In this webinar, Dr. Uliana Dorofeyeva, Director of International Cooperations at IVMED, Ukraine, and a Medical Director at OVOGENE Egg Donor Bank who has talked about some alternative procedures like Spindle or Pronuclear Transfer.
As stated by Dr Uliana Dorofeyeva, as time passes by, focusing on the natural resources of every woman to achieve pregnancy and parenthood is crucial and one important resource is the oocyte, which is based on the ovarian reserve, although it is said to have its limitations.
The specialist later explained that it is a fact that this natural resource is not fully exploited as only one follicle that is ovulating is used during menstrual cycles while the rest are destroyed if the oocyte is not produced at the beginning of the menstrual cycle. This process is known as atresia. Preservation of oocytes is recommended for fertility as age is such a crucial factor.
It is mentioned that the delivery of the first baby is increasing by 2 years every decade according to the average statistics from the world. The question remains: is the delivery of a first baby going to be at 51 in 2100?
For those patients, an oocyte donation is said to be a great decision as the opportunity to have a successful clinical pregnancy and initial treatment cycle will be high independent of patient age on the level over 50%.
Nevertheless, the success rate is said to be decreasing for the usage of oocytes after 35 years old because of decreasing quality and quantity.
Poor egg quality is known to be one of the causes of repeated assisted reproductive treatment and the quality of the oocytes is mainly determined by small organelles called mitochondria that are located in the cytoplasm of the oocyte, whose main role is supplying energy for the cells for biochemical processes.
Between the comparison of an aged and young oocyte, it is evident that the young oocyte has many mitochondria with a high function, whereas decreased mitochondrial DNA levels and morphological changes are perceived.
It is mentioned that age oocyte and mitochondrial dysfunction will result in lower IVF success rate, lower fertilization, and higher aneuploid rates
According to the statistical data presented in a table for the number of blastocysts checking for different categories and patient age. For the groups over 40 years old, the aneuploidy rate is 70% higher and the prospects also consider the number of low blastocysts as well As regards the egg donor groups, there is a 30% percentage of abnormal embryos.
Maternal advanced-age patients who are dealing with poor egg quality experience several IVF failed attempts due to impaired embryo development, and have to be treated with conventional egg donation programs to be able to have a child. Why does egg donation need an alternative?
Egg donation is mentioned to be an easy alternative to achieve pregnancy yet psychological and ethical considerations are still problematic. An alternative to this method is necessary because every individual has a right to have a child with their genetic material during pregnancy.
The spindle is a small organelle inside the cytoplasm of the oocyte, which is responsible for cell division, fertilization, and embryo development. To determine the spindle, special software and polarization system of the microscope are required.
The spindle view system is used in a limited number of clinics in the world due to high-cost investment and experienced specialist.
Advantages of Spindle Transfer:
The Pronuclear Transfer method consists of performing in vitro fertilization using the oocyte of the patient whose mitochondria contain mutant mtDNA and the sperm of the future father, and subsequent extraction of the pronucleus on day 1 of development after 24 hours of Fertilization. These pronuclei are transferred to an enucleated zygote with healthy mitochondria, since the developmental state must be the same. The hybrid zygote is then developed in vitro until it reaches an appropriate state for transfer to the uterus
Advantages of Pronuclear Transfer:
As shown in the results presented, among 38 patients:
Embryo transfer and aneuploidy rate
How is it usually organized in terms of planning? The first visit is avoided for an initial consultation and the screening. Also, the stimulation screening is arranged with the local clinics in the home countries of the patients. Patients are expected to go only for one visit for 7 days for fertilization and embryo transfer.
After receiving the cohort from the donor, all the oocytes are assessed for the strict morphological criteria, and they are divided into groups
Why is it important to genetically screen the oocytes? To check the genetic status of oocytes, a polar body biopsy is required. One unique feature of the female gamete is that polar bodies can provide beneficial information about the genetic background of the oocyte without potentially destroying it. Polar body biopsy has been applied in preimplantation genetic diagnosis (PGD) to detect chromosomal or genetic abnormalities that might be inherited by the offspring.
The exciting role of polar bodies is emerging with the development of new high throughput genome-wide single-cell sequencing techniques. Polar body testing mainly gives a big advantage to avoiding mitochondrial mutation risks while we are fertilizing euploid oocytes.
The advantage of polar body NGS testing from a patient perspective is the fact that oocyte donation programs mostly bring financial responsibilities for patients and each of the oocytes is considered as a potential embryo from a patient perspective. Euploid potential oocytes have a big chance of achieving good-quality euploid blastocysts. Most of the egg donation programs in different clinics do not require NGS or PGD testing before embryo transfer. Euploid oocytes potentially will give a good option to patients.
What is a genetically certified oocyte? They are genetically screened eggs that have been found to have normal chromosomal constitutions.
As shown in the collected data:
To increase the chances of the patients in the treatment of IVF, Oocyte NGS testing and PGT-A testing of embryos should be performed.
Live birth rates after unlimited free IVF can expect:
The regulations in Germany are limiting oocyte donation, so it is impossible to transfer those materials to Germany. You can consider coming to Austria, which is closer, or to some countries where oocyte donation is legal. If you are talking about, for example, NGS testing for your own oocytes and transfer your own embryos back to Germany, this can be done, but with donor materials, it is not possible.
I would not say an age limit but the limit of being able to provide the materials. After we access the patient, and we know the FSH, AMH, AFC level, we are checking the previous outcomes for the stimulation cycles. We are selecting an optimized stimulation protocol, and we expect to receive at least 2-3 zygotes from that patient – this is a good candidate to go ahead with the spindle transfer. The average age we are talking about will be 40 years old, but sometimes we may accept patients if they’re 42. Sometimes, patients who are 39 cannot be accepted for this option due to the ovarian reserve and the previous simulation failures.
Irregular cycles already mean that the patient is in her pre-menopausal period, so it’s better to check the AMH level and AFC, also if there were previous stimulation cycles, what was the outcome, and if the patient was responsive to the gonadotropins. For some patients, we can consider the option of several stimulation cycles and getting all the oocytes or fertilized zygotes together. With an AMH of 0.2, it is unlikely that we would consider that patient into the spindle transfer. For such patients, we are trying to offer also so-called combined oocyte donation. We go ahead with the stimulation of the patient, and then if we are receiving biological material from the patient like 1 or 2 oocytes, we are also fertilizing them with the male partner sperm and cultivate them, own oocytes and donor oocytes. If we are getting embryos, we decide which embryos, we are going to transfer. With 0.2 and being 43 years old considering the spindle, the transfer is unlikely, but we can consider receiving more medical tests and the results, so then it can be possible.
We are expecting at least 2-3 zygotes to start working and scheduling the spindle transfer. 2-3 zygotes if we are expecting a fertilization rate of 80%, we should have 3 4, or even better 5 oocytes collected and for them to be mature.
In spindle transfer, we call a baby being a three-parent baby. There is no opportunity right now to provide a specific percentage of how much you will be related to the baby. The spindle transfer is involved in the cell division, it also consists of your genetic materials, so that baby will be related to you, but also the donor. The donor is providing the genetic material and to the sperm donor as well. That’s why we call those babies three parents baby.
Yes, it is quite easy, and as I said, patients are arriving in Ukraine for their treatments. What we are recommending is to consider international insurance that will cover COVID-19 as well, but we had some time where the borders were closed for foreigners, but now it’s ended. There is no limit for anybody to come into Ukraine.
There is a recommendation of being tested, and probably this is the recommendation from your home country, but there is no need to be quarantined if you have any symptoms, etc., or and there are no requirements for providing any medical confirmation letters or something like this. If the borders will be closed again because it’s been mentioned that maybe this will happen soon for the Christmas period. When the borders were closed before, it was resolved by providing a certificate or the official letter from the clinic that your reason for visiting Ukraine is medical treatment, and this was an exception. For medical treatment, anyone was able to visit Ukraine, even when the borders were closed.
Yes, this is something that is offered for some patients, but we need to understand also the time frames. We are explaining to the patient that one stimulation cycle is one month and then for the second cycle, usually we recommend resting, or we are checking the antral follicle count, and then we are stimulating only after one month break. To perform 3 treatment cycles, we need to have 3 visits to Ukraine, we need to have about 6 months, but yes, it is possible.
In the UK, clinics are having an age limit, they will not accept a patient for IVF treatment if they’re overage. If a patient is coming to the clinic to receive ultrasound diagnostics or hormonal levels measurements, this is possible, and this can be performed. The responsibility for the treatment cycles is totally on us, on the Ukrainian clinic.
We need to coordinate your menstrual periods initially, we need to have all your blood work and the screenings which we are requesting in Ukraine to be done and sent to us. We will check all of those. If everything is fine, also we need to have a GP clarification and confirmation that there are no risks for carrying the pregnancy or the contraindications for IVF. If this is all available, we will be able to assist in preparing the stimulation protocol. The protocol will be given to the patient, and if the patient has a treating physician who is ready to assist, we will be in touch with our doctor, our coordinator, and the doctor of the patient, and the patient herself. Four of us are coordinating the whole process, and we need to see how long we can coordinate this.
What can be performed in the facility in the home country, we decide when patients should come to Ukraine, for example, we also had a practice when clinics performed even egg retrievals for the patients, they fertilized their oocytes, they created zygotes, and those were transferred to Ukraine for further pronuclear transfers. When we are talking about a pronuclear transfer, you need to remember the scheme. We need to work with the pronuclear stage embryos to take the pronuclear from one oocyte and to put it into the cytoplasm of the donor oocyte, so this was done with some clinics by sending zygotes to Ukraine.
