Embryo biopsy & genetic issues – patients stories

In this webinar, Dr Halyna Strelko, the Co-founder & Leading Reproduction Specialist at IVMED Fertility Center, Kyiv, Ukraine, talked about PGT-A, Non-invasive preimplantation genetic testing (niPGT), its benefits and outcomes. Dr Strelko provided a case of her past patient who had 3 previous failed attempts, and after changing the protocol and performing genetic testing, got finally pregnant.

Dr Strelko started her presentation by stating that around 10 years, it was thought that genetic testing on embryos will resolve all problems with repeated implantation failures, spontaneous abortions or unsuccessful IVF treatments, but this is not the case. In her presentation, Dr Strelko stated that sometimes standard genetic approaches may not be helpful and explained how they should be changed and modified and possibly that will become the gold standard in the next 5-10 years.

Genetic problems – real-life patient case

The patient presented by Dr Strelko was already in reproductive advanced age, the woman was 42 years old, and she was trying to conceive for 11 years, she had 1 spontaneous pregnancy 12 years before, and delivered a healthy baby, however, after that was unable to become pregnant.

• a 42-year-old woman with PCOS, trying to conceive for 11 years, 1 spontaneous pregnancy at 30, a healthy boy; 1 IVF – biochemical pregnancy

She had a quite high ovarian reserve, her AMH was 6.4 ng/ml, and she was diagnosed with PCOS with a normal BMI. Her husband had a normal sperm count, and they had gone through 1 IVF attempt in another clinic, they received a lot of eggs, 28 eggs and produced 8 blastocysts, but after PGT-A testing, only 1 blastocyst was euploid. After the transfer, the patient got pregnant, but it ended in a biochemical pregnancy. After that, she decided to change the clinic, and they came to IVMED.

After discussing and taking PCOS into account, we decided to do a standard antagonist GnRH protocol with a-GNRH triggering, which prevents ovarian hyperstimulation syndrome. On the other hand, we knew it was necessary to receive as many as 20-30 eggs because of the low blastocyst formation rate and low euploidy of blastocysts. The standard protocol was done with 225 FSH per day, and we received quite a big number of eggs, it was 50 eggs, no hyperstimulation syndrome, the fertilization was done with ICSI, we received 11 blastocysts out of these eggs, and after genetic testing, we got 4 euploid embryos.

Cryo embryo transfers

The first protocol was a standard replacement hormonal therapy (HRT), we gave her 6 mg of oestrogens and micronized progesterone 600 mg vaginally, unfortunately, the result was negative.

In the second cycle, a natural protocol was suggested with hCG triggering because sometimes a natural cycle can give a more natural level of hormones, better progesterone level, and better functioning of the corpus luteum. Therefore, we modified the protocol, did the hCG triggering, and from the day of ovulation, we started the support of the luteal phase with 400 milligrams of progesterone, the test, however, was also negative.

The third cycle was also a natural cycle done without hCG, the same amount of progesterone 400 milligrams, and again the result was negative.

New protocol

As there were no more good quality blastocysts, we decided to do a second stimulation. At this point, we decided to start a new protocol with follitropin delta because, with this medication, we could calculate the dosage individually and according to AMH level and BMI. In some cases, it gives a better result, a bit fewer eggs, but there was no risk of hyperstimulation syndrome, and we get better quality oocytes with a better blastulation rate. We decided to change the medication, hoping that it will give a better embryological outcome. We retrieved 34 oocytes that were fertilized with ICSI, and we received 5 blastocysts, 3 of them of type CC, which we normally don’t freeze because they never give pregnancy. Type CC means a low number of cells. We only had 2 more blastocysts of not so good quality. The NGS testing revealed that no blastocyst was euploid.

After that, we evaluated and discussed it again. We knew that the patient had a good ovarian reserve, so we could expect quite a good number of eggs, but she had a high level of aneuploidy, therefore, it was probably necessary to modify the embryological approach, and it was possible that biopsying the trophectoderm could be decreasing implantation potential of the embryo. Some scientific publications showed biopsy at the trophectoderm stage may be sometimes harmful. We concluded that it was better to transfer the embryos in a natural cycle, as we saw better endometrium receptivity and a wider implantation window.

In the 3rd protocol, the same dosage was used because, in the first one, a good number of eggs were retrieved. The trigger was with agonists, we received 49 oocytes and we decided to do Piezzoactivation after ICSI, which can improve the cleavage and blastulation rate because this increases the concentration of calcium inside of oocyte, and we know that calcium may improve cleavage and increase the chance of good fertilization. We received 9 blastocysts and decided to do Non-Invasive PGT-A (niPGT-A) to avoid the influence of trophectoderm biopsy. We received only 1 euploid blastocyst, we prepared the patient for transfer in a natural cycle, and finally, after all these attempts, we got a positive test result and a pregnancy, currently at 6 weeks.