Thursday, September 15, 2005

Non Disclosure of a fertility technique that resulted in Abnormal Foetus

Pioneering Fertility Technique Resulted in Abnormal Fetuses
Team Failed to Disclose Genetic Disorder in Science Report

By Rick Weiss
Washington Post Staff Writer
Friday, May 18, 2001; Page A03

When doctors in New Jersey recently touted the success of an experimental treatment they had developed to help infertile women, they were prepared for the controversy that ensued. After all, the technique involves mixing an infertile woman's egg not only with her husband's sperm but also with parts of a younger woman's egg, creating children with three genetic parents -- a biological first.

The team emphasized that virtually all the maternal genes inherited by the children came from their true mothers. And happily, all the children born by the technique appear to be completely healthy, Jacques Cohen and his colleagues at Saint Barnabas Medical Center in Livingston, N.J., reported.

But what Cohen and his colleagues did not mention in their recent scientific report is that the perfect record of healthy births was attained because they aborted a developing fetus that was found to have a rare genetic disorder. Moreover, another pregnancy achieved in the experiment ended in miscarriage and involved a fetus afflicted with the same rare disorder, called Turner's syndrome, in which an entire chromosome is mysteriously missing.

All told, two of the 17 fetuses created by the technique had Turner's syndrome, an incidence at least seven to eight times what experts deem normal.

Internal documents from Saint Barnabas explicitly acknowledge that the novel technique may be causing the problem, perhaps by enhancing the survival of flawed embryos that normally would not live beyond the first days or weeks of embryo development.

Yet, in their recent report, published in the March issue of the journal Human Reproduction, the researchers never mention Turner's syndrome and conclude there is "no reason" to believe that the technique is harmful to fetuses or babies. "Therefore," the team wrote, "we continue to perform these clinical procedures, albeit as an experimental protocol."

Cohen declined to be interviewed for this article, but public relations officials at Saint Barnabas said it's too soon to know if the link to Turner's syndrome is significant and emphasized that they have been open about the risks with women considering the technique.

"It was not a secret," Saint Barnabas spokeswoman Denise Pinney said.

Other experts agreed that the number of cases is still too small to know whether they represent a real trend or just random bad luck. But several fertility experts said that at a minimum the abnormalities should have been mentioned in the recent published report so that doctors and others would be aware of all the facts.

"The failure to disclose the losses is a problem," said John Buster, director of reproductive endocrinology and fertility at Baylor College of Medicine in Houston, echoing others in the field. "If I'm going to be told that there were . . . normal births, I'd like to know the total database from which that's drawn."

Aside from the issues of safety and full disclosure, some ethicists expressed alarm that in the course of a private and unregulated fertility treatment, researchers had crossed a line that many had said should not be crossed, at least not until the implications are better understood: the first human genetic alterations capable of being passed down to future generations. Federal policy precludes such work by federally funded scientists, in part because if the changes lead to problems, they could afflict offspring for generations to come.

Responding to the work at Saint Barnabas, experts writing in the scientific journal Science are today calling for the creation of a public oversight process for research that causes inheritable genetic changes in people.

More generally, several ethicists said the case exemplifies how the fertility industry often rides the line between benevolent heroism in the service of infertile couples and fee-for-service experimentalism in which patients desperate to become pregnant are easily drawn to unproven and often expensive treatments.

The federal government does not support human embryo research, leaving fertility clinics as the only venue for such studies. Because the clinics are privately funded, they are exempt from the federal bureaucracy that oversees the safety of human subjects in research. Although the Food and Drug Administration claims to have some authority over fertility clinic research, it has never exercised that authority.

Jamie Grifo, a fertility doctor at New York University, defended Cohen. "To characterize this as a problem is totally unfair," he said. Cohen has discussed the cases of Turner's syndrome in scientific meetings, Grifo said. He noted that the cases are noted in a published summary of the proceedings of a 1999 fertility meeting in Australia.

Others, though, expressed surprise that the results remain unmentioned in any of the standard peer-reviewed articles the group has published, which doctors would typically look to for details of the experiment's outcome.

Suheil J. Muasher, medical director of the Jones Institute for Reproductive Medicine's Northern Virginia/D.C. Center in Fairfax, has been using the Saint Barnabas technique. He said he had not been aware of the cases of Turner's syndrome until he learned of them from a reporter. The one birth he has achieved so far involved normal twins, he said.

Michael Tucker, an embryologist at the Shady Grove Fertility Center in Rockville, said Cohen never mentioned the problems to him in conversations the two had while Tucker was writing a recent review of the field for publication.

"In retrospect, the authors . . . could have been more cautious," said Helen Beard, managing editor of Human Reproduction, which published the recent article. Since then, she said, the journal has "tightened" its peer review process.

The consent document that prospective participants must sign before enrolling in the experiment mentions the Turner's cases. But the form says Turner's "commonly appears" in fetuses naturally. In fact, it is uncommon, occurring in an estimated 15 out of 1,000 conceptions and, because most of those spontaneously abort, only 1 in 2,500 births.

The Saint Barnabas technique calls for fluid from a young woman's egg to be injected into the egg of an infertile woman whose embryos have failed to develop properly with standard in vitro fertilization. Chromosomal genes, which influence a person's physical and mental traits, are not transferred. But a few tiny pieces of DNA called mitochondrial genes, which help cells produce energy, come along for the ride.

The March publication showed for the first time that some of that mitochondrial DNA is present in 1-year-olds born through the technique, settling the question of whether the extra genes persist after birth and are so securely in place that they are likely to be passed on to the children's offspring.

About 30 such babies are alive around the world and are to be monitored for years to watch for any problems that may arise from their novel genetic makeup. Jacob Levron, a scientist in Israel, said yesterday that all six that he helped create appear healthy.