Advanced maternal age (+38) – patients’ success stories

There are different schools on PGT, which is the genetic testing of the embryos and in fact, I could do another whole topic about that. It’s a discussion topic with gynaecologists and fertility experts everywhere in the world. We try to individualize each case, so I know there are centres where when you reach 40 years old, they always go for an IVF with PGT. Randomized studies have shown us that PGT, which is analysing the embryo, helps us in certain cases reduce the time to obtain a pregnancy and might slightly reduce the risk of miscarriage during the first trimester. Unfortunately, at this point, PGT doesn’t allow us to say that you will have more chances of having a healthy child in the end, considering the cumulative cycle. We usually discuss PGT in patients over 38 years in our facility, there’s always a discussion.

ESHRE society, The European Society and the most recent studies on PGT tell us that if you’re over 38 years old and you have a good ovarian reserve, that is the case where you will most likely benefit from a PGT. In other cases, it depends.

We typically analyse the number of oocytes that we obtain, we analyse the fertilization rates, and then we analyse the evolution of the embryos, which we put in the time-lapse incubators that allow us to control the development of those embryos much better and then on day-3, we see how many embryos there we have, and their characteristics. Depending on that, we advise the patients to go for a day-3 transfer or leave them in culture until day-5. There will be a loss from day-3 to day-5, we’ve had many pregnancies from transferring day-3 embryos. When we have day-5 embryos, it allows us to select better the best embryo, so we try to go there, that’s what we do automatically, for example, with donor eggs, but there’s also a risk.

If we only have 1 or 2 embryos – what are the advantages of waiting longer? We have a huge risk of losing everything. When we have at least 2 blastocysts, and you’re over 38, I would recommend doing a PGT, assuming the risk of limitations in this last case, this patient was 44, we had 2 embryos on day-3. We had beforehand discussed this possibility with the patients, and I told them that if we had a good result, then maybe it will help us, but if they assumed that we might not have any embryos to transfer, we decided to do the transfer on day-3 because there were only 2 embryos.

Your case is relatively more and more common. Regarding the first part, it’s very difficult to say. The blastulation process, which is the process that takes the embryo from day-3 to a blastocyst stage, is around 60%. In good conditions, 60% of the embryos reach the blastocyst stage. If you’re 40, probably this percentage will be slightly lower, and we obtained these percentages using the time-lapse incubators. The EmbryoScope that’s the one we use here, but there are different brands. This is in an environment where we control all the rest of the elements of the equation.
There’s a kind of trend now to think that the best thing is to transfer a euploid blastocyst, and this is true but in a theoretical world. When we do a stimulation for your ovaries, there are different steps, and we don’t like to give you a general road that you have to follow. Each case is different, each patient is different, we have to see the results as they come.

Usually, when we go for a PGT-A, we like to have 10-15 mature oocytes beforehand that will most likely allow us to have at least 2-3 blastocysts. We just need 1 to reach the blastocyst stage, we typically go for a blastocyst culture when we have at least 3 good quality embryos on day-3 and to have that, we would need to have probably 5 or 6 mature oocytes. This is something that we see one step at a time, and reaching the blastocysts stage allows us to select easier the best embryo, and it allows us to minimize the risk of multiple pregnancies. If 1 embryo will implant, it will implant regardless if we transfer them on day-3 or day-5.

I would encourage you to try once again. At 40, you will have a low AMH. What I can advise is, if you’re smoking, quit smoking, if you’re slightly overweight, lose weight and have a healthy lifestyle before starting. You have to be aware of the limitations, but also be positive, once you start the procedure.

I would say endometrium is a complicated element. The most important element for the success of IVF is the oocyte and its quality. Sperm is significant, so is the uterus, but the most significant thing is the oocyte.
When we are not sure if something is happening in the endometrium, we always do a hysteroscopy and an endometrial biopsy to rule out the infection. Also, to make sure there’s not a polyp, etc. and to see the cavity by itself.

When the endometrium does not thicken correctly or does not have a correct pattern for the transfer, we sometimes freeze the embryo. We try another protocol to prepare the endometrium again. I don’t know the details of your case, but probably that’s what we would do in this case.

AMH is an element that we use a lot, but AMH is a hormone that is produced in the ovary, in the follicle, and it gives us an idea of the amount of ovarian reserve left. Unfortunately, it’s not a direct predictor of the success of IVF. It gives us an idea of the quantity that we will have, it gives us an idea of whether this patient will respond correctly to the stimulation or she will be a low responder or a high responder, and it allows us to adjust the dosage of medication, especially when we talk about IVF treatments.

There is a slight correlation between our AMH levels and pregnancy rates, but it’s not direct. We consider normal AMH, we need 2 nanograms per millilitre or more in general. I might have a 39-year-old patient with a very good AMH of 4.0, and she might respond very well to the simulation. I might have many embryos, but her chances of conceiving will still be lower than that of a 29-year-old with an AMH of 2.0. The age of the oocyte is the most important factor when we discuss success rates for both treatments.
AMH allows us to correlate it with the chances of you responding to the treatment and how to adjust the protocol.

It is an excellent thing that you’re trying to lower your BMI to below 30. This is one of the most important things you can do to help yourself. There are other things, polycystic ovary syndrome has to be taken into account. If you have never tried to conceive, we would also have to analyse the presence or absence of a partner, but usually at 39, if your ovarian reserve is acceptable, I would probably recommend going for an IVF to maximize pregnancy rates because chances are still quite reasonable.

IUI is typically for patients who have, for example, never tried to conceive naturally, and who don’t have a partner, who wants to minimize the intake of hormones or have financial difficulties as it is a more economic treatment, but then I would recommend not to wait. You’re still at a point where your chances are reasonably good, so I would probably decide for an IVF to shorten the time to pregnancy and maximize your chances.

We try to individualize decisions with our patients, I give them a recommendation, but this is something that we always discuss. Usually, in the case of a natural cycle where we only do a natural or a mild stimulation cycle, the goal of the treatment is to try to obtain 1 or 2 good quality oocytes, not more. We typically recommend transferring on day-3, we could eventually wait for day-5 but again, what will be the advantage if we only have 1 embryo to take it to day-5.

There’s a school that says that if it doesn’t reach day-5, it will never work. The problem is that we will never know if it would have reached day-5 inside the uterus. Our incubators are perfect, we have the best technology, but many centres have the same technology, but still, it’s not a real uterus. If you only have 1 embryo, I always recommend transferring that on day-3 if the embryo has good characteristics.

If there are doubts about its viability, then I would say, let’s wait a bit more to see, but I don’t see the advantage of waiting when we only have 1 embryo. We won’t select it any better, so if it has to implant, it will implant regardless if we transfer it on day-3 or day-5 in this case in particular. If one of my patients assumes the risk of having 0 embryos to transfer on day-5 and wants to go for the blastocyst to see how it looks on day-5, we could do that eventually.

The egg retrieval itself doesn’t impact the thyroid. Hormonal stimulations might have an impact on thyroid function, around 20 to 30% of women, in general, will have thyroid problems during their life, so it’s quite common to have thyroid alterations.

In fertility, we’re really cautious with thyroid function because studies show us that if TSH (the hormone that makes the thyroid work) is higher than a certain range, the risk of miscarriage during the first trimester increases. That’s why we try to keep it under a regular range, and hormonal treatments might impact thyroid function.

The fact that after stimulation and a pickup procedure, your TSH levels were high means that you’re at a higher risk of developing thyroid issues later on in life. The levels probably will go back to normal in a few weeks, a month, or two. The important thing about thyroid function is to control it regularly, we have ways of controlling it, we have medication that’s easy to take. The impact of hormonal stimulation or hormonal changes on thyroid function exists, and it usually disappears over time.

When we discuss hypothyroidism, which is the real alteration of the thyroid, and you talk to general doctors, they say it should be lower than 4 or 5. For fertility purposes, we like it to be between 0.5 and 2.5, that’s our ideal because if it’s higher than 2.5, it typically slightly increases the risk of first-trimester miscarriage.

Obesity has been determined as one risk factor for infertility, it alters the quality of the oocyte, it doesn’t affect the embryo per se, but it might affect the quality of the oocyte, and therefore, it might be more difficult for this oocyte to be fertilized and to develop into an embryo. Once we transfer the embryo into the uterus, we’ve seen that obesity has been linked to implantation problems, the vascularization of the uterus might be impacted, the hormonal balance might be altered.

When we transfer one embryo to the uterus, there has to be a kind of biochemical dialogue between them, they have to do a mating ritual, the endometrium, and the embryo, they have to get to know each other and decide if they like each other or not.

If there’s obesity, this dialogue might be altered. Therefore, it’s more difficult for the embryo to attach, and then it has also been directly linked to the risk of first-trimester miscarriage. Obesity increases the risk of first-trimester miscarriage and increases the risk of some genetic abnormalities, so losing weight is not always easy, but it’s something that you can change.
We cannot change the egg, the age, but losing weight is possible. It has a direct impact on your health and your chances of having a child.

We do an ovarian simulation, we do a pickup, and then a few days later, usually 2 to 5 days later, we start stimulating again to accumulate oocytes or embryos. It has been done especially for PGT purposes to accumulate embryos to do a genetic biopsy.

We do not do it very often because typically it’s advised for financial reasons because if you have more embryos, it is cheaper to do the biopsy and analysis, it’s not the case here at the clinic (Eugin). We do not typically do that because, for example, if we have at least 2 good quality blastocysts and you want to do a PGT-A, I would go for a PGT-A. If the good embryo is there, what’s the point of repeating and repeating stimulations and accumulating embryos, and maybe the good one was the first one.

I’ve had patients who were 39-40, and they said they would like to try to have at least two children, but for whatever reason, they cannot do the transfer now, they are moving, and they can’t do the stimulation, and in a couple of months they will be able to, then this is a good strategy to gain time. Regarding results, it doesn’t change much, and for me, it’s not the goal of the treatment because the goal of the treatment is to get you pregnant as soon as possible, not to accumulate embryos, but it is a good strategy in some cases.

With donor eggs – plenty. With your own oocytes, which, I’m guessing, the question is leading to, there have been a few in the literature. Here in the clinic, we’ve been working for over 22 years old, we do thousands of cycles every year. We have had a handful of patients at 45 who have conceived and had a child at the end, the oldest we had was 45. We accept patients for IVF with your own eggs until you’re 46, included in very limited and specifically selected cases, but unfortunately, we haven’t had any successful cases at 46, and that’s why we stopped there.