IVF & FERTILITY TREATMENT FOR WOMEN OVER 40 - WHAT ARE YOUR CHANCES?

Egg freezing – indications, limits, outcomes and costs in the UK

Luciano Nardo, MD MRCOG
, Consultant Gynaecologist, Subspecialist in Reproductive Medicine & Surgery, UK

Category:
Egg Freezing

egg-freezing-costs-UK
From this video you will find out:
  • What is egg freezing recommended for?
  • What are the legal/medical/social indications and altruistic reasons?
  • What do reproductive-age women who do egg freezing think about the process as a means to preserve their fertility?
  • Limits and risks of oocyte cryopreservation
  • What are the clinical pregnancy rates per warmed oocyte compared to fresh oocytes?
  • What is the cost in the UK?

 

Egg freezing – indications, limits, outcomes and costs in the UK

Is egg freezing for me?

When should you freeze your eggs? What is the cost? Watch the recording of the live webinar with Prof. Luciano Nardo, MD MRCOG, Consultant Gynaecologist & Specialist in Reproductive Medicine, to find out more about egg freezing. In the last 25 years, scientists and clinicians have worked together to optimize methods and clinical protocols for egg freezing. The first human birth from cryopreserved oocytes was reported in 1986. Various studies have looked at the outcomes of fresh versus frozen oocytes, with comparable results. ASRM (American Society for Reproductive Medicine) found ‘elective egg freezing to be ethically permissible, as enhancing reproductive autonomy and promoting social equality’. However, it should not be used as a form of reproductive insurance. The reason it cannot be considered as a form of reproductive insurance is that there is no guarantee, irrespective of the total number of cryopreserved eggs, that those eggs will fertilize successfully and more importantly will lead to a successful pregnancy outcome. The benefits of egg freezing include the storage of tissue to treat possible future health issues, individuals freezing eggs are healthy individuals at the time of the intervention, it is an established procedure. To some extent, it helps to avoid or reduce the need for egg donation at a later stage. There are various indications for undergoing egg freezing, medical indications, for example, in cancer patients, the use of egg freezing for egg donation purposes and social reasons. One of the most common reasons for egg freezing is delaying pregnancy. Women choose to delay pregnancy for various reasons, including demographic forces, workplace factors, lack of a partner, and raising costs of childbearing. One of the papers published in the American Journal of Fertility and Sterility showed that the reasons for deciding egg cryopreservation in 88% of cases were down to the lack of a partner, which means a lack of a stable relationship. It is established that oocyte freezing technology may bridge the gap between reproductive prime and when a woman is ready to have children. According to the paper, the likelihood of women using their cryopreserved eggs is only 6%, while 34% said it’s very likely that they will be using their cryopreserved eggs, and 60% commented that it is somewhat likely.

Egg freezing – limits & risks

Women that cryopreserve eggs after 35 are likely to have poor-quality eggs, and they should be very well-prepared and counselled about the limitations of egg freezing. Therefore, chronological age itself is not the only determining factor when it comes to fertility potential. Other things include:
  • woman’s ovarian reserve
  • Ovarian Hyperstimulation Syndrome (OHSS)
  • anxiety
  • the surgical procedure to harvest eggs
  • sedation/ anaesthesia
However, on a positive note, there is evidence coming from the publication that said that the use of egg freezing does not increase adverse pregnancy problems or maternal or fetal problems. It’s important to keep in mind that there is a close relationship between the age when the eggs are cryopreserved and the probability of live birth. Chronological age is very essential, and how ovarian reserve is assessed is an essential factor. There are two main tests to check your ovarian reserve. The first one is AMH (Anti-Müllerian hormone), which is done by blood, or by doing an ultrasound scan at the beginning of the cycle to look for the number of antral follicles. Both AMH and antral follicle count correlate very well and can give a prognosis. Women should consider having the ovarian reserve checked irrespective of chronological age by either having a blood test for AMH or an ultrasound scan for AFC before embarking on treatment. The treatment is going to provide the optimum environment for follicles to grow and for eggs to mature, to maximize the chances of the treatment being successful, which means collecting mature eggs that can be preserved in the later stages, survive and be suitable for in vitro fertilization and indeed minimize the risks as well as minimize the disappointment.

Egg-freezing – techniques

For a very long time, embryos, and eggs were frozen using a technique called slow freezing. The use of slow freezing had been shown to increase the damage to the cells, whereas the use of the more recent technique known as vitrification has been shown to maintain the structural integrity as well as the biological viability of the cells. One of the studies published by Prof. Nardo and his colleagues at the ESHRE compared the use of slow freezing with vitrification. The team wanted to see if there was any potential disadvantage of using frozen oocytes compared to fresh oocytes. They looked at eggs that had been vitrified, and they found that the fertilization rate per egg was very much the same. They also looked at the clinical pregnancy rate, and they separated the studies that used donor eggs and those that didn’t use donor eggs, and again there was no difference. If the eggs come from young healthy fertile women, vitrification is not affecting the quality of the eggs and indeed, the chance of clinical pregnancy. It was concluded at the time that there was not a statistically significant difference in terms of clinical pregnancy between fresh and frozen eggs. Another study published by Cochrane Review concluded that the intermediate outcomes, such as oocyte survival rate, fertilization rate and embryo quality appeared to be higher with vitrification compared to slow freezing. The percentage of high-quality embryos with vitrification compared to slow freezing is significantly higher. The number of oocytes that survive is higher with vitrification, it’s 91.8% compared to slow freezing, now at 61%. Looking also at the percentage of oocytes with abnormalities and comparing that to a control group, we can see that vitrification is very similar to the control group. Only 17% of oocytes have abnormalities with vitrification, compared to 39% of oocytes with slow freezing.

Oocytes vs embryo vitrification

One of the papers published shows that oocyte versus embryo vitrification for delayed embryo transfer has the same live birth rate. In a good lab with good technology and established techniques, freezing eggs will lead to the same live birth rate as freezing embryos. Another study looking at the cumulative ongoing pregnancy rate achieved with oocyte vitrification, and cleavage stage (day-2, day-3 embryo) transfer without embryo selection presented that there is no statistically significant difference. The only difference that becomes obvious is looking at the female chronological age. The implantation rate using cryopreserved oocytes is about 30% in women under the age of 34, but 18% in women over the age of 38, and it’s only 9% in women aged 41 and older. The clinical pregnancy rate is 35.9% in women under 34, and there’s less than half in women under 41. The miscarriage rate increases with maternal age. The clinical outcome, according to frozen oocytes with fresh oocytes, is very much the same. Looking at the study that assessed the performance of egg freezing in 7 different clinics across the United States that well identified as being egg banks shows that 6 out of the 7 egg banks used vitrification, and the majority of the egg banks would recommend the use of 6 oocytes to women and working on an egg donation cycle to achieve the best possible outcome. Finally, another controlled study looked at the laboratory and also the clinical outcomes of oocyte vitrification in two age groups, aged 30 to 36, and 37 to 39. The clinical pregnancy rate in the age group 30-36 is 63.6% compared to 27.3% in the advanced age group. The implantation rate is significantly higher in the younger age group as compared to the more advanced age group. The reason for this is that the number of good quality eggs declines with age, so over the age of 35, it is a declining fertility phase of life, which has a significant impact on egg quality. The survival rate is also higher if there is a younger chronological age.

Conclusions

  • oocyte freezing is a realistic approach to preserving fertility, it provides women who are not ready yet to start a family to postpone maternity
  • women undergoing egg freezing should be made fully aware by healthcare professionals, and fertility physicians of the likelihood of success as well as the costs and the risks
  • underlying ovarian performance is a very important determining factor.
  • age is the other significant factor, so 35 years is probably the cut-off point to provide the best chance of success of the egg-freezing program.
  • vitrification of eggs shows a significantly higher performance than slow freezing
  • vitrification causes less damage to the eggs
  • egg freezing is also an effective approach for egg donation cycles
  • fertilization, implantation and clinical pregnancy rates are very similar for fresh and cryopreserved by vitrification eggs
  • oocyte freezing is safe for obstetric and perinatal outcomes

Is egg freezing for me? - Questions and Answers

How many eggs do you recommend to freeze? Is one cycle of egg freezing enough?

There are no recommendations, there’s no evidence of how many eggs you should be freezing, however, the data published in the literature and in relation to the number of oocytes to be used to achieve a successful pregnancy of IVF suggests that perhaps between 12 and 15 eggs is the optimum number. Obviously, that refers to fresh eggs. If you take into account the vitrification and depending on age, probably between 80 – 90% of eggs will survive the freezing and thawing process. Then, in my opinion, a safe number of eggs to be cryopreserved will be probably around 20. If that number can be achieved through 1 cycle, that’s great, but sometimes, I would say in most cases to avoid the risk of OHSS perhaps that number of mature oocytes is achieved in a couple of cycles.

I’m 38 and due to trying to freeze the eggs this year. Realistically, am I wasting my time?

It is not a matter of wasting time or wasting money, it is a matter of you being informed. I would suggest that first of all, you assess your ovarian reserve by having an AMH and perhaps also an ultrasound scan for antral follicle count to see how in relation to your chronological age, how your biological age is, how your ovaries work. You need to be aware that because of your age, you may need to have if you’re embarking on egg freezing, perhaps more than one cycle and realistically more than the 20 eggs that I was referring to earlier on. Some of these eggs that may be mature at the time of freezing may not survive, may not fertilize. Some may not become healthy embryos, so it is not a matter of wasting time or wasting money, it’s a matter of knowing what the chances of success are and knowing that age per se is a limitation, but not a contraindication.

We need to use donor eggs and are torn between doing a fresh cycle and using an egg bank. Frozen eggs require ICSI, but fresh eggs can use normal IVF is that correct? Is using the IVF a more natural selection process for an embryo to develop?

That is correct. If you use frozen eggs, you need to have ICSI because the membrane of the egg is thick and will not allow the sperm to swim inside easily, so ICSI is required to fertilize frozen and thawed eggs. IVF seems to be a more natural form of fertilization because the best sperm will be swimming inside the egg. However, there is no evidence, and there is no study to demonstrate in a comparison between ICSI with frozen eggs and IVF with fresh eggs both coming from donor eggs that one is superior to the other one. I showed you the data from one of the best cryobanks in Europe, showing actually, that there’s no difference whatsoever in the pregnancy outcome using fresh or frozen eggs.

Is there an equivalent to egg washing process as with sperm washing when it comes to egg retrieval and freezing process?

I’m not entirely sure about what you mean by egg washing, we’re not washing the eggs. After egg collection, the eggs are put in a plastic dish and embryologists in the lab will be assessing the eggs a few hours after the collection, to help preserve only those eggs that are mature. So, eggs are put in culture media, and for a couple of hours after the collection, they are cryopreserved only if mature.

Some programs offer ‘Guarantee Embryos’ from buying vitrified oocytes which have been PGD-24 tested as well as underwent the comprehensive 600 panels of genetic carrier diseases. Would the success rate be the same as the statistics you mentioned in your presentation or better if they are transferred to a very good surrogate who already had her own healthy child?

I think so, yes. The statistics are the same provided that there are good quality embryos, and the embryos come from a healthy donor that have been genetically tested. Then the chance of success will be exactly the same. The surrogate obviously plays a role, and I think some investigations will have to be carried out on the surrogate. Especially, if things have changed since she has had a healthy child, but I would not suggest that because you’re intending to use frozen eggs, you will have a significantly lower chance of success.

What is your opinion regarding healthy and good PGD24 tested embryos to be transferred to a healthy surrogate? Should the surrogate still do an amniocentesis to make sure the baby is growing well without problems? What ‘might’ be potential problems later in the pregnancy with good PGD 24 embryos?

No, that’s not needed. If the embryos have been genetically tested, irrespective of coming from a donor or not, from fresh or frozen eggs, there is no need to do an invasive test that increases the risk of miscarriage, such as the amniocentesis.

You said the cut off age of freezing eggs is 35. Can you freeze eggs if you are a 41-year-old woman with good AMH?

It is possible, age is not a contraindication, it’s just a limitation. You can freeze your eggs if you’re over the age of 35. If you have a good AMH that is a bonus, but we know that a good AMH does not guarantee normal, healthy eggs. You need to be aware that chronologically, you will be determining the fate of the eggs by simply preserving eggs at the time in your life when you have already passed the best fertility potential. So, yes you can, it’s good that you got a good AMH level, but you will have a lower chance of success as I presented in my slides compared to somebody who’s younger than the age of 35.

I’m 43, could you please explain again the live birth rates with <35-year-old eggs?

The live birth rate and the pregnancy outcomes overall are twice as high in someone who is under 35 with somebody who is over 35. The chances in your age group, so over the age of 35 are probably 1 in 4 of what would be in someone at the age of 35. It is probably going to be around 10% compared to being around 30% in someone under the age of 35. It is still possible, but it’s not something I would recommend, so freezing eggs at your age but if you have a good ovarian reserve, and probably you will need several cycles of stimulation, egg collection and egg freezing to collect cryopreserve 20 to 25 oocytes.

How many eggs would you ideally like to freeze for an older woman?

I think the number of eggs to freeze for an older woman will be higher than freezing the number of eggs in younger women. Simply, because we know that not all eggs will survive, and not all eggs will fertilize, and not all eggs will form healthy normal embryos. So just, to give you an indication if you were to freeze 20 eggs for somebody’s under the age of 35 probably you’re looking at increasing twice the number of eggs in someone over the age of 35. The problem is whether actually, you’re going to get that number of eggs and whether that number of eggs is realistically based on how many cycles of stimulation and collection the woman will require.

How many embryos would you expect from 10 frozen eggs if someone froze their eggs at 33?

We’re talking about blastocyst, so day-5 or day-6 embryos, and I would probably expect at least 3 good quality blastocysts.

What are the risks of egg freezing when a woman has AIDS or other infectious diseases?

The risk of cross-contamination, those are the risks, but there are no other risks per se. This is the same as treating women that are viral positive in a heterosexual relationship or homosexual relationship and fertilizing the eggs fresh, so the risks are exactly the same. In the UK, the treatment can only be undertaken in some units with a specific viral positive lab, but again it’s not a contraindication to egg freezing.

Can you increase your chances of success with lifestyle, diet changes?

Absolutely, anything that will help your general well-being will increase your chance of success, but I want to be absolutely clear in this context that adapting to a healthy lifestyle, changing diet, nutrition, exercise, normal body mass index, non-smoking, no alcohol – they’re not going to be changing the biological clock. I’m afraid adapting the best possible lifestyle at the age of 32- 33 may improve things, but 10 years later it’s not going to rewind the biological clock, so the chances of success are going to be pretty much the same. Probably there’s going to be a slight benefit in pregnancy, but I would not be saying that healthy women who are over the age of 35 have a significantly better chance of success, as compared to women that maybe not as healthy.

Can you do egg freezing cycles straight after one or do you have to wait?

Yes, you can do it, and we do it in our clinic. We have had patients having 2 up to 3 egg freezing cycles back to back and, in fact, there is some evidence that suggests especially in women with the reduced ovaria reserve that ongoing stimulation may have a cumulative positive effect.

At the age of 43, not having the best AMH, is it irresponsible trying still to have my own child with IVF?

It is not irresponsible at all. It’s a choice, but you have to be prepared to accept a higher chance of negative outcome because compared to somebody who is younger. You can have your own child with IVF, we have had many women at your age with low AMH with normal AMH for their age, having a successful pregnancy outcome. I would not say it is irresponsible, it’s just knowing the limitations and having realistic expectations.

Are there side effects of egg freezing cycles back to back? Like hyperstimulation (OHSS)?

No, there’s no risk of hyperstimulation provided that the ovarian stimulation cycle is monitored carefully and the dose of medications is selected and tailored to the underlying factors such as age and ovarian reserve, so there is no risk of hyperstimulation.

Are there any limitations for egg freezing in cases of woman that suffer from mental disorders or for example, Turner syndrome?

There are no limitations. In mental disorders it is it’s just a matter in receiving adequate support and implications counselling, so making sure that there is a good understanding of the process and more importantly that the patient has good support at home, and with regard to Turner syndrome is making sure that there is a satisfactory ovarian reserve and knowing that there might not be any eggs suitable for harvesting or there may not be eggs that are suitable for fertilization. It’s not a limitation itself, it’s just an underlying and genetic disorder that impacts significantly on the fertility and the productive potential of the woman.
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Authors
Luciano Nardo, MD MRCOG

Luciano Nardo, MD MRCOG

Prof. Luciano Nardo, MD MRCOG, is a Consultant Gynaecologist, Subspecialist in Reproductive Medicine & Surgery, UK. He trained in Italy, London and Manchester before being appointed as a consultant in gynaecology and reproductive medicine at St Mary’s Hospital, Manchester, where he worked full time until 2011. His clinical and academic interests are in infertility, assisted conception, gynaecological endocrinology, pelvic pain, menstrual disorders and hysteroscopic management of uterine abnormalities. He has expertise in gynaecological ultrasound scan and management of early pregnancy problems including recurrent miscarriage. He has vast experience in advanced laparoscopic surgery for the treatment of endometriosis, adhesions, fibroids, ovarian cysts, tubal surgery and other benign gynaecological conditions regularly performing complex laparoscopic procedures such as hysterectomy, myomectomy and reversal of sterilisation as day case procedures. Luciano is a Member of the Royal College of Obstetricians and Gynaecologists and an associate member of many other learned societies. In July 2017 he was appointed as Visiting Professor to both Manchester Metropolitan University and Catania University, in recognition of his long term commitment to research and teaching alongside his clinical career. He has published in excess of 100 papers on many aspects of gynaecology, reproductive medicine and surgery and is regularly an invited speaker at national and international conferences.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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