IVF and Embryo Grading: What It Means

Embryo grading is a helpful tool that is used by embryologists and doctors during an in vitro fertilization (IVF) treatment to determine exactly which of the formed embryos are best to transfer, the best day for the transfer, and how many of the embryos to transfer. Embryo grading is typically carried out on the third and the fifth day from the embryo forming. The grading does not exclusively form the decision but it is used in conjunction with the patient’s age, fertility history, as well as other necessary information for deciding the best embryos to transfer. The grading is largely based on the general appearance of the embryo, and it is a highly subjective assessment.

Day 3 embryos

These are also referred to as the cleavage stage embryos. This means that while they are constantly dividing, they are not increasing in size. They typically consist of 6-8 cells inside an outer covering that is called a zona pellucida. The day 3 embryo is about the same size as an unfertilized egg.

What is the day 3 grading system?

On day 3, embryologists use a high-powered microscope to take a look at the structure of the embryo. They examine the embryo for two main features, these are:

• The number of cells in the embryo – An embryo that is dividing as it should, there should ideally be 6-10 cells by day 3 (the ideal number is 8). Some embryos, however, may have less than 6 cells, but this doesn’t entirely make them bad embryos because not all cells divide at the same time. This means that although the number of cells is usually the best indicator of whether an embryo will thrive or not, it is not always clear-cut.
• The appearance of the embryo – This is a harder feature to grade, much harder than just counting the cells. This is especially so because the embryologist is sometimes not looking at the embryo directly but at a tangent. The day 3 embryos are graded from 1-4 depending on the particular lab protocols with 1 being the highest grade. The embryologist examines these cells to ensure that each cell has a nucleus and that they are equal cells. They also check for fragmentation, which sometimes occurs when cells divide. A fragmentation rate of up to 20% is considered fine. Any more than 20% and the cells lose too much cytoplasm for optimal function.

Some other things that the embryologist looks out for when examining the 3-day embryo are:

• Cytoplasmic pitting – This is checking for any depression in the cell contents.
• Compaction – Are the cells compacted in readiness for the next stage?
• Vacuoles – Are there any fluid-filled pockets?

Day 5 embryos

Some fertility clinics prefer to transfer embryos when they are on day 5. The embryo, now referred to as a blastocyst, is rapidly dividing and building up the cell numbers. Some of the cells also start to specialize in function, with some of the cells forming an inner cell mass that will go on to develop into the fetus. Some of the other cells form the trophectoderm epithelium, which develops into the placenta and the other connective tissues that the fetus needs for the pregnancy. The zona pellucida continues to be pushed to the limits as the cells continue to divide. As the embryo readies to burst through and implant into the inner lining of the uterus, the membrane of the zona pellucid will begin to thin out.

What is the day 5 grading system?

The day 5 grading system is more complicated than what is observed with the day 3 grading. Although there is a general or universal grading system, each fertility center has a unique system that may be responsible for slight differences that are seen in grades. The features that are being graded in the embryo include:

• The amount of expansion of the embryo – The part that will be measured here is the blastocoel. This is a fluid-filled cavity that forms within the embryo. The grades range from 1-6 with 6 being the most developed.
• The quality of the inner cell mass – This is the part of the cell mass that develops into the fetus. The grades here range from A to C, with A being the best quality.
• The quality of the trophectoderm epithelium – This is part of the cell mass that develops into the placenta and other pregnancy-related tissues. The letter grades are A through C, with A being the highest quality.

So, as an example, a day 5 embryo may have a grade of 4AA, or 5AA. This would be described as a hatching blastocyst with the highest quality inner mass cell and the highest quality trophectoderm epithelium cells.

Blastocyst grade per factor

The first part of the grade which is the number represents the expansion of the embryo cavity as follows:

• 1 – blastocoels cavity (BC) is one-third the volume of the embryo
• 2 – BC is half the volume of the embryo
• 3 – full blastocyst is 80%, completely filling the embryo
• 4 – expanded blastocyst, the cavity is larger than the embryo; the zona is thinning
• 5 – expanded blastocyst, beginning to hatch out of the zona
• 6 – expanded blastocyst, fully emerged from the zona

The second part of the grade is represented by the letter A-C which represents the inner cell mass quality as follows:

• A – many cells, tightly packed
• B – several cells, loosely grouped
• C – very few cells

The third part is also represented by the letters A-C, representing the quality of the trophectoderm epithelium as follows:

• A – many cells, forming a cohesive epithelium
• B – few cells, forming loose epithelium
• C – very few large cells

Typically, 5AA on day 5 is the best grade.

How important is this embryo grading?

In order to determine the quality of the embryo, all of the components of the embryo must be taken into account. It is also important to note that embryos will also continue to develop. Because of this, their grading can also change; eventually making lower-graded embryos to be candidates for eventual transfer or freezing. Embryo grading is a tool to help embryologists and doctors, but it is only a part of the decision-making process. The doctors will also consider all of the factors surrounding the case, including the patient’s unique medical history.