Solid data and the evidence to counsel patients accurately
Cristine Magli, an investigator in the ESHRE-sponsored ESTEEM trial, explains more on the design of the study and why the results provide strong evidence about PGT-A.
Is preimplantation genetic testing for aneuploidy - now defined as PGT-A and PGS in the past - beneficial for patients of advanced reproductive age? We have heard this question so many times, and always with the answer: "There is not enough evidence to support application of this technique", even after introduction of the most advanced molecular biology methods with testing of the whole chromosome set.
Indeed, these were the very reasons why ESHRE decided to undertake this RCT - to give an answer to this crucial question. The idea of working with polar bodies arose in 2008, when a pilot study was planned with two main objectives. The first was based on an evaluation of the accuracy of the recently introduced array-CGH technique, which made it possible to assess all the chromosomes in the polar bodies of fertilized oocytes as well as those found in the corresponding oocytes. As the chromosome content of polar bodies represents the mirror image of those retained in the oocyte, the evaluation of the concordance rate would allow a definition of the grade of accuracy of the technique. To do this, two laboratories were selected, the University of Bonn and my own in Bologna (SISMER). I still remember the enthusiasm of those days and nights: it was indeed necessary to work for around 13 almost non-stop hours to have results before the pronuclei in fertilized oocytes entered syngamy. It was tiring, but results were really nice and I learned a lot. It was really meaningful to be part of this trial.
The second reason for polar body testing was because of the well known strong correlation between female age and aneuploidy. So, we hoped to verify how strong the effect of the oocyte was in determining the outcome of the resulting embryos.
The satisfactory results obtained from the pilot study encouraged us to start the RCT, with nine different centres - and results now published in Human Reproduction.(1) The main conclusion of the study is that PGT-A on polar bodies will not increase cumulative live birth rates in IVF. So now we finally have an answer to the original question about PGT-A, at least from oocyte testing.
But there are other important considerations emerging from analysis of these data and pointing to a greater efficiency of transfers after PGT-A: indeed, the same live birth rate was achieved in the study and control groups with a lower number of transfers and fewer miscarriages in the PGT-A group. So the study not only provides a clear answer to the original question - and this is the one that, from a scientific perspective, we must give to our patients - but it also provides important information related to the outcome after embryo transfer. Can we really avoid the dramatic impact that a useless transfer and, even more, a miscarriage will have on the couple, especially the female partner? Of course not, and we now have solid data to adequately counsel our patients in their search for a baby.
ESHRE Chairman Elect
Laboratory Director, SISMER, Bologna
1. Verpoest W, Staessen C, Bossuyt P, et al. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial. Hum Reprod 2018; doi:10.1093/humrep/dey262.