IVF embryo quality issues - day 3 embryo grading after in vitro fertilization

Blastocyst embryo quality and blastocyst grading on day 5

Advanced Fertility Center of Chicago
IVF Specialist Clinic
Gurnee & Crystal Lake, Illinois

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Embryo picture of a "perfect looking" 8-cell embryo (day 3 embryo)
There is no embryo fragmentation and the cells are very even, regular, and similarly sized
We would say that this is a high quality day 3 embryo
Embryo grading: 8 cell, grade 4

In general, the way we assess the "quality" of embryos from in vitro fertilization 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 shell around the embryo, etc.

Usually, determinations of "quality" are not made until about 48 hours (or later) after the egg retrieval. However, some IVF labs have been carefully assessing embryos on the first day after egg retrieval at the zygote, or 1-cell embryo stage. They have used morphological parameters of the pronuclei on day 1 as part of the overall embryo quality assessment and part of their selection for "best embryos for transfer" criteria. This is an interesting and potentailly useful tool, but it has not been shown to be consistently useful in different IVF laboratories at this time.

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 "arrested". By 72 hours ("day 3"), we prefer that some of the embryos are at least 6 cells - and preferably at least a few have 7-9 cells or more. At our center, we have seen babies that came from an embryo as slow as 4 cells on day 3, but the chances for pregnancy increase significantly as the cell number increases.

Embryos with higher cell numbers and regular appearing cells (blastomeres) and little or no fragmentation (see below) have a higher overall chance of implanting than do their counterparts with less cells, more irregularity and more fragmentation.

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.

Another important variable that is too often overlooked is the embryo transfer technique itself. A smooth and transfer with no trauma to the endometrial lining is essential to give the embryos the best chance for continuing with normal development.

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 imperfect, and we always need the pregnancy test (and the pregnancy outcome) to tell us more about "quality" than the microscope could ever reveal.

Most IVF clinics "grade" each embryo using one of many scoring systems. Unfortunately, there is no agreement at all as to which system to use. We all think we have the best one - and that the rest of the world should use our system (there are lots of big egos in the IVF world).

Patients often ask whether embryos that were given a "low grade" by the embryologist will make "low quality kids". As far as we know, 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 live birth.

Embryo quality, to a great extent, is determined by the quality of the egg from which it started. Tests of ovarian reserve, such as the day 3 FSH hormone assessment, and antral follicle countscan give us useful information about egg quantity, but are not very useful in predicting egg (or embryo) quality. The quality of the ovarian stimulation process and the quality of the IVF lab are other significant variables that impact the quality of the resulting embryos.

Learn about what to do if the first IVF cycle fails

A slightly fragmented embryo
Assisted hatching is being performed
The holding pipette is on the far left
A sperm is clearly visible at 7 o'clock (this sperm cell lost the race)

Embryo grading: 8 cell, grade 3

This embryo is also of high quality because it has an optimal cell number, the cells are fairly regular in size, and there is minimal fragmentation
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This embryo is moderately fragmented and has unevenly sized cells (blastomeres)

Embryo grading: 5 cell, grade 2

This embryo is expected to have a significantly lower chance of implanting because it is somewhat "slow" (having more than 5 cells is preferred for day 3 embryos) and because of the fragmentation and irregularity of the cells
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This embryo is severely fragmented and has unevenly sized cells
It is a poor quality day 3 embryo
This embryo is not expected to have much chance to implant and continue to a viable pregnancy
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Embryo grading: 6 cell, grade 1

Photo of a severely fragmented and very low quality day 3 embryo
This embryo is essentially non-viable and is degenerating
It will not be capable of continuing normal development and implantation

Embryo grading: 2 cell, grade 0

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