Embryo & Blastocyst Grading: Which to Transfer, Which to Discard

Currently, when it comes to embryo/blastocyst grading, there is no standard method practiced universally across all IVF centers. There are a variety of systems used in different embryology laboratories; some are orthodox and proven, while others are not. This often leads to confusion when it comes to patients trying to interpret a recommendation to freeze, transfer or discard embryos based upon their microscopic appearance or “grade.” Consider the following:

1. Some IVF programs freeze embryos on day 2 post-fertilization, prior to division or cleavage (i.e. at the pronucleate stage) , while others freeze on day 3 (cleaved embryos). However, more and more IVF programs are starting to recommend that only embryos that make it to the blastocyst stage be frozen.
2. Some programs freeze and transfer embryos regardless of their grade, while others selectively freeze only embryos that are deemed to be viable.
3. Some embryologists (usually, those less experienced) are less courageous in making the important determination of whether an embryo is potentially viable and err on the side of extreme caution by recommending the transfer of all grades of embryos.
4. The poorer the quality of an embryo the less likely it is to propagate a baby even if freshly transferred. Also, the poorer the quality, the less likely it is that the embryo will even survive the freeze/thaw.
5. There comes a point where the quality of an embryo is so poor that it won’t survive the freeze/thaw and if transferred fresh, would NOT propagate a pregnancy.
6. Most embryos that are allowed to develop to blastocyst reach their maximum potential by day 5 post-fertilization. Some take 6 days (and incidentally, there is no indication that these later developing blastocysts necessarily have poorer implantation potential).
7. Those embryos that fail to expand by the 6th day AND do not have a demonstrable inner cell mass from which the baby develops (i.e. grade 3), are without exception non-viable.
8. Some embryologists base their blastocyst grading on morphology as determined on day 5 post-fertilization while others allow blastocysts that have not developed well by day 5 (grade 3 blastocysts) to go to day 6 by which time the grade might improve.
9. Some IVF programs still freeze embryos slowly ("conventional freezing"), while others have adopted ultra-rapid freezing ("vitrification"). Conventional freezing is associated with a much higher rate of freeze/thaw attrition and a much lower baby rate per frozen embryo.

Now to SIRM policy and why we take this position: I conferred with our Executive Director of Embryology, Levent Keskintepe, PhD in formulating the response below:

• Our published as well as yet unpublished data shows that while embryos that develop into Grade 1-2 blastocysts by day 5- 6 post fertilization are not always chromosomally normal, those that do NOT reach this stage of development are almost invariably “incompetent” (non-viable). Thus, the often quoted assumption that an embryo would be better off transferred earlier into the "natural" uterine environment to develop is inaccurate. In fact, it is preferable to allow embryos a chance to prove their potential by reaching the Grade 1-2 blastocyst stage in the laboratory before deciding which ones to transfer or vitrify (freeze/store) for future dispensation. At SIRM, we do transfer cleaved embryos in some cases – generally only those involving women who end up having very few or no other embryos for transfer. As such, they have little risk of a "high order multiple" (triplets or greater) pregnancy. The same would apply to a patient/couple who, in spite of our recommendation to the contrary, still insists on having cleaved embryos (or for that matter even Grade 3 blastocysts) transferred (or frozen).

• Dr Keskintepe has imposed a "uniform embryo grading system" throughout all 7 SIRM embryology laboratories. All of our Laboratory heads are thoroughly trained in the use of this system. Dr Keskintepe informs me that using this rigid system, (in many thousands of cases) our experience is that if an embryo fails to attain Grade 1-2 status by the sixth (6th) post-fertilization day, it will not propagate a viable pregnancy. This has been the case without exception. Furthermore, our CGH embryo karyotyping data shows that those embryos that fail to make it to grade 1-2 blastocysts by day 6, with very few exceptions, are chromosomally abnormal (aneuploid), thereby validating our policy.

There is little doubt that for a variety of reasons (several of which are cited above) some will find fault with this SIRM policy. However, we are confident that using our approach best serves those patients who entrust us with their care and who deserve our best advice based upon our own unique but substantial experience in the field.