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


CONCLUSIONS
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.


BACKGROUND
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.


METHODS
Population-based cohort study, including sibling design with nationwide data from health registers in Sweden, Denmark and Norway.


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).


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.


BACKGROUND
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.
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway signe.opdahl@ntnu.no.
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Opdahl
Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
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Henningsen
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
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Tiitinen
Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Bergh
Department of Obstetrics and Gynecology, Hvidovre Hospital, Institute of Clinical Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
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Pinborg
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.
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Romundstad
Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Wennerholm
THL, National Institute for Health and Welfare, Helsinki, Finland Nordic School of Public Health, Gothenburg, Sweden.
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Gissler
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway Medical Birth Registry of Norway, National Institute of Public Health, Bergen, Norway.
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Skjærven
Department of Public Health and General Practice, Norwegian University of Science and Technology, Trondheim, Norway Fertility Unit, Department of Obstetrics and Gynecology, St Olav's University Hospital, Trondheim, Norway.
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Romundstad
D000328:Adult; D015331:Cohort Studies; D015925:Cryopreservation / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000706:statistics & numerical data; D012042:Registries; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects* / Q000706:statistics & numerical data; D012306:Risk; D012537:Scandinavian and Nordic Countries / Q000453:epidemiology; D035781:Siblings; D055815:Young Adult
assisted reproductive technology; cryopreservation; hypertensive disorders in pregnancy; pre-eclampsia; sibling analysis