ART Risks to Mother/Baby Likely Small, but Remain Uncertain



SANTA BARBARA, CALIF. – To err on the side of caution, couples who are concerned about the risks to mother and baby from in vitro fertilization might be advised to avoid intracytoplasmic sperm injection, to transfer frozen embryos rather than fresh, and to ask their fertility specialists to restrict the estrogen level during stimulation to less than 3,450 pg/mL on the day of HCG administration, according to Dr. Joseph C. Gambone.

The problem is, none of those guidelines is clear-cut, he said at a conference on in vitro fertilization and embryo transfer, sponsored by the University of California, Los Angeles.

Flaws in scientific methodology permeate studies that hint at elevated risks of maternal and childhood cancer, perinatal complications, and birth defects, making it difficult to advise patients about which risks are truly elevated because of assisted reproductive technology (ART).

"It’s just so enticing to get into these big databases and start fishing," said Dr. Gambone, who is in private practice in Durango, Colo. "There certainly are people who violate [valid scientific method] more than others."

Common scientific errors include inappropriate data mining, the failure to include subfertile women as controls, and the failure to consider the potential contribution of male infertility or advanced paternal age to genetic abnormalities.

Pointing to one example, Dr. Gambone reviewed a recent report from an autism conference implying an increased rate of autism among infants born through ART. However, fertile women in the general population were used as the control group, rather than subfertile women who did not undergo ART treatment prior to becoming pregnant.

Other studies failed to control for maternal age, although in vitro fertilization (IVF) mothers are generally far older than women who become pregnant on their own, and would be at higher risk for some negative outcomes based on their age alone.

That said, Dr. Gambone updated the audience on the new studies – albeit with limitations – that might give providers and prospective parents some perspective on the following IVF risks:

Birth defects. A study based on a large Australian registry found significant differences in the rate of birth defects in ART babies, compared with the rate in babies of a control group comprising fertile and subfertile women (8.3% vs. 5.8%); the highest rate of birth defects (9.9%) was in babies conceived via intracytoplasmic sperm injection (N. Engl. J. Med. 2012;366:1803-13). No increase in risk was seen when frozen embryo transfer was employed, noted Dr. Gambone.

Accumulating data suggest that frozen embryo transfer "may be the way for us to head with this technology," he said.

Maternal breast cancer. No overall increase in breast cancer risk was seen in women who underwent IVF in a large, population-based cohort study that was also drawn from Australian hospital and registry data. However, a 59% increase in risk was seen among younger women, defined in this study as those who started IVF at age 24 years (Fertil. Steril. 2012;98:334-40).

Preeclampsia and SGA risks. Like many studies, a new report from the Massachusetts General Hospital in Boston found an increased risk of small-for-gestational-age infants in singleton pregnancies among women who underwent IVF (Fertil. Steril. 2012;97:1374-9). Preeclampsia rates were also higher in pregnancies associated with elevated peak serum estradiol levels during controlled ovarian hyperstimulation, but "this was interesting, and actually gave us a threshold," said Dr. Gambone. "It’s a novel and interesting way of looking at it."

Higher risk for both events was associated with elevated peak serum estradiol levels (greater than 3,450 pg/mL) on the day of HCG administration.

Dr. Gambone reported that he has no relevant financial disclosures.

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