Preimplantation Genetic Diagnosis (PGD)

For couples at risk of having children affected by an inherited disease, preimplantation genetic diagnosis (PGD) is a valuable alternative to conventional prenatal diagnosis by chorion villus sampling or amniocentesis, since it avoids the uncertainty and trauma associated with diagnosis late in an established pregnancy. With PGD, fertile couples have in vitro fertilisation (IVF) so that the early embryo is accessible allowing single cells to be removed by embryo biopsy for genetic analysis and diagnosis before transfer and implantation in the uterus.

Embryo biopsy 
Single cells are removed from each human embryo through an opening in the outer protective coat, 3 days after in vitro fertilization (IVF) or fertilization by intracytoplasmic sperm microinjection (ICSI) using micromanipulation. Single cell genetic analysis then allows the diagnosis of chromosomal or single gene defects.

Compared with prenatal diagnosis, the prospect of knowing a pregnancy should be normal from the beginning makes PGD an attractive option. Other advantages include firstly, the number of embryos available in a single IVF cycle (average of 5-6), which for high risk couples increases the chance of identifying unaffected embryos and establishing an unaffected pregnancy, and secondly, the high cumulative pregnancy rates over two or three cycles. With fertile couples, more than half will get pregnant following two to three cycles, which can be achieved in a relatively short period. However, pregnancy rates are highly dependent on the characteristics of individual patients and it is impossible to generalise. The most important factor determining pregnancy outcome is maternal age. For this reason, PGD may not be a good choice for women in their late thirties or forties. On the other hand, pregnancy rates in fertile women in their twenties and early thirties can be astonishingly high and the number of unaffected embryos transferred needs to be considered very carefully to avoid twin pregnancies.

Over the last 15 years, PGD has become an established clinical alternative to conventional prenatal diagnosis and over 1000 babies have been born world-wide in over 50 clinics. Also, the range of genetic conditions which can be diagnosed has increased from a handful to all of the most common conditions including both chromosomal and single gene defects.

Examples of inherited conditions diagnosed by PGD

Single gene defects Cancer predisposing mutations
Duchenne muscular dystrophy Familial polyposis coli
Cystic fibrosis Retinoblastoma
Spinal muscular atrophy Li-Fraumeni syndrome
Sickle cell disease Chromosomal abnormalities
Tay-Sachs disease Aneuploidy
Gaucher disease Translocations
Late onset
Huntington’s disease Other
Myotonic dystrophy Tissue histocompatibility (HLA)