Debate Over Wider Use of Preimplantation Genetic Diagnosis
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Preimplantation genetic diagnosis—first used in assisted reproduction 15 years ago—is becoming more and more widely used. But whether it should be employed universally drew heated debate here.
Researchers here say that data show preimplantation genetic diagnosis is becoming accurate to the point that in some settings it can dramatically improve the rate of successful pregnancies by winnowing out all but the completely normal embryos.
Preimplantation genetic diagnosis can also pick up a wider variety of genetic abnormalities, including single-gene disorders, aneuploidy (deviation from the normal number of chromosomes), and chromosomal translocations, authorities said at the joint meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society here.
Also, it can be used to reduce the number of embryos transferred to the mother, potentially reducing the number of multiple pregnancies, or for HLA matching to allow parents to select for an embryo that would eventually be able to donate tissue to an existing sibling.
But it remains unclear that every couple needing assisted reproduction should be offered the technique, which involves removing and testing a single cell from a blastocyst at the eight-cell stage. Genetic anomalies, such as extra chromosomes, are picked up using fluorescent in-site hybridization (FISH).
“In the current state of preimplantation genetic diagnosis, until the technology is better, I wouldn’t recommend it for everyone,” said Nicole Noyes, M.D., of the New York University School of Medicine. Currently, she said, preimplantation genetic diagnosis can only look for chromosomal anomalies involving less than half the chromosomes.
Also, she said, such uses as HLA matching raise ethical issues that haven’t been settled.
On the other hand, Yury Verlinsky, Ph.D., of the Reproductive Genetics Institute in Chicago said the use of preimplantation genetic diagnosis—at least for aneuploidy—should be expanded. “I think every IVF attempt has to be done with preimplantation genetic diagnosis,” he said during a wide-ranging debate.
Dr. Verlinsky said there are alternatives to using preimplantation genetic diagnosis for single-gene disorders, although some potential parents would prefer not to start a pregnancy, rather than have to terminate it later.
But for HLA matching and aneuploidy, he said, preimplantation genetic diagnosis is the only game in town.
Jacques Cohen, Ph.D., of Reprogenetics in West Orange, N.J., took a middle stance: “It makes a lot of sense to be quite aggressive,” he said, “but it all depends on how good the technique is.” He said he prefers to limit the technology to women of advanced maternal age who are infertile, but more and more women outside that group are asking for the technique.
Interestingly, Dr. Noyes and colleagues presented data showing that preimplantation genetic diagnosis appears to produce more effective results than the standard ways of judging embryos by morphology.
The researchers conducted a retrospective study of all 86 IVF cycles using preimplantation genetic diagnosis at NYU since September 2001, asking experts, blinded to the genetic outcome, to rate the 787 embryos by standard morphological criteria - fragmentation, cell number and asymmetry.
By preimplantation genetic diagnosis, 79% of the embryos were abnormal, but the morphological assessments rated many of them suitable for transfer. In fact, in the group of embryos rated as having the best quality by morphology, fully 75% were abnormal on preimplantation genetic diagnosis, said Elizabeth Fino, M.D., who presented the data on behalf of the group.
Also, Dr. Fino said, under the morphological assessments 47% of the transfers would have only involved aneuploid embryos—transfers that preimplantation genetic diagnosis prevented.
While that would seem to suggest that preimplantation genetic diagnosis should be used more widely, Dr. Noyes noted that in most cases at least one euploid embryo would have been implanted even under the non-preimplantation genetic diagnosis assessment, although more embryos would have been transferred.
Since preimplantation genetic diagnosis adds significantly to the cost of IVF, she said, it should not be routine.
In what Dr. Cohen called a “huge database” of more than 33,000 embryos analyzed by his company, only 32% were chromosomally normal, he reported here. But transferring these chromosomally normal embryos to the mothers—whose mean age was 37.5—resulted in a 52% pregnancy per transfer rate, and a 13% miscarriage rate.
The low miscarriage rate is “one of the real advantages of doing this,” he said.
He pointed out that, on average, only two embryos were transferred per patient, reducing the odds of multiple pregnancies.
The low miscarriage rate was also cited by Jill Fisher, M.S., also of Reprogenetics, in a study of preimplantation genetic diagnosis and chromosomal translocations. An analysis of 450 patients with a history of lost pregnancies showed a miscarriage rate of 8.9% when the embryos were screened for translocations with preimplantation genetic diagnosis before being transferred.
By contrast, Fisher said, the women in the study had lost 75% of previous pregnancies.
Also, she said, the rate of major malformations among the 110 babies born so far was 2%, which compares favorably to the rate in the general population, which ranges between 3 and 5%.
“This is really a comfort to patients,” Fisher said.
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