What is the best grade of embryos in IVF?

There are different ways of assessing the quality of the embryos. It depends a lot on whether you transfer embryos on day-2 or day-3 or whether you transfer a blastocyst. We usually recommend a transfer on day-5. When day-2 or day-3 embryos are transferred, there are 2 different classifications. The first one is A, B, C, D – A being the best, or you can use and score system from 1 to 10, and 10 is the best. This kind of assessment takes into account things like the symmetry of the cells, whether the embryo has fragmentation if there are abnormalities inside the embryo, or how the fragmentation is distributed inside and based on that, they grade the embryo.

When we transfer a day-5 embryo, and there is a standard classification called the Gardner system, that says different things.  When you see this, you first see a number, which is the grade of expansion of the blastocyst. It is not relevant in terms of success rate because an embryo can be a 1,2,3. When the embryo reaches 4, it means that it started hatching. When the embryo is 5, it means that half of the embryo has done the hatching and a 6 blastocyst means that the embryo is completely out of the zona pellucida.

What is relevant is the other two things that we assess, which is the inner cell mass, which is the part of the embryo that is going to become the embryo, and the trophectoderm, which are the cells that are going to become the placenta and the amniotic fluid later. We grade these two parts with letters A, which is the best. C is the worst. You can have different quality, for example, you can have a 3 BA or a 4 CC or a 2 AA embryo. The number is the expansion, the first letter belongs to the inner cell mass, so it’s telling us how good the embryo is. The second letter is about the trophectoderm, which is telling us how good all the other cells or the structures that are going to be the placenta are. If you have the embryo AA, the prognosis is much better than if the embryo is BC, CB, or CC.

This depends on the day of the transfer. If you have a day 3 or day 5. On day 3 we should expect 8-cell embryos and the eight cells are graded according to the shape, fragmentation and compactness. Each clinic has their own grading system but there are some universals. Like, if we have 8AA, that’s the best thing, meaning the number is right and they are good quality with no fragmentation.

At the blastocyst stage, it depends also on the cavitation, how the inner cell mass is compacted or not, if there is any fragmentation in it or not and what is the shape of the blastocyst. So we are aiming at something called 4AA as well.

We only transfer good quality embryos, where good quality means from 4AA to 4BB. Lower quality embryos, including Cs or Ds, are not considered sustainable with, for example, prolonged cryopreservation. That’s why even if you have 4-5 extra embryos to cryopreserve, you’ll find that the embryologist is assessing them according to the grading. They will tell you: maybe we need to freeze only one, two or three, depending on the quality. We do not cryopreserve embryos of lesser quality because we know that the survival rate after thawing is the problem. They do not survive as good-quality embryos. It’s not that we do not want to cryopreserve them but it’s because statistically, they are not amenable for survival after the thawing procedure. So you can appreciate that it will give you the highest chance of getting pregnant rather than giving you false hope into waiting for something which is of the very low percentage rate of having success after the embryo transfer.

So if transfer is on Day 3 and the embryo is with eight cells without fragments, it will be a good embryo for transfer but now most of the clinics use transfer on Day 5, so in this case a good blastocyst with a score AA. A in a cell mass top rate and an A trophoderm, so it would be a perfect embryo.

We have different grading systems so every laboratory may have a different grading system. As a general rule, the grading systems are tools helping us to predict which embryos have better chances of implantation. We grade differently day 3 embryos and blastocysts, day 5 embryos.

When we are talking about day 3 embryos, the grading depends on the number of cells that they have (6, 8, or 10), where the ideal number here is 8, and, also, it depends on their appearance under the microscope, whether they have fragmentation, pigmentation, etc.

When we have a blastocyst, then we usually have a grading system that has a number in front and has some letters following. The number has to do with the cavity and its size. If it is a fully expanded cavity, this is a grade 4. If it is an embryo that started hatching, this can be 5. If it is completely hatched, it might be 6. The letters, on the other hand, grade the inner mass of the blastocyst from which the final embryo is produced. The second letter grades the trophectoderm which is the part from which the placenta is created.

We measure different aspects and we look at various things under the microscope to see whether the cells are symmetrical, whether they have a grainy appearance, whether they have pigmentation, fragmentation, degeneration, and depending on that we grade the blastocysts. The best blastocyst could be a 5AA but even blastocysts that are worse grading can give pregnancy.

Embryo grading is an easy question and difficult to answer. If we discuss day 5 embryo, a blastocyst, I think that the optimal is blastocyst stage and more. But very often also early blastocyst stages have good results. It is very difficult to answer patients which blastocyst is better, expanding blastocyst or hatching blastocyst. I prefer to tell my patients that they have e.g. three blastocysts good for transfer. I don’t specify the stage, because I think it’s quite confusing. The patients feel that hatching blastocyst is the best and there is nothing better and blastocyst is a bad embryo, but it’s not like this.

It’s a question of only a few hours for a blastocyst to become a hatching blastocyst. Hatching blastocyst can have some chromosomal abnormality. So if we have grade A or A-B, minimum B, it is OK. C embryos are not good. But embryos from B and better are good embryos for transplant, with good success rates.

We can evaluate the embryo quality with two things:  physically and genetically. Physically, there are some criteria according to the daily development of the embryo. On day zero, when we collect the eggs, do the microinjection and put the fertilized eggs in incubators. And every day, every 24 hours, we take them out and check.

On the third day or fifth day, we can do the transfer. On the third day, the embryo must reach the stage of 6-8 cells On the fifth day – the blastocyst stage. This is the criterium for the well-being of the embryo. But on the fifth day, even the blastocyst can be classified by five degrees; 1 is the worst, and 5 is the best. On the fifth day, 5AA is the best embryo that you can give to a patient. Approximately, 40% of infertile couples even their best-looking embryos can be genetically abnormal. In this case, we can check the embryos genetically by doing embryo biopsy. Using a laser we open the wall of the embryo and take one part of the embryo outside. This is not harmful to the embryo’s future development. We send this sample to the genetic laboratory and according to the lab’s workload, we will have the results within 24 hours to 10 days.

There are two tests that we can do. You might know that there are 23 pairs of chromosomes in the human body. We can check 5-10 chromosomes very quickly in one day, or we can check 23 of them. If you choose to check only 5-9, in this case, within 24 hours with the FISH test you will have the result. If you do a 23 chromosome test, in this case, you will have the results in 7-10 days.

Ideally, the trend nowadays is to transfer blastocysts. Blastocysts are embryos that have grown up until day 5or day 6. They seem to be giving very good results. One of the reasons is possibly the fact that when we conceive naturally, it takes around 5 days for the embryo to travel through the fallopian tubes from the time of conception, and then implant in the womb. So a blastocyst, which is a 5-day-old embryo should really find its own environment and familiar environment on day 5 in the womb.

We have had lots of pregnancies also with embryos on day 2, 3 or 4. But there seems to be a trend towards a day 5 embryo transfer or blastocyst transfer. Very rarely do we transfer day 4 embryos, at the morula stage. Morula is a stage before the blastocyst. But sometimes we do, and again we have had pregnancies.

But in terms of success, it seems to be better associated with day 5 embryos. Besides, it’s also important to allow time for the patients to see as well. If she’s developing any signs of hyperstimulation, for example. So by having an embryo transfer on day 5, we have a bit of time to see how the patients feel, and we have time for the progesterone to act on the lining. So it does work in many useful ways, yes. We transfer blastocyst as much as we can.

Ideally grade A and grade B embryos are perfect for the transfer. Patients are very happy if they achieve to transfer an embryo that has been graded A or B and also if they have available embryos for freezing – that means that the embryo should look as it should and for that day. If no grade A embryos or B are available, a grade C embryo can be selected for the transfer as they still have their ability to implant. The chances are smaller compared to A and B but still the chances are there so even if embryo quality is a very important factor it is not the only factor as many other factors can cause implantation failure.