ART linked to higher stroke risk during delivery

Women who underwent assisted reproductive technology (ART) were significantly more likely to experience strokes during delivery hospitalization than those who did not use ART, according to a study presented at ISC 2024.

“This association may reflect effects of ART on stroke risk or a relationship between subfertility and stroke. Subfertility itself has been associated with cardiovascular disease, and endometriosis, a common cause of infertility, is increasingly recognized as a stroke risk factor,” the researchers wrote. [Stroke 2024;doi:10.1161/STROKEAHA.124.046419]

“[ART] is generally considered a safe therapy, [but] there are certain risks and complications that have been associated with it,” said Dr Alis Dicpinigaitis from Weill Cornell Medicine in New York City, US.

Using data from the National Inpatient Sample registry between 2015 and 2020, the researchers conducted a retrospective cohort study of 19,123,125 delivery hospitalizations for women aged 15–55 years, of whom approximately 200,000 were treated with ART.

At baseline, ART users had higher cardiovascular comorbidities and stroke risk factors than women who did not receive ART.

The primary clinical endpoint of the study was any stroke, including ischemic stroke (IS), subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH), and cerebral venous thrombosis (CVT), that occurred during the index delivery hospitalization, and each stroke subtype was evaluated separately as a secondary endpoint.

Women who received ART had a significantly higher rate of any stroke than those who did not (27.1 vs 9.1 per 100,000 person-years; p<0.001). [ISC 2024, abstract 11]

Moreover, the rates of acute IS (9.9 vs 3.4 per 100,000 person-years), SAH (7.4 vs 1.6 per 100,000 person-years), ICH (7.4 vs 2.0 per 100,000 person-years), and CVT (7.4 vs 2.7 per 100,000 person-years) were significantly increased among ART users vs non-ART users (p<0.001 for all).

The association remained after adjusting for age, cardiovascular comorbidity, and stroke risk factors. ART use was associated with a higher likelihood of experiencing any stroke (adjusted odds ratio [adjOR], 2.14; p<0.001), but not CVT (adjOR], 0.82; p<0.002).

Notably, haemorrhagic stroke rates were remarkably higher among ART users than nonusers (adjORs, 3.83 [SAH] and 5.37 [ICH]; p<0.001 for both).

Among patients who developed stroke during delivery hospitalizations, ART-treated patients had significantly higher inhospital mortality rates compared with nontreated patients, (27.3 percent vs 6.1 percent; p<0.001), along with longer hospital stays (median 21 vs 5 days; p<0.001). According to Dicpinigaitis, this result may be attributed to the fact that these ART patients presented with a higher stroke severity at baseline than non-ART patients.

When patients were stratified according to maternal age, stroke risk was also significantly higher among ART users compared with nonusers, regardless of whether the patients were older (≥35 years: 30.6 vs 14.7 per 100,000 person-years; p=0.004) or younger (<35 years: 26.0 vs 8.2 per 100,000 person-years; p<0.001).

“[Overall], using large-scale, population-level data, we found an increased association of ART with any stroke, as well as with ischaemic and haemorrhagic strokes individually following adjustment for age and cardiovascular risk factors,” Dicpinigaitis noted.

“It is important to stipulate that we don't think that ART is an overwhelmingly dangerous therapy, nor do we want to dissuade people interested in pursuing ART to not pursue it,” Dicpinigaitis highlighted. “Instead, we advocate for counselling older patients who are planning to receive it and for those who have risk factors for stroke to initiate appropriate treatments and, additionally, to adequately control known stroke triggers during hospitalization, like psychological distress, as well as the development of infection.”