Preimplantation Genetic Testing (PGT) is a form of early prenatal genetic testing used to detect genetic and chromosomal abnormalities in embryos before implantation.

There are different types of PGT: Preimplantation Genetic Testing for Aneuploidy (PGT-A), Preimplantation Genetic Testing for Monogenic disorders (PGT-M), and Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR). PGT-A is the most widely utilised of the three.

We have 23 pairs of chromosomes. Chromosomes 1-22 are called autosomes (These are primarily associated with metabolic function), and chromosome number 23 is the sex chromosome (Which determines our sex, XX for female or XY for male). The principle of PGT-A is to detect the number of chromosomes present in the embryo, where (46, XX) “Female”, and (46, XY) “Male” are considered regular karyotypes (Note: karyotype is the number and makeup of our chromosomes in our cells). Chromosomal irregularities (or aneuploidies as they are more commonly called) are one of the major culprits for repeated miscarriages and age-related reduction in fertility potential, causing more than 70% of spontaneous miscarriages according to the Jaslok Hospital and Research Centre. PGT-A helps to shorten the time to a viable pregnancy by reducing the need for multiple IVF cycles, and by screening the embryos to identify the ones with the correct number of chromosomes for transfer. Embryos with the correct number of chromosomes are called euploid embryos (as opposed to aneuploid) and their transfer to a patient results in the highest pregnancy and live birth rates.

The testing involves biopsying cells from the embryo on days 3 or 5 of embryo development. For day 3 biopsies, the embryo usually consists of 6-8 cells called blastomeres. 1-2 blastomeres are biopsied from the developing embryo and tested. On day 5, the embryo should have formed a blastocyst which has over 100 cells and is made up of two major structures. The first structure is the inner mass cell (ICM) which gives rise to the definitive structures of the foetus. The other is the trophectoderm (TE) which gives rise to extraembryonic structures like the placenta. 5-6 cells are biopsied from the trophectoderm and tested. It is widely regarded that performing the biopsy on day 5 of embryo development, rather than on day 3, could potentially lead to improved sensitivity of genetic diagnosis and give more accurate results due to the fact that more cells can be tested without having an impact on the development and implantation potential of the embryo.

PGT-A results can take a few weeks, and it identifies the karyotype caused by the gain or loss of a number of chromosomes. Syndromes caused by the gain of 1 autosome chromosome are Down syndrome (Trisomy 21), Edwards' syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). In addition, syndromes caused by a gain or loss of sex chromosomes are Turner syndrome (Loss of the X chromosome), Klinefelter Syndrome (Gain of the X chromosome), Triple X (Gain of the X chromosome), and YY male (Gain of the Y chromosome), these aneuploidies are compatible with life. Trisomy 16 is most frequently detected in the PGT-A; however, it is not compatible with life and causes foetal death.

PGT-A results can identify mosaicism within embryos, one of the concerns in the world of genetics. Mosaic embryos carry two different populations of cells, one which is chromosomally normal, and another which is chromosomally abnormal. This may happen due to abnormal chromosomal rearrangement or abnormal cell division within the embryo. After obtaining the PGT-A results, only chromosomally normal (Euploid) embryos are transferred for implantation.  In the case of mosaic embryos, genetic counselling is required, when no normal (Euploid) embryos are present.

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