Embryo Grading Explained
Many of you who have gone through IVF treatment may have been surprised to find out that each embryo created is assigned a grade! That’s right – your embryos get a ‘report card’ of sorts – and the scores can help us to select the best embryo for transfer. Selecting the best embryo does NOT mean choosing the embryo that will turn into the healthiest child, or the child that will get into an Ivy League school. The grading, which is called a ‘morphology grade’, is associated with an embryo’s odds of implanting and resulting in a live birth. Here’s a breakdown of the commonly used metrics when embryo morphology is graded in the IVF laboratory.
Day 3, or “Cleavage stage” embryos:
A day 3 embryo can undergo only a limited assessment, since at this stage of development the embryo is still relatively simple – it hasn’t yet differentiated into the two major cell types seen at day 5 and beyond, when the embryo turns into a ‘blastocyst’. The main things you can assess about a day 3 embryo are:
- The number of cells the embryo has – this can range from 3-4 cells up to 12-15 cells. In general, having an embryo with 8 or more cells suggests it is growing at a ‘normal’ pace – speed of embryo development is strongly correlated with reproductive potential.,
- How many of the cells appear to have fragments. The percent of the embryos’ cells with fragments is thought to be a quality indicator. Fragments form in the embryo when there is unequal division of cells. Fragments are considered the ‘junk’ of the cell, and are likely not useful to the embryo. The higher the degree of fragmentation, the lower the chance of a pregnancy from a given embryo.
Day 5, or “Blastocyst stage” embryos:
When it comes to the blastocyst stage, there’s a LOT more to talk about. I like to use the analogy of applying to a competitive school for a child – the younger they are, the less can be assessed or asked of them at the interview. When it comes to applying later, let’s say in highschool, there are many more forms of assessment and things to judge the candidate by. (Maybe this is top of mind for me, having just gone through the grueling process of navigating NYC kindergarten admissions!…anyway, I digress!).
The blastocyst stage embryo has grown into 100-200 cells which have differentiated out into two cell types – the ‘inner cell mass’ which becomes the fetus/baby in the future, and the trophectoderm which turns into placenta. There are three major components to blastocyst stage embryo grading (when using a classification system known as ‘Gardner-Schoolcraft scoring’ (named after the two people who came up with it). A three digit score refers to:
Expansion refers to how large the space/cavity in the embryo appears. A blastocyst embryo should have a blastocoel cavity filled with fluid. Under pressure from this accumulation of fluid +/- enzymes in the uterine environment can lead to the embryo’s shell cracking and the embryo hatching from its shell. When the embryo hatches from its shell, prior to implantation, it is automatically at the highest grade of expansion – expansion grade 6. How expanded an embryo appears corresponds with grades that range from 1 to 6. In general, any embryo that can be frozen/biopsied for PGT must be at an expansion grade of 3, at a minimum. Expansion grade 6 is not necessary better than 4/5… a 6, or a fully hatched embryo, is theorized to be slightly more delicate and some data suggests there may be a lower ability to withstand the freezing and thawing process successfully. In general 4 vs. 5 vs. 6 will not be a gamechanger re: chance of an embryo implanting.
2. Inner Cell Mass
These cells one day become the fetus/baby. They cluster together in the embryo and the grade assigned is a reflection of the volume of the cells and how ‘bunched together’ or cohesive they appear. This part of the grading score is known to be the most predictive of implantation and live birth. The grades range from A to D – just like in school, As and Bs are preferred to Cs and Ds. The inner cell mass (ICM) grade is the MOST predictive part of the 3 digit score.
These cells separate out to the periphery of the embryo, lining the inner cell. The trophectoderm one day becomes the placenta. Similar to the inner cell mass, grades of A to D are assigned to the trophectoderm. As and Bs are better than Cs and Ds. The trophectoderm grade is much less predictive of pregnancy than the inner cell mass grade. Trophectoderm is assigned a high grade when there are many cells and they form cohesive, tight bonds, lining the inner shell of the embryo. The trophectoderm grade is the least relevant/predictive marker of implantation.
Not every lab will necessarily use a standardized morphology grading system – they may have their own way of assessing and scoring embryos. I recommend speaking to your doctor about which system they use and what the scores mean.
Besides morphology grading, the other major factor which is associated with odds of an embryo transfer resulting in pregnancy is the speed of embryo development. In the case of frozen embryo transfer, the day the embryo developed enough to meet the lab’s criteria to undergo freezing +/- preimplantation genetic testing (PGT)
In general, faster embryos do better (shocker, I know! ha) – meaning day 5 embryos have a slightly better chance than a day 6 embryo, and a markedly better chance of implantation than a day 7 embryo.
If a patient’s embryos have the following ‘day of freezing’ and morphology grade, this is how I would order them from best to worst:
DAY 5 5AA (expansion grade 5, ICM grade A, trophectoderm grade A)
DAY 6 5AA
DAY 7 5AA
Now here’s an example that’s more complicated, where the speed of development and differences in score are accounted for:
DAY 6 4AC
DAY 5 3CC
DAY 7 5CB
How Morphology Grading Can Be Used:
So why should you care about an embryo’s morphology grade?
Whether or not you genetically tested the embryo, we can use the grades to choose which embryo to use first. For patients with multiple embryos to choose from, we can pick the fastest embryo with the best grade. For those who only have 2-3 embryos and they know they want to have 2 children, I have had some patients ‘game the system’ and preferentially choose the ‘worst’ embryo with the lowest chance of success to be the first to be used for transfer. This way, if it works, the two better embryos can be reserved for future use, versus leaving the embryo with the lowest chance of success for the future, when egg quality/quantity would have likely declined, lowering the chance of being able to make more embryos in the future.
What strategy to use depends on how many embryos you have, and your family building goals, including when you plan to use the embryos in the future and what that means in terms of your age and projected egg quantity/quality.