Fresh or frozen oocytes?
What’s better – using frozen or fresh donor eggs? Is there any difference in success rates? Are different protocols used? Is the quality of frozen oocytes lower than the quality of fresh ones? What are the indications for a frozen embryo transfer? These are some of the questions that many fertility patients ask before their IVF treatment. Would you like to know the answers?
Watch the video recording of a webinar by EggDonationFriends and fertility experts from Assisting Nature to find out the answers to the above questions from experts in the fertility field:
- MD, Vagelis Papanikolaou – Assisting Nature Co-founder,
- MD, Robert Najdecki, – Assisting NatureCo-founder, Scientific Director,
- Evi Tymotheou – Senior Clinical Embryologist, Lab Director.
The world of medically assisted reproduction is constantly moving forwards which, at times, can leave patients feeling overwhelmed as to what is the best path forward for them. Advances in medical and scientific technology have greatly changed the way couples conceive, while new processes of freezing oocytes (eggs) and embryos have opened the door for a new generation of IVF.
In this webinar, Assisting Nature co-founders Dr. Papanikolaou MD Ph.D. and Dr. Robert Najdecki MD Ph.D., discuss the use of IVF with fresh and frozen donor eggs. Their Lab Director, Evi Timotheou MSc, explains the practices behind vitrification and looks at whether the use of frozen eggs and embryos can lead to a successful pregnancy. Assisting Nature is a clinic and college of reproduction based in Greece.
When entering the world of assisted conception, many options are presented – especially concerning oocytes. There is the question of donor gamete use and whether the use of frozen eggs might be more beneficial. How, then, can patients understand what the differences are and which choice might offer the best outcome for their situation?
As with all fertility treatments, it is hugely important to remember that not all cases are the same. Therefore, protocols and procedures are different for every patient. Medical experts now have the capacity to freeze eggs, sperm, and embryos.
Every oocyte is different – not all eggs will be fertilised
Every situation is unique and so is every oocyte. Not all eggs will be fertilised, and the route from oocyte to live birth is not always easy or, indeed, guaranteed.
Dr. Papanikolaou explains how historically, a fresh synchronised cycle was the go-to IVF technique; fresh embryos, created from fresh eggs and sperm would be transferred. However, with these fresh cycles, factors such as uterine cysts or bleeding can have a negative impact on implantation. He advises that the ability to freeze gametes offers a more personal approach to assisted reproduction – individually designed protocols can be developed for each patient, allowing for treatment of any conditions which might arise during an IVF cycle. This approach results in unparalleled flexibility, which can be especially useful when seeking treatment abroad.
While gamete and embryo freezing did take place in the past, Dr Timotheou explains, the slow procedure used back then had a low survival rate, leading to a poorer quality of thawed eggs and embryos, caused by the formation of ice on the embryos and oocytes. Ice crystals can be razor sharp and easily damage the cells. Additionally, water in the cells expands as it turns into ice, increasing the risk of a rupture. In order to successfully cryopreserve an oocyte or embryo, biological matter is – in simple terms – cooled to extreme temperature. How, then, is it possible to achieve cryopreservation without forming ice?
Evi Timotheou explains that the development of new vitrification processes has significantly improved previous freezing methods and higher survival rates have been noted as a result. Vitrification is described as the transformation of a substance into a glass-like state, meaning the eggs, embryos, and surrounding solution are directly solidified to a vitreous state. In order to achieve vitrification and ensure ice crystals do not form, cryoprotectants are used; these are substances used to protect biological tissue from damage caused by freezing. The job of the cryoprotectant is to draw the water out of the permeable cells, and then replace it with itself – thus enabling protection from ice damage. The reverse then happens during the thawing process.
Vitrification has led to a revolution in oocyte and embryo cryopreservation. The Assisting Nature clinic noted an increase in survival rates of frozen oocytes and blastocysts as a result of the technique’s adoption. According to their recorded data, out of 580 cycles performed between the years 2013-2016, there was a 91% survival rate of frozen to thawed eggs from donor vitrified oocytes. This then led to a 79% fertilisation rate for their clients, with an accompanying 41% pregnancy rate. In Dr. Najdecki’s view, there is now no better or worse programs; frozen egg and embryo treatments are as viable for patients as fresh ones. Now, it’s simply a matter of choosing the right treatment for each patient.
While ongoing developments in IVF treatments have opened many doors in the world of fertility treatments, the pace of new developments can be overwhelming for patients. For this reason, the co-founders at Assisting Nature are keen to stress that clinics should not treat all cases in the same way. Every situation is unique and individual protocols need to be created in order to generate the best possible outcome – for every patient under their care.
Questions and Answers from the event
Is it necessary to match the phenotype of the donor with egg donor recipient in Greece?
Yes, in Greece it is required by law to match the blood type and Rhesus, but what we’re trying to do is to match also the appearance: the hair & eye colour, height and weight.
The phenotype matching is not obligatory, but it is a corporate index of the procedure: the better the matching, the more satisfied you will feel with the result afterwards. Once everybody tells you that your child looks like you, it gives you more satisfaction to the couple.
Is there any interest to study the best optimal embryo implantation window via the so called ERA test in case of IVF donation?
This is a very interesting question researched by IVI genomics in Spain. But actually, if you do proper monitoring of the acceptor then it is extremely rare that there is a lack of implantation window, as the test implies. So what happens many times, some acceptors have developing follicles that do ovulate and the treating physician, because they’re not one of our team, misses this ovulation. This is the main reason for not appropriate implantation window and for pregnancy outcome of the acceptor. So it is really very rare that we ask for an ERA test in patients with many blood tests and failures after donor oocytes and until now we have not identified anyone that had positive ERA test meaning that the implantation window was not synchronized.
As far as I understand oocytes have to be thawed before fertilization. So how many oocytes survive thawing?
We have 96% survival rate.
Is it the same survival rate for using donor embryos? I would need a double donor. Is the success rate good? I am 43. I already have a daughter from my own eggs and donor sperm.
The embryo success rate is even higher than of donor oocytes. It’s about 98%. This is the survival rate of embryos. (repeated answer) The double donor success rate is even higher than the vitrified oocytes because they are embryos already and the survival rate is about 98%.
What is the cost of treatment at Assisting Nature in Greece?
The cost of oocyte donation is usually EUR 5,000 but we have a special offer for EggDonationFriends that is EUR 4,500 with up to 6 mature oocytes guaranteed. This is the number of oocytes guaranteed. If the patient asks for a bigger number of oocytes, we have another program for more than EUR 7,000 where we can guarantee 12 mature oocytes. As we have shown you, what really matters is the number of oocytes given. Some IVF centres squeeze down the cost by dividing the oocytes between more than two recipients. But this has a negative effect on the pregnancy outcome. We never share the donor between more than two recipients. Most of our patients have more than six oocytes, because we do not violate the stimulation of the donor to produce more than 15 eggs. As we stated in the beginning, the donor’s health is more important for us. So trying to keep moderate stimulation of the donor, most of them produce from 12 to 15 eggs. But if the patient is about 45 years old, doesn’t have much time left or has had multiple implantation failures, then we advise here to get the full package where you get more than 12 oocytes. The cost is of course higher, it’s more than EUR 7,000, but as you saw the delivery rate can be, in cumulative way of speaking, more than 70%.
Do you guarantee embryo/blastocyst quantity?
We cannot guarantee the blastocyst quantity but what we can guarantee is the number of oocytes. It is because the number of blastocysts depends also on the sperm quality of your husband or your partner. But, in general, with oocyte donation we have 50% blastulation rate on the number of fertilized eggs. So if we get 10 eggs, and you get 8 of them fertilized, so normally you’re going to have 4 blastocysts at the end of the procedure 50% of the fertilized eggs.
What about donors? Is there any waiting list? Have you got a database of donors who are “ready to go” and database of frozen oocytes?
Yes, of course. Our waiting list is very short. We can provide a new donor in two months’ time. We also have a cryobank with a large number of frozen oocytes. This means we have “ready to go” eggs and a list of donors whom it is possible to match within a period of two months.
We have many patients from abroad and their main concern is whether the Greek female phenotype can match the phenotype of European women. Many European patients think that Greek women are of the Mediterranean type like Italian women from Naples or Spanish women from Seville, Spain. Actually, if you come and visit Greece, you’ll find that more than 30% of the population is blonde, more than 17% of the population has blue eyes, especially in northern Greece, because of mixing with many European nations. Actually, this makes an excellent combination of genes, a mixture of Mediterranean, Central European and even Eastern European genotypes and phenotypes. So you shouldn’t have any concerns about the Greek phenotype.
If I decided to come from the UK, are you able to arrange flights, accommodation, etc.?
Yes, of course. We cooperate with tourist company called “First Class Greece”. You can check it on our website. They arrange flights, accommodation, absolutely everything.
Is it 40-45% success rate for each transfer?
If you have, for example, 4 blastocysts, you have 45% with first embryo transfer, and then you have 25% with surplus embryos. It means that, in a cumulative way, you end up with 70% delivery rate. But we mean oocytes from a specific donor.
Is it good idea to do chromosome/embryo testing like PGS for embryos from donor eggs?
That’s our specialty. We are in favour of PGS testing, but not to egg recipients, unless they have two failed attempts at other centres. Then we have to determine if it is the embryo or the uterus that does not allow implantation. Since in oocyte donation, the chance of having a good euploid embryo is very high and the cost is about EUR 2,000 for embryos to be tested, we do not advise PGS for oocyte donation program unless the patient has had multiple failures. In such a case then we have to find out if the reason lies in the embryo itself or the endometrium. Our own experience is that even with thin endometrium, we can have, for example, twin pregnancy in a patient 4.9 mm of endometrium. It may take a little bit more trials but in the end we can succeed. Nature created the uterus in such a way that it can overcome all the difficulties. It is the oocyte that really matters and very rarely endometrium.
What is the maximum sperm recipient and donor egg recipient age in Greece?
The law allows egg donation for recipients up to the age of 50.
Is the age of the recipient important?
Studies are showing that indeed the age of the recipient plays a role, as well as the age of the father. The biological father can also play a negative role. If we try to give it in terms, if you’re between 40-45, your success is approximately 50%, and in cumulative way as we showed you 70% if you have extra frozen embryos for second attempt. But if you are around 48-50, although initial pregnancy success rates are really high (50%), however, the miscarriage rate is increased. So in the end we end up with relatively lower delivery rate about 40-45%.
What if I use a donor sperm as well as donor eggs? Would you guarantee the blastocyst quantity then?
Definitely with donor sperm the blastulation rate would be much better. If someone gets 6 oocytes, then we can guarantee more or less 2 blastocysts. If you get more than 10 oocytes, then we can in quotes guarantee 4 blastocysts. But everything in quotes.
Do you get many patients from the UK?
We have many patients from many countries, from Belgium, Denmark, France, many from Italy. UK patients started to visit us last year. We haven’t done any publications in the UK media so far. We have been establishing our reputation slowly but steadily. We are definitely interested in the UK market but we want to do it step by step.
How many egg donation cycles do you perform each year?
We are running approximately 1,000 cycles per year. Almost half of them are IVF with egg donation. We don’t have patients only from abroad. Many Greek women get married after 35 so we can say that even 50% of female population is of higher reproductive age and need oocyte donation in the end. 50% of our cycles are performed with egg donation.
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