age, which is strongly associated with stroke, as possible contributing factors. 

"We don't know exactly which pathways are acting in this population, but we expect that any one or more of them could be implicated in the association to stroke risk," he said.

According to Al-Safi, clinicians should aim to help patients improve metabolic health prior to pregnancy and monitor for the development of risk factors like hypertension, preeclampsia, or diabetes during pregnancy, as those can increase the risk for cerebrovascular disorders after delivery.

"Hypertension and preeclampsia would be among the most important risk factors, and those can be higher in patients with infertility," Al-Safi said. 

Informing patients about the stroke risk should be a part of the precounseling process in infertility treatment, Ananth said. Physicians should also work with patients to mitigate risk factors like smoking and obesity through lifestyle changes. 

A rigorous approach to follow-up during the postpartum period also is critical, he added.

"Given the increased stroke risk within the first 30 days after delivery, it's incredibly important that physicians follow up within 6 weeks of delivery, as recommended by the American College of Obstetricians and Gynecologists," he said. "Even after the initial 6 weeks, there should be constant follow-up, at 3 months, 6 months, and even at the end of the year."

The study was funded by the National Heart, Lung, and Blood Institute and the National Institute of Environmental Health Sciences. The authors report no relevant financial relationships.

Brittany Vargas is a health, science, and wellness reporter who covers breaking news.

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