Embryo Grading: CGH-Normal Blastocysts Have the Highest Success Rates

We use the term “competent" embryo to refer to one that is chromosomally intact (euploid) and capable - upon reaching a receptive uterine environment - of propagating a healthy pregnancy. In contrast, an "incompetent" embryo is one that has an irregular quota of chromosomes (aneuploid) and will either arrest during development, fail to implant, miscarry, or result in a birth defect.

By the second day post-fertilization, the embryo is usually 2-4 cells. Within 72 hours of fertilization (day 3) it ideally should be 6-9 cells and by day 5 or 6 it should have reached the 100-cell+ stage with a fluid filled cavity inside (expanded blastocyst). Embryos that fail to reach 6-9 cells within 72 hours of fertilization are developing too slow or too fast and more often than not are aneuploid and “incompetent.” Also, cleaved embryos that contain significant cell fragments (fragmented embryos) are also more likely to be aneuploid.

Our research (sequential genetic testing using comparative genomic hybridization [CGH] of pre-fertilized eggs followed by testing on day 1 and again on day 3 after fertilization) has demonstrated that failure of an embryo to reach the expanded blastocyst stage within 5 to 6 days of fertilization is almost always associated with aneuploidy. As stated such aneuploid embryos are thus “incompetent”.

On average, a 6-9 cell day-3 embryos transferred to the uterus would have about a 20-25% chance of propagating a live birth. If left in culture for 2-3 days longer, many (but not all) such aneuploid embryos will stop growing (arrest) and be culled out in the process. Those that make it to blastocysts are then more likely (35-40%) to develop into babies. Those that fail to survive to the blastocyst stage are “incompetent” and even if they had been transferred to the uterus earlier on, would almost always have failed to implant.

However, if the transferred blastocyst is derived from a CGH-normal day 3 embryo, it would have double the chance (60-70%) of producing a live birth. This serves to underscore the fact that chromosomal integrity is the rate limiting factor in determining embryo “competence”. It also serves to dispel the myth that the “natural incubator”, (i.e. the uterus) provides a better environment that the incubator for the developing embryo.

Aneuploidy, the main cause of embryo "incompetence” cannot be recognized with the regular light microscope. Thus, it follows that microscopic examination does not permit reliable differentiation between “incompetent” and “competent” embryos. To show just how deficient microscopic embryo grading is, just consider the fact that a pristine looking day 3 embryo derived from the eggs of a 30 year old is at least 5 times more likely to be "competent" than an identical looking embryo derived from a the eggs of a woman in her mid-forties.

Preimplantation genetic diagnosis (PGD) with commercially available fluorescence in-situ hybridization (FISH) only accesses one third to one half of the embryo’s chromosomes. As such, while PGD/FISH is slightly better than microscopic grading in assessing embryo “competence” it is not nearly as reliable as CGH, which accesses all the embryo’s chromosomes.