Preimplantation Genetic testing ( PGT )

Preimplantation Genetic Testing ( PGT )  is preconception testing where embryos formed by In-vitro Fertilization are screened for chromosomal/ genetic abnormalities and the healthy embryo is implanted.  This should not be confused with gene therapy as it’s only a method of screening.  Also, it should not be  confused with the grading system used I IVF/ ICSI-IVF as those screens embryos based on the morphological criteria While prenatal diagnosis by chorionic villi sampling/amniocentesis can be done post-conception,  this technique is used to screen embryos preconception.    

The embryo is a single cell that divides to form a multicellular organism. An embryo can be grown in the lab for 8 days.  On the 5 the day there would be two kinds of cells observed, an outer ring of a cell which is called the outer cell mass that would form the placenta, and an inner cell mass that would form the baby. A biopsy is taken from the outer cell mass,  without disturbing the sensitive inner cell mass. This is done through a laser microscope by a highly skilled and certified embryologist. The cells are sent to the lab, where DNA is isolated for further molecular diagnosis.

PGT is a blanket term used to describe three screening methods depending on the indications. 

PGT-A is a method of PGT where embryos are screened for aneuploidies. We all have 46 chromosomes and this set is called the euploidy. However, if the number is deviant from 46, we use the term aneuploid which can be a trisomy indicating again or monosomy indicating a  loss in the chromosome number. PGT-A can be used to screen embryos for the magical number of 46.  The indications for PGT-A are advanced maternal age, recurrent implantation failure, Male Factor infertility, and recurrent pregnancy loss apart from genetic diseases involving a gain/loss in chromosomes. This test does not require personalized test preparations and can be offered to anyone who wants to go through an IVF as it can improve the overall IVF success rates

PGT-SR  is indicated in cases where a couple has complex chromosomal rearrangement like a balanced translocation, Robertsonian translocation,  inversions, or where there is a previous child with a microdeletion/ microduplication syndrome / a syndrome related to uniparental disomy. This improves the overall outcome to have a healthy baby and reduced the risk of developmental disorders. In such cases, knowledge of the parental karyotype is needed.

PGT-M is indicated when a previously known single-gene disorder is present in the previous child/ sibling/ close family member.  Many genetic disorders can be inherited in an autosomal dominant/ autosomal recessive / X- linked manner. Most genetic diseases do not have a cure, and for families where such a genetic variant has been confirmed, screening the embryos for the mutation helps to select a healthy embryo.   According to the ACMG guideline only where the disease mutation is established, this method can be used. This also requires making personalized probes that are used to screen for the mutation. PGT  can also be used for HLA matching in embryos which are useful in families with cancer and / thalassemia. 

PGT is a screening test; hence though the embryo is screened and implanted, an amniocentesis is done at 16 weeks to confirm the molecular/genetic status. This technique thus reduces the chances of genetic disorders and also increases the chance of a healthy pregnancy. In addition, it can help couples struggling with   IVF failures / advanced maternal age with improved implantation rates.