PGT-A – preimplantation genetic testing for aneuploidies

A genetically healthy human has 46 chromosomes in each cell. There are 22 pairs of the so-called autosomes, numbered 1 to 22, and one pair of the so-called gonosomes – in women these are two X gonosomes and in men these include one X gonosome and one Y gonosome. Therefore, standard genetic reading of karyotype is 46XX in women and 46XY in men.

If there is an additional chromosome or conversely, if one is missing, this is a case of a so-called aneuploidy. There are aneuploidies in which the embryo can develop until the actual delivery (Edwards syndrome – three chromosomes 18, or Patau syndrome – three chromosomes 13), however, the genetic damage is so severe that most such children die soon after birth. Then there are aneuploidies that individuals can live with for a long time. These include, for example, Down syndrome (instead of a pair of chromosomes 21, such individual has three chromosomes 21 in each cell, either 47XX +21 or 47XY + 21), Turner syndrome (these are women who have only one X chromosome instead of two X chromosomes – 45X0) or Klinefelter syndrome (one extra gonosome X in men – 47XXY).

In general, we can conclude that aneuploidies are very common in embryos. However, most such aneuploid embryos are unable to implant in the uterus or such pregnancies end in early abortion. Aneuploidies account for more than 50% of early miscarriages also after including spontaneous pregnancies. In this case, genetic testing most commonly discovers abnormal numbers of chromosomes 16, 22, X, Y, 21 and 15. In in vitro fertilization, the percentage of genetically abnormal embryos (i.e. those with aneuploidies) increases with the age of the woman. This most often concerns a disorder in the number of chromosomes 22, 16, 21, 14, 15, 19, X and Y. According to the statistics, more than 90% of all embryos with abnormal genetic makeup concern inheritance from the egg. Only a very low percentage of these disorders involve inheritance from the sperm. The older the woman, the higher the percentage of eggs that ovulate with an incorrect number of chromosomes. Around the age of 40, it is more than 90% of all eggs.

Only genetic testing can determine whether or not the embryo has the correct number of chromosomes. Even an embryo with a wrong number of chromosomes can undergo regular development and without genetic testing, the embryologist will be unable to distinguish it from genetically healthy embryos.

There are several groups of patients for whom embryo aneuploidy testing is intended:

1. Patients with recurrent miscarriages after excluding other possible causes of miscarriage. In these patients, the abnormal genotype of the embryo is thought to be the cause of the miscarriage. Testing of embryos and transferring of the genetically healthy embryo to the uterus thus significantly reduces the risk of further miscarriage.
2. Patients with recurrent embryo implant failure after embryo transfer. Most of these so-called implantation failures are indeed caused by the inadequate genetic makeup of the embryo. With each new unsuccessful embryo transfer, the stress and the disappointment due to failed treatment increases. It is this case in particular, where preimplantation diagnostics can prevent such unnecessary transfer of a genetically unhealthy embryo into the uterus.
3. Patients in higher age who are at a statistically high risk of embryo aneuploidy. The age limit for such testing varies according to different experts, Some clinics recommend across-the-board genetic testing of embryos in all women after the age of 38, while other centers consider the age of 40 to be the suitable threshold for testing. Even in this case, genetic diagnostics can prevent unnecessary embryo transfers, which could in no case result in the birth of a healthy child anyway.
4. Patients after induced abortion due to a genetic anomaly of the fetus who want to prevent the situation from recurring in the future.
5. Specific groups of patient couples who are at higher risk of embryonic genetic abnormalities compared to the general population (severe sperm analysis disorders, IVF cycles with surgical collection of sperm from the testis, patients after treatment of oncological diseases using chemotherapy or radiotherapy).