Grades: it feels like we’ve dealt with them all our life — in school, performance reviews at work, even eggs at the supermarket! Well, it turns out grades are a part of the IVF process too.
In vitro fertilization (IVF) can be an effective fertility treatment for people trying to conceive. Part of its success is due to the fact that fertilization happens outside of the body — in other words, the egg and sperm are combined in a lab, resulting in an embryo. That embryo is then transferred back into the body, where hopefully a successful pregnancy can grow.
However, it turns out that not all embryos are created equal. When you are recovering from your egg retrieval, you will get a call from your doctor with the number of embryos and the grade of each embryo. What do these grades mean? How do they impact how successful your upcoming transfer cycle will be?
Let’s break it down.
What is embryo grading?
After fertilization, the embryos are grown in an incubator. In order to assess how many viable embryos have developed and the quality of these embryos, doctors use complex embryo grading systems. Grades are typically presented as a combination of numbers and letters, and they may differ based on your clinic.
The goal of any embryo assessment is to identify the one with the highest pregnancy potential. In most studies on embryo grading, the most valuable outcome we are looking for is the live birth rate, but we can also study the implantation rate (any positive pregnancy test) or the clinical pregnancy rate (any ultrasound-documented pregnancy).
Identifying the embryo with the highest live birth potential maximizes the success of the embryo transfer process and minimizes the number of embryo transfers required to become pregnant and deliver. IVF is an emotionally and financially draining process, so identifying the embryo with the highest live birth potential is critical in saving patients time, money, and energy. Furthermore, identifying and transferring the single embryo with the highest live birth potential means not having to transfer two embryos and therefore avoids the risk of a twin pregnancy.
The typical procedure for grading embryos is a visual assessment of the appearance, or morphology, of the embryo. Most labs limit this assessment to once or twice during development, to reduce the amount of time the embryo is out of the incubator. This is because embryos get “stressed” with the change in pH and temperature when they are removed from the incubator.
When is grading done?
Embryos follow a very specific developmental timeline, changing shape and growing in a very coordinated sequence.
On day one post-fertilization, the embryo has two cells, then on day two the embryo should have four cells, and on day three post-fertilization the embryo should have eight cells.
On day four of embryo development, a major change in the morphology occurs: the cell number increases rapidly and the shape condenses, in the morula stage. Another major change then occurs on day five or six, when the embryo transforms into a blastocyst.
Grading is traditionally done on day three and/or day five or six because embryos can be transferred into the uterus or frozen on those days. The decision to freeze or transfer the embryo, and the day that this occurs, will be based on your specific protocol and goals.
What do the grades mean?
Let’s get into a little more detail on what the specific grades mean so that you can understand your embryology report.
The first thing to note is that the way the embryo quality is described will differ depending on whether it is day three or day five. This is because day-five embryos have had more time to develop, so doctors are looking for different markers.
Day-three embryos
On day three, the embryo is also called a “cleavage stage” embryo. Evaluation typically includes the number of cells, the degree to which the cells are fragmented, and how symmetric the up to eight cells are in size. Each lab may have different methodologies for record-keeping, but on a day-three embryo report, you might see three numbers or an alphanumeric score.
Let’s break each part down:
- Number of cells: The first portion of the grade reflects the number of cells and is very straightforward, i.e. “8” means the embryo has eight cells, “7” means the embryo has seven cells, and “6” means the embryo has six cells, etc.
- Fragmentation: The next part of the grade is the degree of fragmentation. Fragmentation is when the cells have a shaggy or bubbly appearance (which leads to a lower score) as opposed to being smooth and rounded. The highest grade means there is 10% or less fragmentation; this can be denoted as a “1” or a letter grade such as “A” or “G” (for good). Embryos that have 11% to 25% fragmentation are typically given a score of “2” or “F” (for fair). Lastly, embryos that have more than 25% fragmentation would be given a score of “3” or “P” (for poor).
- Symmetry: The third and final part is the symmetry of the cells. Here, “1” means the cells have perfect symmetry, which is observed when all cells have a very similar size. A score of “2” means there is moderate asymmetry among the cells, with slight differences in sizes, and “3” means there is severe asymmetry.
So, for example, if your day-three embryo has a grade of “8-1-1” it means that the embryo has eight cells, very little fragmentation (10% or less), and good to perfect symmetry. Your clinic’s lab might also use letters denoting “good,” “fair,” or “poor,” so be sure to ask what its grading system is.
Day-five or day-six embryos (blastocyst)
The specifics for grading embryos on day five or day six are focused on the size and shape of the blastocyst. The blastocyst should have a ring of cells, called a trophectoderm, surrounding a fluid-filled cavity, and an area of tightly packed cells called the inner cell mass. The trophectoderm will eventually help form the placental tissues, and the inner cell mass will help form the fetus.
The most commonly used grading system for day-five and day-six embryos is called the Gardner system. The score is an alphanumeric grade consisting of a number grade that refers to the degree of expansion of the blastocyst, followed by a letter grade for the inner cell mass, and then a letter grade for the trophectoderm.
Let’s break each part down:
- Expansion: This score looks at how expanded the embryo cavity is. A score of “1” or “2” means the cavity fills a small proportion of the total size of the embryo. A score of “3” means the cavity has expanded and now accounts for most of the volume of the blastocyst. A score of “4” refers to an expanded blastocyst, where the cavity has expanded to occupy the majority of the volume of the embryo. A score of “5” means the embryo volume has expanded so much that the embryo starts to emerge out of the zona pellucida (outer shell). A score of “6” means that the embryo has completely hatched and left the zona pellucida shell behind.
- Inner cell mass: A score of “A” means that the cluster of inner cell mass contains a high number of cells that are tightly packed together. A score of “B” means that it is more loosely packed and contains fewer cells. A score of “C” means that the mass contains very few cells.
- Trophectoderm: The last component of the grade is for the trophectoderm. Here, a score of “A” means there are many trophectoderm cells of uniform size that cohesively cover the blastocyst cavity and inner cell mass. A score of “B” means that there are fewer cells that are larger and less uniform in size and more loosely surround the embryo. A score of “C” means that there are very few large cells making up the trophectoderm.
So based on the Gardner system, you might have a high-quality embryo with a score of 5AA or 6AA. However, you can still have a successful pregnancy with a lower score.
Let’s talk about how you can interpret your grades.
Which grades are most important?
This is a huge area of research in embryology, and there are numerous studies published showing that embryo grades are associated with embryo transfer outcomes.
For day-three embryos, poorer grades on any of the parameters have a lower live birth potential. The strongest marker is the degree the embryo has divided, as represented by the number of cells. There are many studies demonstrating that the number of cells on day three is highly associated with chromosomal abnormalities, implantation, and pregnancy outcome. Lower live birth potential does not mean zero live birth potential, so it is important to talk to your physician, who can help guide expectations heading into an embryo transfer.
There is more debate on day-five embryos. While some studies suggest that the trophectoderm is the most important score, other studies suggest that the inner cell mass is the best predictor of an embryo’s ability to result in a live birth. For example, in one retrospective study of 694 transfers of single embryos, the grade-A trophectoderm embryos had a 17% higher live birth rate than the grade-B embryos. Another recent retrospective study found that embryos with an inner cell mass grade of “A” compared with “C” had a live birth rate of 55.6% versus 32.2%. When the researchers looked at trophectoderm scores, they found that embryos with a score of “A” or “B” were 1.5 to 1.6 times as likely to result in a live birth as an embryo with a trophectoderm score of “C.”
Currently it is debated as to which portion of the score is most helpful in predicting live birth, or whether it is the total composite alphanumeric score. Each embryology lab tracks their own outcomes, so it’s important to talk to your physician about grading, since they should be able to give you a very specific likelihood of live birth for each of your embryos based on the clinic’s outcome data.
What else should you consider before the embryo transfer?
When discussing with your doctor which embryo is planned for transfer, if your embryo has been tested for chromosomal status (PGT-A) and frozen, there are some additional nuances to understand.
It is important to understand that the grade of the blastocyst embryo does not mean that the embryo is chromosomally balanced (or “euploid”). For example, chromosomally abnormal embryos are capable of having very good or excellent grades.
A question you can ask before the embryo transfer is how the embryo appeared after the thawing process the morning of your transfer. The process of being thawed and resuming cellular activity and embryo growth can result in a change in the quality of the embryo. Embryos where the post-thaw grade is lower than the pre-thaw grade had a significant decrease in the live birth rate, while embryos with a higher grade after the thaw have the highest odds of live birth.
Closing thoughts
IVF is an arduous and challenging process, but hopefully this crash course in embryo grading helps you understand how your doctor and embryology lab are assessing your embryos, so that you can participate in informed decision-making while prepping for the embryo transfer process.
The bottom line
- Embryo grading helps identify the embryo with the highest chance of resulting in a live birth, hopefully making the IVF process more efficient.
- Embryos are graded based on development stage—on day 3 (cleavage stage) grading focuses on cell count, fragmentation, and symmetry; on day 5 or 6 (blastocyst stage), the focus shifts to expansion, inner cell mass, and trophectoderm quality.
- The most commonly used grading system for blastocysts is the Gardner System, which assigns a number-letter-letter format (e.g., 4AA) based on specific markers.
- While higher grades often correlate with better outcomes, there is debate about whether the overall score or a specific part plays a bigger role. Lower-grade embryos can still result in successful pregnancies.
- Embryo grading standards can vary by clinic, so it’s important to speak with your physician. They can provide more specific success rates based on their lab’s data.
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This is so helpful – thank you! I’ve never seen it broken down so clearly. My clinic never told me the grades of my embryo and I was glad actually – all I knew was which were genetically normal. While it’s important information, given the immense stress and pressure of navigating IVF already, I think the info needs much more context and counseling if given. Otherwise, I think grading too easily becomes one more proxy for “better and worse” and a source of pressure or failure for women. We know that “lower graded” embryos become healthy pregnancies all the time so I seriously question the cost-benefit of sharing this information at all.