Further Evidence for the Inadequacy of PGS – News from the ASRM Meeting

This article is a part of the November 2015 issue of CHR VOICE, our monthly newsletter.

An oral presentation by CHR’s Medical Director and Chief Scientist, Norbert Gleicher, MD, received great attention at the annual meeting of the American Society for Reproductive Medicine (ASRM). Dr. Gleicher reported the delivery of 3 normal babies after the transfer of embryos, which after preimplantation genetic screening (PGS) in some of the leading national PGS laboratories, had been reported to be aneuploid (chromosomally abnormal), yet still resulted in normal births.

Such embryos are usually discarded. However, as readers of the VOICE will be aware, CHR has questioned the clinical utility of PGS for years. A year ago (10/27/14), CHR published a formal OPINION, in which we for the first time laid out the rationale for transferring such allegedly abnormal embryos. Two other New York IVF centers, Fertility Specialist In New York (Andrea Vidali, MD) and Braverman IVF & Reproductive Immunology (Jeffrey Braverman, MD) joined us in this practice, and contributed successful births to this report.

Dr. Gleicher’s lecture was described as one of the, if not the, most important presentations of the conference by many participants at this year’s ASRM meeting since it called into question the whole concept of PGS, which is rapidly expanding all around the world. Further evidence for the clinical inadequacy of PGS, paradoxically, came from one of the most fervent groups of supporters of PGS, our colleagues at New York’s Fertility Center of NYU Langone Medical Center, headed by James A. Grifo, MD, who reported an unexpectedly high rate of mosaicism in trophectoderm biopsies of embryos at blastocyst stage.

voice_1511_blastocystAn embryo is mosaic if it contains more than one cell lines, usually a mixture of chromosomally normal and abnormal cell lines. That human embryos frequently are mosaic has been known for many years. Indeed, mosaicism was by many considered a principal reason why the original introduction of PGS over 10 years ago failed after it was proven ineffective in improving IVF outcomes. At that time, proponents argued that the effects of mosaicism would play a much diminished role if embryo biopsy was moved from the original cleavage stage (day-3 after fertilization) to the blastocyst stage (days 5/6 after fertilization) since by that stage embryos would have had the chance to “self-correct.” Blastocyst stage embryo biopsy, therefor, has become a mainstay of the “new” PGS now offered by many IVF centers.

That human embryos have the ability to “self-correct” had become apparent by the time the earlier PGS was formally declared useless by most professional organizations in the field. What proponents of blastocyst stage embryo biopsy, however, overlooked was the fact that the mechanism that allows embryos to “self-correct” segregates abnormal cell lines away from the so-called inner cell mass (from which the embryo arises) into the trophectoderm (which becomes the placenta). It is the trophectoderm, as we repeatedly noted in these pages before, from which embryo biopsies are now taken with the “new” PGS, and this trophectoderm can be expected to be highly mosaic (see figure above).

And this is what Dr. Grifo and his co-workers now confirmed in an excellent presentation at ASRM.

Their and others’ observation of a high degree of mosaicism in trophectoderm basically confirms PGS as a “crapshoot,” with results depending on where a biopsy is taken from. If the biopsy is derived from a chromosomally normal part of the trophectoderm, the embryo will be designated as normal; if the biopsy comes from a chromosomally abnormal area of the segregated abnormal cell lines, the embryo will be declared abnormal, while the inner cell mass, from which the embryos really arises, may be chromosomally completely normal. In such a case a false-positive diagnosis would be reached, and perfectly normal embryos would be discarded.

It, therefore, is reasonable to assume that thousands of perfectly healthy embryos are currently discarded daily at IVF centers all around the world because of false-positive diagnoses.

We are publishing an Addendum to CHR’s above cited OPINION on the utilization of allegedly aneuploid embryos in IVF. This Addendum is partially based on these new data reported by colleagues at the ASRM meeting, but to an even larger extent, they are based on new data CHR researchers and collaborators from other centers have developed in recent months. While we currently are not yet at liberty to reveal details (a manuscript is in preparation for submission), these new data, with a high degree of certainty, demonstrate that PGS, even in its most recent incarnation, is clinically not helpful. In women with few embryos after IVF, the procedure will, indeed, actually significantly reduce pregnancy and live birth chances. Stay tuned for much more to come in the very near future!

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.