PGD- Definition

PGD, is a clinical diagnostic procedure employed with IVF for testing human embryos for the presence of genetic abnormalities, or inherited diseases, before transfer to the uterus and pregnancy. Only embryos that are shown by preimplantation genetic diagnosis to be free of the genetic disorder, are transferred to the uterus. PGD is a major advance in treating infertility in couples who may have a genetic disorder.

Preimplantation Genetic Diagnosis- History

PGD is a procedure that has evolved from assisted reproductive technology and medical genetics and therefore is intimately related to both fields . The goal of this page is to point out the original research, which guided development of preimplantation genetic diagnosis in humans.

Preimplantation Genetic Diagnosis- Development

PGD first Human Experience- 1983 -Center for Reproductive Biology, Department of Obstetrics and Gynecology, University of Edinburgh, Edinburgh, United Kingdom- The first evidence to suggest that some human embryos might harbor aneuploid cells were described. These findings provoked further studies into the chromosomal constitution of human embryos, eventually resulting in the development of PGD. Original article: Angell, R. R., Aitken, R. J., van Look, P. F., Lumsden, M. A. & Templeton, A. A. Chromosome abnormalities in human embryos after in vitro fertilization. Nature 303, 336-338, 1983.

Preimplantation Genetic Diagnosis Historical Development

PGD using pre-embryos- 1987- Center for Reproductive Biology, Department of Obstetrics and Gynecology, University of Edinburgh, Edinburgh, United Kingdom-Human male pre-embryos were identified by means of DNA-DNA in-situ hybridization with a commercially available DNA probe for Y-chromosome DNA. This method lead to the diagnosis of genetic disorders based on small numbers of cells that are not necessarily in division, such as cells obtained from a pre-embryo during the course of in-vitro fertilization therapy. Original article: J.D. West, R.R. Angell, S.S. Thatcher, J.R. Gosden, N.D. Hastie, A.F. Glasier and D.T. Baird Sexing the human pre-embryo by DNA-DNA in-situ hybridization. Lancet 1, 1345-1347 (1987)

PGD- Genetic Mutations

Preimplantation genetic diagnosis is used to identify genetic mutations in embryos- 1988- Department of Biological Sciences, University of Southern California, Los Angeles, U.S.A. PCR- The successful PCR amplification of DNA sequences from individual diploid cells and from human sperm not only enabled the analysis of DNA sequence variation at the single-cell level, but also opened up the possibility of applying this technology clinically in preimplantation genetic diagnosis , to identify the presence of genetic mutations in embryos from carrier patients. Original article: Li HH, Gyllensten UB, Cui XF, Saiki RK, Erlich HA, Arnheim N. Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335, 414-417 (1988).

PGD- Sex Linked Genetic Disorders

1990- Institute of Obstetrics and Gynecology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom-PCR, PGD and gender selection- The first pregnancies that resulted from the transfer of embryos that had been genotyped as female were reported. Embryos from couples who were at risk of transmitting two different X-linked disorders were subjected to biopsy and the cell removed was sexed by the PCR of a Y-chromosome specific repeat sequence. Original article: Handyside, A. H., Kontogianni, E. H., Hardy, K. & Winston,R. M. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344, 768-770 1990.

Preimplantation Genetic Diagnosis- Polar Body Testing, Cystic Fibrosis

1990- Reproductive Genetics Institute, Department of Obstetrics and Gynecology, Illinois Masonic Medical Center, Chicago, Il, U.S.A., Polar body testing- Testing of polar bodies of human eggs was suggested as a new approach. The first pregnancy that resulted from the transfer of embryos after polar body testing for the presence of cystic fibrosis mutation. Original article: Strom CM, Verlinsky Y, Milayeva S, Evsikov S, Cieslak J, Lifchez A, Valle J, Moise J, Ginsberg N, Applebaum M. Preconception genetic diagnosis of cystic fibrosis. Lancet. 1990 Aug 4; 336(8710): 306-7.

PGD and Huntington Reproductive Center

1999- Huntington Reproductive Center, Southern California, USA.- Preimplantation genetic diagnosis offered to patients. More than 500 PGD treatment cycles have been performed for different conditions.

PGD is offered by almost 100 reproductive centers worldwide. Dozens of physicians, geneticists and embryologists are continuously contributing into the improvement and expansions of methods of analyzing samples from human embryos transformed preimplantation genetic diagnosis from clinical research into powerful diagnostic tool.

Preimplantation Genetic Diagnosis and Detectable Diseases

At present there is a long, constantly updated list of genetic conditions including single gene disorders, a variety of translocations and chromosomal abnormalities that could be detected by preimplantation genetic diagnosis. See the list of diseases detectable by preimplantation genetic diagnosis.