A question without an answer…for now:

Birth defects are more common after certain infertility treatments, but whether the cause is the assisted reproduction techniques themselves or the underlying biology preventing conception isn’t clear, Australian researchers say. “While treatments appear quite safe, we cannot ignore that there are significant risks that require urgent investigation with additional ongoing studies,” said lead researcher Michael Davies, an associate professor at the Robinson Institute of the University of Adelaide.

For the study, published online May 5 in the New England Journal of Medicine, Davies and colleagues collected data on more than 6,100 births achieved using assisted reproductive technology in South Australia. The investigators compared these births with a registry of more than 300,000 births, looking for the risk of birth defects associated with infertility treatments compared to unassisted pregnancies. “Spontaneous” pregnancies in women who previously had infertility treatments were also considered. Overall, with assisted reproduction methods, the risk of any birth defect was 8.3 percent compared with 5.8 percent for unassisted pregnancies. These included cleft palate, and heart, gastrointestinal and esophageal defects.

For in vitro fertilization (IVF), the risk for birth defects was 7.2 percent. For intracytoplasmic sperm injection (ICSI), it was 9.9 percent. In IVF, eggs are retrieved from a woman’s ovaries and fertilized by sperm in a lab before being returned to her uterus. With ICSI, a form of IVF, a single sperm is injected into the center of an egg cell to aid fertilization.

Women using clomiphene citrate at home to stimulate ovulation had triple the risk of birth defects, the researchers noted. “Although this finding was identified in a small subgroup, it is consistent with a large U.S. study from early 2011,” Davies said. “The excess risk for IVF could be explained by patient characteristics, such as age or weight,” Davies said. “In contrast, the risk for ICSI could not be explained by available factors.”

It appears that a history of infertility may be associated with increased risk, independent of treatment, he noted. “This may be due to underlying patient factors,” he said. Using frozen embryos substantially reduced the risks from ICSI, suggesting the association is related to the embryo, Davies said.

A limitation of the study is that the most recent data is 10 years old, which was necessary to allow five years of follow-up for all births, Davies pointed out. “However, treatments have evolved and ICSI pregnancy rates have improved since, perhaps suggesting risks may be lower today,” he added.

Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore University Hospital in Manhasset, N.Y., said it is important to interpret these findings for patients “so they don’t freak out.” The risk of having a baby with a birth defect is only 2.5 percent greater in those using assisted reproduction than in those having a baby without it, Hershlag said.

Also, most people who use assisted reproduction are older than those who have children on their own, and older patients have a greater risk of having a child with birth defects, he said. “So when they take age and other factors into account, IVF no longer poses an increased risk,” Hershlag added. “This is excellent news for our patients.”