Assisted Reproductive Technologies Increase Risk of In-Hospital Stroke in Pregnant Women

In a new retrospective cohort study of population-level data, findings showed an increased risk of any stroke among patients hospitalized for delivery in the United States who used assisted reproductive technologies (ART) compared with nonART users, suggesting an association between ART and stroke among this patient population.¹ Authors recommended clinicians counsel patients who are undergoing ART therapy, regarding potential increased stroke risk, and consider initiating treatments proven to reduce stroke risk before ART.

Among 19,123,125 delivery hospitalizations, patients who used ART prior to hospitalization delivery (n = 202,815; 1.1%) showed significantly higher rates of any stroke (27.1/100,000 vs. 9.1/100,000) in comparison with nonART users (P <.001). The subtypes of stroke observed in these patients included ischemic stroke (IS)(9.9/100,000 vs. 3.3/100,000), subarachnoid hemorrhage (SAH) (7.4/100,000 vs. 1.6/100,000), intracerebral hemorrhage (ICH) (7.4/100,000 vs. 2.0/100,000), and cerebral venous thrombosis (CVT) (7.4/100,000 vs. 2.7/100,000).

“Infertility with ARTs is rapidly increasing in the United States and we were curious about the relationship between use of these technologies and stroke risk during the hospitalization for delivery. It's important to note that this work really is focused on that index hospitalization where the pregnant patients delivers not subsequent stroke risk or preceding stroke risk,” senior author Ava L. Liberman, MD, medical director of the LMH Stroke Center and assistant professor of neurology at Weill Cornell Medicine, told NeurologyLive®.

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Presented at the 2024 International Stroke Conference (ISC), held February 7-9, in Phoenix, Arizona, investigators used data on delivery hospitalizations for patients aged between 15 and 55 years from the National Inpatient Sample registry between 2015 and 2020. The study exposure was use of ART. The primary end point was stroke defined as IS, SAH, ICH, or CVT during index delivery hospitalization and secondary end points were the individual stroke subtypes. Authors used Standard International Classification of Diseases, Tenth Revision, Clinical Modification algorithms to define study exposure, comorbidities, and prespecified end points. Additionally, authors used propensity score adjustment by inverse probability weighting to mimic the effects of randomization by balancing baseline clinical characteristics associated with stroke between ART and nonART users.

In the IPW adjustment and multivariable logistic regression analysis, investigators observed an association between ART and increased odds of any stroke (aOR 2.14; 95% CI, 2.02-2.26; P <.001) including IS (aOR 2.75; 95% CI, 2.51-3.02; P <.001), SAH (aOR 3.83; 95% CI, 3.38-4.33; P <.001), and ICH (aOR 5.37; 95% CI, 4.82-5.98; P <.001). Authors noted an observation of association with decreased odds of CVT (aOR 0.82; 95% CI, 0.72-0.93); P = .002) and stroke in patients.

“I think I think some limitations that we had is that the codes that we use to identify patients who have received ART are not well validated. They've been used in previous studies, but they haven't been compared in detail to chart review of patients,” Liberman added. “Another limitation is that we don't know the timing of ART regarding these delivery hospitalizations; it's possible that a patient could have conceived having nothing to do with the ART they received years ago and still have had that code. Since our focus was on delivery hospitalizations in hospitals, homebirth patients who did not end up having a hospitalization for delivery were not included."

For in-delivery hospitalizations associated with cerebrovascular events (n = 1,785), ART users (n = 55, 3.1%) had significantly greater rates of in-hospital mortality (27.3% vs. 6.1%; P <.001). Investigators observed longer durations of hospital stay (21 [3 – 35] vs. 5 [3 – 10] median days, P < 0.001) in ART as compared with nonART users. In a subgroup analysis of 2,696,309 patients older than 35 years (14.1% of total study cohort), 49,010 (1.8%) of such patients were treated with ART. Those treated with these therapies had significantly higher rates of any stroke (30.6/100,000 vs. 14.7/100,000; P = .004). Additionally, patients younger than 35 years old (n = 16,426,326) treated with ART (n = 153,805, 1.0%) experienced higher rates of any stroke (26.0/100,000 vs. 8.2/100,000; P <.001).

These findings were similar with a different cohort study recently published in JAMA Network Open where investigators observed an association of infertility treatment and an increased risk of stroke-related hospitalization in 12 months of delivery.² “I think the practical takeaways are that in patients who are thinking about undergoing ART and have known vascular risk factors, that we should address those in the established ways that we know how primary prevention for stroke is important. I think more work needs to be done to understand the association that we observed,” Liberman told.

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REFERENCES
1. Dicpinigaitis AJ, Seitz A, Berkin J, et al. Association of Assisted Reproductive Technology and Stroke During Hospitalization for Delivery in the United States. Presented at: International Stroke Conference; February 7-9, 2024; Abstract 11.
2. Sachdev D, Yamada R, Lee R, Sauer MV, Ananth CV. Risk of Stroke Hospitalization After Infertility Treatment. JAMA Netw Open. 2023;6(8):e2331470. Published 2023 Aug 1. doi:10.1001/jamanetworkopen.2023.31470