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Preimplantation genetic diagnosis

A Correction to this article was published on 01 February 2003

Key Points

  • Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting serious genetic disorder to their offspring.

  • For PGD, assisted conception techniques are used to generate embryos in vitro and a polar body or a cell is removed as a biopsy either before fertilization or later in preimplantation embryo development (at cleavage or blastocyst stage). This biopsy is used as a tissue representative of the whole embryo and is analysed for the presence of a specific genetic abnormality. Embryos found to be unaffected are replaced into the uterus.

  • PGD provides an alternative way forward, not only for couples at risk of having a child with a severe or life threatening abnormality, but also for couples who are unable to establish a viable pregnancy due to miscarriage caused by chromosome rearrangements.

  • PGD for inherited genetic diseases in fertile couples should be distinguished from PGD for the detection of sporadic chromosomal abnormality to enhance in vitro fertilization success in infertile couples who seek assisted conception treatment. The latter procedure has been designated as PGD-AS (aneuploidy screening) by the ESHRE consortium and PGS (preimplantation genetic screening) by the Human Fertilisation and Embryology Authority, although it tends to be included in the definition of PGD in the United States.

  • The increasing availability of PGD raises many new ethical issues such as sexing for non-medical reasons, selection of affected embryos so they will be the same as their parents for a specific characteristic (such as deafness) and HLA typing to save the life of an affected living sibling.

  • Regulation of PGD varies around the world, with some countries having strict legislation to prevent it, as is the case in Germany, and some having permissive but highly regulated legislation, as in the United Kingdom. However, many countries, including the United States do not have any specific legislation that regulates the use of PGD.


Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting a serious genetic disorder to their offspring. Samples for genetic testing are obtained from oocytes or cleaving embryos after in vitro fertilization. Only embryos that are shown to be free of the genetic disorders are made available for replacement in the uterus, in the hope of establishing a pregnancy. PGD has provided unique insights into aspects of reproductive genetics and early human development, but has also raised important new ethical issues about assisted human reproduction.

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Figure 1: Principle of preimplantation genetic diagnosis.
Figure 2: Early human preimplantation development in vitro.
Figure 3: Polar body and cleavage stage biopsies.
Figure 4: PGD of X-linked disorders using FISH.
Figure 5: Chromosome translocations.
Figure 6: Aneuploidy screening using FISH.
Figure 7: Comparative genomic hybridization.


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The authors thank the other members of the Centre for Preimplantation Genetic Diagnosis for helpful and regular discussion about the issues raised in this review.

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Correspondence to Peter Braude.

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Becker muscular dystrophies

cystic fibrosis

DiGeorge syndrome

Down syndrome

Duchenne muscular dystrophy

Fanconi anaemia

Huntington disease

incontinentia pigmenti

Lesch–Nyhan syndrome

Marfan syndrome

myotonic dystrophy

severe combined immunodeficiency disorder

sickle cell disease

Tay–Sach's disease

Velocardiofacial syndrome

X-linked mental retardation


American Society for Reproductive Medicine (ASRM)

European Society of Human Reproduction and Embryology (ESHRE)



Reproductive Genetics Institute

UK Human Fertilisation and Embryology Authority



The risk of establishing a pregnancy in which a fetus miscarries or has a phenotypic abnormality as a consequence of the familial genetic condition.


The presence of extra copies, or fewer copies, of some chromosomes.


A preimplantation embryo that contains a fluid-filled cavity called a blastocoel.


A procedure in which a small sample of amniotic fluid is drawn out of the uterus through a needle that is inserted into the abdomen. The fluid is then analysed to detect genetic abnormalities in the fetus or to determine the sex of the fetus.


(CUS). Sampling of the placental tissue of the conceptus for laboratory analysis.


One of the 12-week stages into which pregnancy is divided for clinical purposes.


(FACS). A method whereby dissociated and individual living cells are sorted, in a liquid stream, according to the intensity of fluorescence that they emit as they pass through a laser beam.


Hormones that are produced by the pituitary gland, which act on the gonads to control endocrine functions. Examples include follicle stimulating hormone and luteinizing hormone.


Structures in the ovary in which primary oocytes develop into mature oocytes before ovulation.


A technique in which sound waves are bounced off tissues and the echoes are converted into a picture (a sonogram).


The glycoprotein coat that surrounds the oocytes and the early embryos of mammals.


The haploid nucleus of an egg or sperm.


A cell that results from embryonic cleavage.


A small haploid cell that is produced during oogenesis and that does not develop into a functional ovum.


A chromosome that has undergone replication. The two identical sister chromatids remain joined at the centromere.


The abnormal separation of chromatids during meiosis I (normally, sister chromatids separate during meiosis II) usually gives rise to gametes with a genetic imbalance.


A connection between individual cells in an epithelium that forms a diffusion barrier between the two surfaces of an epithelium.


The capacity of an undifferentiated cell to develop into any type of cell.


The outer layer of the blastocyst-stage embryo.


The individual variation in the length of a particular region of DNA (such as a dinucleotide repeat), which, if the DNA is cut with a restriction enzyme or amplified using PCR, gives rise to the generation of differently sized fragments.


A technique for improving the sensitivity and specificity of PCR by the sequential use of two sets of oligonucleotide primers in two rounds of PCR. The second pair (known as 'nested primers') are located in the segment of DNA that is amplified by the first pair.


(ADO). The failure to detect an allele in a sample or the failure to amplify an allele during PCR.


The proportion of affected individuals among the carriers of a particular genotype. If all individuals with a disease genotype show the disease phenotype, then the disease is said to be 'completely penetrant'.


A chromosome with the centromere located at one end.


Repetitive DNA sequences arranged in tandem arrays that usually lie near the centromere.


A method for in vitro DNA labelling. Nicks are introduced into the DNA by an endonuclease and are subsequently repaired using labelled residues.


The ascertainment of chromosome constitution by the light microscopy analysis of stained metaphase chromosomes.


The result of a cytogenetic method in which dividing cells are artificially arrested at metaphase, when chromosomes are shortened and condensed. The fixed material from such preparations is dropped onto microscope slides, where the chromosomes from individual cells form clusters or spreads, which can be stained and analysed.


The number of sets of chromosomes in a cell (n). Normal human somatic cells are diploid (2n), with 2 sets of 23 chromosomes.

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Braude, P., Pickering, S., Flinter, F. et al. Preimplantation genetic diagnosis. Nat Rev Genet 3, 941–953 (2002).

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