Ovarian stimulation and low birth weight in newborns conceived through in vitro fertilization

Abstract

Objective: Singleton neonates born after in vitro fertilization (IVF) are at increased risk for low birth weight, preterm delivery, or both. We sought to assess whether the alteration of the peri-implantation maternal environment resulting from ovarian stimulation may contribute to increased risk of low birth weight in IVF births.

Methods: The Society for Assisted Reproductive Technologies database was used to identify IVF-conceived neonates born in the United States between 2004 and 2006. Associations were assessed in neonates born after fresh compared with frozen and thawed embryo transfer in women of similar ovarian responsiveness, in paired analysis of neonates born to the same woman after both types of embryo transfer, and in neonates born after oocyte donation.

Results: Of 56,792 neonates identified, 38,626 and 18,166 were conceived after transfer of fresh and frozen embryos, respectively. In singletons, there was no difference in preterm delivery. However, the odds of overall low birth weight (10% compared with 7.2%; adjusted odds ratio [OR] 1.35; 95% confidence interval [CI] 1.20-1.51), low birth weight at term (2.5% compared with 1.2%, adjusted OR 1.73, 95% CI 1.31-2.29), and preterm low birth weight (34.1% compared with 23.8%, adjusted OR 1.49, 95% CI 1.24-1.78) were all significantly higher after fresh embryo transfer. In singletons, after either fresh or frozen embryo transfer in the same patient, this association was even stronger (low birth weight: 11.5% compared with 5.6%, adjusted OR 4.66, 95% CI 1.18-18.38). In oocyte donor recipients who do not undergo any ovarian hormonal stimulation for either a fresh or a frozen embryo transfer, no difference in low birth weight was demonstrated (11.5% compared with 11.3% adjusted OR 0.99, 95% CI 0.82-1.18).

Conclusion: The ovarian stimulation-induced maternal environment appears to represent an independent mediator contributing to the risk of low birth weight, but not preterm delivery, in neonates conceived after IVF.

Level of evidence: II.