How Are Embryos Graded?
If you have completed an IVF cycle, you are probably well aware that embryos are graded after a few days of development. While some clinics grade embryos three days after insemination (known as day 3 in the IVF lab), others wait until day 5 to begin grading embryos.
As a reminder, embryos all begin as one cell: a fertilized egg, or zygote. This one cell then undergoes a process known as mitosis, or cell division, during which it replicates its DNA so the new cell and the original cell have identical DNA. These two cells (called blastomeres) then also undergo mitosis, resulting in four cells, and so on.
Day 3 Grading
Roughly three days after insemination, embryos can be graded based on the following criteria:
Their number of cells. At this stage, embryos should consist of 6+ cells, with 8 being the ideal number. It’s okay to see an odd number of cells since cells may divide at different times.
How much fragmentation is present. Fragmentation occurs when small pieces of cells break during cell division. Some fragmentation is normal, but it should not take up >20% of the embryo’s space.
The symmetry of the cells. As mitosis occurs, the embryo remains the same size until around day 5. However, as the number of cells increases, their size decreases. A lot of people compare this to a pizza: if you cut more slices, they will each be smaller but the pizza will remain the same diameter. If an embryo’s cells are the same size, it means that mitosis is occurring at a similar pace for each of the cells. If the cells are grossly asymmetrical, it indicates that all of the cells are not dividing at the same pace, which could stem from a developmental issue within the embryo. It’s okay for an embryo’s cells to be somewhat asymmetrical.
Embryos that are not showing normal signs of development on day 3 can still lead to successful outcomes, though their success rates tend to be lower than embryos that appear normal on day 3. However, embryos that appear normal on day 3 do not necessarily develop properly after this point.
Day 5 Grading
Many clinics wait until day 5 to begin grading embryos. At this point, the embryo should enter the blastocyst stage of development, during which a cavity (blastocoel) forms inside of the embryo and the cells inside the embryo begin to differentiate (have different fates). Each clinic may have its own grading system, but a common system utilized is the Gardner scale, which includes the following criteria:
The embryo’s level of expansion (stage of development), which is usually written as a number from 1-6:
1 = early blastocyst: the blastocoel has begun to form but takes up <50% of the embryo’s space
2 = blastocyst: the blastocoel takes up >50% of the embryo’s space
3 = full blastocyst: the blastocoel takes up 100% of the embryo’s space, but the embryo’s diameter has not increased
4 = expanded blastocyst: the blastocoel has increased in size and the shell (zona pellucida) surrounding the embryo has begun to thin
5 = hatching blastocyst: a hole forms in the embryo’s shell, and it begins to hatch from its shell (which is required for implantation to occur)
6 = fully hatched blastocyst: the embryo has fully hatched from its shell
The appearance of the embryo’s inner cell mass (ICM), which ultimately develops into the fetus. Most clinics grade this on an A, B, C scale:
A = perfect or above average, compact, normal in appearance
B = average, present but not completely compact
C = below average or non-existent, not compact
The appearance of the trophectoderm (TE), which ultimately develops into the placenta and other non-fetal tissues. Most clinics also grade this on an A, B, C scale:
A = perfect or above average, uniform in size, no gaps
B = average, present but with gaps, mostly uniform cells
C = below average or non-existent, many gaps, not uniform
While an embryo’s grade can help predict its chance of success, it is only one factor in an embryo’s overall success rate. For example, an embryo’s grade cannot determine if it has the correct number of chromosomes (PGT-A is required for this).
