Introduction To Preimplantation Genetic Diagnosis (PGD)

Preimplantation genetic diagnosis (PGD) is an early form of prenatal diagnosis in which embryos created in vitro are analysed for well-defined genetic defects.
Defect-free embryos are then used for implantation.

Indications: It is used in

• those with high risk of genetic disease, e.g carriers of monogenic disease or chromosome structural abnormalities (e.g translocations) 
• who have repeatedly terminated pregnancies due to prenatal tests showing abnormality,
• who have concurrent infertility, 
• who have had recurrent miscarriage (as occurs with translocation carriers), and 
• for those with moral or religious objections to termination.
• It has also been used to screen for aneuploidy (PGD-AS) in those undergoing in vitro fertilization hoping to enhance chance of ongoing pregnancy (e.g in the case for women >37–40 years old).

Background: Pioneered in the early 1990's, PGD has resulted in >1200 pregnancies (pregnancy rate 24%), of which 5% of babies had some kind of abnormality.

PGD selection of embryos by HLA type so that a child born after using this technology can be used as a stem cell donor to save a sibling from certain conditions (eg with Fanconi anaemia, thalassaemia, or leukaemia) is controversial, but possible.

Some clinics select sex of implanted embryo e.g for ‘family balancing’.


Physiology: Genetic analysis at the single cell level occurs using 1st polar body of an egg, or 2nd polar body (extruded after fertilization and completion of second meiotic division), or using blastomeres from cleavage-stage embryos. The blastocyst is the latest stage from which cells can be used but is little used as it leaves little time for analysis as embryos must be transferred before day
5 or 6.
Biopsied surplus embryos can be cryopreserved but implantation rate for these is only 12%.

Fluorescence in situ hybridization (FISH) is used for analysis of chromosomes and polymerase chain reaction (PCR) for analysis of genes in monogenic diseases.

PGD can currently be applied for detecting 33 monogenic diseases. Gene analysis for X-linked conditions has the advantage that healthy male embryos and non-carrier female embryos can be transferred. Sexing embryos for X linked conditions remains useful for conditions where the single gene is not known (e.g non-fragile-X X-linked mental retardation), has been judged too difficult a search, and for women eg over 37 who do not wish to wait for specific tests to be developed.

Results: Pregnancy rates are 17% after testing for structural chromosome abnormality (including translocations), 16% after sexing, 21% after testing for monogenic diseases. This is lower than the expected rate of 20–25% expected for regular IVF.
For PGD-AS 25% pregnancy rates are achieved overall for women of previously poor prognosis due to advanced maternal age (a lower proportion than those where preimplantation genetic screening is not used), repeated IVF failure (but only 8% do get pregnant), and recurrent miscarriage (28% pregnancy rate achieved).