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”).