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Preimplantation Genetic Diagnosis (PGD)

 

Initially an experimental genetic screening tool for human embryos,49 now it is well established clinically and used in several thousand cycles worldwide. It is used for the diagnosis of single gene defects as well as chromosomal disorders e.g. aneuploidy, translocations. Genetically normal embryos are identified and selectively transferred thereby preventing transmission of genetic disorders. Polar bodies, blastomeres or blastocyst trophectoderm cells can be analyzed. The cells to be biopsied are obtained by partial zona dissection done trough chemical, mechanical or laser methods.

Either pre or post-fertilization polar body may be biopsied. The advantages include extraembryonic handling as well as time duration available between biopsy and subsequent embryo transfer. However information about sex of the embryo and the paternal genome is not available. Also fragmentation and incomplete biopsy hinders the diagnosis.

Embryos are usually biopsied at the 6-8 cell stage on day 3 where 1-2 blastomeres are selectively obtained. The disadvantages are reduction of implantation rates if the embryo is damaged; also time between biopsy and transfer is limited hence rapid diagnosis is essential. Further the trophectoderm may be at variance with the inner cell mass.

Various autosomal conditions like cystic fibrosis, histiocytosis as well as X linked fragile X syndrome can be diagnosed on PGD.

PCR polymerase chain reaction is the most commonly used technique with its quick and highly sensitive diagnosis. Multiplex PCR and real time PCR are also being used. Contamination from cumulus cells may cause an erroneous diagnosis, also DNA amplification failure can occur.

FISH( Fluorescence in situ hybridization) is commonly used for the diagnosis of chromosomal disorders50 with 9-10 chromosomes being currently studied as well as for translocations. Thus fluorescent DNA probes for sex chromosomes as well as chromosomes 13,14,15,16,18,21,22 are available.
Target population includes high maternal age, cases of recurrent abortions, repeated IVF cycle failures, and genetically abnormal couples with translocations and inversions.

PGD is a safe and effective means of identifying genetically abnormal embryos with pregnancy and implantation rates comparable to conventional IVF cycles.51 With further advances the scope of PGD will widen to encompass more and more genetic disorders.

 
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