In this webinar, Dr Daniel Bodri, MD, MSc, PhD, Gynaecologist & Fertility Specialist at IVF-Spain, Alicante, Spain, has discussed social freezing for women, the reasons behind the decision to freeze the eggs, how it is done and the success rates.
Egg freezing is not a very recent method. Already some three years after the first frozen embryo was produced, the pregnancy of a researcher has managed to freeze eggs in 1986 with still a less efficient slow freezing method.
However, egg freezing really took off when a much more efficient ultra-rapid method of freezing, vitrification, was discovered or put into everyday practice, practically from the early 2000s or mid-2000s onward. The HFEA in the UK allowed treatment with frozen eggs in 2000. Somewhat later, in 2013, also American society lifted the experimental label, and since then we have witnessed an exponential increase, especially in social freezing.
This graph shows the evolution of egg-freezing cycles, both for medical and for social indications, in the UK from the latest data. From the age of egg-freezing cycles, you can appreciate that the lower line shows a relatively less important increase for medical indications, like cancer and others. There is an exponential increase in social freezing, reaching almost one and a half thousand cycles in 2016. Since then, there have been even more cycles.
This increase was basically achieved in private clinics because, in the UK, there’s a dichotomy between NHS-funded and private clinics in terms of indications.
As you can see, the picture is similar in Spain. This is registry data from the Spanish Fertility Society, and you can see here that the number of cycles involving own eggs was also steadily increasing, reaching more than 6,000 cycles in 2018.
These egg collections involving own eggs constituted 15% of the cycles that were social freezing cycles or egg freezing cycles. Similarly, with oocyte donation, more cycles involved freezing all or part of the eggs. So, there was a sort of switch from fresh to frozen eggs in oocyte donation treatment in Spain. There are still clinics, like ART Next, which in the majority of cases use fresh donor eggs, but also frozen donor eggs are a possibility.
From this, we could conclude that, in Spain, where most of the egg donation cycles involve egg freezing, those clinics that have larger egg donation programs and donor egg banks have significant expertise in the vitrification method. This gives assurance to patients that when they freeze their own eggs, their outcomes will be very good.
I encourage everybody to read the articles of Zeynep Gurtin, an excellent social scientist who investigates many aspects of assisted reproduction and has done quite a lot of research on the motivation of egg freezers. These are very informative and interesting articles in The Guardian.
Based on this research and our experience, too, we could distinguish different profiles. There are the early or young egg freezers, who are often even in their 20s or usually in their early 30s. These are very well-informed, proactive planners, women who prefer to invest a couple of thousands of pounds in freezing their eggs while young, when they have a good amount of good quality eggs so that they can fully concentrate on their professional goals.
There’s also another group of late freezers in their late 30s or early 40s. These women are already very much aware of the decline in their fertility, and mostly they are single. They still don’t have the ideal partner with whom to start a family. By freezing their eggs, they’re buying a few extra years to find this ideal partner. As we know, there’s a lack of eligible men who could be ideal partners. If this endeavour is unsuccessful, they often choose the solo motherhood route.
We have also seen egg freezers in heterosexual relationships who do have a partner, but maybe the partner is not ready, doesn’t want to have children, isn’t committed enough, or is too young or too old. The partner may already have children from a previous relationship. Another group includes recently divorced or separated women who freeze their eggs for a potential future second relationship.
It’s a well-known fact that the quality of eggs and their chromosomal composition gradually decline with advancing female age. From the age of 35, this decline happens exponentially. This is the reason there are these unemployed eggs and also embryos that are created from these eggs, which explains why live birth rates are decreasing with advancing female age, and miscarriage rates are increasing, either in spontaneous conceptions or after IVF.
Indications:
We all know that there are classical social and medical indications. Social egg freezing has other synonyms too, for example, elective or planned fertility preservation. There’s also the concept of preventing age-related fertility loss, which emphasizes that it’s not just a social indication but could also be regarded as a medical indication. It falls within the scope of preventive medicine to freeze eggs at an earlier age when they are of better quality.
In the UK, there’s also this very interesting freeze and share scheme, which allows women who are considering altruistically donating their eggs—if they are below the age of 35—to donate these eggs in exchange for a discount on the cost of freezing their own eggs.
There are classical medical indications, for example, before oncological treatments like for breast cancer or haematological malignancies. In these cases, it is often urgent to proceed to ovarian stimulation and freeze eggs before chemotherapy or radiotherapy is initiated. Nowadays, some protocols allow practically immediate treatment after the diagnosis has been made.
But there are also benign gynaecological diseases, for example, severe endometriosis or benign ovarian tumours that could destroy the ovaries. In these cases, it is a medical indication to freeze eggs. In some cases, with severe autoimmune diseases, where the treatment could damage the ovaries, it is recommended to freeze eggs.
There are also some genetic conditions, like Turner syndrome or a history of premature ovarian failure, when it is recommended to freeze eggs before the ovaries are exhausted. A new indication that is emerging is for transgender patients—female-to-male transgender patients—who could freeze their eggs before gender reassignment therapy is initiated.
There are other situations when egg freezing could be done. For example, it’s clinical egg freezing for low-responder patients who have a low ovarian reserve and produce a few eggs, usually less than three. In this case, it is possible to do several stimulation cycles, accumulate the eggs, and only fertilize them when there is enough to perform fertilization, embryo culture, and submit the resulting embryos to pre-implantation genetic testing (PGT). For example, the cost of the IVF treatment itself—the laboratory part, including vitrification, embryo culture, and PGT—is only incurred once when a suitable number of eggs have already been obtained from previous cycles.
Then, there are also some unexpected scenarios during an IVF treatment when egg freezing might be practised. For example, when there’s no sperm available unexpectedly on the day of the egg collection. In this case, we have no other option but to freeze the eggs and thaw them later for fertilization when sperm becomes available. We have also seen the so-called partial egg freezing, where too many eggs are produced. To avoid creating too many embryos, with all its ethical implications, some eggs could be frozen.
If we look at guidelines from different countries, they are quite concordant in indicating an ideal age of below 35 or below 38 as the ideal age to freeze eggs. For example:
How many eggs do we need to have a good result with social egg freezing? We could use this counselling tool from Goldman and colleagues from the U.S. They managed to or rather tried to, establish this counselling tool by analyzing all their IVF cycles from their centre. We should emphasize that this is not real-life data from actual social egg freezers but more an extrapolation from pooled IVF data.
We can see that the number of potential eggs can range from 0 to 100, which is, of course, an impossible number. But if you look at, for example, 20 eggs, then we could see that in the case of patients (this is a quite detailed age breakdown), patients who are less than 35, the chances of pregnancy with 20 eggs are very good chances of live birth are 90%. Then it gradually declines; for example, for a 38-year-old patient, it’s only 70%, and above 40, we are in this lower range, where the chances of pregnancy are much lower, ranging from 50% to only 15%. This presents quite a sobering picture. We could see that the curves are much flatter for the ages of 40 and above.
Another publication from Spain, which is the largest available publication on social egg freezers involving some 7,000 cycles, provides actual real-life data and is very useful for counselling. We can see that in this publication, there are two age groups: less than 35 (the blue line) and above 35 (the green line). We can see that the chances of obtaining one live birth range from 16% if someone has five eggs to up to 94% if someone has 24 eggs frozen in young patients under 35. You can see that the blue line is steadily increasing compared to older patients above 35. If we have five eggs, then the chances of a live birth are only about 6%, and with 20 eggs, it increases up to 50%. So, it’s a lower chance, and then we see that the curve plateaus, representing the maximal cumulative live birth rate that we could expect for older patients.
There is often this target number of 15 to 20 mature eggs. The expected results, of course, largely depend on age. One should also consider that if someone wants more than one child, even more eggs might be needed. However, in any case, any amount of frozen eggs is better than having no eggs.
I would like to introduce you to the concept of the IVF funnel to show what happens, for example, for two different hypothetical patients: someone who is less than 35 years of age or an older patient. Let’s imagine that a younger patient managed to freeze 16 to 20 mature eggs. When these eggs are thawed, the average survival rate for a younger patient is around 90%, so maybe one out of 10 eggs might be lost during the thawing procedure, and we would end up with 14 to 18 thawed eggs.
These eggs are fertilized, and with a 70% fertilization rate on average, we could end up with 10 to 12 fertilized eggs on day one. Then, embryo culture is done until day 5 or 6 of development until we have obtained 4 to 6 blastocysts, as the blastocyst formation rate on average is 40% to 50% in younger patients. If we implant these embryos one by one, then with a 50% live birth rate (taking into account failed embryo transfers and miscarriages), we could expect two to three live births, which is an excellent outcome.
In comparison, an older patient might not be able to produce 16 to 20 eggs. So, let’s assume 8 to 10 eggs. If the thawing survival rate, which is slightly lower at around 80%, is considered, we could have 6 to 8 thawed eggs that have survived. After fertilization, we might obtain 4 to 6 fertilized eggs on day one, and then 1 to 2 blastocysts, given the lower blastocyst formation rate and live birth rate. In the best-case scenario, we could have one live birth if we’re lucky, or maybe no live births if we started with only 8 to 10 eggs.
This funnel shows that even if you start with a certain amount of eggs until you have blastocysts and live births, the numbers would decrease. There is no guarantee of a live birth with social egg freezing, and we should counsel patients about this fact.
Some data regarding our own experience in IVF Spain at the Alicante clinic. These are some demographic and cycle data from egg freezers over the last 2 years.
You can see that their mean age is relatively young, at 35.8 years. However, it might be more interesting to look at the age distribution. We can see that patients in their 20s constitute 15% of the total, while those in their early 30s make up 32%. These are the best age categories for social egg freezing. Still, we have 36% of egg freezers in their late 30s, which is still acceptable. However, we have 17% of patients in their early 40s, who likely have a diminished success rate with social egg freezing, as expected.
We can also see that more than 80% of the egg freezers are highly educated white-collar workers. Most of them are single, but some are in heterosexual or lesbian relationships. Only 5% of them have children. In our clinic in Alicante, which attracts many patients from abroad, up to 73% of our patients were cross-border reproductive care patients, meaning they came to freeze eggs from another country. Only 27% were Spanish.
The average number of egg-freezing cycles performed by patients was about 1.5. This is perhaps a bit low because we would recommend having on average, at least two or maybe even three cycles per patient to obtain, for example, the target number of 16 to 20 mature eggs.
Regarding the number of eggs obtained, the total number of eggs per cycle was, on average, 11.2, with the number of mature eggs being 9. This is the average amount of eggs frozen in one cycle. When you distinguish between total eggs and mature eggs, normally around 78% to 80% of the total eggs are mature, and only mature eggs are freezable. So, it is always the number of mature eggs that is the definitive result of an egg-freezing cycle. We see that if we freeze approximately 9 eggs per cycle, then we need at least two cycles to reach a suitable number.
If we look at the situation of egg freezing in Europe, we can see that there are countries like Spain or the UK where it is a well-established practice. You have seen the results from the registries. However, there are some other countries where social egg freezing is not allowed; this was the case until recently in France, Hungary, or Norway, where social egg freezing is currently not allowed because it is judged experimental.
There are also countries where access to any fertility treatment is not allowed for single women, who are the prime users of social egg freezing. In other countries where fertility treatment is usually done in public centres, some of these centres do not regard social egg freezing as a real indication of infertility. If no private clinics are offering this kind of treatment, patients have no other choice but to go abroad for this kind of treatment.
In some cases, this is simply not something that is routinely offered, or it is a too costly treatment. For example, in the UK, where it is quite expensive to freeze eggs, patients may also seek treatment abroad.
This is practically the scheme that we follow at our clinics in the IVF Spain group.
Apart from some blood work, which includes infectious screening tests, blood count, and clotting tests, the most important test is to evaluate the ovarian reserve. This is done with a hormone test for the AMH (Anti-Mullerian Hormone) level.
Additionally, we count the number of follicles on a baseline scan, usually conducted at the beginning of a menstrual period, to see how many potential eggs we could expect from a successful ovarian stimulation. These numbers are very helpful in predicting the possibility of an ovarian response, but it’s the stimulation itself that will give the definitive answer about the outcome.
Nowadays, we practically always use the short protocol with the GnRH antagonist, which is a convenient protocol lasting a little less than two weeks. To avoid any kind of ovarian hyperstimulation syndrome, we use the so-called short-acting triggering agent, which is a very safe and convenient option.
Egg collection is done under conscious sedation, making it a 15–20-minute procedure. The patient would sleep during the intervention and wouldn’t feel any pain or inconvenience. After a one-and-a-half-hour observation, the patient could return to her hotel and, after a 24-hour stay in Spain, she could already fly home.
Vitrification is done using the Japanese method, which is the most efficient method nowadays for freezing eggs or embryos. The survival rate is expected to be, on average, between 80% and 90%. In younger women, it could be as high as 90% to 100%, while in older women, as egg quality declines, sometimes the survival rate might be lower, and it is possible to lose one or two out of 10 eggs during the thawing step.
There are some common side effects like lower abdominal pain, discomfort, swelling, breast tenderness, and mood swings. These are temporary side effects, usually present towards the end of the stimulation and a couple of days after the egg collection, but they quickly disappear within a week after the collection.
Regarding more serious side effects, we can practically say that the risk of ovarian hyperstimulation is eliminated because of the type of protocols we use. There’s a small risk of abdominal bleeding; sometimes, a small vessel on the surface of the ovary could be damaged. If this happens, it is quite rare (less than one in a thousand cases) and is usually managed conservatively without any surgical intervention.
In terms of long-term side effects, ovarian stimulation has not been demonstrated to have any effect on future fertility or ovarian reserve. It could be repeated, and that’s why we recommend, after a short pause of one and a half to two months, restarting another stimulation cycle and doing two or three cycles until we have a suitable number of 15 to 20 mature eggs.
There’s still limited data on the safety of vitrification procedure itself, regarding the offspring limited published data but, we could be quite confident that it’s a safe procedure because there are many children born from egg donation using frozen vitrified eggs. So far, we haven’t had evidence of increased risk. These children should be followed up during several years to have a definitive answer on that.
Prices vary quite largely depending on the country. In our clinic, you can see that the price is a little bit more on the lower side. We include a five-year storage fee for those who freeze their eggs. This process is much more expensive in the UK, where it can be around seven to eight thousand pounds. The cost is important in the US; that’s why we often have patients who come over to Spain to do egg freezing.
What happens if the eggs are not used? This could happen especially to patients in their 20s or early 30s who have a high possibility of conceiving spontaneously. If eggs are not used, then they could be donated if they have been frozen before the age of 35 years. They could also be destined for research or training or simply discarded. It is much easier to discard eggs than embryos. So, freezing eggs does have this kind of advantage. Also, there are no parenthood issues because frozen eggs are only the property of the patient who freezes the eggs.
Eggs could also be transported to other centres. It’s quite straightforward between EU countries, but a little bit more complicated now because of Brexit with the UK, or for example, countries like Switzerland. It’s quite costly if it’s done overseas. In any case, these are specialized transport companies who do the transport and charge accordingly.
It has to be a well-established centre because eggs might be frozen for several years. The experience of the lab in vitrification is important. If the clinic has a donor egg bank, this is a good sign that the lab itself is proficient with vitrification. If the clinic is well-staffed and has non-stop operation logistically, it’s a positive thing in case of monitoring and scheduling the collection.
Embryo freezing is another option for fertility preservation for couples. One obvious difference is a sperm sample is needed to fertilize eggs. This could be partner sperm or donor sperm, and also, freezing embryos is at a much more advanced stage in the IVF funnel. It’s not the same to have, for example, 16 to 20 eggs compared to 4 or 6 blastocysts. Based on the patient’s age, the success of a future embryo transfer could be predicted better if you already know how many embryos were created from a certain number of eggs.
They don’t know until they submit these eggs to the thawing process, fertilization, and embryo culture how many embryos they will have. But there are also some disadvantages of embryo freezing because there are parenthood issues. Both partners have equal rights and could dispose differently of these embryos in case of, for example, divorce, separation, or even the death of one of the partners. Also, the cost is different if somebody freezes eggs or embryos because if embryo freezing is done, then practically the whole IVF process needs to be done.
There’s a difference. If you’re 36, you’re still presumed to have good egg quality. Some guidelines suggest freezing eggs before the age of 38 or before 35. However, in publications by Kobo and colleagues, it has been shown that at 36, the chances of pregnancy are quite good if a good amount of eggs is frozen. Ideally, up to 20 mature eggs give you probably a 75-80% chance of having a live birth. The more eggs, the better, but this has cost implications. It depends largely on ovarian reserve markers like AMH and the number of antral follicle counts on the scan. Some patients with a high ovarian reserve might be able to produce close to 20 eggs even from one stimulation cycle, but stimulation cycles could be repeated.
It depends on each clinic. In the Alicante clinic, we have a high proportion of patients coming from abroad. I would estimate it to be similar to the statistics from the Spanish Fertility Society, around 12 to 15%. It is increasing, and we expect to increase it to up to 20% of the cycles with own eggs.
Less than 35 is an ideal age, but even 36 to 39 is acceptable for freezing eggs. The only group that might need more counselling are patients above 40. We have requests from patients in their early 40s who still wish to freeze eggs. Our approach is that any amount of frozen eggs is better than no frozen eggs. The alternative for older patients is egg donation, which is always.
