Risk of birth defects higher for ICSI compared with IVF

In a study identifying the risk of major birth defects associated with different types of assisted reproductive technology, Australian researchers have reported a significantly higher risk of birth defects involving intracytoplasmic sperm injection (ICSI) compared to in vitro fertilization (IVF).

The study, which was published in the New England Journal of Medicine (2012; 366:1803-13), involved 6,163 births resulting from assisted conception out of a total of 308,974 births and terminations of pregnancy and found that 8.3% of those involving assisted conception resulted in a birth defect diagnosed before a child’s fifth birthday, compared to 5.8% in pregnancies not involving assisted conception. The risk of birth defects for IVF and ICSI were 7.3% and 9.9%, respectively.

The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors, but the risk of birth defects associated with ICSI remained increased after multivariate adjustment.

"In the case of ICSI, but not IVF, the increased risk of birth defects persisted after adjustment for maternal age and several other risk factors," wrote the authors, led by Michael J. Davies, PhD, MPH, of the University of Adelaide, Adelaide, Australia. "Although we cannot rule out the possibility that other patient factors contribute to or explain the observed associations, our findings can help provide guidance in counseling patients who are considering treatment for infertility.

"The possibility of treatment effects that are specific to ICSI is biologically plausible, although differences in male infertility factors that lead to the use of ICSI may also underlie the association," the authors wrote.

The researchers also found a significant increase in the risk of birth defects associated with fresh-embryo cycles compared to frozen-embryo cycles, with a significantly higher risk in fresh-embryo cycles of ICSI compared to IVF. Cryopreservation of embryos was associated with a substantially reduced risk of birth defects, particularly for ICSI, and may be due to developmentally compromised embryos failing to survive the freeze/thaw process.

"This study confirms what has been known for quite some time: Patients who need medical assistance to conceive have a somewhat higher risk of having children with birth defects than parents able to conceive on their own," said Linda Guidice, MD, PhD, of the American Society for Reproductive Medicine in a statement following the study’s release. "Patients considering medically assisted conception have been, and should continue to be, counseled on those risks prior to undergoing any treatment."

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