Source:Kanavakis E, Traeger-Synodinos J. Preimplantation genetic diagnosis in clinical practice.
J Med Genet.

Preimplantation genetic diagnosis (PGD) involves the testing of an in vitro fertilization (IVF) derived embryo at risk for a specific genetic disorder, thereby enabling selection of unaffected embryos for implantation. This review article from Aghia Sophia Children’s Hospital, Athens, Greece, points out that PGD is an alternative genetic test to chorionic villus sampling (CVS) or amniocentesis, genetic testing techniques used in an already established pregnancy that carries an increased risk for a genetic disorder.

Embryonic cells for testing may be obtained from polar bodies of the oocyte/zygote stage, trophectoderm cells from blastocyst stage embryos, and blastomere cells from cleavage stage embryos. Although polar bodies are useful for detecting maternally derived numerical chromosome abnormalities associated with advancing maternal age, it is usually not preferred because the paternal contribution is unknown. Blastocyst biopsy has not yet been reported for PGD because only 40–50% of in vitro embryos successfully reach the blastocyst stage. The cleavage stage embryo has 6–8 blastomere cells on the 3rd day post-insemination, 1 cell of which is used for testing, and is the most commonly used source despite the limited amount of material available for analysis. Single cell diagnosis is the most difficult technical part of PGD and genetic diagnosis must be completed and embryo transfer accomplished within 48 hours so that embryo viability is not compromised.

PGD applications include diagnosis of chromosome abnormalities using fluorescence in situ hybridization (FISH) and monogenic disorders using polymerase chain reaction (PCR). Approximately half of all PGD done to date have been done because of advanced maternal age and the associated increased risk for chromosome abnormalities. The monogenic disorders for which PGD has been done include disorders which are autosomal recessive (eg, hemoglobinopathies, Tay-Sachs disease, and cystic fibrosis), autosomal dominant (eg, myotonic dystrophy and Charcot-Marie-Tooth disease 1A), and X-linked (eg, muscular dystrophy, hemophilia, and fragile X syndrome). Although PGD has been valuable and worthwhile in averting serious inherited diseases for many couples, it will probably not replace first and second trimester prenatal diagnosis because it is a technically difficult, complex, labor intensive, and expensive procedure.

PGD appears to be safe without adverse consequences on early development based on the experience of 250 babies born after PGD1,2; however, IVF is the only way in which a blastomere cell can be obtained for testing, even for those couples without fertility problems. PGD results in a low rate of successful pregnancies: the testing is successful in about 80–90% of blastomere cells obtained and only 50% have normal results. Consequently, approximately 40–50% of tested embryos are suitable for transfer/implantation with pregnancies resulting in no more than 33% of all cycles initiated for IVF.3,4

As the authors indicate, at this time PGD is most appropriate for couples who have a fertility problem and a significantly increased risk for having a child with a severe genetic disorder. PGD may be worthwhile for couples who have an affected child, have...

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