Watch the webinar in which Elisa Moya Gutiérrez, an embryologist from UR Vistahermosa, is discussing different techniques to improve IVF results in patients with previous IVF failures.
Elisa Moya Gutiérrez started her talk by explaining that even if the number of embryos is high, very often the quality is not good, and this can lead to implantation failures o miscarriages. Laboratory techniques are constantly being improved and with this better selection of the embryos and even better development. Some of those techniques have increased pregnancy effectiveness by 20-30%.
The basic procedure for IVF treatment includes the appointment with a gynaecologist specialising in IVF, then the diagnosis of the specific case because every case is different and needs a different protocol. When the diagnosis is made and the treatment protocol chosen, it is time for ovarian stimulation. It lasts approx. 10 or 15 days of medication, the doctors try to increase the number of eggs produced in the ovary, so instead of having one egg in one cycle, they can obtain more so that the chances of pregnancy will be higher. The patient has to come for ultrasound control around 2 or 3 times during this process until the eggs inside the ovaries are mature. Then the eggs will be collected in the egg retrieval process, which is a procedure where the gynaecologist takes the eggs from the patient under sedation. It lasts around 20 minutes, then the eggs will be selected by the embryologist and lab. All the eggs are put in the incubator with a specific media until the sperm is ready because the sperm sample must be prepared also in the laboratory using a sperm capacitation technique.
Depending on the quality and quantity of the sperm, the embryologist will decide if it’s better to do a conventional IVF or ICSI fertilization. Once the fertilization is done even with conventional IVF or ICSI, the embryos are created the next day, then the embryologists watch ass the embryos are developing every day in the laboratory and will classify them accordingly.
If there is a low number of embryos, less than 3, it is recommended to have a culture of 3 days and then do the embryo transfer, but if there are more embryos than 3, it is recommended to take them to day 5 and do a better selection and do the embryo transfer. The embryos that are transferred have the best morphology or classification and in Spain, for example, a maximum of 3 embryos can be transferred, however, this is not a common practice. The recommendation is to do a single or double embryo transfer most of the time.
The seminal quality and its influence on embryo development is a crucial factor when it comes to achieving pregnancy, since it affects both fertilization and subsequent embryo quality. There are some cases in which spermatozoa that have been prepared in the laboratory, fertilize their oocytes correctly, but after 3 days of embryo culture, these embryos begin to lose their quality. This happens because the sperm DNA begins to express itself on day 3 of the embryo culture, so to prevent this from happening, the MACS technique can be used. It’s Magnetic Activated Cell Sorting, it’s an immunomagnetic technique allowing the selection of those spermatozoa that do not show signs of cell or DNA damage or even death of the cell, this is called apoptosis. These damaged sperm can be removed from the sample using this technique because the membranes of damaged cells contain markers that can be detected and then can obtain a fraction that is free of these dead cells, therefore, we have better quality.
The embryologists incubate the selected sperm with Annexin coated with magnetic microparticles and pass it through a column where a magnetic field has been applied. The apoptotic sperm will be retained in the column while the non-apoptotic will be passed through it without being retained, so the fraction obtained will only contain healthy spermatozoa with the best physiological quality.
When is it recommended?
This procedure can be used with conventional IVF or ICSI. This non-apoptotic sperm fraction increases the fertilization capacity of the sperm and allows it to achieve a higher gestation rate by approximately 10- 15%.
It’s a pioneering technique that maintains the culture conditions intact and reduces the handling of the embryo. It allows embryo cell division to be recorded and viewed on a monitor in real-time. We can watch the cell division of the embryos anytime without manipulation. When traditional incubators were used, the embryos had to be removed at certain hours from the incubator to check them and their development under the microscope, although these intervals were very short, the environmental conditions were altered during that time.
Time-lapse incubators offer the possibility to view the morphological characteristics without the need to remove the embryos from the incubator so that environmental stress experienced by the embryo is reduced. The conventional way of monitoring and the evolution of the embryos is to extract the embryos from the conventional incubator every day and morphological parameters will be evaluated under the microscope. Among them, we see the number of cells, the symmetry of the cells, and the fragments of the embryo. With this information a quality rank is assigned to each embryo, in this way, it allows the selection of the best quality embryo for transfer.
Time-lapse technology provides highly accurate information throughout embryologic development, allowing us to select a group of embryos that have the greatest potential to implant and lead to a pregnancy. In addition, it allows us to explain those cases in which good-quality embryos do not implant. This type of incubator can be used for all assisted reproduction patients. It is recommended for all treatments including IVF, egg donation, and embryo donation but especially for those who have a higher number of embryos. When there are more than 2 embryos, the selection of those with the best quality and the highest potential to achieve pregnancy is done more precisely. Thanks to time-lapse, there is between 10-20% higher probability of implantation than using conventional culture and selection techniques.
It’s a genetic test performed on embryos produced through IVF, and it has to be done with ICSI fertilization. PGT-A detects abnormalities in the number of chromosomes in the embryos, also known as aneuploidies. Chromosomes are very important for healthy growth and development. The embryos with the incorrect number of these chromosomes typically do not result in a successful pregnancy or may lead to a birth with a genetic condition, for example, Down syndrome, Turner syndrome, etc. The embryos with the correct number of chromosomes have a better chance of give a successful pregnancy. PGT-A identifies those embryos with the correct number of chromosomes, so the embryologists can select the best embryo with the best chance of leading to IVF success.
When is it recommended?
How does it work? First, the ICSI procedure is done, and then the next day the embryologists will see how many embryos they have and then they will see the embryonic development. There can be an embryonic development until day 3 or 5, if there are a lot of embryos, it’s better to take them to day 5. If there are not so many of them, it’s better to do it on day 3. When the biopsy is done, a few cells are carefully removed from the part of the embryo that will form the placenta and is taken for biopsy. The samples are sent to a genetic laboratory while the embryos remain safe in the culture, or in some cases, they can be frozen. In the genetic laboratory, they have all the techniques to analyse the genetic material present in each embryo, and they will check which embryos don’t have any abnormalities. These are the ones that are going to be transferred because they’re most likely to result in success. If there are more than 1 or 2 embryos without aneuploidies, they can be frozen for future use.
What are the advantages of PGT-A?
Yes, frozen sperm is enough for ICSI. When we do ICSI, we just need the spermatozoa that we’re going to use for fertilization, so if we have 5 eggs, we just need 5 good spermatozoa, so a frozen sperm is enough. If the patient has a good sperm and not a severe condition, so yes, it’s enough.
It’s not new, maybe it’s been used for 5 years, and we use it all the time in our clinics, and it’s working very well. We can say that it’s nothing that just came out, it’s something that we’ve been using for a few years and it’s very useful.
I think other clinics use it, but every clinic is different. Every clinic has different protocols. I think they use it, but not every clinic for sure.
Embryoglue works very well, we use it at our clinic, and it’s been scientifically proven that it helps to make the implantation in the endometrium and, so we use it, and we recommend it every time. When it comes to EmbryoGen culture, I have never heard about it, so I can’t say anything about this.
Every case has its own complications, and there are a lot of factors that are involved in the pregnancy, not only the eggs, not only the sperm but also the uterus, the endometriosis, which you’ve mentioned, the best thing would be to do a skype consultation with a doctor to advise properly. As there were 18 eggs and 12 embryos, it’s a very good cycle, but maybe there are other things that are missing, so it’s better to talk in a private and consult with a doctor.
Embryoglue is a medium that we use, it has some specific qualities, we use it before doing a transfer. The embryo will be in culture, in a normal culture during the 5 days or the 3 days and then before we do the transfer, we leave the embryos in EmbryoGlue for about a half-hour because the EmbryoGlue has specific material and thanks to that the embryo can attach better to the endometrium, it’s proven that it helps and we use it a lot.
It’s different. Sperm sorting, we don’t use it. What we do is capacitation of the sperm, which is having only the mobile spermatozoa and then after that, we do the MACS.
We used to do that, we don’t do it anymore, and it’s not that it doesn’t improve that much the implantation, at least it’s what we have seen in our clinic. There are some embryos, which would benefit from that, but the embryos. If they are of good quality, they can do their own hatching and implant on their own, so we don’t really believe in this technique. I mean, it can help, of course, but we don’t do it.
It’s been studied that there is no difference in frozen egg donation. There’s no difference between frozen or fresh cycles. Both of them are good, both of them have the same implantation rates, so it doesn’t really matter. We do both of them, and none of them has a better rate than the other or a better chance, so we recommend both. It depends on the patient. If the patient is synchronized with the donor, then we do it in fresh. If for, some reason, it doesn’t work, we do a frozen egg donation, and there is no difference.
We don’t give too high doses, 300 -350 at most, we don’t want to give too high doses of gonadotropins.
Your AMH is a little bit low, it’s true, and it depends on how the eggs were when you did the IVF because maybe you had 2 embryos, but they weren’t of good quality, it depends on the quality of the embryos that you had and the transfer. If they were very good embryos, I would maybe try it again, but it also depends on your age, but of course, the chances with egg donation will be much better.
First of all, maybe we should see the quality of the eggs. If it is not good, one option is to try egg donation, I know it’s tough sometimes to estimate this decision. If you accumulate embryos and then do a PGT-A for not having miscarriages or for avoiding these implantation failures because maybe you don’t know if the embryos that you’re transferring are genetically okay, so maybe they look good, but they have an aneuploidy. This could be one option to do a PGT-A, and if this doesn’t work, I would recommend the egg donation. Aneuploid embryos are one of the most common causes of miscarriages, so that’s why it helps to do a screening of those embryos, and maybe you have good embryos, but you if you don’t know how the genetics are, maybe this could be one solution.
You can try it, I mean everyone, I think everyone wants to try with her own eggs, and sometimes it helps, even if your AMH is a little bit low, you can try it. If this doesn’t work, egg donation is always an answer for this type of case, but in Spain, the egg donation is totally anonymous, so you can’t choose the sperm donor or the egg donor, so it would be totally anonymous. We use Fenomatch, as I’ve mentioned in my presentation, and we select a donor that is most similar to the patient genetically and physically.
Here, it could be good to do MACS or a PGT-A as well because if the sperm has abnormalities, it can influence the genetics of the embryos, so maybe here there is a genetic problem. We would like to know what quality these embryos have because they were of bad quality. If they were of good quality and it did fail, I would recommend doing a PGT-A having the information that I have.
This can happen, it’s something that sometimes can happen because the embryos have to be of very good quality to survive the freezing. Some embryos can survive it very well, but others don’t survive it, and we can’t really explain why. One of the reasons is because maybe they were frozen and are not of good quality, other times it happens and nowadays we still don’t know why. This is a little bit of a risk that can happen, but most of the time, embryos survive the freezing.
Egg quality depends on a lot of factors, age, genetics, lifestyle, and we can’t really do something to improve the egg quality. Women are born with eggs, and during the time and after a few years, the egg quality starts to diminish, and this is something that we cannot change. We can say that perhaps our lifestyle changes can help, but the most important thing is age and genetics.
Nowadays, it can’t be tested. We can say that for sure, there is no scientific evidence about it because there are many factors that we don’t know, and we try to work with the factors that we do know and the factors that are scientifically proven, but in our experience, we see that should not be a problem with the immune system. We always do our best to make sure that the genetics are compatible with the receiver, and we don’t have any issues with that.
