There are many genetic diseases that can be transferred from parents to children including Tay-Sachs, hemophilia, Sickle Cell Anemia, Cystic Fibrosis, Down's syndrome and many others. Preimplantation genetic diagnosis allows the physician and embryologist to screen the embryos for specific genetic disorders if the specific mutation is known. It is also used to screen embryos for chromosomal disorders such as Downs Syndrome. Evaluation of the chromosomal content can also be performed to increase the quality of the embryos selected for embryo transfer in cases involving recurrent pregnancy wastage, repeated IVF failure, and advanced maternal age.

PGD is a micromanipulation procedure performed in conjunction with an in vitro fertilization cycle. In PGD, a small biopsy of the embryo is taken and one or two cells of the 6+ cell embryo are removed and examined using fluorescent in situ hybridization (FISH) used to count chromosomal number and/or the polymerase chain reaction (PCR) which is used to amplify the mutation point around a disease-causing gene.

FISH is used to identify the sex of the embryo, to identify balanced translocations, and to rule out aneuploidies. It works by attaching a probe specific for a certain chromosome allowing us to count the number of these chromosomes. (SEE FIGURE 1) An aneuploidy occurs when there are an incorrect number of chromosomes in the cells. Aneuploidy is a common cause of miscarriage in older women and the rate is reduced when only embryos screened for the most common aneuploidies are transferred. FISH aneuploidy evaluation increases the effectiveness of the process for selecting the normal embryos for transfer. Usually, 8 or 9 different chromosomal probes are used so the embryo might still have an abnormal makeup involving chromosomes that are not evaluated.

There are not yet routine techniques to evaluate every chromosome and it is possible that because the embryo may be mosaic, i.e. have different chromosomal counts in each cell, that there still could be differences between the biopsied cell and the embryo. So, the process is not perfect, but it represents an improvement in our ability to improve implantation and pregnancy.

Some genetic diseases such as hemophilia can only be transferred to a child of a particular sex. In these cases, FISH allows the embryologist to separate the embryos by sex and only the unaffected sex will be transferred to the uterus. PCR is used to identify single gene defects such as cystic fibrosis, Tay Sachs Disease, Spinal Muscular Atrophy, Muscular Dystrophy, etc. In the PCR process, thousands of copies of the suspected gene are made and the DNA base pairs of the gene are examined for the presence of the abnormality. (SEE FIGURE 2) PCR enables the creation of enough genetic material to make the gene examination possible. Samples of the parent's genetic material are used to make the DNA probe. Since there can be hundreds of mutations within the same gene, the parent's mutation has to be characterized before the PGD procedure.

Biopsy of the embryo does not appear to cause damage. The effectiveness of the process depends on the specific use. Every month more diseases are characterized for their genetic abnormality and the quality of our testing procedures improves. This area will continue to evolve rapidly.

Figure 1
The nucleus of a biopsied cell from the embryo that has been 'stained' with fluorescent probes for the chromosomes 13/21 (red), 18 (blue), X (green), and Y (yellow). This cell has the correct number of these chromosomes.

Figure 2
This gel shows the amplified gene products for the gene causing Tay Sachs. The pattern and size of the amplification products allow the discrimination of embryos as either being affected by the disease, carriers for the disease, or completely normal.

 

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