In this session, Dr Belén Marqueta, Gynaecologist, Specialist in Human Reproduction at Clínica Eugin, Barcelona, has been talking about the egg freezing process, when it is recommended and how to start.
Social fertility preservation has become more and more popular, and several factors took place in the last half of the 20th century when women started to work outside their homes and good contraception methods appeared. These factors allow women to control their fertility, and they were able to decide when they want to get pregnant. From the biological point of view, the best age to get pregnant is between 18 and 30 years old, more or less. Unfortunately, this is the period when people usually develop their professional careers and their personal life, and this could drive a conflict of interest, and consequently, there will be a high percentage of women who voluntarily will delay motherhood.
According to data from United Nations, in the last 4 years, the motherhood delay is generalized in North America and European countries, the mean age for the first birth in Europe in 2010 was 28.7 years. What is important to remember is that with age, there is a progressive decrease in the oocyte quantity and quality, and this means that a woman is going to have a lower ovarian reserve, it is a physiological ageing of the ovary.
How can we test ovarian reserve? Two things have to be taken into account, the first one is the quality of the oocytes and the second is the quantity of the oocytes. There are no markers that can check the quality, but it is well known that age is going to decrease the quality of the oocytes.
It is possible to assess the quantity of the oocytes through a blood test by doing an AMH (Anti-Müllerian hormone) test, and it is also possible to do a simple ultrasound to see how many antral follicles are there. From 30 years of age, fertility starts to decline slowly, and it’s getting to drop faster after 35 years and so on, it is going to get more difficult to get pregnant and also that there is going to be a higher risk of miscarriage related to maternal age.
When we talk about oocyte quality, we refer to oocyte competence, which is mainly due to some chromosomal abnormalities that are going to appear in a woman’s eggs as her age increases These chromosomal abnormalities make it more difficult for the embryo to implant, and sometimes the embryos may fail to implant or cause miscarriage during the first semester of pregnancy.
Nowadays, the only way to preserve a woman’s fertility is oocyte verification. How does it work? The patient can start an ovarian stimulation treatment from the 2nd or the 3rd day of the cycle, it is performed with some hormones with subcutaneous punctures, and we ask the patients to come to do the follicular checks, we do these follicular checks with ultrasound, and also we do these follicular checks with blood tests. The follicles of the patient are monitored while they start growing depending on the response, and then the patient is asked to come for a second follicular check, usually, they need to have 3 or 4 follicular checks. When we see that all the follicles are big enough, more or less, we give them the last injection to induct the ovulation and this way, we know that 36 hours later, we can see our patient in the operation room and perform the egg retrieval.
Egg retrieval is always performed in the operating room, and it is always done under anaesthesia. Every follicle is punctured, and the liquid that is inside the follicles is taken into the laboratory where the embryologists select the eggs that are inside the liquid, and after that, the embryologists can perform the cryopreservation of the eggs in their laboratory.
How many eggs do we recommend freezing? That always depends on the patient’s age. Each curve is going to show the probability of having at least 1 live birth at home, depending on the age of the patient and the number of mature oocytes obtained on the day of the follicular puncture. The best outcomes of this procedure are obtained when a woman freezes her eggs at a proper age.
At Eugin, the oocyte preservation program started in 2011, and since that time, more than 1 500 cycles were performed. The reason behind this is mostly due to lack of a partner at that moment in life, the second reason was because of their professional careers, and also some women manifested they had late childbearing.
Studies performed at Eugin show that there is a significant decline in the mean age at the time of oocyte preservation. In 2011, the mean age was 40 years old, while in 2019, it was 37.2.
The main factor to determine motherhood chances is the age of the oocyte. Women that undergo this kind of treatment have a better prognosis than the ones that performed this treatment 8 years ago. It’s probably because nowadays, there is more information available as well as more data and studies performed.
Who returns to attempt to get pregnant with these vitrified oocytes? According to Eugin’s data, from 1 500 patients, there were 123 that have come to use their eggs and there were already 131 transfers performed. The returning rate is 8%, and the mean age at the moment of the cryopreservation was 38.5 years old, while the mean age at the time of transfer was more or less 41.5 years old. Almost 100% of those patients didn’t have a partner at the moment of performing cryopreservation. At the time of returning, more the half of them had a partner.
What happens when you decide to use those vitrified eggs? The eggs are thawed in the lab, the survival rates are over 90%. After that, we can perform the fertilization of these eggs with partner or donor sperm depending on each case, and the fertilization rate is more or less 75%. Such embryos have similar pregnancy rates compared to those patients who use fresh oocytes.
The pregnancy rates of the patients that come and use their eggs after freezing them show that the rates depend on the patient’s age, but it depends on the moment when the patient performs the cryopreservation, not the moment when the patient is performing the transfer. It’s important to do this kind of treatment as soon as possible, and it’s good to note that obstetric outcomes are similar to those of the general population.
No, there’s no maximum or minimum time to use those eggs. This treatment gives women the freedom to postpone their maternity. They can wait until the moment they feel ready. Regarding your age, I don’t think you’re late as you are under 35 years old, so I think that you’re in a perfect moment to start thinking about performing elective oocyte cryopreservation.
There is a big difference. In fact, during the presentation, I have shown a graphic, the number of eggs that we have to freeze depends on your age because the younger the patient is, the lowest the number of eggs is needed to have one baby at home. There is going to be a decrease in the quantity, but also the quality of the eggs. We need to freeze more eggs if we are older to compensate for the lack of quality that we are going to have because of maternal age.
Social cryopreservation is not covered by insurance here in Spain. This is because, in the end, it’s an option for women to do this treatment, so it’s not covered nowadays by our national insurance. Regarding the advantages of performing this here in Spain, we have lots of experience in IVF treatments and fertility cryopreservation treatments, just because we have been performing these treatments for a long now.
I think that we have lots of experience, and we have many clinics, such as our clinic where we are used to treating patients that live in other countries, and we know we can make it easier for the patient to perform such treatment in their countries so that they can come here only for ovarian puncture or just a part of the treatment.
We always use antagonist treatment, and we always induct the ovulation with Decapeptyl just to avoid the risk of hyperstimulation. We perform the follicular puncture in the operation room, and we cryopreserve the embryos, well the embryologist cryopreserve the embryos here in our laboratory in Barcelona.
Yes, absolutely. There has been an increase, and more and more patients want to perform this treatment and also, as we explained, they are younger, so we are really happy about that because the prognosis is going to be better. Also, during this last year of pandemic, I think that many women had more time to think about their own issues, and we have had an increase of patients that want to do egg freezing treatment with us.
We have an internal limit for that, and it’s 47 years, but we have to assess every patient individually, we cannot generalize. Every patient has a different ovarian reserve. We have to perform a complete study of the patient.
We have to perform the ultrasound, blood test just to assess if it’s going to be worth it or not to cryopreserve the eggs. Usually, in patients 42-44 years old, we know that the egg quality is not going to be good, so we don’t recommend performing these treatments.
It’s not just the quantity of the eggs that matters, and quantity can be evaluated with the Anti-Mullerian hormone with the antral follicle count. What is also important is the quality of the eggs, and, unfortunately, we don’t have any markers to assess the quality of eggs, but we know that age is going to have a high impact on the egg quality. Even if we have a good ovarian reserve, the quality of these eggs may not be so good. This can lead to implantation failures if we create and transfer embryos or miscarriages during the first semester.
There is a legal part that we have to take into account here. If we freeze eggs, these eggs are ours, they will be the women’s eggs. On the other hand, if we freeze embryos with a partner, these embryos are from these two people, so in the end, it’s not the same from a legal point of view. If you want to use your eggs, you can use them whenever you want, you don’t have to ask for permission, but if you want to use the embryos that you have frozen with a partner, you have to know that both of you have to sign the consent form for performing a treatment. In the end, they are not just yours anymore.
We can’t forget that embryos are more advanced cells than eggs, so the survival rate of the thawing process and the manipulation of the embryos will have a better response in our laboratory than the eggs. We have patients that do so many treatments. Some patients want to freeze eggs and embryos with a partner, but they also freeze some eggs because they have such good ovarian response that they have good numbers for performing both treatments.
Some patients freeze embryos because they have a partner, and they want to have a child with this partner, and they go ahead with freezing the embryos. On the other hand, we have patients that are just waiting to see if they can have a baby with their partner or not. At that moment, they freeze the eggs, and they keep trying, or they talk to their partners and make some plans.
We have a really good egg donation program here in our clinic in Barcelona, and we have many donors. We do the match between the biological mother and the recipient, we always perform a physical matching. We have a matching team that specializes in performing physical matching between the donor and the recipient. We can also add a genetic matching if the patient decides to do it. This genetic matching is for some recessive genetic disease, and we can add it to the treatment to avoid having a child affected by one recessive disease.
I’m sure that we do have some results after the PGS. I don’t have the numbers at this point, and we don’t always advise our patients to do the PGS. We advise them depending on their age or their medical history, but we don’t do that treatment in every case.
