PREIMPLANTATION GENETIC DIAGNOSIS

What is Preimplantation Genetic Diagnosis?

Preimplantation Genetic Diagnosis (PGD) is a relatively new diagnostic procedure that enables patients to pick embryos free of genetic defects. It was first performed in 1988 and since then, through the use of PGD screening and selection techniques in about thirty clinics worldwide, over 2,000 children have been born free of genetic defects that were present in their family gene pool.

For couples at risk of having children with an inherited disease, PGD is a new alternative approach to preventing the birth of children with inherited disease. Traditional methods of prenatal diagnosis such as amniocentesis or chorion villus sampling (CVS) involve taking samples from an established pregnancy. If the fetus is diagnosed as affected, couples then have to decide whether or not to terminate the pregnancy. Some couples may have to undergo several terminations in their attempt to produce a healthy child. With PGD, In Vitro Fertilization (IVF) treatment is used to screen early embryos (within a few days of conception) for the inherited defect causing the disease. Couples can then choose to have only those embryos identified as free of the disease implanted in the woman's uterus, in the hope that any resulting pregnancy should be normal. In its ability to intervene before the pregnancy is established in utero, PGD offers patients a great advantage over both amniocentesis and CVS.

Pre-Implantation Genetic Diagnosis is used during an IVF cycle to identify specific embryos that carry abnormal genes. PGD can also be used to help select embryos of a particular sex, usually to avoid sex-specific diseases, but it can also be done for family balancing. PGD is normally recommended for couples where one or both of the parents are a known carrier of a genetic disease (i.e. hemophilia or cystic fibrosis). PGD is usually performed after a woman's eggs have been harvested and fertilized by her partner's sperm, but before the eggs have been transferred back to her uterus. When the fertilized egg has reached between the four- and ten-cell development stage, one or two cells (known as blastomeres) are gently removed from each embryo using a microsurgery technique similar to that used in ICSI. The DNA from the removed blastomeres is then analyzed for genetic diseases or disorders. If any chromosmal abnormalities indicative of disease are found, the results will be carefully explained to the potential parents. It is then for the parents to decide which embryos they wish to transfer. This is an important and sometimes difficult decision, which has to be made in a short space of time on the day of transfer. We recommend, therefore, that patients and families electing for PGD talk over the possible outcomes beforehand, so that they have adequate time to think through all the issues.

What Genetic Diseases Can PGD Test For?

Numerous diseases and disorders classified as either chromosomal disorders, single gene defects or sex-linked disorders can be tested for through PGD. Specific chromosomes are tested for specific disorders, including:

Chromosome 13: Breast and ovarian cancers, deafness, Wilson Disease
Chromosome 15: Marfan Syndrome, Tay-Sach's Disease
Chromosome 16: Polycystic kidney disease, Alpha thalassemia
Chromosome 17: Charcot-Marie-Tooth Disease
Chromosome 18: Niemann-Pick Disease, pancreatic cancer
Chromosome 21: Down's Syndrome
Chromosome X: Duchenne muscular dystrophy (DMD), Turner's Syndrome, Fragile X Syndrome
Chromosome Y: Acute myeloid leukemia

We can also test for X-linked diseases, which only affect boys, (e.g. hemophilia A, drenoleukodystrophy, Hunter's disease) by identifying the sex of embryos and transferring only female embryos. We also offer PGD for single gene defects such as cystic fibrosis (CF), the common deletion (^F508), spinal muscular atrophy (SMA), and Myotonic Dystrophy (DM). We also perform aneuploidy screening and chromosome translocations to detect abnormalities that may cause spontaneous abortions in early pregnancy. We can perform PGD for all single gene defects where the specific mutation is identified and as long as we can develop a special genetic probe for the disease.

What is PGD Accuracy?

While PGD is an important diagnostic tool, it is not without limitation. Genetic analysis of single cells is technically demanding and prone to errors of various kinds. PGD-FISH (fluorescent in-situ hybridization) can only test for a limited number of chromosomes. Abnormalities in the remaining chromosomes cannot be detected. PGD-PCR (polymerase chain reaction) can sometimes fail to detect single gene defects. For chromosomal translocations, PGD cannot detect abnormalities in chromosomes other than the one known to be involved in the translocation. The error rate for PGD in detecting chromosomal abnormalities is approximately 10%. In cases of genetic mosaicism, where a given genetic abnormalities may exist in one cell of an embryo but not in another, PGD if often is inadequate for diagnostic purposes. On the other hand, because of the limitations of PGD, it is possible that no embryo will appear normal, while an embryo may in fact be normal, so PGD can create both false positives and false negatives.

IVF, Egg Donation, PGD & Pregnancy

One concern of many couples is whether or not the procedure will affect their chances of pregnancy or, more importantly, the health of their embryo. Because the procedure is done so early in the developmental process, at a time when any cell from the embryo can potentially be removed, PGD does not cause any harm to the developing embryo. More debatable is, however, is the degree to which PGD affects your chances of a successful pregnancy. Studies on PGD and pregnancy success rates have reported conflicting findings, with some suggesting that it lessens the chances of pregnancy and others finding it increases those chances.

What Are the Risks of PGD?

In rare cases, it is possible that an embryo may be accidentally damaged during biopsy, resulting in developmental arrest. Embryo biopsy may delay cell division by a few hours, and some embryos fail to recover from biopsy, and fail to result in a live birth. In other cases, embryo biopsy and/or genetic analysis may fail due to technical problems.

Despite these risks and limitations, PGD is an important diagnostic tool for many couples with a family history of genetic defects.