Research about preimplantation genetic diagnosis (PGD) for aneuploidy recently grabbed headlines in news outlets worldwide when a team of scientists reported that the procedure decreased pregnancy rates and the chance of having a healthy baby for infertile women of advanced maternal age (35 or older). The research was conducted in the Netherlands and reported in the New England Journal of Medicine.

Too few or too many chromosomes in an embryo (known as aneuploidy) can prevent implantation of an embryo or lead to miscarriage, and increasingly PGD has been offered to infertile couples without a known inherited genetic risk as a way to potentially improve the likelihood of becoming pregnant and having a healthy baby. PGD involves removing a single cell from an embryo in the first few days of development after in vitro fertilization (IVF), analyzing the DNA (to look for a single-gene disorder such as cystic fibrosis or Tay-Sachs disease) or chromosomes, and selecting the genetically healthy embryos for transfer to the woman’s uterus. Many embryos are aneuploid, and the percentage increases with age (50 percent of embryos are aneuploid among young women, 80 percent among older women). Thus, it seemed likely that picking chromosomally normal embryos would increase older women’s chances of becoming pregnant and having a healthy baby. Indeed, some PGD providers have suggested that all infertility patients would benefit from this genetic “screen” of embryos before choosing which to transfer.

However, medical practices must be based on evidence. PGD for aneuploidy may be one of the most understudied medical technologies in use today, in a field (assisted reproductive medicine) that often has been accused of moving new techniques into clinical practice prematurely.

This study compared two groups of women aged 35-41. The control group went through normal IVF. The experimental group had anueploidy screening of the embryos, analyzing seven chromosomes. The researchers compared the two groups’ implantation rates after seven weeks, pregnancy rates after 12 weeks, and live birth rates. Both pregnancy rates and birth rates were higher in the control group: The pregnancy rate for those who did not use PGD was 37 percent, compared with 25 percent for those who did use PGD.

The researchers conclude that aneuploidy screening of embryos does not increase the chances of having a healthy baby for women of advanced maternal age – in fact, it actually decreases the chances. The leader of the study suggested in one news report that embryo biopsy could be “more harmful to the ultimate development of the embryo than we had previously thought.” News reports have referred to this study variously as a “wake-up call” or a “death knell” for PGD for aneuploidy. Ultimately, the question for both patients and providers is whether the positive effect of selecting chromosomally normal embryos is eliminated by the detrimental effect of removing a cell for analysis.

But several critical facts should be noted. First, PGD for aneuploidy is currently used for a variety of fertility patients, including women of all ages who have had repeated miscarriages or IVF failures, and this study does not look at the usefulness of aneuploidy screening for those indications. It is known that miscarriage in particular is often caused by anueploidy, so the usefulness of screening may be higher for women who repeatedly miscarry than for women of advanced maternal age, whose fertility problems may or may not stem from aneuploidy. Second, the scientists reporting this work were unable to get a result from the genetic screen for 20 percent of the embryos, yet those embryos were transferred when no other embryos were available and included in the results. Biopsy performance and genetic analysis is of critical importance to the success of PGD, and it matters greatly in whose hands these difficult procedures are carried out. Third, more of the women in the control group had two embryos transferred back than in the experimental group, but the data on success rates were not analyzed based on whether one embryo was transferred or two. Finally, the chromosomes analyzed in this study do not include all the chromosomes that are often checked by PGD laboratories.

There is no formal governmental review and approval process for medical interventions such as PGD. And in the United States, a federal prohibition on funding research on embryos means that clinical trials in this area rely on private money. In the absence of a gatekeeper, there is sometimes a rush to move in advance of the data and offer services to patients without a solid fact base.

PGD for aneuploidy is already in widespread use in the United States. According to GPPC’s own survey of IVF clinics, 74 percent of U.S. IVF clinics are offering some form of PGD, and approximately two-thirds of PGD cycles performed in 2005 were for aneuploidy.

More research on PGD for aneuploidy will continue to emerge, but patients and providers must evaluate the potential risks and benefits based on what little we know now. GPPC and others have long called for well-controlled and well-designed clinical studies looking at PGD’s efficacy and safety. We have spearheaded an effort with the American Society of Reproductive Medicine, the Society for Assisted Reproductive Technology, and the PGD International Society to establish a U.S. PGD database. This database, now nearing fruition, will permit robust research and enable studies that can track outcomes over time, allowing us to understand whether, and for whom, PGD for aneuploidy is effective. – Susannah Baruch, director, reproductive genetics

Read the original article, “In Vitro Fertilization with Preimplantation Genetic Screening”

Read the article, “Genetic testing of embryos: practices and perspectives of U.S. IVF clinics”

Read the article, “Genetic testing of embryos: a critical need for data”

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