PGT-A

Introduction. PGT-A (also called Preimplantation Genetic Screening or PGS) is a PMA technique that allows embryos to be checked for abnormalities in chromosome number. Embryos with missing or extra chromosomes (aneuploid embryos) have less chance of becoming a child or, more rarely, may result in the birth of a foetus with a genetic condition. Embryos with the correct number of chromosomes are called euploids. PGT-A is therefore offered to some patients as a technique to help identify euploid embryos and avoid the transfer of aneuploid embryos.

 

Indications. The main indications for PGT-A are: advanced age of the partners; polyabortion; repeated implantation failures in previous cycles of Medically Assisted Procreation. Chromosomal abnormalities are the most common cause of In Vitro Fertilisation failure and their incidence increases significantly with the age of women. PGT-A is a controversial test, which the Human Fertilisation and Embryology Authority (HFEA), the regulatory body for PMA in England, has classified as an ‘add-on’. This means that they do not yet believe there is sufficient evidence to justify its routine use for most IVF patients.

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​​ How it is performed. When the embryo is at the blastocyst stage (day +5 or +6 of embryonic development), a sample of 4-6 cells is obtained from the trophectoderm of the blastocyst. The biopsy is frozen for shipment and subsequent analysis in the genetics laboratory, while the embryos are vitrified. The cells are analysed for chromosomal abnormalities. Only chromosomally normal embryos are selected for transfer into the uterus.

 

Types of pre-implantation diagnosis. There are 3 types of PGT: PGT-A, PGT-M and PGT-SR:

 

• The PGT-A, as already mentioned, makes it possible to assess any alterations in the number of chromosomes. An embryo should in fact contain 46 chromosomes (euploid embryo). For various causes, such as chromosomal alterations in the oocyte and/or spermatozoon or due to errors during cell division, the presence of supernumerary chromosomes or the absence of one or more chromosomes can occur (we therefore speak of an aneuploid embryo). If we have one extra chromosome we speak of trisomy (e.g. Down's syndrome or trisomy of chromosome 21), if we have one less chromosome we speak of monosomy (e.g. Turner syndrome or monosomy of chromosome X). The risk of Trisomy 21 increases with a woman's age from about 1 in 900 cases at the age of 30 to about 1 in 25 cases at the age of 45.

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• PGT-M allows the analysis of a known gene whose alteration can produce a certain disease. From the analysis it will be possible to determine whether the embryo is affected (has the disease) or not (does not have the disease). It will also show whether the embryo is a carrier of the disease but is not affected. An unaffected carrier is one that can transmit the disease to its offspring, but does not personally have any effect of the disease.

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• PGT-SR makes it possible to identify the presence of alterations in the structure of chromosomes. These abnormalities are caused by various types of breaks in a chromosome that are repaired incorrectly, resulting in a change in their characteristic shape. Chromosomal abnormalities can result in the failure to achieve pregnancy, either spontaneously or following PMA treatment, but can also be the cause of miscarriages, particularly in the first trimester, foetal deaths or the birth of babies with chromosomal abnormalities.

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Conclusions. In addition to the advantages offered by these technologies, there are a number of challenges, both technical and ethical, that need to be addressed and resolved before PGT and DNA sequencing technologies definitively enter the clinical arena of embryo diagnosis. In any case, it will be the medical specialist who will assess the possible indication for PGT-A during the PMA pathway, detailing its advantages and limitations according to the specific situation.