The application of molecular genetic tests like fluorescence in situ 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 failure of implantation or 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 by 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- A aims to improve pregnancy rates in sub-fertile couples undergoing IVF/ICSI treatment. PGT-M aims to prevent the birth of affected children in fertile couples with a high risk of transmitting genetic disorders. PGS or aneuploidy screening is important as 50% of cleavage embryos are abnormal, 80% of embryos in women > 42yrs of age. Most aneuploidy embryos arrest before cavitation and prior to blast development.  Aneuploidy causes 60% sporadic miscarriages, 40% recurrent miscarriages.

Preimplantation Genetic Testing for Monogenic/Single-Gene Disorders (PGT-M) of single gene disorder by DNA amplification-depends on DNA amplification using PCR -has pitfalls as allele drop outs, contamination reduced amplification efficiency. Improved multiplex PCR, fluorescent PCR, whole genome amplification can be used to overcome these pitfalls. Can be used to avoid X- linked disorders-DMD, Retinitis pigmentosa. Sex of embryos was determined by PCR for primers specific for DNA sequences found only on Y chromosome. 50%chance of inheriting the disorder. Several girls were born as amplification error did occur. Can be used to avoid embryos with familial cancer predisposingmutations-breasts, ovarian colon cancer. Detection of mutations have use of targeted screening and prevention strategies for probands, genetic counseling and testing for family members  and 5-10% of breast cancers caused by germ line mutations- mc BRCA1, 2- increased risk of breast and ovarian cancer.

  • The most common single gene disorders that PGT-M has been used for are:
    • Cystic fibrosis
    • Tay-Sachs disease
    • Spinal muscular atrophy (SMA)
    • Hemophilia
    • Sickle cell disease
    • Duchennes muscular dystrophy
    • Thalassemia
    • However, there are hundreds more genetic diseases that can have single gene testing done using IVF and PGD. A partial list of relatively common single gene diseases is below.
  • Autosomal recessive disorders
    • Sanhoff disease, Gaucher disease, adenosine Deaminase deficiency, glycogen storage disease, Fanconi anemia, adrenal hyperplasia, phenylketonuria (PKU).
  • Autosomal dominant disorders
    • Neurofibromatosis, Von-Hippel Lindau, myotonis dystrophy, Huntington’s Disease, Marfan syndrome, osteogenesis imperfecta, Charcot-Marie-Tooth, APP early onset Alzheimers, polycystic kidney disease, retinitis pigmentosa, familial adenomatous polyposis, achondroplasia.
  • X-linked disorders
    • Ornithine carbamyl transferase deficiency, Fragile X, X-linked hydrocephalus.