By fertility experts from Spain.
Assisted reproductive methods can be performed to help pregnancy. However, some fertility problems need extraordinary solutions. Embryo development problems are one such case.. Is there any other option available? What techniques, apart from egg donation, may ensure the possible positive outcome of the IVF treatment? During this webinar, Birol Aуdin, a leading clinical embryologist and head of embryology laboratory at IVMED , talked about an interesting alternative to egg donation: nuclear and spindle transfer for women with embryo development problems.
Birol Aуdin admits that poor egg quality is one of the main causes of repeated assisted reproduction treatments. The quality of the eggs is mainly determined by small organelles named mitochondria (the energy suppliers of the cells), together with other factors present in the cytoplasm of the eggs. Patients who are dealing with poor egg quality can experience multiple IVF failed attempts due to the impaired embryo development and have to be treated with conventional egg donation programmes to be able to have a child.
The causes of poor egg quality can be different. They include maternal age (the older the woman, the lower the quality), PCOS (polycystic ovary syndrome – recognised in 5%-10% of women nowadays), low ovarian reserve (connected with maternal age, PCOS and endometriosis), genetic factors and endometriosis. One of the reasons is also mitochondria in an egg cell break down affected by the lack of the energy for the egg.
Mitochondria degeneration will decrease a woman’s chances of getting pregnant. They start to get mutations in their DNA and that lack of energy doesn’t allow embryos to sustain fertilisation. If doctors are able to stop the mitochondrial degeneration from happening they will have a chance to repair nuclear function inside of the oocyte.
Birol Aуdin stresses that each couple have a social and genetic right to both have a child and carry up their genetic material during pregnancy. Egg donation seems to be an easy alternative to achieve pregnancy but it involves a lot of psychological and ethical aspects, too. Aspects which are not always considered by doctors but by patients themselves.
So what are the alternatives for egg donation? According to Birol Aуdin, there are two solutions: spindle transfer and nuclear transfer. During cell division, chromosomes in the cell can be shared equally because of the spine. Spindle has a very important role foe the cell division and for the genetic potential of the egg. However, it is quite difficult to determine the spindle in the egg cell. It is only possible by special software and the polarisation system on the microscope. Spindle view system is used in a still limited number of clinics nowadays as it requires experienced specialists and high financial investments.
Spindle transfer is described as the replacement of the entire cytoplasm of poor quality eggs. The procedure is based on transferring the egg spindle (containing the genetic material) from an affected woman into donor eggs with healthy cytoplasm. Prior to that, the donor’s eggs have their spindle removed. The eggs resulting from that procedure have their cytoplasm repaired and can be inseminated by conventional techniques (ICSI) with the sperm of the woman’s partner. The embryo develops in vitro and is then transferred to the womb of the woman who will carry the child. Spindle transfer has the unquestionable advantage: it gives the intended parents the chance to have a child that is genetically related to them.
However, Birol Aуdin says that genetic continuity is not the only advantage of spindle transfer. It may also give families affected by a serious and life-limiting mitochondrial disease the chance of having healthy children. The study suggests that in the US alone 770 babies could be saved from these diseases annually. Maternal spindle transfer tested on human eggs led to the development of blastocysts and has proved to cause less mechanical and morphological damage during the manipulation.
Pronuclear transfer (PNT) is about performing in vitro fertilisation using the eggs of the affected woman whose mitochondria DNA contains mutant mtDNA, and the sperm of the father. Thanks to the subsequent extraction of the pronucleus on day 1 of the development, most of the mutated mitochondria is left behind. These pronuclei are then transferred to an enucleated zygote with healthy mitochondria. The hybrid zygote is developed in vitro until it reaches the appropriate state for the transfer to the uterus.
According to Birol Aуdin, advantages of pronuclear transfer are not to be ignored. Firstly, there is no risk of fertilisation as the transfer takes place already between zygotes. The blastocyst outcome is better and the families affected by mitochondrial diseases get the chance to have healthy offspring.
Summing up: both spindle and nuclear transfer are innovative techniques that require extensive specialist experience on the part of the medical staff and special cultivation methods during manipulation. However, their advantages and new hope they give to many people struggling with infertility are not to be underestimated.
Actually as IVMED, we don’t have any live births yet. With our partner clinics, we will have the first live birth in December so I will try to share all the information with you. Of course, there are several reported live births in the world. There are five live births from spindle transfer and two live births from nuclear transfer already in the world. There haven’t been any fatal or morphological development problems in the babies till now. The first baby from spindle transfer is already 13 years old and there aren’t any development problems.
Of course, the age limit is quite crucial and important. It’s up to 40 years old. As you know, follicular development is decreasing as well as the number of follicles. Oocyte quality is also worse. So that’s why technology has more chances if a woman is less than 40 years old. However, if there are up to three dominant follicles in a patient that is about 40 years old, there is still a chance to get mature eggs and to proceed with the nuclear transfer and spindle transfer. If we talk about egg donors, then, of course, their age is important. Our egg donors should be 20-28 years old.
Of course, all of our patients who are going for spindle and nuclear transfers have their embryos tested using PGT-A or NGS technology. We have to be sure about the euploid blastocyst. Also, if it is possible, we make a genetic carrier testing for the donor, the mother and the father.
If you want to talk about the cost of the treatment, then please contact our clinic and you will get all the answers from the International Department.
Actually, nowadays there is no mechanical or technical risk during nuclear and spindle transfers. So there’s no need to worry about the technique or the damage to the cell. Of course, this is a kind of process that is still being developed more and more every day. There are different regulations in different countries and some of the countries do not allow to use such technologies yet. But as my clinical experience shows, now most of the people are fighting many mitochondrial diseases. And these techniques help to avoid the chance of mitochondrial diseases, so it’s a big feature.
Actually, many countries don’t have any special regulations for that and even totally ban it. Even in Ukraine and several other countries, there is no special regulation for nuclear transfer and spindle transfer but we are still able to offer these services.
As I said, the procedure is quite interesting and new. It is being discussed in many countries and according to the regulations in many of them, it is banned. We, IVMED, are an international clinic and we have many international patients. In this respect, we didn’t include it in the list of our services on our website.
Of course, if you are more than 40 years old and you have a good ovarian reserve, you still have a chance. But you have to consider the quality of endometrium and its receptivity, too. It is the main factor. When we get the euploid blastocyst after nuclear or spindle transfer, we need to have a really good condition of endometrium in order to have a chance of pregnancy.
IVMED clinic, as well as other clinics, have different strategies and different facilities. Of course, we are following all the regulations and laws but everyone is giving a different kind of services. We are not able to know what kind of techniques they’re using and what kind of services they are giving.
So that’s why there are differences between clinics in regard to the offer of services and other issues.
Of course, a donor egg program is always an alternative. If you’re not considering carrying your own genetic material only, it is still available to use a donor egg program. But you have to know that if you choose the donor program, you will carry just a father gene. It will not be possible to carry any of the mother’s genes.
The whole process will not give any complications during the patient’s preparation. It’s not different than classical IVF treatment. We have to prepare a donor and a patient at the same time for the egg pick-up with the hormonal stimulation. We are doing the same test for the donor and for the intended mother during the stimulation. So there is no kind of risk of complication during the preparation or during the manipulation.
Basically, you need to come only 2 times to Kiev. The first time, when we pick up the eggs and second time, when you need to get a transfer. But of course, this is your choice. If you trust your own doctor in your country, your IVF specialist can prepare you for the oocyte pickup and for the embryo transfer. In this case, you can just come for one or two days to make this process and then go back to your country. IVMED clinic will give you all these services. You need to spend 15 to 20 days for the stimulation, then the pickup and of course, approximately the period for the embryo transfer preparation.
Of course, you can transfer your own egg and embryos from other countries to Ukraine. Our International Department will help you with the process, the transport and carrying the material. There isn’t any risk in carrying the frozen embryos or frozen oocyte under the cryo dry shipper condition. There are many responsible and professional cryo transport companies which will help you. As I say, our International Department will give you maximal support for that.
Actually, it is quite crucial if we transfer one or two embryos. The last research shows that there is no reason to make a two-embryo transfer because we are using PGT-A techniques to choose euploid embryos. These embryos are giving much more chance to make implantation in the endometrium. Of course, there are a lot of different factors which we are not able to understand about the receptivity of the endometrium. That’s why one embryo transfer is always a smarter strategy to get the pregnancy. Especially if we are using spindle or nuclear transfer techniques where the higher number of embryos means the bigger chance of pregnancy. In this situation, it is better to have one embryo transfer and keep many embryos reserved for the next tries.
If we talk about the percentage of success for above forty-five-year-olds, I cannot say it’s very high. But for the egg donation program, or let’s say spindle and nuclear transfer program, if we get euploid embryos and we have really high endometrial standards, there is still a chance. At the moment the regular pregnancy rate in the world is 20%-30% for the women above forty years old. Of course with these techniques, we are increasing the chances much more. If endometrial receptivity is fine and if and the endometrium doesn’t have any kind of problematic situation, there is a big chance to assure a pregnancy.