- Good clinical practice in the selective transfer of a single embryo
- PGT-A testing as a necessary component of IVF refund program
- Endometrium – a biosensor of embryo quality
- How to prepare endometrium? The golden standard
- What are the benefits of IVF refund program?
- Things to consider before going for an IVF refund program
Should I consider a IVF refund and guarantee programme abroad?
We all know there are no “guarantees” in medicine – every doctor can confirm that. That is why although the term ‘refund and guarantee programme’ sounds promising, the only guarantees we can discuss here are in fact the financial ones.
IVF Refund Program is a term used for IVF programs that guarantee patients a refund in case of no success. There are various reasons why refund programs are starting to become more and more popular. Some of the reasons include a detailed treatment plan, breakdown of costs and full or partial refund in case of IVF failure.
In this webinar Dr Diana Obidniak, Head of the International Cooperation Department at Scandinavia AVA-Peter fertility clinic in St. Petersburg, presents the topic of refund and guarantee programmes offered by clinics abroad.
At the beginning of her presentation, Dr Diana Obidniak gives her own definition of IVF refund programme. According to her, it should be understood as sharing responsibilities with a patient. She also gives some reasons why patients drop out of IVF treatment. The most important one is the physical and emotional burn-out. Unfortunately, it is common that couples cannot achieve pregnancy in the first attempt. Faced with the failure, they realise they are not ready to continue the treatment – although they still have very good chances of getting pregnant from the second or the third attempt. By giving up, they very often close the door to parenthood.
Common IVF refund programmes promise clinical pregnancy in three attempts
Dr Obidniak says that common IVF refund programmes promise clinical pregnancy in three attempts. It has been proved that when offered the possibility of several attempts, patients feel much more confident and calmer from the beginning. The doctors meanwhile know that even if the journey takes a little bit longer than expected, they will get the positive result in the end.
However, Dr Obidniak admits that there cannot be any guarantees when it comes to IVF programmes. IVF outcomes depend mainly on patient’s age. There is a negative correlation between the advancing age of a woman and the positive IVF result. Until 2012, it was thought that implantation was the process of delicate interaction between the embryo and the endometrium. Latterly, data began demonstrating that there were other factors in the process, such as e.g. cumulus cells, microenvironment and various growth factors that contribute to either a success or a failure of the implantation. When talking about failures, we must take into account the genetic status of the embryo, the competence of the endometrium and the presence of concomitant pathology.
Dr Obidniak highlights the significance of the genetic status of the embryo. Human beings have a rather high frequency of meiotic errors. Even if, according to morphology, the appearance of the embryo may be considered as excellent, about 40% of the embryos happen to be abnormal. Thus, the doctors should always assess the real status of the embryo. Today, good clinical practice involves preimplantation genetic testing and a selective transfer of one embryo.
Preimplantation genetic testing (PGT) is the diagnosis of genetic and chromosomal alterations in embryos before they are implanted – in order to ensure that children are born free of hereditary diseases. The use of preimplantation genetic testing for aneuploidy (PGT-A) is recommended when couples are at risk of transmitting chromosomal alterations or monogenic diseases, when they have a medical history of repeated miscarriages, in case of implantation failure after several attempts with IVF and also when there is a severe male factor involved.
Dr Obidniak says that another important point to pay attention to is the endometrium. It is crucial in the implantation process as it plays a role of microenvironment. It contains many growth factors that either contribute or hinder the implantation. Endometrium is a biosensor of embryo quality – it has both the capability to accept the embryo (receptivity) and select it (selectivity). In this way, it usually protects the uterus from an abnormal pregnancy leading to a miscarriage. Thus, it is very important to assess it in terms of functional and morphological alterations. According to Dr Obidniak, doctors today are in possession of the so-called ‘golden standards’ of endometrial competence assessment. These include a hysteroscopy (allowing to treat most of endometrial pathology at the same time) and the implantation window evaluation (in case of recurrent implantation failure).
Taking everything into account, Dr Obidniak believes that IVF refund is a great tool for patients – but under the condition they collaborate with a reliable IVF clinic. It should always include PGT testing of embryos – only then it gives a real chance of IVF success. However, if one’s own resources are exhausted, there is always an alternative solution. It is either an egg donation or surrogacy programme. In case one of these solutions has to be implemented, an IVF refund programme is a great insurance for the patient. It proves that an IVF clinic is reliable and will do its best to find the best candidate for you.
Summing up, Dr Obidniak mentions the undisputable pros of an IVF refund programme. It is a good way to estimate financial expenses beforehand as well as to assure full responsibility of a clinic in egg donation/surrogacy programme (‘shared risks’). Additionally, the risk of patient’s emotional burn-out is expected to be lower because of the guarantee they get. However, Dr Obidniak strongly advises to always pay attention to the clinic’s reputation and clearly assess both one’s own chances of success and emotional readiness. It is always an individual decision whether an IVF refund programme is really the right solution.
Questions and Answers from the event
How many IVF cycles are available in a guarantee program?
I can give you information about IVF guarantee programs in our clinic. We have guarantee programs for all the cases: IVF with own eggs, IVF with donor eggs and IVF with a surrogacy program. We guarantee to obtain not less than 4 embryos. Why 4? According to the actual data, we need precisely 4 embryos to have at least 1 euploid (genetically normal) embryo. We also include PGT of all the 4 embryos in this program. We have also included 3 attempts of embryo transfer. We insist on transferring just one embryo. But in very rare situations (3-5% of the whole practice), if a couple is confident that they want to have twins, we can make the transfer of two embryos – of course, after providing the information on all the risks of such a situation. 3 embryo transfers are usually more than enough. By the implementation of PGT-A and by paying great attention to the endometrium, we have very good results. In our clinic, in 3 attempts we have a success rate close to 91%. And we have about 7000 IVF cycles per year.
You’ve mentioned that microenvironmental and other factors play a role in the implementation and development of an embryo. Do you have any data or opinion on the increased possibility of having an autistic child with a surrogate mother who’s had one autistic child due to her uterine environment or/and having had a C-section – even though she’s not at all genetically linked to the child (who would be from donor eggs)? As far as I know, there is no test in NGS that will check all 23 pairs of chromosomes to judge this?
It’s a long question so I will provide answers to each part. Firstly: unfortunately up to now, genetic testing has not been able to exclude autism in children. Nowadays, it is believed to be more associated with a delivery process, the so-called microflora and the prevalence of some sort of bacteria. But there is no association with a genetic basis. Secondly, if a surrogate mother has already had an autistic child, it is not recommended to use her help. Similarly, we do not consider surrogate mothers who have undergone C-section. C-section is always associated with some risks during the delivery process. So if you consider a candidate who has already had a C-section or has autistic kids of her own, we would never recommend it. There won’t be of course any genetic association between a child and a surrogate mother, but if she already had some problems which led to autism in her own baby, then we cannot exclude that these risks have been already dealt with. We cannot be sure that your embryo will not be affected by the same risks. That’s why I would never accept this woman for a surrogacy program.
What is the age limit for the program?
The age limit is associated with the person we are going to do the embryo transfer to. In a more conventional program, when we do the transfer to a patient, then there is the age limit approved by WHO and it is 50 years old. From 51 years old, we can consider only a surrogacy program. This is the only age limit.
In which case can we decide the gender?
For sure, it is not the primary goal to select gender. But as we implement PGT-A of embryos, in a standardised medical report there is information about the gender of the embryos. In cases when a couple has a preference not to know the gender, I would have to exclude this information artificially. If we have both a healthy boy and a healthy girl, you together with your partner will be the only people to decide which embryo you want to transfer. But our main role is to provide the information that this embryo is healthy and is recommended for the embryo transfer.
Are foreign heterosexual IPs (intended parents) the legal parents on the baby’s birth certificate if we do the program? Is this a live birth with a donor guarantee program or is there a full refund?
According to Russian law, even if a couple has to implement surrogacy, the birth certificate will only include the intended parents. No matter which country you are from, you will appear on your baby’s birth certificate. Our lawyers will help you to prepare a package of documents if you want to undergo a delivery process in Russia. We have vast experience and a special department dealing with patients coming to us for delivery from other countries, as well as a lot of surrogate mothers – so it’s not going to be a problem. The guarantee program promises a clinical pregnancy in 3 attempts. In case there is no clinical pregnancy (for some reason), the decision is up to you: you can either take the refund of your financial expenses or you can continue to collaborate with the clinic and the doctor until a happy clinical pregnancy – without any additional expenses. We had one program with a very dramatic history when we got a pregnancy but it was a very severe genetic situation and a couple had a very high risk of a recurrent miscarriage. According to that program, the couple could choose: if they want to take a refund or continue our work. We are very grateful to them because they trusted us and continued to work with us. My team and my doctors helped them and now we have twins because we had two embryos transferred at the end. They had no additional expenses because they wanted to continue working with us although they had a difficult situation. They were determined not to receive a refund but to continue treatment till the happy end. So it’s up to you: if you want a refund or if you want to continue the treatment.
How many cycles are allowed until a live birth?
If you mean the guarantee program, then 3 embryo transfers are allowed.
Which country has the highest success rates?
I think it’s better to assess clinics and not countries. I believe that in each country there are very good clinics with great professionals and also – unfortunately – average clinics with rather low success rates. The clinics that implement the so-called IVF refund programs are always on the top because of great responsibility. It’s always a great challenge at first. To tell you the truth, we have implemented this program several years ago and it was not very widespread in Russia. It is still not widespread but we have collaborations in scientific terms with the United States. I remember that at the beginning, my team, my doctors and embryologists were a little bit scared of the public opinion. We understood that our practice was transparent, we had external and internal audits. Although we had a license from the European Society of Reproductive Medicine, even my specialists were frightened. I remember that everyone was scared while the first three cycles and they told me: How can we just guarantee live birth rate? But our clinic has more than 20 years of experience in the field of IVF and we have the reputation of the clinic that collaborates with the so-called ‘difficult’ patients. That’s why we are not afraid of treating tough cases. It’s a challenge for us but we know that we can. When it comes to success rates, I can provide information about us. When we talk about conventional IVF cycles with PGT, it’s 64-65% per embryo transfer. When we talk about egg donation programs, it’s always more than 72% for an embryo transfer. In terms of 3 attempts, we achieve close to 91% success rate. This data comes from the external audit made in 2018.
Are PGT-A and NGS the same thing? If not, what are the most comprehensive tests that can be done to provide the best outcome?
Yes, these are the same tests but with different names. PGT-A stands for preimplantation genetic testing for aneuploidies. NGS is the so-called next-generation sequencing, so it’s the name of the technology. Today NGS is the most modern type of PGT-A. Some years ago we had the so-called array CGH – close to NGS but NGS is considered to be more actual and objective. About 10 years ago, the FISH method of assessment was widespread. It wasn’t very popular among fertility specialists because it couldn’t provide the information about all the chromosomes and the whole embryo. That’s why we did not see much sense in recommending it to couples. Even after the diagnosis, which was called PGS (preimplantation genetic screening), we could not assure that the embryo is capable and we could not recommend it for a transfer. Thus, NGS is the recommended actual method of genetic testing.
Can you do anything if AMH is zero?
Usually, we do not see AMH just as zero. It’s generally zero point something, for example, 0.11 or 0.16. In this situation, we should take a few factors into account: your age and the number of antral follicles. AMH is a sign of your ovarian reserve. Sometimes if you are 37 or 38 or maybe younger but with low AMH after some surgery on your ovaries, we will have the result but we will have to implement the so-called banking of the embryos. These cases will require double stimulations. Now we have in our tools 19 schemes of ovarian simulations. So we will obtain eggs but the crucial thing is to obtain an euploid embryo. We will obtain eggs, we will fertilise them with different methods and we will do our best to obtain the embryos. But unfortunately, if a woman is of advanced age, there is a great risk that the embryo would be abnormal. And we cannot recommend transferring such an embryo. That’s why when we have low AMH in women of advanced age, we would often have to implement egg donation. But if only we have a chance, we always struggle to make fertilisation with your own eggs. To answer this equation precisely, I would need more information: your FSH levels or your ultrasound scans. Only AMH level is not enough for me to give you a real treatment plan.
Are there any qualification requirements/restrictions to the refund program (with donor eggs)?
With donor eggs – no. Maybe just the age limit. But I want you to understand that there are no restrictions if you are under 50 years old and you want to make an embryo transfer to your uterus. But for sure, our aim is to prepare your endometrium. Usually, we ask you to provide some primary information, including some data of hormone levels (TSH, prolactin), we will also need to have the information about your uterus. It is not the basis for rejection or restrictions but our aim is to prepare it for the treatment. In most cases, you can make those preparation stages in your country and our team will just lead you from a distance. Sometimes, if it is convenient for you, you can come for 1-2 days to make close consultations. We consider your uterus as an apartment for your baby. We need to make sure that egg donation embryos will be of great quality and we will find the euploid ones according to PGT-A. But we also need to be sure that we place embryos into good conditions to be implanted. That’s why we don’t have restrictions but our doctors can provide you with some recommendations on how to prepare for the embryo transfer.
Is there a low cost guarantee programme?
The cost will differ in case we can use your own eggs. Then the cost will be lower because we won’t have to make compensations for the donor. It will be about 10 000 €. Usually, the manager will provide you with information on certain details of the price. In case we have to implement egg donation, the cost will be higher. It will be €40,000.
Can you list all the countries where guarantee programs are available?
I know that the USA and Russia use such programs. I cannot tell you about European countries because I’m not sure if the programs are open there. Certainly there is no guarantee program in Germany, Denmark and Norway. Russia and the USA are two big players because in our countries preimplantation genetic testing is allowed and open and our specialists have the most intensive experience. From my point of view, if preimplantation genetic testing is not included in this program for some reason, it shouldn’t be assessed seriously. To tell you the truth, without PGT-A we cannot guarantee anything, we cannot say if the embryo is good or if there is a chance for it to be implanted. I think the USA and Russia are the two countries where these programs are available.
Are the surrogates allowed to live in their own home during pregnancy? How are they monitored/visited to check that they are doing the right things?
We have our own database of surrogate mothers and we have an affiliated agency. We have two possibilities. The basis is the location of a surrogate mother’s apartment. For us, it is very important that a surrogate mother lives near to the clinic. In case of an urgent situation, it cannot take more than 5 minutes to get qualified help. If we have set that their apartment is situated very close and the conditions there are good, we can allow her to live in that apartment. But in most cases, we have our own apartments where surrogate mothers live. Each surrogate mother has her own tutor. The tutor is not only the person who would check her but also would give her support. This tutor is in touch with a surrogate mother for 24 hours. It is usually a very young woman because according to our law, surrogate mothers cannot be more than 35 years old. We consider these women very prospective for normal physiological childbearing. But sometimes even a natural pregnancy requires urgent help. That’s why the tutor makes her the so-called checklist and visits her in her apartment – whether she lives alone or in our apartment. He brings her food and he is in control of all her medications. A surrogate mother can never have visits at a physician without the tutor. So we have no problems with controlling her because usually a surrogate mother is surrounded by the whole team, including the tutor, the nurse and a physician who is on the phone whenever he’s needed. If it’s needed, we make an urgent appointment with a doctor. So we have no problems with monitoring the surrogates.
14k Euros – is this the cost of the guarantee live birth program including an egg donor and a surrogate?
No, it’s just the cost including all the medical issues you can find in IVF. When it comes to the surrogacy costs and fees, it’s better to have the information from the surrogacy agency because I’m afraid I don’t have actual searching data concerning financial expenses on surrogacy. There are different packages. I just can provide all the financial expenses concerning medical issues. Surrogacy programs also require a compensation fee for a surrogate mother and lawyer’s assistance. We understand that the relationship between you and a surrogate mother should be under legal control from the very beginning till the happy end. So in order for this information to be reliable, it is better to have it provided by the surrogacy agency. You can leave your contact and the manager from the surrogacy agency will provide you with the proper information on the price.
In case IVF with donor eggs fails, how much money will I get refunded?
It depends on the case. In case we don’t have enough embryos, we will make another IVF with an egg donor without any financial expenses. You probably want to know what happens if there are three IVF attempts with no effect. To tell you the truth, this is a very rare situation because our egg donors are genetically tested and an egg donor program will for sure bring a result after three attempts. The implantation failure can be associated only with the condition of the uterus. Sometimes there can be very severe defects associated with chronic inflammation or previous surgery. Sometimes it takes one or two embryo transfers to find some rare reasons if there are so. But usually, in three attempts, we obtain the result. If after three attempts there is no pregnancy, you will decide if you want to have a refund or if you are ready to continue the treatment till you have the child – without any extra financial expenses.
Just to clarify: if the guaranteed live birth cycle and 3 embryo transfers don’t work with an egg donor and a surrogate, does your program include a second IVF cycle with other 3 transfers I will have to pay for again or does the first payment keep repeating in order to have a live birth? So i.e. unlimited IVF?
We guarantee at least four embryos. If after 3 failed IVF attempts we still have embryos that can be transferred, we will make an embryo transfer without any financial expenses. If we have to produce an IVF cycle once again, we will make a great discount – for example 70%. To tell you the truth, we have never had the basis to make another IVF cycle. But in the agreement, there is a point that we will produce another IVF cycle with a discount of 70% with keeping these 3 transfers. But it just never happened – especially if we talk about egg donation programs. If we have to make IVF with your own eggs, it can be different for sure because the number of embryos is usually limited – that’s why then it’s an applicable question. But in terms of an egg donation program, we will make an IVF cycle once again for sure.
In which country can I see the photos of an egg donor?
I can answer only about Russia. Generally, egg donation in Russia is anonymous. A donor can provide their infant pictures only if they want to do it. We have a large database of donors who are ready to present their adult pictures and they are even ready to make videos and have meetings with intended parents. We mention it to the patients but it is not very significant for many of them. In some cases, women don’t even want to see the donor. But if you are interested only in donors who are ready to present you their pictures, at the moment we can provide you about 130 profiles of donors who are ready to start treatment at your earliest convenience. The database is very dynamic. We do not make donor stimulations more than twice and that’s why we all the time have to work with new donors.
Do you have donors of African descent?
Unfortunately, in our donor database, we don’t have such donors. But we have our partners from the United States so we can make an arrangement and then profile by portfolios of these donors. We will invite the donor to Russia to make an ovarian stimulation. Unfortunately, at this moment we have only European and Asian phenotypes. In Russia, it is very difficult to find an African donor because we don’t talk only about their race but we have to assess all the medical basis as well. We have very strict criteria and I approve only about 20-25% of all the applications.
What would be the ideal egg donor’s age? What about the maximum age?
According to the law, we can consider egg donors who are under 35 years old. But we usually stop working with donors who are over 31-32 years old. In our clinic, we only accept donors who have their own healthy children. That’s why, for example, we don’t have donors who are at the age of 18 because we don’t know if they have a good quality of eggs. For us, the perfect age is about 23-29 years old. By this age, a woman has a mature fertility system and she usually already had a chance to realise herself as a mother. We have the information not only on her genetic status but also on the data concerning your children. That’s why for us it’s a perfect age.
Can I bring my own egg donor if she passes all the pre-screening tests but doesn’t have a child? I am very tall (1.79 m) and I’m an ex-model. I am very particular about who I would like. And I don’t want an anonymous egg donor.
Yes, for sure – if your donor undergoes all the screening tests, you can make an arrangement. You can make the screening tests in your country. We will just assess them and make a preliminary approval of the donor. Having a baby is an additional requirement and in most countries, it is not an obligatory point. For us, it is just a point to provide more guarantees that the quality of eggs is good. In other programs we will provide the same screening tests of a donor. It is very significant for us that the children of this woman are also healthy. But I understand your situation. In some cases, we can just close the eyes and assess the screening test – even if the donor doesn’t have her own babies.
Is there a risk of having a child with a genetic disease, such as e.g. a trisomy, in case of IVF with egg donation when the donor is young and in good health? What are the techniques your embryologists use to rule out any genetic mutation and to select the right embryos to be transferred?
Unfortunately, we can find abnormal embryos even in egg donation programs. Of course, it is an obligatory point for egg donation programs to implement only good, young and healthy donors. But we know that spermatozoa are just the same genital cells and they also bring DNA inside. That’s why the embryos will have the impact and all the competence of the spermatozoa as well. If it is recommended to make the pre-implantation genetic test (PGT-A) and it identifies some problems like trisomy, monosomy or other diseases, we will not transfer this embryo. In the medical report, you’ll have the information on the defects which are identified in the embryo and the conclusion of whether this embryo is recommended for transfer or not. I have to tell you that nowadays IVF is a great basis for the selection of the embryo. But it is the negative selection which means that we can only exclude the bad embryo. We can find one or two perfect embryos suitable for the embryo transfer that can be effective from the first attempt. So we will implement a good egg donor who was for sure genetically tested before and then we will make the pre-implantation genetic testing of your embryos. Sometimes couples have a dramatic history and emotional fears. We understand that so in pregnancy we can obtain even more information. If you want to obtain more information at the stage of nine weeks of pregnancy, you can make the so-called non-invasive pregnancy test which will provide more information on the fetus. But technically PGT-A will be enough.
Do you make nuclear and spindle transfer or cytoplasmic transfers?
Yes, we make them. But I want you to understand that worldwide, it is still an experimental method. That’s why we can make them in our clinic but only in terms of an experiment or a scientific trial. We can never make it in our routine practice. Sometimes, if it is the so-called ‘last hope’ for our patients, we discuss everything because we understand that this is the last chance. Unfortunately, the method is not approved sufficiently to make strong recommendations and to implement it into a conventional IVF cycle.
How often do the intended parents get reports from their dedicated coordinator? How many intended parents does one coordinator handle?
Each coordinator has not more than two couples. It is our standardised logistics that each visit to a doctor is followed by a medical report. As a surrogate mother and a physician are Russian, the primary documentation will be filled in Russian. That’s why we will provide you with the original report and the translation. The frequency depends on the stage of pregnancy. Usually, it will be every 2-3 weeks when we talk about the stage close to the delivery. After the 30th week of the pregnancy, the visits are once a week.
Is an egg donor available for women who can conceive with their own eggs?
I think that it’s a very personal case and if you don’t mind, I would discuss it with you personally. I know that the situation in life can be very different and if you provide me a little bit more information about your reasons, I will try to understand it. I will inform you if it’s applicable. Usually, we recommend egg donation programs on a medical basis. I think that it’s better to discuss the details to find out if it’s really necessary for you.
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