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Hum. Reprod. Advance Access published online on October 5, 2006
Human Reproduction, doi:10.1093/humrep/del311
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 8, 2005
Revised June 19, 2006
Accepted July 7, 2006

Article

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

K. Kapiteijn 1, C.S. de Bruijn 1, E. de Boer 2, A.J.M. de Craen 3, C.W. Burger 4, F.E. van Leeuwen 2, and F.M. Helmerhorst 5 *

1 Division of Reproductive Medicine, Department of Gynaecology, Leiden University Medical Center, Leiden, the Netherlands
2 Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
3 Department of Gerontology and Geriatrics, the Netherlands
4 Department of Obstetrics and Gynaecology, Erasmus Medical Centre, Rotterdam, the Netherlands
5 Division of Reproductive Medicine, Department of Gynaecology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

* To whom correspondence should be addressed.
F.M. Helmerhorst, E-mail: f.m.helmerhorst{at}lumc.nl


  Abstract

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

Keywords: adverse effects/low birthweight/ovulation induction/pregnancy outcome/premature infant.

E.de Boer, C.W.Burger and F.E.van Leeuwen: On behalf of the OMEGA project group of which members are listed in the Acknowledgement section.


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