Preimplantation genetic screening: what is the clinical efficiency?

Inklings

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Volume 108, Issue 2, Pages 228–230

Authors:

Richard J. Paulson, M.D.

Abstract:

In the current practice of in vitro fertilization (IVF), preimplantation genetic screening (PGS) is increasingly used to select embryos for transfer. This strategy is designed to maximize the probability of embryo implantation by eliminating embryos with low implantation potential from the cohort. However, PGS is inherently imperfect. Errors may occur during the genetic analysis of the small amount of DNA collected. More importantly, mitotic mosaicism, whose precise incidence in the preimplantation embryo is not known, may lead to sampling errors due to the intentionally limited collection of cells in the trophectoderm biopsy. In this manner, abnormal cells may be collected in an otherwise euploid embryo and vice versa. Therefore, it is inevitable that some normal embryos will be discarded, leading to an overall decrease in the cumulative pregnancy rate achievable by the eventual transfer of all embryos in the cohort.

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Fertility and Sterility

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5 Comments

Go to the profile of Alexander Quaas
Alexander Quaas about 3 years ago

This thought-provoking inklings piece provides an interesting perspective on the efficiency of PGS, including the potential discarding of normal embryos.


While the widespread use of PGS is a relatively new phenomenon, choosing embryos for transfer by other means was always necessary. Could the same model presented not also be applied to the selection and discarding process used based on embryo morphology? 


Or do you believe that the embryo loss rate with morphology based selection is 0%? Meaning no embryos with the potential to implant are ever discarded?


Otherwise wouldn't it be conceivable that PGS could "rescue" embryos that would have been discarded by morphology (for example CC grade) but turn out to be euploid? If that were the case then this phenomenon would have to be factored into the equations and figures presented.

Go to the profile of Richard J. Paulson
Richard J. Paulson about 3 years ago

In the field of clinical medicine, mathematical modeling will always be just an approximation. Your point is well taken, there are indeed other criteria that are being used to decide when to discard embryos.

But in the clinical practice of PGS, I would argue that morphology is still being used to decide about the fate of embryos, in conjunction with PGS, rather than PGS being used to "rescue" bad-looking embryos. For example, a poor quality blastocyst may not be "good enough for biopsy." Additionally, when multiple euploid embryos are available for transfer, the morphologically best embryo is generally transferred. If multiple euploid blastocysts are cryopreserved, 2 or 3 may be thawed, and then the best one transferred to maximize the chance of implantation.

This is a strategy that maximizes the per-embryo implantation rate, and the argument for this approach is that it minimizes the time to pregnancy. It is the opposite of the "every last baby out of every last egg" approach that I prefer, especially in women over 40.

Most practitioners think that they are losing 5-10% of potential implantations when they use PGS. The point of my inklings piece was to point out that even a very good increase in implantation rate would be associated with a 20% loss of potential implantations. Since most programs are not seeing an appreciable increase in implantations among women under 35, this represents approximately a 40% loss of potential implantations.

Go to the profile of Alexander Quaas
Alexander Quaas about 3 years ago

Dear Rick- thank you for your response and the additional explanation of your points made in the inklings piece. This is a fascinating debate which I am sure will continue over the next months and years, in this forum and at meetings.

Go to the profile of Robert Wagner
Robert Wagner over 2 years ago

I am a molecular geneticist and am somewhat confused by your paper.  You seem to assume that PGS finds "abnormal" embryos only from the population of embryos that will not implant in any event (which would appear to make PGS completely useless).  I am unaware of any evidence supporting that assumption.  Is there any?  In fact, isn't the finding that the implantation rate of screened vs unscreened embryos is basically equal as likely to mean that PGS takes equally from both of your red and blue groups?  In addition, don't we already know that embryos with severe genetic abnormalities (e.g., trisomy 21 - Down syndrome) successfully implant and lead to full term pregnancies? And aren't those (red group embryos) precisely the kinds of embryos that PGS is intended to detect?

Go to the profile of Richard J. Paulson
Richard J. Paulson over 2 years ago

Thanks so much for your comments! The one non-selection study performed to date (Scott et al, Fertil Steril 2012;97:870) showed a false positive rate of about 10% (41% implantation rate in "euploid" embryos and 4% implantation rate in "aneuploid" embryos. That's not where the lost embryos are going to. The point is that when you test embryos to see which are less likely to implant and then remove those from the population, the remaining embryos should logically implant at a much higher rate. The fact that they don't implies that the biopsy process itself causes sufficient damage to decrease the implantation rate back to the baseline observed before the testing was done.