By fertility experts from Spain.
In this online event, dr. Rami Wakim, Reproductive Medicine Consultant, explains what you can expect when undergoing IVF treatment and what tests and studies are available to investigate difficult patient cases.
There are some supplements that we see in the market that are, actually, for both men and women, they’re becoming addressed to both men and women. I cannot recommend one thing in particular. I cannot say evidence-based like all the evidence that we have gathered regarding what can work to improve the sperm parameter, for example, or the egg quality. They have put them together now. This does not imply that if you take this, your chances will become much better. This cannot be interpreted like this, however, if you have a supplement that covers everything that this sperm or the egg needs to nurture in order to help not do to deteriorate things in itself is an improvement, is helpful.
I have touched it in my slide and the improvement of the quality of the egg is, unfortunately, the quantity and the quality is very difficult to improve. The IVF concept is, basically, trying to help you with what you have. If you are at a certain age, we cannot change it. The quality of the egg will always be in relation to your age. If you are 20, you have young eggs behaving like 20, 30 the same, 40 the same so I cannot improve the quality of the egg but what I can do is to try to get the most out of this scenario which is whether quantity or quality and improve things by trying to create embryos through IVF. This will mainly act on the time to conceive.
Instead of trying naturally, for example, at home or with less successful procedures. IVF is successful eventually, not necessarily in every case, however, if IVF you are expecting from it getting more eggs than you are already having this is amiss, this is not true because if you have an antral follicle count on that cycle that you are starting any form of treatment I cannot generate more than this. If you have 5 antral follicles do not expect to have, for example, 8-9 eggs.
Regarding the quality, can I improve my egg quality? The only thing, for now, is cryopreservation of the egg so. My advice to you is if you are in this category that you would like to have or to proceed with egg freezing, go for it. Because this is the only way to improve dramatically the quality of the egg and hence the quality of the embryo in the future.
Let me reassure you that the current preservation of the sperm is completely different than cryopreservation of the egg. The reason we had a very high success now in egg freezing is because we have shifted from the actual way that we were doing the cryopreservation to vitrification. The main difference here was that the egg using slow freezing that we used to do has given us very low success rates in the past maximum maybe 10% and the problem was with the thawing. Thawing what the problem because eggs were frozen and when you defrost them, ice particles form and this is where the problem was.
Vitrification is a completely different issue. Vitrification is instant freezing that there is no time even for ice to form when you defrost it. That’s why we are giving high success rates now as 50% for the egg. However, this does not apply for sperm. The sperm do very well. It has always been frozen the way we started freezing sperm a long time ago before freezing the eggs.
We started freezing eggs in around 2000, however, the freezing the sperm was known long before that and it was always the slow frozen. I wouldn’t worry about it much because sperm behaves very well after being slow frozen or frozen using the new techniques. Regarding the second question: how many straws should I be using? This is a completely lab discussion. From a clinician’s point of view, I would abide by what the lab is advising.
That’s a common question that I get in a scenario of a busy IVF clinic so it’s not uncommon to come across this. Unfortunately, I’m so sorry to hear this that you were not successful but there is a lot of information here that we need to know like the kind of stimulation you had, your BMI, whether the eggs produced were of good quality, how many mature, how many fertilized, so it’s not only like what is the end result but I would like to know this is the whole sequence of events until you produce all these eggs and the final result. How many good quality embryos as well as how many frozen?
Don’t forget that I don’t know the age, I don’t know what is the state of the lining of the womb, what was the thickness. Did you think about using one of these techniques that we use for implantation failure? Because if they were good quality blastocysts as you said I would ask if you get enough progesterone? Do we need to know more, take a biopsy, and see.
On the other hand, if your age is, say for example about 40, I would definitely advise you to test the embryos because we need to know one way or another. Are the embryos problem chromosomally speaking or is there a problem in the implantation? That’s an end result but, however, leading to this I should know a very thorough study of your stimulation protocol.
It’s a good question. You had two failed attempts both with IVF and ICSI and you had the kind of diagnosis that this was due to having natural killer cells and this is the first myth that we have to clarify. As I have mentioned, the papers have been published and the randomized control studies did not show any relation between the natural killer cells, both uterine or in peripheral blood, and the reason for you not having a successful attempt.
This is the first thing that we need to realize – that it doesn’t mean that treating them will definitely make this pregnancy successful. However, there are centers that treat immunology, of course, but do I believe in it? I believe only the evidence and what has been published in the scientific papers. I am very critical but I don’t mean by that I have to ignore any attempts to see like if there is an improvement from a technique that I can use. But the most important thing to know and to realize that don’t fall into this idea that if you are not treated through this immunological technique, that means that this was the only reason for your failure.
If you are 45, as you said, there is a major issue here to talk about more – this is the quality of the eggs. The quality of the egg is, results from the age and has implications on the quality of the embryo. If you have tried twice and the outcomes were unsuccessful, egg donation at 45 would give you a higher success rate in comparison with trying with your own eggs. But, obviously, everything has to be balanced, and would this work if you have NK cells? If you have an egg donor and egg donation cycle, a lot of IVF clinics would recommend running a basic study of NK cells. However, this is not the mainstream in the IVF field for now.
VA is in vitro activation and this has started in Japan with a breakthrough idea that gave a successful outcome. This is very limited to a very specific group of people who have premature ovarian insufficiency as long as they have some antral follicles. By this scientific breakthrough, they take these antral follicles and they will grow them outside, in the lab, with the eggs as well and injecting them with so many factors and then replacing it back to the ovary and therefore they will be responding to the actual simulation drugs. This concept is still in a scientific issue, we cannot recommend it only for a clinical aspect. However, it is promising to know what it will lead us to. There are like a few recorded cases worldwide but we will want to know more about whether or not it is going to be in the mainstream in the near future.
I have mentioned this already and I advise you to read this paper published very recently in 2020 about add-ons and they have all the information about Q10. I’m putting this information because it was fascinating to know what is the outcome of all this information. I have no inclination to be favoring this but this is for everyone to read and to know exactly whether this is helpful or not.
There is no harm but we are talking about whether there are any benefits. If there are no proven benefits, so it’s very hard to argue whether taking it will improve things.
It’s not detrimental as I said but we have to be aware of the evidence. It’s not detrimental. I want to have a more green light to say it does definitely improve things. There is a big difference. I cannot say it is detrimental. At the same time, is there any trial that has improved the outcome of live birth? There wasn’t.
Folic acid is either taken alone or as a part of prenatal vitamins. Folic acid is 400 micrograms per day, vitamin D is 1,000 units per day and usually, multivitamins contain everything including folic acid and vitamin D. Every vitamin combination is in a way good but as long as they have at least 400 micrograms of folic acid.
The folate is taken mainly in relation to pregnancy so the donor whether she takes vitamin D or folic acid will not make a huge impact on the egg. Because you need the vitamins for your actual pregnancy.
Definitely high doses of vitamin D are not recommended so if you have the 5,000 units, 10,000, or 80,000 so this is not recommended. A thousand unit should be more than enough and folic acid or folate unless you had a proven recurrent miscarriage then we can advise these 5 milligrams or you had diabetes, previous neural tube defect baby so we recommend the higher dose which is the 5 milligrams.
The amniocentesis now is not based on age or whether the donor was young. We take all this into a statistical equation and then have an assessment with a mutant screening test, with all the other blood tests that we do in the first trimester, and based on that we would recommend if you are at high-risk or low-risk.
Antagonist protocol is a shorter version of the agonist protocol. The agonist protocol was the one that was the classic one to start with. It was meant to shut down the ovaries basically by what we call agonists or GnRH agonists and this makes the ovaries dormant so when we start the actual stimulation, the FSH, it will help us improve the number and the progress of these follicles without a premature LH surge. We start them on day 21 before the actual start of the period and two weeks after we start with the actual medication.
The antagonist came back as a newer version and it’s a very good idea. We start with the FSH stimulation and we add up a general antagonist to inhibit the average search. They both function the same so one is an agonist protocol starting before starting the cycle, on day 21, before the actual commencement of the treatment, and the other one we start 5-6 days after we start the medication. Both of them are, basically, to prevent the LH surge and premature ovulation.
I just wanted to know what was the outcome with genetic counseling so did you have genetic counseling? And what kind of aneuploidy? It’s not only aneuploidy or mosaicism, other types? So if there was no genetic counseling, it’s very difficult to know exactly what. Because some hereditary problems are repetitive and they should be managed differently from something that is less likely to happen again. I advise you strongly to have genetic counseling and take it from there. Chromosome 16 or 13 – ok. The main chromosomes that we look for are 13, 18 and 21 and this is, unfortunately, incompatible. In a way, it is good that they were detected before replacing them back so what is the next step forward? It will depend on the whole scenario, the age, and whether you accept egg donation or not and stuff like that.
I think perhaps you should combine it with an ERA testing that would be the best way forward, actually. At least, I know that the embryo is normal and then I would like to know more about why you are not having implantation. Maybe hysteroscopy, maybe ERA testing. I understand banking for sibling is good but I think, on the balance, you could go away with simple things like transferring an abnormal embryo. However, if you’d like to go ahead, this has to be definitely geared and directed by genetic counseling.
Since you have said, unfortunately, you didn’t have genetic counseling so I really recommend you to have and see what the recommendation is. And, yes, sometimes, the normal-looking embryos had aneuploidy. I showed you a slide that no matter what you cannot judge by the looks if they are euploidy or aneuploidy, so you have a very good quality embryo, good-looking under the microscope, however, it is not okay later.
After careful examination, we have to make a decision. For example, four times we have done PGT-A and then we had a repetitive abnormality. If PGT-A has been recommended because of your age alone and then repeated aneuploidy, then the benefit of it might overcome the risks of having PGT-A.
There are two issues here: one is the egg quality in relation to blastocyst. We know that in the initial phase of the blastocyst formation, during days 1-3, they are predetermined by the egg quality, however, from day 4-5, they are more sperm driven. What we are trying to say by this that if you have a good number of eggs and a good number of embryos that you have developed up to Day 3 and then after having, for example, six Day 3 embryos we end up with one blastocyst. We often say that this is more likely to be driven by sperm so that this means that we have to transfer only Day 3 regarding your age. It’s not relevant because till the blastocyst is the most embryo proven to have an implantation potential. If I compare the implantation potential of Day 3 or Day 5 definitely the blastocyst has got the highest implantation potential.
There is nothing called developing Day 5 is “too” late in the embryo development and age. I don’t know where you found this information, or perhaps I’m not understanding what you mean by “too late” here. This is the known practice of having an embryo developing till Day 5. However, it all depends also on the number. If, for example, I have one or two embryos and after counseling, you’re happy to have two embryos put back, I don’t see a reason why I should wait until Day 5. That’s the issue here. The issue is mainly dependent on the risk of multiple pregnancy, the risk of having a late diagnosis of failed development into blastocyst by just observing them under the microscope which would have eventually have happened anyway.
However, this myth of being “too late” in the embryo development age, I don’t think this terminology is something I would go with. However, as I said if you have 1-2 embryos, then this is more than enough to transfer them on Day 3 and most of the IVF clinics would not wait to Day 5 to transfer.
It’s a good question. Low stimulation/mild stimulation/natural stimulation has got the advantage of having a very low dose and once we know that the there is a low AMH on board and especially in very poor ovarian reserve, a low stimulation has proven that it is much milder into stimulating the eggs and providing better quality eggs. You have to understand that I’m not challenging the ovaries to produce many eggs – this is number one. We have to accept that low AMH, no matter what I do, I will not be able to produce more. Remember what I have said before. If, for example, you have 2-3 antral follicles to start with, if I give you an antagonist with 450 units, it doesn’t mean that I’m going to get 8 or 9 eggs out of these 2-3 antral follicles – so that’s number one.
If I have 1-2 antral follicles that I’m aiming to get into maturity so they grow so that I can collect them, on one hand, pushing very hard will not benefit you, the ovaries may not be responding, on the other hand, the egg quality demonstrated by this high dose of FSH are proven to yield more aneuploidy embryos. If I have, for example, three eggs developed into 2-3 embryos in the mild stimulation, I’m expecting to have at least 1-2 normal embryos. However, if I do an antagonist cycle and then I try to produce 3-4, I may have all 4 aneuploidy. There is a concept that has come out of this which is banking of embryos.
When you hear about a three-cycle package that is exactly the situation that we are in here. We know that low AMH is not going to respond with a higher number of eggs. The way around this is to do, for example, a three-cycle package. That means that I stimulate, collect the eggs, create embryos and bank them and not transfer.
The same in the second cycle and the same in the third cycle. That means that after these three cycles, I have more choice: to know how many embryos can be produced and this comes in dual advantage. Firstly, I’m transferring, for example, two embryos and then out of this 3-4 I have collected five embryos so we still have still three frozen so that’s fantastic. If you, for example, would like to have PGT-A on these embryos, that means that I have a choice and doing PGT-A on five embryos is much better than doing PGT-A on one because then it is not worth it. So this type of stimulation has got advantages: it’s milder, it’s less harmful to the body and is less expensive. So there is a lot of advantages in this.
It’s a good question. Low and mild stimulation protocols are labeled as for poor prognosis patients so, in IVF clinics, if they want to be transparent, they should include this in their success rates. This is an honest answer so, yes, they would be included. Even if the success rate is low, as long as we know that they are offering low or mild stimulation… because some units do not offer this mild stimulation protocol simply because maybe they don’t believe in it. But if it is in a clinic’s offer, you will see it even on their website. There should be a section with information on patients aged 30-35 and those patients who had mild stimulation, especially in the age category older than 32-40 will be included and will have obviously smaller success rates. However, this is more than enough to make someone happy with their own eggs.
This is a very good question. However, in older age to have high AMH is debatable or very unlikely. However, I see this on occasion so it’s not something that we are talking about on a daily basis. For example, I’ve seen AMH of 33 and 35 in a patient who was 41-42 years old – it’s very good. But remember I’ve spoken about two things: one is the quantity and the other is quality. So AMH is 22 at 41 – that’s very good. In that sense, both protocols can be used. It depends on what has already been done. So the short answer for a 41-year-old who has an AMH of 22 a full classic IVF stimulation would work better in this case. However, mild stimulation is dedicated to much lower AMH or much older group of patients.
There is always the risk that an embryo does not survive the biopsy. However, the biopsy, if you are talking about PGT-A at the blastocyst stage when using it from a perfect donor is very risky. We are saying that less than 5% are not surviving the biopsy and then on thawing, then you see that the embryo did not survive. Yes, there are risks of PGT-A like in any other procedure but, definitely, the risk of biopsy in the trophectoderm on the blastocyst is much lesser than a biopsy on a Day 3 embryo.
I cannot say that. Every patient is different. At 42-43, I need to know what is the antral follicle count, what is her AMH, has she already done classic protocols before, what kind of eggs she has produced, how much was the level of the E2 that she has produced. It’s very different. It’s not categorizing people based on age 40-43. I’d rather have a medically fit patient at 42-43 with AMH which is not as low below 2-5. In a scenario of having at least an average AMH, where the woman has not tried IVF antagonist cycle or agonist cycle, definitely in that scenario, I would go for the antagonist cycle. The key thing is here if I can get as many eggs as possible.
Because you can get a much higher number of eggs but end up with a lower number of embryos. This lower number of embryos I want to use them for fresh transfer (one embryo) and then see if I can freeze the rest. For mild stimulation, if a woman has very good AMH, she will not have a good chance of reaching her potential in it. It would be a good trial to recruit as many eggs as possible before reaching the age of 43-44. FSH at 7.5 at 42 years old is excellent so any FSH of less than 10 we considered as normal.