In this session, Dr. Evangelos Papanikolaou, MD, Ph.D., Founder of Assisting Nature, Thessaloniki, Greece has been discussing RIF patients’ cases and talked about preimplantation genetic diagnosis and when it is indicated.
Firstly, according to Dr Papanikolaou, the aim of higher success in IVF is the standard goal for reproductive specialists. It is mentioned that although the establishment of pregnancy is perceived, there is a prevalent 50% percent of implantation failure or miscarriages. Therefore, the goal is not only limited to pregnancies but to live births.
Two scenarios of implantation failure are prevalent. On the one hand, real implantation failure implies no implantation with a negative HCG test. On the other hand, there is no visible formation of a gestational sac despite detectable HCG, which is called chemical pregnancy. Thus, it is common knowledge that recurrent implantation failure encompasses the transfer of three high-quality embryos at least or more than six blastocysts.
The first reason is said to be mother-related as age plays an essential factor in implantation since the higher the age of the patient, the higher the chances of abnormalities occurring because of genetic factors. Anatomical reasons, such as the uterine septum, are also said to be a second reason.
Some other factors include immunological reasons, infections, subclinical endometritis, and others that can also alter the endometrium receptivity. For instance, the ability of the uterus to allow implantation of the blastocyst can be improved either by performing endometrial scratching or infusion of growth factors into the cavity.
Factors arising from the male part involve DNA sperm fragmentation and a low number of sperm.
The correct term for this situation is termed as aneuploidy, which implies the abnormal number of chromosomes, which is normally 46. Aneuploidy is the most significant single factor affecting early pregnancy failure.
Aneuploidy can result in:
The reason for abnormal embryos in 80% of the cases is due to advanced maternal age. As regards sperm, only an evident 2% is present, while errors in embryo cell divisions after fertilization encompass 20%.
Looking at the graph shown, we can see that the higher the maternal age, the higher the percentage of aneuploidy. The higher the aneuploidy rate, the lower the pregnancy rate. Even if a good-quality blastocyst is transferred, the pregnancy rate decreases with age.
What are the most frequent aneuploidies?
Until 2000, only morphological criteria were available for the selection of embryo transfer, as a shortage of knowledge about the genetic background of the embryos was evident. In addition, 44% of good morphology embryos are said to be aneuploid after genetic testing, although this has changed due to preimplantation genetic diagnosis (PGT-A) arrival.
Only a very small part of the embryo is used, and it is called the trophectoderm, which later on will become the placenta. After the testing, the results will show whether the embryo is euploid, aneuploid, or a mosaic embryo (euploid and aneuploid cell lines). After many studies performed, nowadays, mosaic embryos can be transferred as well, as long as up to 40% of mosaic embryos are transferred which can result in a live birth. Trophectoderm (day 5) biopsy followed by vitrification of the embryos for later selection of embryos after PGT-A testing with NGS is a gold standard nowadays.
Who should have IVF-PGT-A?
It is of the utmost importance to know exactly in which lab PGT-A, which is a complex technique, is performed, as it is an invasive procedure. In case performance is well executed, precise genetic results and an improvement in IVF outcomes are expected.
Case 1 – a 36-year-old woman, with a partner who had normal sperm parameters, had gone through 5 frozen embryo transfers, they had 9 blastocysts, 2 were the negative result, 1 chemical pregnancy, and 1 spontaneous abortion
They came to the clinic (Assisting Nature), for their next cycle, and this time PGT-A testing has been suggested. They got 7 blastocysts, however, only 3 blastocysts were euploid. After the first single embryo transfer, the patient got positive results that ended in a live birth.
Case 2 – a 29-year-old woman, with a partner (33) had azoospermia, ICIS with TESE procedure was performed, and 5 embryos have become blastocysts, they had gone through 3 embryo transfers, which resulted in 2 negatives and 1 spontaneous abortion.
Once again, PGT-A testing has been suggested, only 3 blastocysts were obtained that were tested, 1 embryo was euploid, and 1 was a transferrable mosaic embryo. The first euploid embryo was transferred, and the patient got pregnant.
Case 3 – a 37-year-old woman with autoimmune syndrome and relatively normal AMH level, her partner had normal sperm parameters, they had gone through 2 previous IUIs, that were negative and 3 frozen embryo transfers that did not work as well
After coming to the clinic, they were advised to go for PGT-A, they got 5 blastocysts, from which 4 were aneuploid and 1 transferable mosaic embryo. After the transfer of this 1 transferable mosaic, she got pregnant (ongoing pregnancy at 7 weeks).
Recurrent implantation failure (RIF) is a complex problem with various etiologies and mechanisms. It’s crucial to reevaluate the couple, only after identifying the problem, it’s possible to proceed with the right protocol.
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