In this session, Dr Uliana Dorofeyeva, Director of International Cooperation sat IVMED, Kiev, Ukraine & Medical Director at OVOGENE Egg Donor Bank has been talking about age and its impact on IVF success as well as provided information on some new techniques like PRP that can increase your chances.
All women are born with a certain number of follicles. The maximum number of follicles in a woman’s ovaries is during the antenatal growth when she’s 7 months of development until puberty, there are around 400,000 follicles, and during the fertile period, which is between 11 and 45 years old, there are about 400-500 ovulated cycles, meaning only a tiny percent of the oocytes are used during a woman’s whole life, 99.9% of oocytes are lost. Nowadays, we have options to preserve oocytes or embryos, however, those alternatives were not possible several years ago, even 5-10 years ago. Therefore, we need to focus on opportunities given to those patients who are considering getting pregnant now, and because of their age and having fewer follicles, they need to look for some other options.
When a patient who is over 35 years old is coming to visit the clinic, her chances are already lower, and they are getting lower as her age progresses. Therefore, there is an alternative option available that has high success rates in the case of using oocyte donation or cryopreserved oocytes from before when she was younger.
The average baby delivery age in the world is increasing, the trend is that every decade a woman’s age delivering her first baby increases per two years, so by 2100, the first delivery would take place at 51. One in 25 UK births is to women over 40.
Another thing we need to remember is that the rate of genetic abnormalities also increases with age. Even in young patients, some percentage of the quality of the oocyte or embryos will be aneuploid, even in the case of egg donation. Up to 30% of oocytes donated by the egg donor will be aneuploid. The older a woman is, the higher percentage of aneuploidy will occur. This is also the reason for the unsuccessful treatment cycle.
Factors for the successful oocyte development
The first factor is age, AMH (Anti-Müllerian Hormone), which helps to predict your outcomes based on these, Antral Follicle Count (AFC), which changes from cycle to cycle. During one cycle, you can have 2 follicles that are seen on the ultrasound, and in another cycle, you can see 4 or 5, etc. Once you start your IVF treatment, proper medication and type of stimulation protocol are crucial. There are also some additions like supplements and vitamins or testosterone, growth factor, etc. as well as some experimental treatments.
Ovarian rejuvenation (PRP)
One of the unique techniques is the ovarian rejuvenation of the oocytes and endometrium by using platelet-rich plasma, which is injected into the ovaries and endometrium. It works well for patients with very low ovarian reserve but still have several follicles or even a few follicles, and a low AMH level. The platelet-rich plasma gives the possibility to awake those small antral follicles or pre-antral follicles to make them grow in the next cycle in order to perform the stimulation. This method is recommended for patients with primary ovarian insufficiency, advanced maternal age, premature ovarian failure (POF), and loss of ovarian functions due to surgeries or chemotherapy or ovarian dysfunctions. How it is performed?
First, the PRP plasma is prepared. Around 20 millilitres of your blood will be drawn, it will be centrifugated to separate the plasma and platelet from white and red cells. The procedure will take around 1–2 hours, and about 2 to 1 millilitre will be injected into the ovaries. The procedure will be scheduled immediately as soon as the material is ready, and the injection will be done the same. The doctor will use a tiny needle and under the ultrasound guidance, he will inject the PRP distributing the material across the ovary. This procedure is done under anaesthesia. It’s safe because this is the patient’s own blood, so there is no risk of infections or allergic reactions.
This procedure is still an experimental treatment, it is allowed in Ukraine, and it works for patients with a low ovarian reserve, but who are not ready for oocyte donation yet and would like to increase their chances to use their own eggs.
Genetic status of the embryo
Once the oocyte is retrieved, it is very important to check the genetic status of the material. It’s also possible to check the oocyte status by performing NGS testing of the oocyte, it’s possible to check it with Polar body diagnosis (PBD), which is a method for the indirect genetic analysis of oocytes. It is also recommended to do the embryo biopsy, as soon as the blastocyst is developed, the biopsy can be performed and it’s possible to check the genetic status of this embryo, and it is always best to transfer 1 euploid embryo to increase the chances of success.
It’s not only about a healthy embryo, another significant aspect is well-prepared endometrium, it should have a proper structure and proper thickness. You also need to remember about the endocrine status, the initial tests should include testing the thyroid function. Sometimes immunological status might need to be checked, as the potential for implantation by accessing the window of implantation and many tests based on the medical status and the previous outcomes.
In oocyte donation, it’s possible to use fresh or vitrified oocytes. In Ukraine, there is a wide variety of phenotypes, there are over 3000 available immediately. You will have a wide variety of donors according to your phenotype. All donors in Ukraine are with proven fertility and are genetically tested.
In some cases, when a woman produces 1–2 oocytes, there is a high chance of not being able to create embryos, and in order not to lose the possibility to have embryo transfer, there is another option available so-called combined oocyte donation. This is for patients with a low ovarian reserve who are not ready for conventional oocyte donation and for those who are most likely to have cancelled embryo transfers. This is almost 100% guarantee, there will be 2 dishes, in one dish, your oocytes will be put, and in the other dish, the donor’s oocytes. Both will be fertilized with the sperm of your male partner, and on the day of the embryo transfer, we will check the quality of the materials and the doctor altogether with a patient will decide which materials should be transferred.
Alternative for oocyte donation
In Ukraine, there are alternative possibilities for oocyte donation, so-called spindle transfer or nuclear transfer. It’s still an experimental treatment. Starting with mitochondria, which are like a battery of the cell, 90% of the cellular energy is produced by the mitochondria. It also has a genome, it’s about 37 genes. The young oocyte has a lot of mitochondria and their potential is high, but with the increased age of the patient, the levels of the mitochondrial’s DNA are morphologically changed and have increased deletions.
By getting mitochondrial dysfunction, we have lower IVF success rates, lower fertilization and higher aneuploidy rates. Transferring the mitochondria and the pronuclear, we can receive mitochondria from the young oocyte, and we can use nuclear mitochondria from the mother’s oocyte and the sperm from the father. This is a unique technique, it’s done only in a few centres in the world, it requires specific equipment and the knowledge of the embryologist, but this might be done.
Live birth rates in advanced maternal age
Data from the UK demonstrated that in over 150 000 cycles and over 257 treatment cycles in 9 treatment cycles performed in patients at 40–42 years old with own oocytes, the cumulative live birth rate got up to 30%. In IVF treatments with own eggs up to the age of 40 within 6 IVF cycles, the rate was over 60% up to 75%. In egg donation cycles within 5 treatment cycles, it was already over 80% up to 95%. Therefore, this is something you should ask yourself, how many cycles have you already had and how different they were? Getting a second opinion from another doctor or another centre from another country might be beneficial because the way they treat patients can be different.
Another publication showed no big increase after the 3rd attempt in cumulative pregnancy and live birth rates in women at 44–45 years. You can try for the 1st and then the 2nd time, but the cumulative live birth rate would not be higher than 7%. This might something you need to consider, and probably think about alternative options.
- Different treatment options may be recommended in IVF to achieve the goal of parenthood.
- A second opinion is recommended due to specific limits in the countries.
- The most effective treatment for patients in advanced age is oocyte donation.
- Experimental treatments in IVF are available, some of them are already effective and may be accepted widely in the future.
- The most effective treatment for patients in advanced age is oocyte donation.
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