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Contemporary and effective alternatives after failed IVF with donor eggs

Uliana Dorofeyeva, MD
Director of International Cooperations, Medical Director, IVMED

Category:
Donor Eggs, Failed IVF Cycles

Effective alternatives after failed IVF attempts
From this video you will find out:
  • What are the age-related changes in oocyte mitochondria?
  • Why egg donation needs an alternative?
  • What is spindle transfer and pronuclear transfer?
  • What are the advantages?
  • How to prepare for an IVF treatment in Ukraine?
  • Why is it important to genetically screen the oocytes?
  • What is the advantage of polar body NGS testing?
  • When to stop egg donation treatments after failures?

 

 

What is spindle transfer and pronuclear transfer?

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.

Oocyte quality

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.

What is the main solution?

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.

Spindle Transfer

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.

  • It is the replacement of the entire cytoplasm of poor-quality eggs.
  • This procedure is based on transferring the Spindle of the egg from an affected woman into donor eggs with healthy cytoplasm, which had their Spindle removed.
  • The eggs resulting from the procedure with repaired cytoplasm can then be inseminated by conventional techniques (ICSI) with the sperm of the patient’s partner, giving the intended parents a chance of having a child genetically related to them.

Advantages of Spindle Transfer:

  • It will give families affected by serious mitochondrial diseases a chance of having healthy children free of a devastating limiting disease.
  • Maternal Spindle Transfer has been tested on human eggs and this method led to the development of blastocysts.
  • Less mechanical and morphological damage during manipulation

Pronuclear 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:

  • There is no risk of fertilization because of the transfer already between zygotes.
  • Better blastocyst outcome.
  • It will give families affected by serious mitochondrial diseases a chance of having healthy children free of devastating and limiting diseases.
  • Technique and mechanical micromanipulation, requesting experience and special cultivation method.

Results achieved

As shown in the results presented, among 38 patients:

  • The blastocyst rate after the Spindle Transfer is 67, 54%
  • The blastocyst rate after the nucleus transfer is 74, 66%

Embryo transfer and aneuploidy rate

  • Number of embryo transfers; 18 patients
  • Number of clinical pregnant patients 9
  • Number of live births: 4
  • Number of ongoing pregnancies: 5
  • Age average: 41, 58%
  • Aneuploidy rate: 58, 64%

Organization for the treatment

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.

Genetically certified oocyte technology

After receiving the cohort from the donor, all the oocytes are assessed for the strict morphological criteria, and they are divided into groups

  • Quality 1 oocytes: Ideal oocytes
  • Quality 2 oocytes: Oocytes with some morphological disorders (not used for vitrification of the bank)

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:

  • Number of polar body biopsied oocytes: 1978
  • Number of vitrified oocytes after biopsy: 1978 (%100)
  • Number of euploid oocytes (NGS TESTING): 1483 (%74,97)
  • Number of aneuploid oocytes 495 (%25, 03)
  • Number of survived oocytes after thawing: 1947 (%98,43)
  • Number of fertilized oocytes: 1921 (%98, 66)
  • Number of blastocysts (AA, BA, AB QUALITY): 1009 (%52,52)
  • Implantation rate: 58,82%

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:

  • 95.5% of couples conceived
  • 89.6% gave birth to a live infant
  • 81.3% achieved a live birth within the first 4 years
  • 85.1% within 8 treatment cycles

Conclusions

  • Different treatment options might be recommended in IVF to achieve the goal of parenthood.
  • A second opinion is recommended due to specific limits and availability in the countries.
  • The most effective treatment for patients in advanced age is oocyte donation.
  • Experimental treatments available in IVF are effective and might be accepted widely in the future.
  • The genetically certified oocyte is an advanced technology which is offered by Ovogene Egg Bank to increase the chance of euploid blastocyst outcome and pregnancy chance.
  • Genetically tested oocytes have significantly better euploid blastocyst and implementation outcomes.
  • Chromosomal abnormality risk dramatically decreases after the polar body NGS testing.

 

 

- Questions and Answers

Is it possible to ship biological material (donor oocytes) to Germany?

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.

Regarding spindle transfers. Is there an age limit for this treatment?

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.

For a patient over 45 who has irregular ovulation, would it be possible to use own eggs and spindle egg donation in the UK?

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.

If I want to try the spindle transfer, how many eggs will I need to provide?

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.

The spindle transfer is an option to consider after using own oocytes is exhausted? How will I be related to my baby? I am using a sperm donor, so it is important to be related to the baby.

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.

Is it easy to get to Ukraine for treatment these days?

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.

Can the eggs be collected over several cycles, and those can be vitrified, for example, like 2+1+2 to get 5?

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.

Do you have partner clinics in the UK that will treat a patient over 45 in combination with your clinic?

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.

I am ok with collecting oocytes over several cycles and coming to Ukraine. How much time do I need to reserve for this?

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.
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Authors
Uliana Dorofeyeva, MD

Uliana Dorofeyeva, MD

Dr Uliana Dorofeyeva is a Director of International Cooperation at IVMED, Ukraine, and a Medical Director at OVOGENE Egg Donor Bank. She is a multi-talented, engaging and results-oriented fertility specialist with significant experience in ART. She is trained in all aspects of andrology and reproductive endocrinology with exceptional knowledge in the areas of laboratory quality control, vitrification of oocytes, cryopreservation of gametes, embryos and unique ovarian tissue, micromanipulation of gametes including Intracytoplasmic Sperm Injection and Assisted Hatching. Worth mentioning that Dr Uliana is a member of ASRM and ESHRE (American and European Society of Reproductive Medicine).
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.