Risk of Stroke Hospitalization After Infertility Treatment

Abstract

ImportanceStroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results.ObjectiveTo evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment.Design, Setting, and ParticipantsThis population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023.ExposureHospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception.Main Outcomes and MeasuresThe primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis.ResultsOf 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, −6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases.Conclusions and RelevanceIn this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.

Association of Assisted Reproductive Technology and Stroke During Hospitalization for Delivery in the United States

“…10 We are unable to determine the specific treatment regimen used in ART or the time of ART treatment relative to hospitalization or to stroke onset. Although we used previously validated algorithms to identify all stroke events, 10,[16][17][18][19][20][21][22] we recognize that this approach could have led to imperfect end point ascertainment as other researchers have used alternate ICD-10-CM algorithms to define stroke in pregnancy. Third, we lack specific details regarding the size, location, and etiology of stroke since radiographic data are not included in NIS.…”

Risk of stroke the year following a delivery after using assisted reproductive technologies

“…Data from all countries were pooled, and the multivariable analysis adjusted for age (linear and squared term) and year at the start of follow-up, country, and multiple birth, similar to the adjustment strategy in the study by Sachdev and colleagues. 8 In addition, we explored adjustment for chronic hypertension and diabetes mellitus. We do not show country-specific estimates due to small numbers.…”

“…In secondary analyses, we defined ischemic stroke as ICD‐8 and 9 codes 433–437; ICD‐10 codes I63, I65–I67and haemorrhagic stroke as ICD‐8 and 9 codes 430–432; ICD‐10 codes I60–I62 and I69. The outcome definitions are in line with Sachdev et al 8 …”

“…In addition, we obtained information on pre‐pregnancy diabetes mellitus (yes vs. no), pre‐pregnancy chronic hypertension (yes vs. no), stillbirth (yes vs. no), delivery by caesarean (yes vs. no) and whether there were complications such as pre‐eclampsia (yes vs. no), preterm birth (<37 completed gestational weeks; yes vs. no) and small‐for‐gestational age (based on Marsál equations 10 ; yes vs. no). We only included descriptive information on pregnancy outcomes and did not adjust for these, as they could be potential intermediates, similar to what the U.S. study did 8 …”

“…[3][4][5][6][7] A recently published U.S. study using the Nationwide Readmissions Database (NRD) found a higher risk of stroke during the first year after delivery following ART. 8 It was not possible to follow individuals in this database across calendar years, meaning that only deliveries occurring in January had a full year of follow-up, and data on parity were not available, possibly representing uncontrolled confounding. Our objective was to replicate the analyses in a large Nordic registry linkage on an unselected population in countries with universal health care.…”