During this webinar session, Dr Halyna Strelko
, the Co-founder & Leading Reproduction Specialist at IVMED Fertility Center, Kyiv, Ukraine, talked about advanced maternal age (AMA) patients & presented 2 IVF cases where all the steps were thoroughly discussed.
Advanced maternal age – real-life cases
The first case described by Dr Strelko presented a couple where a woman was of advanced age. In most cases of advanced maternal age, it is quite difficult to receive oocytes that will produce normal embryos. The patient had 1 previous attempt where 8 eggs in total were obtained, however, they only got 1 poor quality embryo which after PGT-A testing turned out to be abnormal.
- a 46-year-old with a partner with normal egg quality,1 failed IVF cycle, partner with normal quality sperm count
Due to the patient’s age and previous attempt, which revealed an abnormal embryo, the egg donation program was suggested, but the couple wanted to proceed with own eggs. Therefore, considering that the patient had a good ovarian reserve and they got 1 blastocyst even though it was of poor quality, we decided to try the stimulation.
The patient had normal hormonal levels, she had quite a good AMH level for her age, it was 1.1 ng/ml, infections, coagulation, karyotype as well as other tests were normal. Her husband had a normal sperm count and a normal DNA fragmentation rate. The patient was a bit overweight, her BMI was 31.3, but otherwise, all was fine.
We decided to do a natural cycle because of a low number of blastocysts, so we wanted to try with less stimulation, and we were hoping to receive better quality eggs. We also wanted to perform PGT-A, if we received at least 1 blastocyst and then the cryotransfer in a natural cycle.
We received 1 mature egg, it was fertilized, but after 72 hours of development, the embryo arrested. With 1 embryo, it may sometimes happen, even at a young reproductive age. Therefore, we decided to move to another strategy and try a new stimulation with the use of a high dosage of FSH and LH because we know that in late reproductive age, there is a lack of LH receptors, and the LH activity is necessary for the final egg maturation. We decided to add growth hormone and use special sperm selection methods. If we received good-quality embryos, we would perform genetic testing and cryotransfer in a natural cycle.
We started the stimulation, but we saw that only 1 follicle was growing, we obtained 1 mature egg that was fertilized, unfortunately, 72 hours later, the embryo arrested again. In such a situation, on the egg collection day, 3 follicles were seen in the right ovary and 3 in the left ovary, and we decided to do the second stimulation in the same cycle, it’s called double stimulation, which means that one day after the egg retrieval, we restart the second stimulation with the same medication. In the end, we got better quality.
The stimulation was performed with a high dose of gonadotrophin 3000 IU of urinary FSH, we obtained 8 follicles, and then we got 7 eggs, 6 were mature, 5 were fertilized, we got 6 embryos, and only 1 reached the morula stage, but this one arrested on the 6th day of stimulation as well.
All our interventions with changing the protocol, the medication, the fertilization method, and using the stimulation in the second phase of the cycle improved the response, but we still didn’t receive viable embryos. This is the main problem in the late reproductive age, where we can change a lot of things, but we cannot influence the crucial problem, which is producing a good quality embryo.
- a 46-year-old, 1 child, secondary infertility, no previous treatments, partner with normal sperm parameters
The patient was 46 years old, her main clinical diagnosis was advanced reproductive age, and she had a second marriage and 1 healthy baby from her first marriage. Her AMH level was not so bad (0.9 ng/ml) for her age. She was a bit overweight, she never had any fertility treatment before, and her husband had normal sperm parameters.
We suggested starting the egg donation process, the couple agreed, and we have chosen a donor from the database, we fertilized the eggs and receive good results, 5 excellent blastocysts, 4AB and 5AA, we also did a genetic test, and only 1 embryo was abnormal, other embryos were normal. We decided to do the cryotransfer, and prescribed replacement hormonal therapy protocol, a standard protocol of 8 milligrams of estradiol and 800 milligrams of progesterone. However, the endometrium was always 6-7 millimetres, and in the 2 consecutive attempts, HCG was negative. We decided to do the natural cycle protocol, and when we saw the ovulation, we waited for 120 hours, and we performed the transfer. During the natural cycle, there are different types of oestrogens circulating in the blood, and sometimes it improves the endometrium quality and thickness. It worked in this case as well, the endometrium was 8.5 millimetres, and we received a positive HCG result.
We know that follicles grow in groups, and in waves. In some patients, we can have 2 waves during the cycle, for example, 1 in the follicular phase and another 1 in the luteal phase. In some others, we can have 3 waves, and we should follow these waves as it permits us to receive a much better response when we choose the right wave.
The study presented they compared starting the ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor. It showed mostly the same results in the quality of eggs. We can use that and stimulate in the most convenient period of the cycle, and thanks to that, we can achieve a good response.
Embryo arrest – factors
Why do we have such a problem? Some studies showed all these mechanisms that can end in the arrest of the embryo. These factors and mechanisms are due to the male and female partner as well, because as we know, in late reproductive age, in most cases, the male partner also is of advanced age, these factors together give us the result that the embryo may arrest. There is also a genetic mechanism involved, which means that there is an abnormal number and quality of chromosomes in the nucleus. When we compare the embryos that arrested and developing embryos, we can see that in developing embryos, the probability of genetic abnormality is lower than in arrested embryos. In arrested embryos, we can detect a mostly complex abnormality, which means that not only one chromosome is wrong but different, so all these mechanisms do not work. If it is only one chromosome problem, sometimes it may correct itself, but if it is a complex abnormality, it means that oocytes and embryos cannot correct all these disorders.
The statistics on IVF outcome and age show that in all eggs after 42 years old, the probability of live birth in the first cycle is quite low, and at 43 and over, it is less than 2-3%. After 40 to 43 years old, the success rate is very low and only 0.2% of women theoretically have a more or less good chance to become pregnant and have a live birth after 42-43 years old with their eggs.
- the probability of achieving a viable and genetically normal blastocyst is very low in patients over 40 to 43 years old
- the best treatment option for advanced reproductive age is an egg donation, even in case of good ovarian reserve
- in some cases, the natural cycle protocol may be the best option for the endometrium preparation in cryotransfers