What if embryos available on day-3 are of very poor quality?

The quality of embryos on day 3 it’s important because the higher number of embryos of bad quality at day 3, that means that not many of them are going to reach blastocyst stage at day 5. It depends also on the policy of the lab, because some labs will prefer if they have not too much embryos and not good quality embryos on day 3 to transfer one or two embryos at that stage and then culture the rest of the embryos till day 5 and they will freeze if there are any embryos reaching the stage at day 5. Other labs’ policies are to always transfer on day 5 ,so of course the quality on Day 5 will be a marker of how many embryos will reach stage on day 5.
It depends finally on the policy of your lab – what is going to be the right decision in your case.

That’s a key predictor of success. Embryos on Day 3 should be about seven or eight cells in size and it’s quite difficult to grade the quality at that stage. In fact, five or ten years ago, when most embryos were transferred on Day 3, that’s when we put multiple embryos back because we didn’t know which ones were going to be successful. If the embryos are very poor quality on Day 3 most units now would suggest doing blastocyst culture which is rather than transferring the embryos at Day 3, waiting until Day 5. In our unit, for example, we stopped doing Day 3 transfers because if an embryo (even if it’s poor quality on Day 3), makes it to a blastocyst, then it’s a really good sign that actually it’s gonna go on and can develop and go on and form a pregnancy but if they don’t make it to Day 5, that gives you that information a bit sooner and yes, it’s disappointing – you’ve not had an embryo transfer but in some ways it gives you that information sooner rather than transferring the embryo back and ending up with a negative test two weeks later. Some embryos that are poor quality on Day 3 do want to become blastocysts and go on to form babies and it’s certainly not worth writing it off at that point but obviously it’s better to have good quality embryos rather than less good quality.

First of all, I want to clarify what we understand about a Day 3 embryo. A day 3 embryo is when we can observe after 72 hours of fertilization at least 6 cells (preferable 8) that have developed normally. And what do I mean by “normally”? Well, there are a lot of factors that can affect the quality of the embryo and that can determine the potential estimation of the outcome of embryo development.

In day 3 of development, we can observe different parameters to grade an embryo and, in some way, predict the likelihood of success. These parameters are the number of blastomeres, uneven cleavage, fragmentation, presence of vacuoles, multinucleation and speed of development. Moreover, other parameters such as the cytoplasmic anomalies like Smooth endoplasmic reticulum aggregation or the spatial distribution of cells can affect the grade of the day 3 embryo. So, we evaluate morphological and kinetic parameters. 

Therefore, embryos with a higher number of blastomeres in that stage of development, less than 10% of fragmentation, equally sized blastomeres and a lack of cytoplasmic anomalies have a higher overall chance of implanting than other embryos with less blastomeres, uneven cleavage and significant amount of vacuoles and fragmentation.

While we can more easily predict when an embryo is going to have a bad outcome, it is important to highlight that it is more difficult to predict when a day 3 embryo will have a good outcome and result in pregnancy. That’s because during the first 3 days, the development of the embryo depends more on the oocyte machinery, while from day 4, the embryo activates its own genome and begins its expression, reflecting the sperm effect on the quality of the embryo.

Due to all these reasons, it is difficult to predict how a day 3 embryo is going to develop even if it is rated with a very good grade. We can find evidence in the bibliography that show different studies in which day 3 embryo is a poor predictor of the outcome of the cycle.

That’s why nowadays, extended culture of human embryos seems to increase discrimination of potential embryos, while embryo selection on day 3 seems to be inadequate. So, extended in vitro culture may therefore be an effective means of optimizing IVF clinical success. For that reason it seems that the time has arrived for the culture period to be extended to day 5 or 6. That allows the embryos to “select” themselves by growing to the blastocyst stage.

However, it is important to evaluate every patient individually and decide if it’s better for the patient to wait until day 5 of development or not. And it will also depend on the number of embryos that the patient has and also the criteria of the clinic and the embryologist.

Sometimes it can be a bit different so what we do see on day 3 as being a very good quality embryo can for example not make it on day 5 and vice versa an embryo that we would think not gonna make it on day 3 can make it to day 5. I do think the day 3 key predictor is not as much of a key predictor as it should be. Most important on day 3 is that the embryos are dividing so the embryos should have between six and eight cells at that moment and as long as they’re dividing it’s okay. We define the quality of an embryo depending on the symmetry of the cells and also on fragments. The fragment is when an embryo is dividing it excluding parts of the cells that it doesn’t like and doesn’t need. The less fragments we see, the better for an embryo. Top quality embryos wouldn’t have any fragments but again as I said the most important thing on day 3 is that they are dividing even though they’re poor quality we would certainly let them until day 5 to see if they can get on. Sometimes it’s quite surprising.

This problem is very individual. Even the embryos of poor quality may become a healthy child. So the best selection time for the transfer is day 5. And if we have more embryos on day-3, we advise the patient to carry on with the cultivation and select embryos later on day 5.

Firstly, embryo morphology correlates with successful implantation. For an embryologist, it is really difficult to predict if an embryo can go for implantation or not. Sometimes bad quality embryos can go to implantation surprisingly, and sometimes a good quality embryo can fail. So it is not a predictable thing. Day 3 embryos have higher aneuploidy rates compared to day 5 embryos. So it is really important to go to day 5 to see which ones are going to form the blastocyst. Basically, embryos on day 5 can have a natural selection process themselves. The ones that can go on to day 5 basically are naturally selected and eliminated. The successful ones can go on to day 5, make blastocysts, and hopefully – pregnancy.
Recent research shows that actually low scoring day 3 embryos, which are not considered to be transferable, can give a good result of the blastolation and the live birth. So according to literature, it is ideal to go to day 5 and make a day 5 embryo transfer.

There is also a second parameter that supports the idea of the day 3 embryo culture to day 5, which is the uterine environment. When we are thinking about the normal conditions in naturally conceiving people, the embryo development takes from the fallopian tube to the uterus. So on day 3 and day 4, in the ideal conditions, the embryo is still in the fallopian tubes and not in the uterus. According to some researchers, the ideal location for day 3 embryos is not the uterus. Basically, the synchronization of the uterus with the embryo is not really suitable for day 3. So according, to some embryologists and some researchers, making day 3 embryos go to day 5 would be more synchronized with the uterus. So day 5 transfers would be more ideal, than those on day 3.

So on day 3, if we have a poor quality of embryos, it is ideal to go to day 5 to see if there are any transferable embryos to select the best ones. And then transfer them with a more synchronized uterus on day 5.

First, day 3 is the intermediate stage of embryo development. Day 5, the blastocyst stage, is the final stage of embryo development when we finally understand if we have a good quality or a bad quality embryo. We can have the situation when on day 3, we have a bad quality embryo, but on day 5, we receive a blastocyst of intermediate or even good quality. We can also have the opposite situation. On day 3, we can have a very good quality embryo, but after day 4, a sperm factor can influence the embryo quality, and we will not receive a blastocyst-stage embryo on day 5.

Intersono IVF clinic recommends cultivating all embryos up to day 5. On that day, we can have a better embryo selection, and we understand that we will transfer only good quality embryos. This is the final development stage of the embryo.