IVF add-ons – embryologist perspective

When there is a problem like a varicocele, it’s always best to speak to a urologist, not any urologist, I would suggest a urologist who deals with infertility or a very good surgeon urologist. It would be good to do a scrotum or testicular ultrasound, have a set of blood hormones checked, do a semen assessment as well as semen culture. As you did mention, either perform sperm DNA fragmentation or even test the oxidative stress. 

The answer to your question is simple, I would advise going ahead and test all the parameters, especially if there is a varicocele present.

That is a huge conversation between scientists on that. We know that on day-3 it exists, and it’s more difficult to assess it because, on day-3, the embryos are of eight cells, therefore it means that when we take one cell out, we only take one out of eight, we don’t know if it’s representative,  we do know that it’s present on day-3. When we do day-5 because we do take part of the trophectoderm, not the inner cell mass of the blastocyst, not to affect the embryo proper. There is a low level of mosaicism as well on day-5, however, you always must remember that when you take a chunk of cells from a trophectoderm of a blastocyst, you do get better quality results.  

Mosaicism is present on both. However, the big controversy is that we’re not sure, and this is what we’re trying to find out if mosaicism is a normal phenomenon. The fact that we have different cell lines is not something abnormal as long as it is low level.

The answer is yes. The difficult aspect is that we cannot be sure if the add-on helped or it was just the patient’s or the couple’s time to get pregnant. Even if you try an add-on, which I haven’t mentioned because this talk would take ages, it’s called PRP (Plasma Rich Platelet) infusion either in the ovaries or the endometrium. Some patients after PRP have had pregnancies, however, we are we cannot know for sure if the add-on was responsible for the pregnancy or the patient would have got pregnant anyway.

It increases the success rate of a very specific group of patients. It is important to do PGT-A when you have repeated implantation failures because chromosomal abnormalities can affect, or you should do it when you are of advanced maternal age.

Lately, I have had patients doing an egg donation cycle, and they asked if we should do PGT-A, which might affect chances of implantation. In advanced maternal age and repeated IVF failures, it does have a benefit, in my experience.

You can go to immunologists or haematologists, each one of them will subscribe to your own set of tests and subsequently give you specific regimes like Prednisolone. They should give you low-molecular-weight heparin (LMWH), they will do intralipid infusions, they might even ask you to do vaccines and stuff with anti-paternal antibodies. 

The basic fact, unfortunately, is that none of this is scientifically proven.  There are no randomized controlled trials or studies that have been performed by reputable laboratories that have been able to prove it.  The scientific aspect is that they’re not adding to your chances of getting pregnant at all.

In our lab, we have seen that in advanced maternal age patients, there is a benefit. If that increases pregnancy rates from 20 to 60%, I would not say it increases threefold. There is an increase in chances of getting pregnant, however, I doubt that it’s from 20 to 60%.

I would not want to quote that centres are lying because that’s not correct. If you go back to the trials, the randomized control trials, you will see that there’s no such big increase in the percentage of getting pregnant after PGT-A.

EmbryoGlue is a specific media, it contains hyaluronic acid, which supposedly increases implantation, and any lab can use it. It’s fairly easy, it’s not that expensive, it’s one of the least expensive add-ons. You just utilize it to culture the blastocyst and use it to do the actual embryo transfer with EmbryoGlue. To increase the chances of the blastocyst attaching to your womb, it’s as simple as that. 

No specific data is out on whether it works. Some studies say yes, some studies say no. It’s not an expensive add-on, so I think it’s one of the add-ons that you can use.

There’s no way to know if you have an FDF, as we call it a failure to fertilize following conventional IVF, not ICSI. Unfortunately, 10 to 12 of normal parameter sperm, even if you’ve done DNA fragmentation, even if you’ve done FISH sperm DNA, there’s no way to determine that the sperm is going to fail to fertilize. 

Remember, it might not be the sperm’s fault, it might be that the eggs have a hardened zona pellucida, the outer membrane, and it’s not permeable to the sperm. You always have to consider that as well, so the sperm might be of very good quality, but it’s the egg’s fault for not allowing the sperm to go in.

I would start with the second part of your sentence, you do not know that there is no viable embryo because of age. Transferring 3 or 4 embryos depends if you’re talking about blastocysts, I would say it’s quite a risk to transfer 4 blastocysts, it’s a little bit too much. However, it depends on how many IVFs you’ve done, how many attempts you’ve done, it depends on the quality of those blastocysts or day-3 embryos that you’re going to transfer. If you have done it quite many times and it’s not working, then I would advise you to do PGT-A because you’re above 38 years of age, it might have a positive effect.

To answer the question properly, I would require more data and give you the correct response.

We do both. There is no reason to choose one or the other. It depends on each patient, on the way you want to treat the patient, but you do both. With vitrification, it’s quite good to perform it, and you don’t lose embryo quality as long as the vitrified embryos are of good quality to start with. I’ve seen it many times if I vitrify medium quality or not good quality embryos, they tend not to survive, whereas good quality embryos or blastocysts almost have 95-98% chances of surviving.

The answer to the question is we do both, and I think most centres do both.

It’s quite new, it uses time-lapse imaging to do the mitochondrial score. I’ve used it only three times, and the reason behind that is there’s not enough evidence, or let me say, there’s not enough data at the moment to know what is best to look for.

Therefore, at the moment, everybody’s keeping at bay. Some big laboratories in the U.S. and Belgium are looking more into it.  My answer to this is that it’s quite new, we have no good or bad data to support it at the moment.

In my experience, patients of advanced maternal age might have a beneficial effect of PGT-A however it also has to depend on each patient’s parameters because there are ladies who are above 39-40 years of age who make good quality blastocysts, you can have 3-4 or 5-6 good quality blastocysts. On the other hand, we have some ladies who are not able to get 1 or 2 blastocysts. 

As you can imagine, doing PGT-A testing on these 2 blastocysts is also a little of a waste of money. Your doctor should always take into consideration your specific requirements. If the couple produces good quality blastocysts and a good number of quality blastocysts, then yes, I would advise them to do PGT-A testing just to make sure.

If you look at conventional IVF rates and live birth rates, and ICSI rates for patients who don’t have a problem with a male factor, you do see that the rates are comparable. The answer would be no, it’s not worth it. However, we always have to take into consideration specific problems.

Let’s say that you have a patient who is coming from overseas, they’re coming from Australia to do an egg donation cycle. When you have egg donation, you tend to do ICSI. Why is that? If there is this chance of 10 to 12 failure to fertilize because the eggs were hardened or the sperm’s capacity to fertilize is not good, then you can imagine it’s a waste of time, money, and of course, the psychology of the couple.

If you’re looking at it on simple base terms, the answer to your question, it’s not worth doing ICSI if there’s no male factor, however, there are cases in which you should consider doing ICSI for the sake and benefit of the patient.

I would probably agree with you when there is enough data to be able to assess MitoScore. That is the point of the MitoScrore, to help advance the maternal age of the patient and select embryos, which can become babies. I want to stress that there’s not enough data out yet to make this assessment.

If you hear me being hesitant, it’s not because I don’t agree with it, it’s because I always come back to the fact that it has to be evidence-based, not just something that 2 or 3 laboratories have come up with. Let us get more data, and that would be able to help you at that point.

It was a very good idea to test the cumulus cells that came out from the egg as a non-invasive technique. People thought that whatever covers the egg before we strip them to do ICSI, you can test them, you can do DNA fragmentation.

However, there’s no way to know that because cumulus cells are damaged, or not, that’s the egg being damaged or not damaged, it’s not directly linked to the egg quality, it was a very good idea, but it was abandoned quite quickly.

Mature eggs would not signify a specific number, you can have 2 mature eggs to be of spectacular quality and get a baby at the end of the day.  There’s no correlation if you have many mature eggs, then you will get pregnant. 

There was one study that said that the more eggs you have, the more chances you get to get pregnant. However, nobody has stipulated a specific number of mature eggs to get a live birth at 38.