Freeze all – IVF strategy explained. Why and when should I freeze all embryos?

We consider high progesterone levels over 1 ng/ml because then we know that the implantation rates could be reduced, and that is the reason for freezing the embryos.

First, it’s important to exclude potential factors that could play a role in terms of the endometrium. Sometimes it could be infections inside the uterus, also patients that have undergone previous surgeries on the uterus could have issues with the lining. Therefore, so start by trying to improve the results, increase the estradiol doses, and if it doesn’t work, we normally recommend doing hysteroscopy or a 3D scan to check if there is something wrong inside the uterus at that moment. We can exclude any kind of problems inside the uterus, and it’s also recommended to perform some tests to discard potential infections inside the uterus.

Sometimes, it’s difficult to make the endometrial lining to be thicker, many patients could also be good candidates in terms of trying to change the preparation we normally do. We normally use oestrogens, but some patients can do a natural cycle, and it can work quite well, in some others, we can use gonadotropins similar to the ones that we use to stimulate the ovaries but in a lower dose to get 1 or 2 follicles and for them to grow properly. We need to add aspirin, a low dose of vitamin E, and sometimes, also some kind of medication that can improve the blood flow in the uterus. It can be very difficult to have a good endometrium even when we do our best, but sometimes it’s a matter of finding the main cause and then finding the best way to prepare the uterus for this particular patient.

I would suggest having those embryos tested first. Seven blastocysts are great, I would propose performing the test on the embryos as you are 43, the potential chances of having a healthy embryo for transfer is around 12%. It means that 1 of all those 7 blastocysts could be healthy, or more, but in the end, I would recommend at least defrosting the embryos, doing the biopsy and then freezing them again to get the results from the geneticists in terms of having a better chance of implantation. You can keep on trying several times.

If the embryos have good quality, it’s possible to do it. It’s not the ideal situation, but in terms of implantation rate, in terms of chances, and of course, in terms of time to pregnancy, we can do it. If the embryos are of good quality, they can tolerate the procedure of defrosting, then doing the biopsy and freezing them again, of course, it also depends on the quality of the embryo, as I mentioned, it’s really important to classify the embryos properly. First, we need to classify the embryos, and then, as I mentioned, it’s possible, although it’s not the ideal situation, we can do it.

I’m afraid there isn’t, I mean, it’s impossible to know exactly when the ovulation may happen. We normally use a special medication to make the ovulation happen at a specific moment, but it’s impossible to exactly know when the egg will go out from the ovaries and will be taken by the fallopian tubes. We go directly to the ovaries, take the eggs, fertilize the eggs, everything that should happen in the fallopian tube will happen in the laboratory, and then we put the embryo back. I’m afraid there is no new technique that could do that.

As I mentioned, the highest production level should be 1 ng/ml, the main reason is that it has been proven that when progesterone is over that level, the chances of implantation are reduced. In the past, we didn’t measure that, and we didn’t know that it was important, now we are completely conscious of that, and we always measure it.

The moment it should be measured is the day when the trigger happens, so it’s normally 2 days before the egg retrieval takes place. If the embryo transfer takes place in the blastocyst stage, it would be 1 week before the embryo transfer. Generally, we test progesterone and estradiol, at least at Clinica Tambre, at the beginning of the treatment and then when we are doing the trigger injection. There are many studies that I can give you, but it’s quite easy to find online, you’ll find more than 10 or 20 papers.

Sometimes, it can be detected with a normal scan that can be performed at a consultation, or through hysteroscopy. We may perform a hysteroscopy for a different reason, and we find small implants of endometriosis inside the uterus. The most common situation is that we do a 3D scan, and we can see that as a small implant of implants of adenomyosis. When there is mild adenomyosis, we can also see the muscle of the uterus that is quite thick, and because of that, the uterine cavity could be reduced. It’s not only having potential adenomyosis but it’s also related to the place where we are leaving the embryo.

It has to be big enough to accept that embryo, and because of the adenomyosis, if the uterine and the muscle are thick, sometimes the uterine cavity could be quite reduced as well. Therefore, we should consider doing surgery to try to widen that cavity. Normally it can be detected with a vaginal scan, a normal one.

I’m afraid, they don’t. EMMA/ ALICE will give you the information in terms of potential infections inside the uterus and what we call the microbiome, which is the good bacteria that should be inside the uterus. However, they don’t detect potential adenomyosis, so sometimes, as I mentioned, it’s a matter of doing a special scan or a normal scan. If the patient suffers from endometriosis, we should consider that the endometriosis is affecting the uterus.

We recommend dual stimulation in patients with low ovarian reserve because we don’t expect a high number of embryos at the end of the protocol. It’s highly recommended in patients that for any different reason may expect a low number of embryos at the end of a day of the stimulation. Indeed, the luteal phase works more or less the same as the initial phase, but we have many patients that obtain better results in a luteal phase. In the end, it’s a different way to stimulate the ovaries in a different moment of the cycle, and we don’t know the main reason, but in the end, what we see is that some patients obtain a better and higher number of eggs in the luteal phase than in the previous one.

We are quite used to doing that stimulation to our patients, and we are happy with the results. If the ovarian reserve is really low, we wouldn’t expect a complete change, but in the end, we can retrieve a higher number of eggs and potential embryos in a shorter period, which is also important for our patients.

No, it just starts 5 days after the retrieval, so if the egg retrieval takes place, let’s say today, which is Tuesday, the dual stimulation and the second stimulation should start on Sunday, which is 5 days later. Then 3 days after, the ovarian stimulation happens.

It’s not only a matter of being 44 or 40 years old, the main risk is related to the quality of the embryos. If the patient is 44 years old, but the embryo has a good quality and the chances of having a good survival rate are high. Apart from the quality, it also depends on the laboratory expertise, and how the stimulation went, so it’s not only a matter of age. We should consider the quality, how the laboratory works, its protocols and so on, but in general, the quality of the embryo is most important.

Salpingectomy is a technique to remove the tubes, and salpingotomy is a different technique where we do like a small hole in the tubes to avoid the liquid to spread out. Currently, all the protocols say that it’s much better to remove the tubes to get rid of the problem, otherwise, if we make a small hole in the tube, the liquid can go back again, and in the end, we’ll be starting from the beginning. If the patient doesn’t have a very high risk of undergoing surgery, we prefer to do a laparoscopy and have the chance of removing the tubes.

It depends on the patient, if we are talking about patients that want to get pregnant in a short period, I would suggest freezing embryos rather than eggs. The main reason is that eggs are more fragile because they are just one call, and the vitrification could also do more damage. In terms of implantation, it’s better to freeze the embryos, as they may have a higher survival rate.

If we are talking about a patient who doesn’t want to get pregnant, we recommend freezing eggs without any doubt. For patients undergoing fertility treatment because they want to get pregnant at this moment, we recommend freezing the embryos because the chances and the results are much better.

If someone has 10 healthy embryos, it could be great, but of course, I’m the gynaecologist, and we are always in touch with our laboratory staff, who classify the embryos based on their development into the blastocyst stage. Since the eggs are fertilized, the embryologists check the embryos. When we talk about quality, we talk about the potential the embryos may have, how regular the cells are, how are the cells divided, and when they reach the blastocyst stage, we classify the embryos depending on how the blastocyst expanded. The more expanded blastocyst, the better quality.

Apart from that, we also classify how the inner cell mass is, The embryologists give us some advice in terms of classification and let us know which embryo should be the first to be transferred. They also give us a list of embryos to be transferred from the first one, and so on.

If the embryo is of good quality 1, it can tolerate the biopsy procedure, but it’s indeed an invasive technique, and in the end, it also has its risks, so it’s not possible to guarantee 100% that the embryo won’t be damaged. If the embryo is of good quality, the chances of having good chances of tolerating that procedure are quite high. The embryologist will tell you if that embryo is suitable to be tested or not if the quality is not high.

Here, there is a different factor which is shipping the embryos, so if that transportation is done, for example, in the same city, it’s quite a safe procedure, but if the oocytes have to go from the UK, let’s say Denmark, the risk will be higher. If it’s from Europe to the U.S., there is a risk, that something can happen during the shipping of the embryos or the eggs. Then it could be an issue because if the temperature suddenly rises or if there is any kind of problem with the transportation, it can also affect the quality and the survival rate.

I would suggest moving forward with the fresh embryo transfer. I think we are not adding any benefit of freezing the embryos unless you want to have the embryos genetically tested, so I would recommend doing a fresh embryo transfer without freezing the embryos because we are not adding any benefits to the treatment.

Mosaics are embryos that, after being tested, have some normal and some altered depending on the chromosomes affected and also depending on the number of cells affected by alteration. On many occasions, we can also transfer those embryos, having some alterations in the external part of the embryo doesn’t mean that the embryo is also impacted. Many babies were born after being mosaic embryos, and it seems that the inner cell mass keeps the healthy cells and pushes the non-healthy cells to be in the placenta, and the end, ends in a healthy baby, and they don’t need to be part of the baby itself.

We find the mosaics while we are testing the embryos, but if the chromosomes impacted are not high-risk chromosomes such as sex chromosomes, chromosome number 21, 13 or even chromosome number 18, we move forward with the embryo transfer with good expectations.

When we do the PGT test on the embryos, we are not thinking about the mosaics, we are thinking about the potential of aneuploid embryos, so not healthy ones. Many patients are quite concerned about the potential risk of doing the transfer with an altered embryo that may be affected by many genetic problems, but many of them can be transferred. The risk is there, but we know that this is not related to age, so it doesn’t matter if you are 40 years old or 30 years old, the mosaic rate is the same. It’s not the same with the non-healthy embryos, in the aneuploid embryos, the rate increases as the patient gets older.

Normally, it takes 3 weeks between when the menstruation comes and the embryo transfer, but not all patients indeed are the same. The idea is that we need to check the uterine lining, it takes 10 days to 2 weeks to have the endometrium ready, and then depending on the embryos, we may decide when to do the transfer. If the embryo is 3 days old and is not a blastocyst, we need 3 days of progesterone, however, if the embryo is a blastocyst, we need 5 days, so it will be also added to the other day that we were doing the endometrial preparation.

It’s also important to consider if the patient has undergone any kind of tests to have more information about the window of implantation. The day of the embryo transfer could be changed, so we might need to add some more hours of progesterone, or we should remove some more hours of progesterone, it could also be related to the result of the test. Some patients undergo a standard protocol, but on many occasions, we have to change it.

Normally, it starts after 5 days, but it’s true that at that moment, what we find in ultrasound is the corpus luteum from the previous cycle. We see a Haemorrhagic ovarian cyst (HOC) from the previous egg retrieval. Sometimes, it’s really difficult to see small follicles, but in patients that we know are undergoing dual stimulation, we try not to do the egg retrieval from the smallest follicles so that we can let them grow in the next stimulation. We do a scan 5 days after the stimulation, and then, if it’s possible, we do a new stimulation. Sometimes, it’s not possible to start in some situations, but in general, if we see that the ovaries are doing fine, we can start. At the same time, the small follicles grow during the dual stimulation the big ones that are like the rest of the other pregnancy start decreasing in size, it’s quite normal for us to see that.

It’s quite likely that your embryo transfer takes place between a day 19 and 21, which is like 3 weeks after your period start, so it’s quite likely that it happens at that moment. The ERA test will give you information about the window of implantation, so we are not talking about lining, we are talking about the genetic expression of your endometrium related to implantation, but normally the embryo transfer takes place 3 weeks after the menstruation.

If you decide to do the ERA test in a cycle with an artificial cycle, you should do the embryo transfer the same way. The same happens with the natural cycle, so if a patient wants to undergo a natural cycle, do the ERA test as the results are related to how the preparation took place, it’s really important to follow the same protocol that the patient followed to do the mock cycle for the ERA. Not necessarily it has to be done with medications, it can be also done with a natural cycle.

The embryologists may have more information about the embryos, when we are using the time-lapse device, we have the chance of knowing more about the embryos, so they can classify embryos that maybe were not classified as good quality, seeing when the cells are dividing, they know how the cells are doing every day as the embryos are in the lab.

Not all of them, what we know is that they’re like different waves of follicular growth. In the past, we thought that the follicles don’t grow after the proliferative phase, and now there are different waves of follicular growing, so in the end, it means that some follicles will die for sure but not all of them. If the follicles have not been pre-selected because they are not reacting to the medication, they will be there, and they can be selected afterwards.

The quality is the same because blastocyst 5AA is the top quality blastocyst, but the implantation rate is higher in a patient that is 30 years old. The embryo in a patient that is 30 years old is stronger, and it has a higher chance of implantation. Apart from the quality, the potential rate of embryo implantation will be higher in a younger patient.

After doing the retrieval, the patient should wait until the period comes, so at that moment, they can start the preparation, the mock cycle to prepare for the ERA test and then what the laboratory suggests is that the closest to the embryo transfer, the better. The results are indeed quite reliable, even after 1 year of having done the biopsy, but if the patient is planning the embryo transfer, let’s say in December, I would suggest doing the ERA test in October or November, not before because the results will be more reliable.