Embryo Grading: Looks Can Be Deceiving
One egg, one embryo, one baby. This is what I refer to as the “Holy Grail” of IVF. If we could predict which egg would fertilize, become a viable embryo, implant successfully in the uterus and develop into a healthy baby, everyone’s IVF problems would be solved. Of course, there are too many variables involved to make IVF a 100% success proposition. For years, the biggest unknown has been determining which embryos are most likely to make a baby. Many methods have been developed and refined for embryo selection/grading over the past 30 years. These include:
Morphological (appearance) grading: this is what I call the “beauty pageant” of the microscope. Most centers use some form of grading based on microscopic appearance. Unfortunately, these methods are helpful, but by no means reliable. For example, a microscopically pristine looking day-3 embryo derived from the fertilized egg of a 30 year old is at least 5 times more likely to be chromosomally normal than would an identical looking embryo derived from an egg taken from a woman in her mid-forties. An improper number of chromosomes (aneuploidy) is the main cause of embryo “incompetence”, and will result in a failure to implant, a miscarriage, or a birth defect if it is carried to term. Simply put, it is not possible to accurately or confidently discern between aneuploid and euploid embryos microscopically.
Blastocyst Culture: by allowing an embryo to develop to the blastocyst stage in the lab, we are able to “weed out” many of the embryos that are not competent. Our research has shown that those embryos that don’t make it to this stage are highly likely to be chromosomally abnormal. Thus the argument that an embryo might be better off being transferred on day two or day three post-fertilization because it would be more likely to develop into a blastocyst in the uterus than in the incubator, is erroneous.
Preimplantation Genetic Diagnosis (PGD) via Fluorescence In Situ Hybridization (FISH): This method of genetic analysis examines 8-12 pairs of chromosomes in the embryo, allowing diagnosis of some of the most common aneuploidy conditions. The shortcoming of this method is that it neglects approximately half of the chromosome pairs in the embryo.
Comparative Genomic Hybridization (CGH) Embryo Testing: this method allows us to assess all 23 pairs of chromosomes in the embryo, filling in the gaps in the PGD/FISH method. In our experience over the past several years, a single CGH-normal embryo has about a 60% chance of making a healthy baby when transferred to a “receptive” uterus.
Clearly, embryo aneuploidy is a rate limiting factor in human reproduction and neither microscopic embryo grading nor PGD/FISH is able to accurately assess it. In fact it was not until the recent introduction of CGH as an embryo selection tool that this was possible. That is why CGH embryo selection has the potential to significantly enhance the efficiency of IVF. (See my previous post on CGH for more detailed information).