Surrogacy 101: PGD Testing Continued

This series continued the Surrogacy 101 series on our blog.

It is a fact that the full karyotyping of a single day 3 blastomere will not completely exclude the possibility of aneuploidy in the other blastomeres of that embryo. Aneuploidy can sometimes arise sporadically during regular cell division (i.e mitosis) as a consequence of abnormal chromosome dispersion. Thus it is possible even in cases where full karyotyping (CGH) reveals the tested single blastomere to be euploid that one or more of the untested blastomeres might be aneuploid. This so called mitotic aneuploidy is referred to as mosaicism. Conversely, the finding through CGH that a single blastomere is aneuploid, does not inevitably mean that all the entire embryo is aneuploid since the aneuploidy affecting the randomly selected single could (albeit rare) have resulted from mitotic (rather than meiotic) aneuploidy. So, a single mitotically aneuploid cell might in fact be a “loner” with the remaining cells being euploid.

Mosaicism commonly arises in blastocysts and in further advanced healthy concepti. In such cases it affects a small percentage of the total number of cells and the aneuploidy usually proves to be harmless. Perhaps such mitotically aneuploid cells (“overwhelmed” by the majority of its euploid neighbor cells) undergo accelerated death (apoptosis) and are so kept in check. In contrast, when mitotic aneuploidy occurs in early embryos (e.g. by day 3) the percentage of aneuploid cells in the later embryo is likely to be so high as to render ultimate embryo viability unlikely.

What is true and indeed relevant is that the detection of a single euploid single cell in the 3 day embryo provides valuable and irrefutable evidence that:

  • The egg of origin was euploid
  • The fertilizing sperm was euploid and,
  • Fertilization took place in an orderly fashion.

Against this background, it is important to understand that the diagnosis of “embryo competency based upon single cell (blastomere) full karyotyping (i.e. by CGH) is a presumptive diagnosis that is likely to be accurate in about 80% of cases. Furthermore, even if the embryo is fully euploid throughout uterine receptivity and technical prowess in performing the embryo transfer, can preclude a successful pregnancy. That is why, based on available limited (albeit growing) data, we currently project a 60-70% viable pregnancy rate when ≤ 2 CGH normal embryos are transferred to a “presumably receptive” uterus. Time will undoubtedly refine and modify these statistical projections.

In summary: PGD/FISH for gender selection and for the diagnosis of translocations is of indisputable relevance. However, the performance of PGD/FISH for the diagnosis of embryo aneuploidy has little if any value in selecting the” best embryos” for transfer. Full embryo karyotyping (by CGH) is optimally suited to the selection of the most “competent” concepti for transfer. The following indications should be considered in deciding upon PGD/CGH for embryo selection:

1) Cases where there are >5, 6-9 cell day 3 embryos (derived from egg providers <39Y) available. Here the decision as to which one should be transferred is pivotal.

2) In cases of unexplained repeated IVF failure where it is necessary for diagnostic purposes to differentiate between an implantation versus an embryo factor.

3) In selected cases of unexplained recurrent pregnancy loss ; to differentiate between an implantation versus an embryo factor.

4) In certain cases of male factor infertility when trying to decide whether to proceed to DS. In such cases it is sometimes necessary to perform both PB-1 and blastomere CGH.

5) To stockpile euploid, “competent” embryos over time in older women undergoing IVF.

6) For egg donation at a distance where the recipient prefers to limit the time away from home. Here St-IVF will per permit fertilization of donor eggs while she waits for the results.

7) Cases where expensive treatments such as IVIG, and or surgical/medical treatments in preparation for pregnancy could be deferred until “competent euploid embryos have been safely cryo banked for subsequent dispensation.

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