PGS & PGDDr Chinmayie R
The application of molecular genetic tests like fluorescence in hybridization (FISH) and polymerase chain reaction (PCR) has been extended to detect embryos with major sporadic chromosomal or age-related aneuploidies that may result in implantation failure spontaneous miscarriage and to remove them from the cohort available for transfer. This technique is called preimplantation genetic screening (PGS), according to the European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG). PGS was renamed Preimplantation Genetic Testing for aneuploidy (PGT-A), and PGD was renamed Preimplantation Genetic Testing for Monogenic/Single-Gene Disorders (PGT-M) by Preimplantation Genetic Diagnosis International Society (PGDIS) in 2016. The technology used by both PGD and PGS is nearly identical. PGT aims to improve pregnancy rates in sub-fertile couples undergoing IVF/ICSI treatment. PGT-M seeks to prevent the birth of affected children in infertile couples with a high risk of transmitting genetic disorders. PGS or aneuploidy screening is vital when 50% of cleavage embryos are abnormal, 80% of embryos in women > 42yrs of age. Most aneuploidy embryos arrest before cavitation and before development. Aneuploidy causes 60% sporadic miscarriages 40% recurrent miscarriages.
Preimplantation Genetic Testing for Monogenic/Single-Gene Disorders (PGT-M) of single gene single-gene DNA amplification-depends on DNA amplification using PCR -has pitfalls as reduced amplification efficiency. Improved multiplex PCR, fluorescent PCR, whole genome amplification can be used to overcome these pitfalls. It can be used to avoid X- linked disorders-DMD, Retinitis pigmentosa. PCR determined the sex of embryos PCR for primers specific for DNA sequences found only on Y the chromosome 50%chance of inheriting the disorder. Several girls were born because amplification errors can avoid embryos with familial predisposing mutations, breasts, and ovarian cancer. Detection of mutations uses targeted screening and prevention strategies for genetic counseling and testing for family members. 5-10% of breast cancers are caused by germline mutations- mc BRCA1, 2- increased breast and ovarian cancer risk.
The most common single-gene disorders that PGT-M has been used for are:
o Cystic fibrosis
o Tay-Sachs disease
o Spinal muscular atrophy (SMA)
o Sickle cell disease
o Duchenne muscular dystrophy
However, hundreds of more genetic diseases have single gene single-genetic IVF and PGD.
Autosomal recessive disorders
o Sanhoff disease, Gaucher disease, adenosine Deaminase deficiency, glycogen storage disease, Fanconi anemia, adrEnal hyperplasia, phenylketonuria (PKU).
Auautosomal dominant disorders
o Neurofibromatosis, Von-Hippel Lindau, myotonic dystrophy, Huntington’s Disease, Marfan syndRome, osteogenesis imperfecta, Charcot-Marie-Tooth, APP early-onset Alzheimers, polycystic kidney disease, retinitis pigmentosa, familial adenomatous polyposis, achondroplasia.
o Ornithine carbamyl transferase deficiency, Fragile X, X-linked hydrocephalus.