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July 29, 2003

Embryo Diagnosis Stirs Controversy

From: Newsday - Jul 29, 2003

By Melissa Healy The Los Angeles Times

Peering into the genetic code of an eight-cell creature scarcely stirs excitement anymore in labs across America. But when the eight-cell creature is a human embryo -- an egg and sperm united in a petri dish just 72 hours earlier -- the sight of chromosomes lighted up in neat, color-coded pairs stirs excitement, and something deeper as well.

It stirs hope.

This is preimplantation genetic diagnosis, fertility's new frontier, where advanced genetics meets the thriving science and booming business of in vitro fertilization.

Twenty-five years after the birth of the first child conceived by human egg and sperm in a laboratory, preimplantation genetic diagnosis -- or PGD -- is touted as the next big thing: a technology that could eliminate inherited diseases, boost birth rates among infertile couples for whom nothing else has worked and reduce the incidence of potentially risky multiple births.

"I see this as a trend for the future, and I do see that in the future, every embryo [produced in the course of IVF cycles] will be tested," says Dr. Harvey Stern, head of the Genetics & IVF Institute's PGD program in Fairfax, Va.

To the dismay of ethicists, however, PGD may open the door to a "new eugenics," as parents seize an emerging opportunity to customize their babies for anything from tissue type to eye color, broad shoulders to extreme intelligence.

A process of detecting genetic abnormalities in embryos while they are still in a lab's incubator, PGD allows a couple to choose embryos free of evident flaws for transfer into a woman's uterus. For many who suffer from or carry the gene for an inherited disease, PGD offers the promise of a baby free of a known stalker. For many among the infertile, it offers a better prospect that an embryo will take hold, result in pregnancy and produce a healthy baby. For some opposed to abortion, it allows "choice" to occur before a pregnancy begins. For the nation's roughly 400 fertility doctors, PGD -- and a related technique called aneuploidy screening -- brings in a new and fertile class of patient (genetic disease carriers) and offers a new service to infertility patients who have failed with lesser therapies.

Beyond that, the procedure, which costs about $3,500 to $4,000, offers fertility clinics a lure that they cannot refuse: better pregnancy rates.

Around the world, about 1,000 babies have been born following PGD, making it a procedure still in its infancy next to IVF, with roughly a million births worldwide. But PGD already is being used to help would-be parents choose the gender of a child and to weed out embryos that would carry any one of nearly 60 inheritable diseases, such as early-onset Alzheimer's and Huntington's disease. The ability to screen for a wider range of things is certain to follow, as scientists identify with ever-greater precision the role of genes in transmitting across generations everything from mental illness and physical afflictions to temperament and physical traits.

But some question how far the process should go. Early this month, an Australian fertility clinic announced that it had used PGD to screen out embryos carrying a gene that would predispose its carriers to deafness. That prompted an outcry from disabilities activists, who noted that deafness is neither life-threatening nor a certainty for those who carry the gene. They argued that if PGD were to come into wide use for such purposes, it could reduce the deaf population and isolate a thriving culture.

Ethicists, meanwhile, fear that this latest use could make the trivial use of such powerful technologies easier to contemplate.

"If you give people the idea that it's perfectly OK -- and doable -- to pick out this, that and the other trait" in an embryo, "then you're opening the door to shopping for babies as accessories to your life," says Marcy Darnovsky, an analyst with the Center for Genetics and Society in Oakland. "You're on the way to designer babies right there."

Already, concerns about the implication of the technology have prompted Austria, Germany, Ireland and Switzerland to outlaw the procedure. France, Belgium, the Netherlands and Italy all have adopted regulations limiting its use. The United Kingdom, after an extraordinary national debate in 2001, has placed a range of restrictions on PGD providers, including a ban on the procedure's use for gender selection.

In the United States, clinics offering PGD have burgeoned, even as American lawmakers have been loath to regulate infertility services. But PGD has sparked debate close to the Oval Office and last December, in Washington, The President's Council on Bioethics -- a special panel of advisers named by President George W. Bush -- met to discuss the power and pitfalls of PGD. In a staff report guiding that discussion, PGD is portrayed as a technology that could, with broad use, shift the nation's genetic composition and "tempt the unwitting or the unscrupulous toward experiments" in which embryos' genetic code is not only screened, but also modified.

More simply, the staff ventured, PGD could change the way that parents love their children, undermining parents' "unconditional acceptance" as they strive to dictate their children's makeup.

For Eve Rubell, a carrier of Fabry's disease who plans to use PGD in her next cycle of IVF, such arguments have merit. Still, PGD feels "like a lifeline" to her, one that she is unwilling to let go.

"It's not about eugenics or designer babies," says Rubell, a Los Angeles health educator who, at 40, has already had several rounds of unsuccessful infertility treatments. When she learned that she carried the gene for Fabry's, an inherited enzyme deficiency that can cause body pain, kidney failure, strokes and premature death, her infertility quest took a new turn. It was not only about having a healthy baby, it was about her professional mission: to prevent preventable disease.

"Certainly, if I have a child with a disability or a health problem, I'm going to love that child like any other. But if it was something I knowingly could have prevented, I would want to do that, and I would feel guilty if I didn't at least try."

The responsibility that such people feel to their not-yet-conceived children is evident in discussions with them. When Kristy Echelberger discovered she was a carrier for Duchenne muscular dystrophy, she and her husband, Mark, a Navy mechanic, "first talked of not doing PGD and letting the higher power make the ultimate decision." But as they watched a young nephew suffer from the disease (only boys develop Duchenne muscular dystrophy's symptoms, although girls can carry and pass on the gene), they decided to pay out of pocket for the $4,000 treatment and try for an unaffected baby. Their cycle ended without a pregnancy last month. But with time on their side (both are 27), they think they may try again later.

"If we did have a male affected, my husband was so afraid we would have to explain to a son, 'We knew when we conceived you that this was going to be your fate,'" says Echelberger. "That kind of put things in perspective for me." Sociologist Barbara Katz Rothman finds stories of PGD's inheritable disease carriers compelling. But the expert on reproductive technologies and their social consequences argues that sometimes, having choices -- to try another procedure, to preserve a genetic relationship, to erase flaws from a baby -- takes away the choice of moving on to a second option, such as adoption, or accepting a baby for whoever he or she will be.

PGD makes it possible to choose, at a cost that can reach $15,000 per IVF cycle. And for many patients caught up in infertility treatments, "it's an offer you can't refuse."

Like many medical drugs and procedures, PGD was developed in the late 1980s for a single class of patients: those suffering from or carrying the gene for devastating inheritable disease. Carriers of the gene for cystic fibrosis, muscular dystrophy and Huntington's disease were among the first patients to try PGD with success.

But some of the patients seeking PGD early on were parents of children born with Down syndrome, a genetic abnormality that causes mental retardation and whose incidence rises as the mother gets older. Researchers surmised that it might be an increase in such genetic abnormalities that causes the well-documented decline in fertility as a woman ages. And tests on the embryos of these older women produced in IVF cycles confirmed the link: not age, but genetic abnormalities that increase in a woman's eggs with age, were making it more difficult for them to conceive and reducing their ability to conceive and carry through to term. For women older than 40 undergoing IVF, it was typical for more than 3 in 4 embryos produced to have genetic flaws.

If PGD could be used to weed out embryos bearing these abnormalities, fertility doctors surmised they could transfer only normal embryos and boost pregnancies among these 35-and-older women, whose success rates fell below 10 percent per IVF cycle as they approached 40.

Throughout the 1980s and 1990s, these "older" patients began flocking to infertility clinics in droves, having postponed childbearing for education and careers. Today, experts reckon that women whose infertility stems from "advanced maternal age" -- and who theoretically could benefit from PGD -- make up at least half the nation's infertility patients.

But even its champions acknowledge that initial results with this group have been somewhat disappointing: in the first years of its use, PGD seemed to boost the number of pregnancies that resulted from IVF, but those gains were erased by later miscarriages. The net effect was that the proportion of women who conceived, carried and delivered babies -- what fertility specialists call the "take-home baby rate" -- barely budged.

More recent studies have shown that PGD may offer measurable improvements for women older than 40. Stern, of the Virginia-based Genetics & IVF Institute, said that among this group, the addition of PGD now more than doubles the "take-home" rate from a dismal 8 to 9 percent to about 20 percent.

Many, including Dr. Robert E. Anderson, director of the Southern California Center for Reproductive Medicine, are careful to call PGD a promising technology that, for now, offers limited help for infertility's older patients and those with IVF failures. Anderson and others believe that the act of removing a cell from an eight-cell embryo is traumatic to some embryos and can weaken them for the long haul of pregnancy. In addition, the fact that PGD can scan only eight of the 23 pairs of chromosomes means that some genetic abnormalities that are not being screened for are being missed.

Nevertheless, today, at two of the nation's largest centers for PGD, almost 3 in 4 of the procedures are for aneuploidy screening, which detects an abnormal number of chromosomes, largely for women older than 35 or those who have had repeated IVF failures or miscarriages.

Chicago-based geneticist Dr. Yuri Verlinsky has done some 3,000 PGD screens since the procedure's earliest days. He once flatly refused a couple who asked him to identify an embryo with Down syndrome, so they could give their Down-affected child a similar sibling. But this pioneer of PGD is untroubled by charges of genetic tinkering and complaints of modest results.

"In the future, there will be no IVF without PGD," says Verlinsky flatly. "It's human nature. It's better to check."

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