Dr Maria Arqué, International Medical Director at Fertty International is talking about fertility preservation and egg freezing options.
Essentially, all women have an important limitation: we are born with all the eggs we will ever have, and we do not produce new eggs throughout our lives. Both the quality and quantity of our eggs decrease with time and age. Typically, the moment in our lives when we have the most eggs is around 7 months old while still in our mothers’ wombs. By the time we are born, around 1 million eggs are left in our ovaries, and by puberty, there are around half a million eggs.
Each month, a pool of eggs in our ovaries is recruited and has the potential to grow, but since humans usually have only 1 child at a time, the body naturally selects just 1 egg each month. At the beginning of the cycle, the follicle-stimulating hormone (FSH) increases slightly, causing one of the follicles (each containing 1 egg) to be selected, usually the one with more FSH receptors. The other follicles are discarded. The selected follicle grows and produces estrogen, which prepares the endometrium (the lining of the uterus) for embryo implantation. When the follicle matures, estrogen levels rise significantly, triggering ovulation, and the egg moves from the ovary to the fallopian tube. If fertilization occurs, the embryo develops and implants in the uterus, leading to pregnancy.
One key takeaway is that each month, we lose many eggs, regardless of our actions. Only one egg is typically selected for potential pregnancy, while the others are lost. Scientists Wallace and Kelsey have modelled the decline in egg quality and quantity with age, showing a significant decline starting around age 35. At age 25, most eggs are of good quality, but as we age, both the quality and quantity of eggs decline. This decline affects the likelihood of achieving pregnancy and increases the risk of miscarriage due to chromosomal abnormalities, such as Down syndrome.
Our reproductive patterns have changed significantly for various reasons, such as work commitments, building careers, not finding the right partner, or lacking the economic resources to have a child. Additionally, we are well-educated about contraception but not warned enough about how fertility declines with time, often earlier than we expect. In today’s world, our 30s and 40s are perceived as the new 30s, which may give us a false sense of not ageing. However, while we may not feel or look 40 or 30, our eggs are still 40 or 30 years old, and their quality declines accordingly.
Advantages of egg freezing include:
Whether they want to be solo moms, wait a little longer to have children, or have children as soon as possible, egg freezing offers them flexibility. Women often sacrifice a lot in their lives for children. In a survey comparing why men and women seek part-time jobs, 43% of men did so because they couldn’t find full-time work, while 42% of women did so to care for children or elderly adults. This highlights the tough decisions women face, balancing career and motherhood. Egg freezing can give them the chance not to choose between one or the other, but rather to choose the right time for them.
Regarding trends in fertility preservation, it appears that social reasons for postponing motherhood are growing, with an increase of over 16% in the last 3 years. Most fertility preservation cycles are now for social reasons. Historically, we did this primarily for medical reasons, such as for oncology patients or those undergoing surgeries that could impact fertility.
When looking at the age distribution of patients who freeze their eggs, most are between 36 and 39 years old. However, the ideal time to freeze eggs is before 35 to avoid the decline in egg quality and quantity. If you want to maximize your chances of having a child and be cost-efficient in the process, you should consider freezing eggs earlier. Additionally, more educated people tend to freeze their eggs, likely for various reasons.
First, education is power, and when patients are educated, they have more choices. The second thing is that most likely, more educated people tend to postpone motherhood because they have other commitments in life and might be prioritizing their careers for some years.
As shown on the slide, a survey was done by gynaecologists in the US, examining how they viewed fertility preservation and whether they were informing their patients about it. The results showed that:
When asked why they were not discussing it, the results showed that:
That’s the main thing we should try to change as gynaecologists and fertility specialists—spreading awareness that we should be doing this much earlier. I insist on these ideas because it’s super important for everyone to understand why ideally this should be done before 35.
As seen on the slide, some data from Anna Cabo, who is probably one of the people who have the most experience with egg freezing and its results. If we see the likelihood of having a child or a live birth depending on age for every egg that we retrieve, it decreases dramatically with age. When we are younger than 35, our likelihood of having a child is 6.6%, but after 40 years, it’s less than 2%.
Another study group, Santiago Munne, also researches the quality of embryos and embryos with chromosomal abnormalities. Regardless of the number of embryos, what’s most important in terms of how many embryos are chromosomally normal is age. With egg donors, 61% of embryos are chromosomally normal in women younger than 35, 48 % in women around 35, and only 11 % in women older than 42. It’s possible to notice that from the study by Anna Cabo, we see that the older we get, the fewer eggs we can collect, and fewer of those eggs are mature enough to freeze. It’s not just about how many eggs we collect during the process, but also about whether those eggs are mature and usable for freezing.
The data about the clinical pregnancy rate and the survival rate of the eggs after warming them shows that the survival rate depends on age. For patients younger than 29, the survival rate is around 95 %, but for patients older than 40, it’s around 85 %. The clinical pregnancy rates also decline with age. Thanks to vitrification, the survival rates of eggs after thawing are generally around 95 %. The same study also looks at clinical live birth rates depending on the number of eggs collected when we are younger than 35 or older than 35. The likelihood of having a live birth is dependent directly on the number of eggs collected and the patient’s age, so the cut-off at 35 is very clear.
Another graphic shows the likelihood of having 1 child, 2 children, or 3 children depending on the number of eggs collected. The more eggs we freeze at a younger age, the better our chances of having children. This part of the presentation concludes that the survival rate of oocytes after vitrification is greater than:
How is fertility preservation performed? Going back to the history of fertility preservation, the first birth from a vitrified egg was in Australia in 1986, and since 2012, the American Society for Reproductive Medicine has declared that egg freezing is no longer an experimental technique. It’s already considered an established technique with many indications, and it’s a solution to the ethical or moral concerns associated with embryo freezing and the potential for unused embryos.
In the past, the slow freezing technique was used, as vitrification technology was not there yet. With slow freezing, crystals would form inside the oocytes, damaging their quality. That’s why the results of egg freezing were not as good as they are nowadays. Now, with vitrification, a superfast freezing technique that decreases the temperature of the eggs within 1 second is used, and it reduces damage to the intracellular structures. The survival and pregnancy rates are much higher with vitrification than with slow freezing. Comparing the data between the survival rate and fertilization rate when using vitrification or slow freezing, it’s clear that vitrification is the preferred method.
What are the steps involved in fertility preservation? The first step is to do some diagnostics tests to assess your ovarian reserve. This includes your age, AMH (a hormone produced by the small granulosa cells surrounding the eggs), and a transvaginal scan to check your antral follicle count. AMH is a blood test that gives us an idea of how many eggs are in the ovaries. The antral follicle count complements this information to determine your ovarian reserve. With your age, AMH, antral follicle count, and BMI, we can calculate the medication dose needed for the best response to ovarian stimulation.
You’ll also need a full blood count and coagulation test since we want to ensure there are no coagulation problems during egg collection. European legislation requires virology tests for all patients undergoing fertility treatment. While the karyotype (a map of chromosomes) is not mandatory, it is recommended because you’ll likely use the eggs in the future. The karyotype can reveal small chromosomal changes that might not affect you but could increase the chances of having a baby with chromosomal abnormalities. It’s important and useful information to have.
Then, you undergo ovarian stimulation. How does that work? Ovarian stimulation usually starts around day 5 of your period. You will have to start taking injections, which contain FSH, the same hormone that helps the follicles grow. During this time, you’ll need to come in for blood tests and scans to monitor how your ovaries are responding. Typically, you start injections, and after 5 days, you come for a scan and blood test. Two days later, you come back, and then again 2 days later. Usually, around 10 to 12 days after starting the injections, most of the follicles have grown, and the final maturation of the eggs is followed by egg collection.
Egg collection is a small procedure, usually done under conscious sedation. With a transvaginal ultrasound, the doctors collect the eggs from the ovaries. The embryologist in the lab then assesses the eggs to check which are mature and can be frozen, while the immature ones are discarded. The final step is potentially coming back in the future to use the frozen eggs for IVF or ICSI and have a baby.
How many eggs should you freeze? Keep in mind that it’s not a 100% guarantee that you’re going to be able to have children with all those eggs. The objective is to collect between 16 and 20 eggs before the age of 35. When an AMH level is more than 2.5 nanograms, with mild stimulation, around 15 to 20 eggs are expected to be collected. With an AMH level that’s not where it would be expected, around 8 to 10 eggs would be collected. That can vary according to a lot of other parameters; it’s very general.
To give you an idea, let’s say you’re going through stimulation and end up collecting 15 mature eggs. Of those 15 mature eggs, around 90% of them will survive. Let’s say you have 13 eggs, and of those 13, there are 10 that fertilize. Of those that fertilize, they arrive at the stage of being embryos. Let’s say 5 embryos will be created, and then when PGT-A (Preimplantation Genetic Testing for Aneuploidy), it’s possible that only 1 embryo will be normal. It’s kind of a natural selection process that’s happening in the lab. Unfortunately, humans as a species are very subfertile, and it takes a good number of eggs to end up having 1 baby.
What are the risks of the process? In the past, there was the risk of ovarian hyperstimulation syndrome, which is a complication after undergoing treatment with all the drugs that are used for ovarian stimulation. Nowadays, with the protocols that are used and with all the available drugs, ovarian hyperstimulation syndrome (OHSS) is a complication that practically doesn’t exist anymore in clinics that work properly.
The risk of egg collection, which has any surgery, has some risks. There’s a risk of bleeding, but it happens in less than 1% of cases, and most of the time, if there’s small bleeding, it stops spontaneously. There is no need to do anything. There is a small risk of infection; that’s the reason why usually prophylactic antibiotics are given when the egg collection is performed. There’s a small risk of damaging the bowel or the bladder with a needle, to the surrounding structures, but it’s extremely unlikely. It’s less than 0.7% to 0.5% in general, so extremely low. Then, the risks with the anaesthesia—if you’re generally healthy, you have had anaesthesia before, or you don’t have any medical problems—should not be a concern.
It is true that with age, the obstetric risks of pregnancy increase. You need to keep in mind that if your eggs are frozen, you will be able to use them in the future. When you get pregnant and perhaps you are 40, the risk is higher for complications during the pregnancy, and also perinatal complications like preeclampsia, high blood pressure during pregnancy, gestational diabetes, or preterm delivery are among those risks.
Does egg freezing increase the risk of breast cancer? A study was published in JAMA, which is one of the most highly regarded journals and is referenced worldwide. They did this study with 25,000 women and followed them for 21 years. They saw that those patients had the same risk of developing breast cancer as the general population. There’s no evidence to say that there is a higher risk of breast cancer when egg freezing is performed.
What are the most common side effects of the process?
For how long can you have your eggs frozen, and do they deteriorate with time? The duration for how long you can have your eggs frozen depends on each country, as legislation can be different. In Spain, you can keep your eggs frozen up to the age at which you can legally undergo fertility treatment, which is up to the age of 50 years old.
Regarding whether eggs deteriorate with time, there was a study done by Anna Cobo, in which they analyzed 42,000 egg donors. They saw that there was no difference in fertilization rate, clinical pregnancy rate, or ongoing pregnancy rate when using eggs frozen for less than 6 months or over 5 years of storage. There were no differences found. The longest period of storage resulting in a live birth was 14 years.
What can you do with your frozen eggs if you don’t want to use them? Legislation can differ in every country. In Spain, the possible uses of frozen eggs are: either keep them frozen in storage in case you want to use them in the future, donate them to another woman if you meet the same criteria as egg donors—you must be younger than 35 when you have done your egg freezing and also cannot have any infectious or genetic diseases—or donate them for scientific purposes. You can also opt to discard them if you don’t want to use them for any of the other uses explained before.
Related reading:
The AFC means antral follicle count, so when we’re doing a transvaginal scan, we can count how many follicles we have, as I’ve explained before the follicles are the ones that are containing the eggs, and when we’re doing that test, we usually try to do it once you just got your period, which is the best moment in which we can do the antral follicle count that gives us an idea about how many eggs more or less can we expect that is going to grow with one cycle of stimulation. It gives us complementary information on the AMH, which is the blood test that we will use for also assessing your ovarian reserve.
There is not a test to check for chromosomal issues of the oocytes. We can do that when we’re freezing embryos because at the end of the day, and that’s what’s important, so what we can do, is before deciding which embryos are worth being transferred, once we have fertilized the eggs with sperm, and we have them at the stage of the blastocyst, we can do a biopsy of those embryos. We can do the karyotype and see which of those are worth being transferred and are chromosomally normal, but currently, there’s no test to check directly which eggs are chromosomally normal. That would be great because that would be a way to have a clear idea of the realistic chances of those eggs being worth using in the future. Regardless of that, I just want to point out as well that even though the egg is mature and it’s chromosomally normal, that’s not a 100% guarantee that you’re going to get a blastocyst and you’re going to get a healthy pregnancy.
This is a very tricky question. If we’re looking at the best quality of the eggs obviously your eggs are going to be better at 25, than when you are 30 or 35. Usually, we don’t recommend to freeze your eggs when you are very young, we’re seeing that f.e. women that are 18 or 19, we’ve seen that a lot with egg donors that there is some kind of eggs that are not mature, the process of maturation is not exactly the best sometimes, not always but it happens. I would not consider egg freezing unless you’re doing that for oncology purposes or because you have a medical issue. Having said that, obviously, your eggs are going to be of better quality at 22 than at 30, but when you’re 22 you still have a lot of time to think about when you want to have children and what are your options. I think that probably what I would recommend is that from a very early age since you start going to the gynaecologist, usually it’s when you start having intercourse or when you are 18, and you start having Pap smears and regular checkups, I think that’s something that should be checked is the ovarian reserve. If we know what is the patient’s ovarian reserve, at least we can Warn patients and say, if you are not planning to have babies soon, most likely in the future you might struggle, so maybe in your case, we should be doing the fertility preservation. Obviously, all women who have already some infertility issues or some gynaecological problems like endometriosis, PCOS or other problems, I think that they should have a chat with their gynaecologist or with a fertility specialist even when they are young to assess all the options and how those pathologies can affect their fertility in the future.
I’d say that as I pointed out before our goal would be to get around 16-20 frozen eggs in Total, so obviously before you’re 35 ideally. In the terms, of how often can we do the cycles, probably I would do stimulation one cycle after the other unless you’re feeling unwell. Because we’re seeing that we’re having exactly the same results, we can even stimulate during the luteal phase and do something that is called DuoStim, we can do one cycle after the other without having to Lose more time which is something that for some patients is more convenient. I’d say that the number of cycles that leads us to have at least 15-20 frozen eggs.
First of all, even though for a lot of time we thought that male age was not that important when we were about to do fertility treatments, we have currently more data saying that sperm quality also declines with age. There is a more important decline after the age of 40, and there is a slightly higher risk of having chromosomal abnormalities on the embryos after 40. So this is something that we have to count for, even though you had 3 boys before and I assume they are healthy, so that’s reassuring as well. Regarding the egg donor and the number of blastocysts to expect, it will mainly depend on how many mature eggs will be guaranteed by the clinic that you’re using. Usually, there’s a minimum number of mature eggs guarantee, and it is around 8 eggs from the donor, so you should be expecting to have at least 2 blastocysts more or less. Sometimes, there might be donors that we don’t know why we end up having poorer results, but I’d say that a minimum of 2 blastocysts should be the normal thing.
