Embryo Quality & Embryo “Competence” – Part III – Testing the Seed

04 Oct
Biochemistry research
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This is the third and final post in three part series on embryo quality. In the prior two posts, I outlined the intrinsic/physiological factors and the clinical factors that can impact embryo “competence”.  In this post, I will discuss the role, indications, and benefits of genetic/chromosomal testing of embryos.


The role of Embryo Chromosomal Testing (Karyotyping)
Elsewhere on this blog I have described embryo chromosomal tests that can accurately count all the chromosomes in eggs and embryos. Such testing involves the use of comparative genomic hybridization (CGH), which we first introduced into the IVF clinical setting about 6 years ago. Hitherto, fluorescence in situ hybridization (FISH) had been used, but this method lacked reliability. This having been said, it is important to recognize that CGH cannot improve embryo competence, it can only identify those embryos that are most likely to be competent.

We have previously reported on the fact that the transfer of up to two CGH-normal, advanced embryos (blastocyst) into a “receptive” uterus, results in about a 60% chance of a live birth and at the same time significantly reduces the chance of chromosomal birth defects. However, it does not consistently and reliably identify all structural chromosomal anomalies and is not capable of identifying non-chromosomal (genetic/metabolomic) causes of “embryo incompetence”.

Finally, we do not know the extent to which maternal and/or paternal age and/or exposure to extrinsic (outside) and environmental affect impact genetic (non-chromosomal) “embryo competence” and whether or to what degree such factors increase with maternal or paternal age. If they do, then one would expect CGH-normal embryos derived from older women’s/men’s gametes to be less “competent” than those derived from the gametes of younger parents. So while, CGH-embryo normality is indeed likely to be most of the “embryo competency” story, it might well not be the “entire story”.

Who should have their embryos CGH tested?
As stated above, older women and those with DOR are at increased risk of producing incompetent, aneuploid embryos. However, CGH testing, while improving the efficiency of IVF, does not improve embryo quality. Thus it should never be mandated in all such cases. There is, however, one notable exception, and this applies in cases where “Embryo Banking” is done in order to try and stockpile competent embryos for future dispensation. Here, by selectively stockpiling CGH-normal embryos it is possible to increase the reproductive options available to women who otherwise would clearly be running out of time on the “biological clock”.

Diagnostic benefits of CGH testing
The following are examples of where CGH embryo testing can identifying whether numerical chromosomal factors are contributing to the reproductive failure while at the same time can select only the most “competent embryos” for transfer to the uterus:
o Unexplained infertility
o Unexplained/recurrent IVF failure
o Recurrent pregnancy loss (RPL)
o Differentiating between egg and embryo aneuploidy as a cause of failed fertilization, poor embryo quality or failed IVF (egg and embryo CGH testing).

Notwithstanding the fact that “embryo competence” is certainly the most important factor contributing to reproductive failure, it is essential that possible causes of implantation dysfunction (anatomical or immunologic)be identified and if detected, be addressed when it comes to cases of “unexplained” infertility, recurrent pregnancy loss, or repeated IVF failure. This becomes even more critical in cases where IVF failure has occurred in spite of CGH-normal embryos having been transferred. After all, even a “good seed “ (i.e., a “competent embryo”) will fail to thrive if planted in a “poor soil” (“non-receptive uterus”).

27 Comments

  • Kelly Kay says:

    Thank so much, that’s very reassuring that the 60% is a figure us patients can rely on.

  • Kelly Kay says:

    Dear Dr Sher, I am aware of the 60% success rate of a blastocyst transfer but I recently read an article that broke this down to 46.6% for a Grade 1 blastocyst and 17.4% for a Grade 2 blastocyst (46.6+17.4 making 60%). The article (ncbi.nlm.nih.gov/pmc2700678/) looked at 604 cycles from 2002-2006 i.e. prior to CGH testing, but does this still stand, because 17.4% is far lower for a blastocyst transfer than most would expect and I was quite shocked by this. I think most people would presume the 60% figure means 60% whether the blast was Grade 1 or 2 and would be very disappointed. Now that CGH is used is the 60% figure commonly given true of each individual Grade 1 and Grade 2 blastocyst transferred, and not a cumulative success rate which can be misinterpreted to seem more positive than it is? I ask because I am wondering if my 60% expectations of success were overly optimistic.

    • Geoffrey Sher says:

      The implantation rate for blastocysts (G1 and G2) untested is about 30% per blastocyst and for chromosomally normal (CGH-normal) blastocysts…50-60% regardless of G1 or G2. However, both these rates , decline progressively with advancing age beyond 35y(primarily for untested blastocysts).

      Geoff Sher

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