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

Hum Reprod. 2015 Jul;30(7):1724-31. doi: 10.1093/humrep/dev090. Epub 2015 Apr 29.


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 pregnancies in each woman's history, and could therefore not compare risk in ART versus SC pregnancies in the same mother.

Wider implications of the findings: Pregnancies following frozen-thawed cycles have a higher risk of hypertensive disorders, also when compared with fresh cycle pregnancies by the same mother. The safety aspects in frozen-thawed cycles merit further attention.

Study funding/competing interests: Funding was received from the European Society for Human Reproduction and Embryology, the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, the Nordic Federation of Societies of Obstetrics and Gynecology and the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology. None of the authors has any competing interests to declare.

Keywords: assisted reproductive technology; cryopreservation; hypertensive disorders in pregnancy; pre-eclampsia; sibling analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Cryopreservation* / statistics & numerical data
  • Female
  • Humans
  • Hypertension, Pregnancy-Induced / epidemiology
  • Hypertension, Pregnancy-Induced / etiology*
  • Pregnancy
  • Pregnancy, Twin* / statistics & numerical data
  • Registries*
  • Reproductive Techniques, Assisted / adverse effects*
  • Reproductive Techniques, Assisted / statistics & numerical data
  • Risk
  • Scandinavian and Nordic Countries / epidemiology
  • Siblings
  • Young Adult