Embryo grading is one of the most subjective things an embryologist does in the IVF lab. Embryo grading systems are different among IVF labs. Embryologists will make their choice of which embryos to transfer or cryopreserve based upon a grade given to an embryo. It is important to realize that regardless of which embryo grading system is used in an IVF lab, the embryo grade does not tell us what is going on inside the embryo genetically. In our experience we have seen many cases of embryos with poor grades that make a pregnancy and many that do not. We have also seen the exact opposite, we have seen many cases where embryos with good grades make a pregnancy and many that do not.
At RHS, we do embryo transfers on either day 3 (cleavage stage) or day 5 (blastocyst stage). The embryo grading systems for day 3 embryos and day 5 embryos are very different.
Day 3 embryos are called cleavage stage embryos. During embryo grading, these embryos are given a cell number (i.e. 4, 6, 8 cell) and a grade (i.e. A, B, C) to signify what cell stage the embryo is at in development. Not all of the cells within the cleavage stage embryos divide at the same rate. Therefore, it is not uncommon to have an odd number of cells at the day 3 embryo grade. Cleavage stage embryos are typically at the 6-8 cell stage by day 3 of culture. As cleavage embryos divide, sometimes a small portion of cytoplasm breaks off and forms a fragment. Fragments are not considered cells because they do not contain nuclei. The cause of fragmentation is not understood completely, but it is thought that embryos that contain a lot of fragmentation are at a disadvantage because the embryo loses a lot of the cytoplasm needed to sustain the cell. Below is an explanation of the embryo grading system used by RHS’ IVF lab for cleavage stage embryos:
Day 3 / Cleavage Stage Embryo Grading Guidelines
(Occasionally a “+” or “-“will be added to distinguish slight variations within each grade.)
Grade-A embryo characteristics: blastomeres of equal size, little or no fragmentation, and a zona pellucida that is not extremely thick or dark in appearance.
Grade-B embryo characteristics: blastomeres of equal size, minor cyotplasmic fragmentation covering < 10% of the embryo surface.
Grade-C embryo characteristics: blastomeres of distinctly unequal size and moderate-to-significant cytoplasmic fragmentation covering >10% of the embryo surface.
Day 5 embryos are called blastocyst stage embryos. The blastocyst stage is the stage of development that an embryo must reach before it can implant in the uterus. The structure of a blastocyst is more complex than that of a cleavage stage embryo. Once the embryos start to reach the blastocyst stage the cells start to rapidly divide, a blastocoel starts to form which causes the embryo to start to expand and increase in overall size. Blastocyst stage embryos become organized into two distinct parts, the inner cell mass (these cells will develop and become the fetus), and the trophectoderm cells (these cells will develop into tissues needed to sustain the pregnancy, i.e. placenta). During embryo grading, our IVF laboratory uses a blastocyst culture to help determine which embryos have the best chance of being able to implant as we can watch the embryos in culture develop into the blastocyst stage. The blastocyst is given a grade based upon the three main components of the blastocyst embryo. The three components are given grades used to describe the expansion (or overall size), the inner cell mass development, and the trophectoderm cell quality. Below is an explanation of the embryo grading system used by RHS’ IVF lab for blastocyst stage grading:
Day 5 / Blastocyst Stage Embryo Grading Guidelines
- Early Blastocyst: the blastocoel filling more than ½ the volume of the embryo, but not expansion in overall size compared to earlier stages.
- Blastocyst: the blastocoel filling more than ½ the volume of the embryo, with slight expansion in overall size and notable thinning of the zona.
- Full Blastocyst: a blastocoel filling more than 50% of the embryo volume and overall size fully enlarged with a very thin zona.
- Hatching Blastocyst: The trophectoderm has started to herniate through the zona.
- Fully Hatched Blastocyst: Free blastocyst fully removed from the zona.
Inner Cell Mass
A Tightly packed compacted cells.
B Large, loose cells
C No ICM distinguishable
D Cells of the inner cell mass appear degenerative
A Many healthy cells forming a cohesive epithelium
B Few but healthy cells, large in size
C Poor, unevenly distributed cells. Many appear as few cells squeezed to the side
D Cells of the trophectoderm appear degenerative embryo surface.
In conjunction with the patient’s age and fertility history, embryo grading is used as a tool by the physician and the embryologist to determine the optimal day for transfer. Embryo grading is also used to help determine which embryos in culture should be chosen for transfer or cryopreservation. The physicians at RHS adhere to ASRM guidelines for number of embryos to transfer. Providing the physicians with an idea of what the embryos look like and how the embryos are developing in culture helps the physician counsel our IVF patients at transfer and help determine the appropriate number of embryos to transfer to the patient.
To learn more about how your embryos develop, link to our blog, A Guide to Embryo Development After Retrieval.
Reproductive Health Specialists is Western Pennsylvania’s only independent, female-owned, fertility center. We accept both Highmark Blue Cross/Blue Shield and UPMC insurance as well as Cigna, Aetna and Untied Health Care. Contact us to make an appointment.