One of the trickiest jobs facing a clinical embryologist is the visual assessment of human embryos. Embryo selection prior to embryo transfer clearly has an enormous impact on the success of the treatment and embryo selection for cryopreservation is equally important to the future success of frozen embryo transfers.
Patients are often awestruck when they see a photo of their embryos for the first time on the morning of their transfer. That morning each embryo is carefully observed under a powerful microscope and the information about the quality of the individual embryos is given to patients prior to their transfer. In general, the way we assess the “quality” of embryos at Rotunda is by determining 3 major components. Cell number, cell regularity (regularity of size), and degree of fragmentation. There are also other things that are also noted about the embryos appearance, such as multinucleation, presence of vacuoles, granularity, thickness of the zona around the embryo, etc. Using this information, decisions are then made about how many embryos to transfer and how many to freeze, and importantly, what to do with embryos that are not developing very well.
When eggs are retrieved from a patient’s ovaries, they are surrounded by thousands of cumulus cells that prevent us from seeing eggs directly or making any comments about quality. For patients having ICSI (Intra-Cytoplasmic Sperm Injection), we strip away the cumulus cells, but even then, very little information on quality can be ascertained. Only when eggs are of particularly poor quality are we able to observe obvious differences from healthy eggs. The vast majority of eggs do not show any characteristics to indicate quality. Therefore, the embryologist will not typically convey any information about egg quality.
Usually, determinations of “quality” are not made until about 48 hours (or later) after the egg retrieval. By 48 hours (“day 2”), we prefer that at least some of the embryos are at least 3 cells – and preferably 4 cells or more. They must be at least 2 cells by then – or they have basically “arrested”. By 72 hours (“day 3”), we prefer that some of the embryos are at least 6 cells – and preferably at least a few that have 7 cells or more. At Rotunda, we have seen babies that came from an embryo as slow as a 4 cell on day 3, but the chances for pregnancy increase greatly as the cell number increases.
Fragmentation is a normal feature in embryos and only about 20% of embryos have no fragments at all. However, the absence of fragments does not guarantee pregnancy as there are many other factors involved in embryo quality. The degree of fragmentation and cell asymmetry is given as a grade, usually A,B,C 0r 1, 2, 3. Grade A embryos look beautiful and normal in every way. Grade B embryos will have a small degree of fragmentation and or unevenness, but are still considered high quality. Only if an embryo is in real trouble and has more fragments than cells, will we assign the dreaded Grade C. These embryos very rarely implant after transfer and are not considered viable enough to freeze regardless of how many cells they contain. Patients often ask whether embryos that were given a “low grade” by the embryologist will make “low quality kids”. The children born from low grade embryos are just as cute, intelligent, strong, etc. as those born after transferring high grade embryos. The only difference as far as we know is in the relative chance that the transfer of the embryo(s) will result in a pregnancy and a live birth.
Embryo quality as we see it under the microscope in the IVF lab gives us some reasonable ability to predict the chances for pregnancy from an embryo transfer. However, because there are many other contributing factors involved that we can not measure, these generalizations do not always apply. We see some cycles fail after transferring 3 perfect looking embryos, and we also see beautiful babies born after transferring low grade embryos. The true genetic potential of the embryo to continue development and the quality and receptivity of the uterine lining are really impossible to measure. Hopefully, that will be something for the future.
Ultimately, the only true test of embryo quality is whether it implants and develops normally and eventually goes home from the hospital with mom. In other words, embryo grading systems are very imperfect, and we always need the pregnancy test to tell us much more about “quality” than the microscope can reveal.
Posted by : Goral Gandhi, MSc,
Rotunda – Center for Human Reproduction (Pvt) Ltd