CONTROVERSIES IN OB/GYN

Should IVF centers offer preimplantation genetic diagnosis?

By David B. Sable, MD

No. PGD's technical difficulty, learning curve, and costs warrant caution.

Preimplantation genetic diagnosis (PGD) is one of the most promising and exciting areas of assisted reproduction technology (ART). Indeed, the potential for PGD as a diagnostic test for aneuploidy, chromosomal derangements and single-gene disorders goes far beyond the treatment of infertility. However, PGD should be approached with caution by most IVF centers due to its technical difficulty, limitations, steep learning curve, and costs.

PGD testing for aneuploidy provides the best example of both the promise and limitations of the technology. At Saint Barnabas we offer blastomere testing of chromosomes 13, 15, 16, 17, 18, 21, 22, X and Y, which our research shows account for a large proportion of early embryonic aneuploidies. In women aged 38 to 42, over half of tested embryos prove to be genetically abnormal. Further, there is no reliable correlation between embryo morphology and genetics in this age group, meaning that genetically competent embryos can potentially be discarded in favor of genetically abnormal embryos with more efficient cell division.

The Saint Barnabas experience

Given this situation, we expected a dramatic increase in implantation and a reduction in early pregnancy loss in biopsied embryos. Indeed, in our experience, implantation rates in biopsied embryos that underwent PGD did rise when compared to controls, but less dramatically than expected, and not in proportion to the number of chromosomally abnormal embryos not replaced. Could the biopsy process itself adversely affect implantation, thus blunting the benefit of the aneuploidy screening?

The limit on the number of chromosomes in the PGD panel further accounts for the 5% to 7% false-negative rate seen in blastomere biopsy. PGD is not yet the hoped- for "mini-amniocentesis." Complete and reliable chromosomal screening of a single blastomere is at least 6 months away. Even after we can screen for all chromosomes we still face false-negatives and -positives from mosaic embryos.

Technical concerns

PGD is a costly procedure to set-up, requiring fluorescent in situ hybridization, polymerase chain reaction (in the case of single-gene disorders) and, most important, the ability to perform blastomere biopsy without harming the embryo. Our experience at Saint Barnabas shows a significant learning curve for this procedure due to the large opening needed in the zona pellucida, the varying degrees of compacting in the cell-stage embryos biopsied, and the instability of some of the embryos undergoing testing. Poor technique arising from inexperience could adversely affect implantation, reversing any benefits derived from the genetic diagnosis. There is also a considerable learning curve in correctly assessing the results based on a single cell.

Finally, cost considerations suggest that PGD technology be limited to a small number of referral centers. The cost of the additional equipment, embryologists, and cytogeneticists needed to perform PGD is most efficiently allocated by performing both the cases native to one center and referral cases from other centers. Biopsies can be performed off-site and transported, with the results available for a day-4 embryo transfer and no decrease in pregnancy rates associated with the delay.

Dr. Sable is Director, Division of Reproductive Endocrinology, Saint Barnabas Medical Center, Livingston, N.J.

Reader Response Form

Should IVF centers offer preimplantation genetic diagnosis?

What's your call on the controversy presented by Drs. Kuliev, Verlinsky, and Sable? Let us know and learn later how your view compares with those of others when we print a sampling of reader responses.

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No. PGD's technical difficulty, learning curve, and costs warrant caution.

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David Sable. Should IVF centers offer preiplantation genetic diagnosis? No..

Contemporary Ob/Gyn

2003;3:54-60.