Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group

• Published in: Human reproduction (Oxford) 2015-07, Vol.30 (7), p.1724-1731
• Main Authors: Opdahl, S., Henningsen, A.A., Tiitinen, A., Bergh, C., Pinborg, A., Romundstad, P.R., Wennerholm, U.B., Gissler, M., Skjærven, R., Romundstad, L.B.
• Format: Article
• Language: English
• Subjects: Adult; assisted reproductive technology; Cohort Studies; cryopreservation; Cryopreservation - statistics & numerical data; EMBRYO-TRANSFER; EUROPEAN; Female; GESTATIONAL HYPERTENSION; Humans; Hypertension, Pregnancy-Induced - epidemiology; Hypertension, Pregnancy-Induced - etiology; hypertensive disorders in pregnancy; IN-VITRO FERTILIZATION; MATERNAL FACTORS; MEDICAL BIRTH REGISTRY; METAANALYSIS; Obstetrics & Gynecology; Obstetrics, Gynecology and Reproductive Medicine; PERINATAL OUTCOMES; POPULATION-BASED COHORT; pre; PREECLAMPSIA; Pregnancy; Pregnancy, Twin - statistics & numerical data; REGISTERS; Registries; Reproductive Biology; Reproductive Techniques, Assisted - adverse effects; Reproductive Techniques, Assisted - statistics & numerical data; Reproduktionsmedicin och gynekologi; Risk; Scandinavian and Nordic Countries - epidemiology; Siblings; Young Adult
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dev090

STUDY QUESTION Is the risk of hypertensive disorders in pregnancies conceived following specific assisted reproductive technology (ART) procedures different from the risk in spontaneously conceived (SC) pregnancies? SUMMARY ANSWER ART pregnancies had a higher risk of hypertensive disorders, in particular following cryopreservation, with the highest risk seen in twin pregnancies following frozen–thawed cycles. WHAT IS KNOWN ALREADY The risk of hypertensive disorders is higher in ART pregnancies than in SC pregnancies. The increased risk may be partly explained by multiple pregnancies and underlying infertility, but a contribution from specific ART procedures has not been excluded. STUDY DESIGN, SIZE, DURATION Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS All registered ART pregnancies and a sample of SC pregnancies with gestational age ≥22 weeks from 1988 to 2007 were included. ART singleton pregnancies (n = 47 088) were compared with SC singleton pregnancies (n = 268 599), matched on parity and birth year. ART twin pregnancies (n = 10 918) were compared with SC twin pregnancies (46 674). We used logistic regression to estimate adjusted odds ratios and risk differences for hypertensive disorders in pregnancies following IVF, ICSI and fresh or frozen–thawed cycles. We also compared fresh and frozen–thawed cycles within mothers who had conceived following both procedures using conditional logistic regression (sibling analysis). MAIN RESULTS AND THE ROLE OF CHANCE Hypertensive disorders were reported in 5.9% of ART singleton and 12.6% of ART twin pregnancies. Comparing singleton pregnancies, the risk of hypertensive disorders was higher after all ART procedures. The highest risk in singleton pregnancies was seen after frozen–thawed cycles [risk 7.0%, risk difference 1.8%, 95% confidence interval (CI) 1.2–2.8]. Comparing twin pregnancies, the risk was higher after frozen–thawed cycles (risk 19.6%, risk difference 5.1%, 95% CI 3.0–7.1), but not after fresh cycles. In siblings, the risk was higher after frozen–thawed cycles compared with fresh cycles within the same mother (odds ratio 2.63, 95% CI 1.73–3.99). There were no clear differences in risk for IVF and ICSI. LIMITATIONS, REASONS FOR CAUTION The number of ART siblings in the study was limited. Residual confounding cannot be excluded. In addition, we did not have information on all SC