Risky Business?

By MICHAEL D. LEMONICK

In the 24 years since the birth of Louise Brown, the world's first test-tube baby, thousands of would-be parents have been assured that as far as scientists knew there was no extra risk of genetic damage associated with in-vitro fertilization, or IVF. No matter how sperm meets egg--whether in a woman's body or in a Petri dish (and even if the sperm needs some help getting inside the egg)--nature is equally vigilant about preventing serious genetic mishaps from coming to term. With those assurances, test-tube births have soared from a few hundred a year in the early 1980s to tens of thousands today.

But according to a pair of reports in last week's New England Journal of Medicine, that conventional wisdom may be wrong. In the first study, doctors in Britain and Australia found that infants conceived with both straightforward test-tube methods and a more invasive technique called intracytoplasmic sperm injection, in which sperm is injected directly into the egg, have an 8.6% risk of major birth defects--including heart and kidney abnormalities, cleft palate and undescended testicles--compared with the 4.2% rate in babies made the old-fashioned way.

The second study, conducted by the U.S. Centers for Disease Control and Prevention (CDC), reported that babies conceived through what doctors call assisted reproductive technologies (ART) have 2.6 times the risk of low or very low birth weight--a significant risk factor for cardiac and cognitive problems. "Our findings are controversial," concedes Dr. Jennifer Kurinczuk, a perinatal epidemiologist at the University of Leicester in England, who co-authored the birth-defects study, "and they aren't going to be the final word on the issue. But parents should be aware of the controversy."

There are plenty of reasons to take both studies seriously. In the low-birth-weight study, for example, the researchers allowed for the fact that parents who use assisted reproduction tend to be older than average and to have more multiple births--twins, triplets and so on. Even when they corrected for these factors, the disparity between babies conceived through ART and those conceived normally remained.

But there's no need to panic. Independent experts are quick to point out that the reports are hardly definitive. Couples who seek reproductive help are not just older; they are also--though it may seem like stating the obvious--infertile. "You're comparing two different groups of patients here," says Dr. William Schoolcraft, director of the Colorado Center for Reproductive Medicine. "You have women with the disease of infertility, and you're comparing them with women who don't have the disease."

Another problem, says Jamie Grifo, director of the division of reproductive endocrinology at New York University School of Medicine and president of the Society for Assisted Reproductive Technology, is that the only information recorded about these babies was their low birth weight. There was no assessment of their outcome or follow-up through the years.

Richard Scott, the former director of a respected IVF program at St. Barnabas Hospital in Livingston, N.J., has doubts as well. The CDC study, he notes, found lower birth weight in single pregnancies only, not multiple ones. "If technologies were somehow 'changing the fetus,'" he reasons, "you'd think there would be an amplified effect on twins and triplets. But there wasn't." Moreover, earlier research in the U.S., Belgium and Israel found no such effects. Scott does take the new research seriously. But, he says, "this one study does not undermine all the previous work."

Some of the same caveats apply to the birth-defects study, say experts. Here, too, earlier research had found no significant differences between test-tube babies and conventionally conceived kids. And here, again, the new study didn't correct for the fact that women who get reproductive assistance often have something wrong with their reproductive system in the first place.

Dr. David Adamson, a Stanford professor, fertility expert and the director of Fertility Physicians of Northern California, is reminded of a celebrated 1992 Stanford study suggesting that fertility drugs might raise the risk of ovarian cancer. Later research cast doubt on that finding--but only after thousands of women were terrified. "It does not do the country a service," he says, "to present this out of perspective."

Even if these new studies are borne out by later research--already under way in infertility programs in Australia and the U.S.--the risks to kids conceived by assisted reproduction remain reassuringly small. And even if the danger is twice what doctors previously believed, 91% of ART babies would still be born perfectly healthy. Says Dr. Zev Rosenwaks, director of New York Presbyterian Hospital's infertility program: "If you ask a couple if they would rather not have a child at all or try to have a child that over 90% of the time will be normal, I think they will choose to have the child."

No doubt about it, agrees Pamela Madsen, executive director of the nonprofit American Infertility Association: "Infertile people want the joy of a biological child. If you tell us we have to be careful--in fact, if you tell us we have to stand on our head for nine months--we'll do it."

--Reported by Janice M. Horowitz, Alice Park and Sora Song/New York

With reporting by Janice M. Horowitz, Alice Park and Sora Song/New York