In this webinar, Dr Clara Colomé, Deputy Medical Director at Eugin Barcelona, has shared with patients various success stories and how they’ve achieved their goals.
Dr Clara Colomé introduces the topic by stating that nowadays women can control their fertility and when to have children. Therefore, women can decide to delay motherhood, yet this might impact their chances and possibilities of eventually having a child.
Dr Colomé further explains that it’s well-known that fertility declines with age, as can be seen in the graph. This graph shows the decline from 35 to 39 years old and then 40, where there’s a sharp decline starting at 35 and, especially, after 40. This means that the older a woman is, the more difficult it gets to conceive. On the other hand, the chances of miscarriage due to genetic abnormalities, for example, increase with age because the remaining oocytes, the many eggs on the ovaries. have more alterations with advancing age. Therefore, the chances of having a child at the end are much, much lower when a woman passes 40 years old.
Dr Colomé states that another option to conceive, apart from conceiving between 18 and 30 years old, is the possibility of oocyte vitrification. This allows women to stop the biological clock. To do that, Dr Colomé says:
Women have to perform medical treatment, and ovarian stimulation for a couple of weeks, and then we retrieve the eggs through a very short and simple procedure, and then we try to preserve them. We vitrify them in our egg bank to keep them here with the same quality stable during the following years.
She later adds that the goal of this treatment is to use the eggs in the future.
Dr Colomé shows a study in which it analysed the probability of having at least one life birth, depending on age and the number of matured oocytes preserved.
She explains that when women are younger than 35, with 10 vitrified eggs, their chances of having a child at home are around 70%, which is great. However, for women who are 40, their chances of having a child with 10 matured eggs are a bit less than 30%. Dr Colomé says:
The younger you are, the fewer oocytes, we’ll need to achieve a child.
Therefore, the ideal number of oocytes to preserve is linked to the age the woman has when she preserves as well as their life plan, meaning how many children she wants to have. Dr Colomé adds a section about Eugin’s experience. She explains that Eugin was one of the first clinics to establish a very complete vitrification program in 2011 called “time freeze”, which they have done for around 1500 patients who have preserved their fertility at Eugin.
The doctor moves on to show the results of patients who go for fertility preservation. Most of the patients, 93%, are single when they preserve their fertility.
Dr Clara Colomé shows another graph with the evolution of the mean age of their patients that preserve their fertility from the beginning of their program in 2011 up until 2020.
According to the doctor, the percentage has to keep declining, but as it can be seen in the graphic, at first, the general population’s knowledge about the subject and also the gynaecologist on the general doctor’s knowledge about this topic was lower than in age for patients who went to preserve their fertility was higher, around 40 years old.
With more widespread information about the topic, the decline of fertility with age and the fact that gynaecologists and general doctors are more aware that they have to advise their patients to preserve their fertility or to ask them about their strategic options when younger.
Dr Colomé goes on by stating that the mean age decreased to 37. The fact that patients are younger and younger is also correlated with the results Eugin has when they do a pickup. The blue columns shown are the mean number of all oocytes obtained per cycle so currently, they’re at almost 10 oocytes per cycle, which is a quite good number. The younger the women are, the more oocytes will be obtained per pickup.
It’s further explained that in some patients, to have a reasonable number of oocytes preserved for the future, they do more than one cycle. The mean number of cycles per person is 1.3. This means that with only one pickup, most of the patients obtain a reasonable number of oocytes.
Dr Colomé reiterates that the goal of the treatment would be to eventually use the oocyte in the future and explains what happens to those patients who come back to the clinic. Most patients who preserved their fertility were single, but when they came back, half of them already had a male partner, and those who didn’t have a male partner, around 45%, used donor sperm, which is possible in Barcelona, Spain. Also, around 5% have a female partner, which also means that they’ll need a donor sperm for the treatment.
The mean age at the moment of the transfer was 41 years and a half, and the mean age at cryopreservation was 38.5. This means that around three years passed between the year of the preservation of the oocytes and the year that patients decide to use them, and the group of patients who’ve started using those oocytes are the ones that vitrified later on, while the younger patients haven’t used the oocytes yet.
Dr Colomé thinks that in the following years, this mean age at transfer and the mean age at cryopreservation will decline since the mean age of their preserving patients has also declined since the beginning of the program, especially in the last three or four years.
To evaluate her ovarian reserve, the doctor, and her team used the antral follicle count with an ultrasound and a blood test to check AMH levels. This patient had, for example, an antral follicle count of 14, which is a good ovarian reserve. She did the stimulation cycle, and it was able to vitrify 8 mature eggs.
A couple of years later, this patient found a male partner and decided to have a child. She was 40 years old and tried conceiving naturally for a few months because, according to Dr Colomé, “it’s what we usually recommend.” This patient got pregnant and had their first baby boy. So far, she hasn’t used her vitrified eggs, however, the patient was planning on having a larger family. Later on, when her baby boy was 2 years old, she returned to the clinic, being 42 years old. She wasn’t able to conceive naturally, and the advice given was to use the vitrified eggs.
The eight eggs were thawed, and seven survived the process. Dr Colomé obtained 4 embryos; they transferred 2 embryos on day 3 of embryo development, and the patient got pregnant, resulting in another baby boy. At that time, the patient was under treatment to use her other 2 embryos and see if she could have a third child.
As the patient wanted to have a large family, Dr Colomé along with the patient, evaluated the different options they had and finally decided to try artificial insemination. The patient didn’t have a male partner at that point, and therefore, she hadn’t tried to conceive naturally. So, she wanted to give it a try. According to Dr Colomé, everything was okay since there were no ultra results on her previous exams, and therefore, they went for artificial insemination.
Unfortunately, after 2 cycles, it hadn’t worked. They had a conversation to analyse what the patient’s options were and decided to use the frozen eggs so that the patient didn’t have to go through an IVF stimulation process again. Since the patient had 21 mature oocytes vitrified and didn’t have a male partner, Dr Colomé decided to just thaw part of the eggs so that in the future, if she met someone and decided to have a child with a male partner, she had the option of using his sperm.
Dr Colomé explains that they thawed 12 eggs, 11 survived and 10 were fertilized. Eventually, they had 5 good quality blastocysts that were up for transfer. They tried just one blastocyst and the patient got pregnant. She had a baby girl and, by that time, she had 9 vitrified eggs and still 4 blastocysts, in case she wanted to increase her family.
Moreover, Dr Colomé states that:
There’s not a maximal age for receiving an embryo here in Spain, but the Spanish Fertility Society advises to accept it, maximum up until 50 years old. So, of course, the younger you get pregnant the better, regarding pregnancy complications even with the vitrified eggs.
She then adds that the patient still has time if she wants to have a bigger family.
However, the patient was lucky as her gynaecologist, during a checkup, did an analysis of her ovarian reserve and found out she had a very low antral follicle count during a routine ultrasound. The patient also had a very low AMH level.
At that point, the patient already had a male partner, but she didn’t want to conceive yet because she was very young and still wanted to do other things before that. Dr Colomé explains that the mean age in Spain for the first child is 32. Therefore, the doctor stated that the patient was very young for their standards.
The patient decided to do preservation, and even though her ovarian reserve was low, she was very young. Dr Colomé goes on by stating that they had to do a double stimulation, meaning 2 stimulations and 2 pickups. They managed to obtain 11 mature eggs that were preserved and kept in the clinic.
Four years later, the patient was still very young, but she was already in perimenopause and wanted to have a child with her male partner. The eggs vitrified were all thawed, and they all survived because they were of very good quality. They inseminated the 11 eggs with the patient’s partner sperm through the ICSI method and obtained 8 embryos, all of which reached the blastocyst stage. Therefore, they had 8 blastocysts preserved, did an endometrial preparation and did the embryo transfer of one of those blastocysts. The patient got pregnant and had a baby boy. As she’s still young and has 7 good-quality blastocysts, she can increase her family in the future.
Usually, at 40 they advise patients to have a child at that point to do an IVF or an artificial insemination, depending on the case. Nevertheless, fertility preservation isn’t the first option that they offer to patients at that point, but this patient didn’t have a male partner, and she was certain that she didn’t want to conceive at that point.
She had a very good ovarian reserve considering her age and, therefore, Dr Colomé went on with this procedure. The patient did 2 stimulation cycles in which they obtained 6 matured eggs in one of them. However, Dr Colomé reiterates that the graph showed the number of effects and chances of having a healthy child at home with 10 eggs at 40, the chances were 30%. For this reason, with 6 matured eggs, it was agreed that it was better to increase the number of oocytes for greater chances in the future. The patient did a second cycle and, eventually, obtained a total of 16 frozen eggs that were kept in the clinic.
A year later, in 2019, the patient decided to conceive but still didn’t want to use her vitrified eggs, so she decided to go for an artificial insemination. Her ovarian reserve was still correct considering her age and she did six artificial inseminations with a donor’s sperm because she didn’t have a partner. Unfortunately, it didn’t work which was something expected at 42 years old. Therefore, the doctor as well as the patient, decided to use the vitrified eggs because her chances of an IVF with her own eggs at 42 were much lower than with the eggs they had frozen at 40. So, all oocytes they had vitrified, 14 out of the 16 survived, and 10 were fertilized, obtaining 5 embryos.
Dr Colomé goes on by saying that:
If you compare this case to the one of the 28-year-old, you can see that there’s a higher loss here, fertilization rates and embryo development are lower, probably due to the ovarian quality linked to the age at the moment of vitrification.
They did an embryo transfer of two embryos on day three of embryo development, and she got pregnant but had a first-trimester miscarriage. The risk of this increases with age, especially after turning 40. The patient still has 3 embryos, and she’s planning on doing another transfer in the following months, but as Dr Colomé says, preserved oocytes give them chances to have a child, but the older a patient gets, those chances unfortunately don’t work.
In conclusion, Dr Clara Colomé says that fertility preservation is related to social changes, and its use has been steadily increasing for the last 10 years, and advanced age harms oocyte quality and quantity. She goes on by saying the following:
Once you’ve decided that you do not want to conceive at a certain point, the sooner you vitrify your eggs, the better.
Moreover, she clarifies that oocyte freezing gives the freedom to put off the decision to become a mother and that this is a big advantage women have compared to 30 years ago. Nevertheless, women have to be aware that it does not give them a 100% warranty that they will be able to have a child.
Indeed, if you are too young, it’s not worth it if your ovarian reserve is good because the chances of needing them in the future are very low. If you’re 28 and your ovarian reserve is good, I wouldn’t recommend preserving your fertility at that point. I would recommend you to check your fertility yearly. The older you get, the more difficult it gets, so we usually recommend preserving your fertility between 35 and 38, which would be ideal or between 33 and 38 and until 40. After 40 years old, we do not recommend it. We accept it in specific selected cases up until 42 years old but only in cases where ovarian reserve is very good, and we expect to obtain a good number of oocytes and where the patient doesn’t want a pregnancy at that point.
My first question would be if you want to have children now. If you’re planning on having children, my first advice would be not to freeze eggs or embryos but to have a child ideally now naturally or through the help of fertility treatment. If you are not planning on having a child right away, of course, fertility preservation is the best option, and regarding survival rates on pregnancy rate in the future, we have very good results with vitrified eggs. Embryos survive the thawing process better.
In a younger patient, the survival rate that we have, at least in our centre where we use vitrification for freezing the embryos, the survival rate of embryos to the thawing process is around 98%. The survival rate for eggs to the thawing process is between 85 to 90%, so embryos survive better in the thawing process. From a biological point of view, maybe I would recommend freezing embryos. I think it’s important to check the details from a social and a personal point of view. Your partner today may not be your partner in the future, we’ve seen all situations, and once embryos are created, if you change a partner in the future, you won’t be able to use them. My advice would be unless you plan a pregnancy in the following year to preserve your eggs.
The treatment starts with menstruation, and the whole process lasts about two weeks if we do just one cycle. You do an ovarian stimulation with a subcutaneous injection that you inject yourself on your belly, and you do that for 8 to 12 days. Then we usually trigger the ovulation, and 2 days later, you come to the clinic for the pickup and then that’s it, so it’s around two weeks more or less.
The number of eggs that I recommend freezing depends on your age, and then again your expectations, and for example, the type of family you want to have. If you are 37 years old, we usually recommend obtaining between 12 or 15 mature eggs ideally, but this also depends on the type of family you want to have. I have patients who preserve 8 oocytes at 38 or 39, and they are positive that if it doesn’t work, it doesn’t work, and if it works, they only want to have one child. Therefore, this is a good result for them. I have patients who want to have a large family with 3 children, in that case, they will need more oocytes.
Regarding the number of cycles needed to preserve these oocytes, it depends on your ovarian reserve. As I’ve mentioned, most of the patients do cycle, but the older you get, the most likely you’ll need more oocytes, and therefore you will need more cycles. I would say between 12 and 15 mature oocytes is required.
We freeze mature oocytes because these are the ones that in the future these are the ones that will be inseminated, but in some cases, we can do what we call in vitro maturation of oocytes before they are preserved. During the ovarian cycle, they change their maturation stage. They go from immature or metaphase 1 to mature or metaphase 2.
The ones that are metaphase 2 are the ones that are capable of being fertilized by spermatozoa, therefore these are the ones that we need. If we inseminate a metaphase 1 or immature oocyte, it will never result in an embryo. However, we’ve seen that some of these metaphase 1 immature oocytes, if we leave them in an incubator for a certain time, they might change stage to metaphase 2 to mature oocytes. In those cases, what we call in vitro mature oocytes might be preserved in some cases.
The main exams that all fertility gynaecologists ask for is especially a vaginal ultrasound. We use vaginal ultrasound every day for almost all patients. We can see the shape of the uterus if there are any alterations in the uterus and check the ovaries. But also to check for cysts and other alterations such as endometriosis, for example. We also analyse the antral follicle count, which gives us a direct idea of your ovarian reserve. This is the main exam that we will ask you to do, we might ask you to do a blood test to check your AMH levels, which also gives us an idea of your ovarian reserve, your weight also gives us an idea of it and the regularity of your cycles, and then we will also ask you for basic exams to make sure you’re in good health, so a full blood count. We’ll have a look at sexually transmitted diseases.
Depending on the case, we will also ask you to do an exam to check if your tubes are opened, which is usually very difficult to check, called hysterosalpingography. It’s an exam where we introduce some liquid, and then we check if the tubes are open. Especially when you’re doing artificial insemination with your partner or if you have any history of infertility. Basically, for artificial insemination, we need to know that you’re in good health, that your ovarian reserve is okay and that your tubes are open.
This is something that I haven’t told you. When we usually preserve oocytes when we are talking about fertility preservation, the quality of oocytes doesn’t change with time, so that’s a good thing. The embryo quality, blastocyst, which is a day-5 embryo, doesn’t change with time once it’s frozen. Once embryos are vitrified or preserved, their quality remains the same, no matter the time passing, and that’s one of the reasons why vitrification is so good and useful if you preserve your fertility at 37, and you want to use your oocytes at 45. If you were using your own eggs or your own embryos at 45 years old, your chances of having a child will be near zero. However, if you have your preserved oocytes or embryos at 37, your chances of success at 40, 45 will be the same as you would have had when you were 37, which is the goal of the treatment.
