Women's risk of hypertension and cardiovascular disease subtypes by number of cycles of assisted reproductive technologies: a Norwegian registry-linkage study

AIMS: To assess the risk of hypertension and cardiovascular disease (CVD) in relation to the number of assisted reproductive technologies (ART) cycles. METHODS AND RESULTS: In this registry-based study, we studied women in Norway born between 1965 and 2000 still alive and residing in Norway on 1 January 2009. ART cycles were identified according to a sequence of dispensed prescriptions relating to ART treatments. We used Cox regression to evaluate the risk of hypertension (1 611 843 women/42 292 used ART) and CVD (1 625 301 women/42 763 used ART) according to the number of ART cycles the women had undergone as a time-varying exposure, adjusting for age, education, diabetes, PCOS, endometriosis, and parity. The median follow-up time was 12 years (IQR 10-12). We conducted two analyses, first using those who had not undergone ART as reference, and subsequently using those who had undergone one ART cycle as reference. Each additional ART cycle was associated with a modest increased CVD risk (HR 1.07; 95% CI: 1.04-1.10), but no clear increased risk of hypertension (HR 1.02; 95% CI: 1.00-1.04). Elevated CVD risk was primarily driven by pulmonary embolism and deep vein thrombosis. We observed weak evidence for an increased risk among those with four or more cycles (HR 1.34; 95% CI: 0.99-1.81). Programmed frozen cycles were more strongly associated with CVD risk (HR 1.35; 95% CI: 1.18-1.55). CONCLUSION: Although a clear dose-response relationship was not observed, women who underwent ART had an increased risk of CVD, mainly driven by thromboembolism.