Recently one of my readers had a question that I think many patients who go through IVF may have. She wanted to understand what blastocyst grading means in terms of embryo quality and then, obviously the implications for her  chances of pregnancy. Her question was: ” I just had two expanded blastocysts transferred on day 5.  Both were graded CC.  With my last IVF we did a SET with expanded blastocyst, grade BB that resulted in a chemical pregnancy.  In your mind is it more important that they are expanding blastocyst or the grade? (would an early blastocyst grade AA be better)….should we consider implanting on Day 3 (when we had 8 embryos still around)?”

Probably the most widely used blastocyst grading system is the David Gardner system which separately judges the functional milestones the embryo reached (namely how expanded the embryo is and its progress in hatching out from the zona pellucida (1-6 with 6 being completely hatched) and the number of cells in the inner cell mass (A-C) and trophectoderm layer (A-C where an A means the greatest number and most tightly organized cells).

What is a blastocyst? A blastocyst describes an embryo stage reached usually after about five days of development post-fertilization. It has about 50-150 cells and has started to develop specific regions with different cellular destinies. The blastocyst is working hard; pumping fluids towards its center, creating a fluid-filled center and expanding like a water filled balloon. The inner cell mass is a clump of cells  protruding into  the middle of the fluid-filled cavity. This inner cell mass will continue to grow and ultimately will be the source for all the cells of the future baby. The trophectoderm cells line the inner surface of the zona pellucida (the glycoprotein shell around the embryo) and play a supporting role, supplying cells to form the fetal part of the future placenta. So the grading system takes into account how much progress the embryo makes in hatching from the “shell” and also how richly endowed the inner cell mass and trophectoderm are in terms of cell number and quality. More expansion is better than less and more cells are better than fewer cells.

The expansion grade scale ranges from 1 (least expanded) to 6 (completely hatched).

Grade 1: the fluid-filled cavity takes up less than half the space of the embryo.

Grade 2: the fluid-filled cavity takes up more than half the space of the embryo.

Grade 3: the blastocyst cavity has expanded into the entire volume of the embryo, pressing the trophectoderm cells up tightly against the inside of the zona.

Grade 4: Expanded blastocyst, where the blastocyst has increased beyond the original volume of the embryo and caused the zona pellucida “shell” to become super thin.

Grade 5: Embryo has breached the zona and is hatching out of its shell

Grade 6: Embryo is completely hatched.

So the embryo is given a number grade (1-6), followed by a letter grade for the inner cell mass and then the trophectoderm (A,B or C).

For the inner cell mass:

A: Many cells, tightly packed

B: several cells, loosely packed

C:  very few cells

The trophectoderm grading goes like this:

A: many cells, forming a cohesive layer

B: Few cells, forming a loose layer

C: Very few large cells.

So a blastocyst with grade 5AA is partially hatched with many cells in the inner cell mass (cells for the future baby) and many tightly packed cells in the trophectoderm.

One thing to remember is the grading also represents a continuum. A healthy blastocyst starts out unhatched with a small space and few cells, then progresses to a hatching blast with many cells. When we pick a blastocyst to transfer on day 5 of culture, we preferentially pick the most advanced embryos that seem most “eager” to implant. That doesn’t mean that a blastocyst with a lesser grade won’t implant. They do. Remember we are looking at  a snap shot of embryo development and not all embryos in a group started the developmental pathway at the same instant.

A picture is worth a thousand words.

Here are a group of expanded but not yet hatched blastocysts (grade 4AA).

Here is a partially hatched blastocyst (grade 5AA). You can see the clear zona pellucida shell barely attached to one end of the blastocyst.

For more pictures of  graded blastocysts in various stages of development, look at these  (copyrighted) embryo pics  at this link  http://www.advancedfertility.com/blastocystimages.htm . These pics should help clarify the grading system.

Regarding my reader’s question of whether the degree of expansion or whether the cell number is more important in a successful implantation and pregnancy…well, it’s not usually a question of one or the other. In a healthy embryo, they tend to go together. Typically, as the cell number increases, so does the level of expansion.  What is a deal killer is if we don’t see a clump of cells corresponding to an inner cell mass because that means that none of the cells in the embryo have been allocated to make the future baby. Other than that, there is a lot of flexibility in the embryonic program and I wouldn’t despair if my blastocyst had a lesser grade. I have seen morulas (the stage before blastocyst) transferred on day 5 result in pregnancies so our preconceived notions of where an embryo must be on day 5 are not always predictive. However,  if an embryo is delayed by more than a day- say 8 cells on day 5, it probably will not be result in a pregnancy because it has likely stopped developing.

Hope that helps demystify embryo grading. Best Wishes.

© 2011, Carole. All rights reserved.

Posted on December 18, 2011 at 8:28 pm
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