Pre-implantation Genetic Diagnosis:

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Choosing to Have a Healthy Child

Human genetic disease affects about 3% of the population at birth and it contributes to serious illness and infant mortality. Half of these defects are caused by chromosomal abnormalities and the other half includes genetic contributions to congenital abnormalities and other common diseases including single gene defects.

With the development of new molecular technologies and use of in vitro fertilization techniques, several inherited genetic diseases can now be diagnosed in the eggs and in early stages of human embryos. The technique known as pre-implantation genetic diagnosis (PGD) provides an alternative to prenatal diagnosis for couples at risk of transmitting genetic disorders to their children. Selective transfer of only unaffected embryos to the uterus avoids the possibility of termination later in gestation.

PGD was first developed in London, United Kingdom and in 1989 the first successful pregnancy following this technique was achieved. PGD has since been offered in more than 40 centres around the world and the number of diseases that can be screened by this technique has increased considerably.

There are three groups of patients who benefit greatly from PGD.

•The first group consists of patients who have already experienced the birth of an affected child and do not wish to repeat the physical and mental trauma associated with a terminated pregnancy after prenatal diagnosis. These patients do not want to risk miscarrying a healthy fetus (amniocentesis and CVS sampling) or developing fertility problems caused by repeated terminated pregnancies.

•The second group are subfertile couples (perhaps as a result of a genetic abnormality) who seek IVF and wish to increase their chances of conceiving a normal fetus by choosing PGD.

•The third group often have strong moral or religious objections to pregnancy termination. For these couples, PGD may be more acceptable because genetic diagnosis is performed in vitro prior to embryo transfer and in some cases the eggs can be tested before fertilization, if the mother is the carrier of the disease.

While most patients are fertile, they need to undergo IVF treatment so that enough eggs and embryos are obtained for genetic testing. PGD is also being offered to infertile couples to increase the chances of becoming pregnant. In most centers the genetic testing is done in one or two cells (blastomeres) removed from day 3 embryos by microsurgery.

The following conditions are now being diagnosed by using PGD:

 A defect in a particular gene can cause a disease. It can be inherited from their parents. The first clinical PGD for single gene defects was applied to couples at risk of transmitting cystic fibrosis. Following this procedure a healthy baby girl, unaffected by the disease, was born in 1992. Since then, an increasing number of single gene defects are being screened by PGD. For example, Cystic Fibrosis, Myotonic Dystrophy, Spinal muscular atrophy, Tay-Sachs, sickle cell anemia.

There are reportedly more than 300 sex linked recessive diseases and for most of them there is no specific molecular diagnosis. The current alternative to these patients are either perform sex selection by looking at the chromosomes by PGD and transfer only the female embryos back to the mother or termination of all male fetuses after prenatal diagnosis. Until more specific tests are developed there is no alternative to the present procedure.

 Women over the age of 35 tend to produce more chromosomally abnormal eggs than younger women. There are 23 pairs of identical chromosomes in each cell. However, in some individuals there is an extra chromosome, which is known as ‘trisomy’. The most well known trisomy is known as Down’s syndrome, where an individual carries three copies of chromosome 21 instead of two. This usually happens during the last stages of egg maturation and leads to an extra or missing chromosome. Eggs and embryos with such abnormalities are called aneuploids.

Recent studies show that the percentage of such abnormalities far exceed the number of healthy live births. This discrepancy is due to the fact that most of these embryos will either not lead to pregnancy or will result in spontaneous abortion. Therefore screening of embryos should increase the chance of having a healthy child and reduce the abortion rate. In addition to offering aneuploidy screening to women of advanced maternal age, it is also offered to patients with repeated spontaneous abortions and repeated IVF failures.

Translocation is the rearrangement of two or more chromosomes where chromosomes are attached to each other. An individual with carriers for translocation is unaffected if there is no missing or extra pieces of chromosome materials and such translocations are called ‘balanced’. The presence of extra or missing chromosome material is termed ‘unbalanced’ translocation. Individuals with balanced translocation do not have any health or developmental problems; the primary risk is the production of unbalanced eggs and embryos.

When one partner carries a balanced translocation, repeated miscarriages or a child born with multiple birth defects may be experienced. PGD can be used in these cases to reduce the chance of spontaneous abortion and significantly increase the chance of having a healthy child.

Because only one or two cells are used for genetic analysis, there is a possibility of misdiagnosis. The accuracy rate has improved considerably from the time it started however the patients are always advised to undergo prenatal diagnosis to confirm PGD results.

For some couples PGD may be the only way to have a healthy child. Ensuring that the embryo transferred is unaffected, PGD for aneuploidy screening will not only increase the couple’s overall chances of a successful pregnancy, it will also reduce the risk of carrying a trisomic fetus and reduce the need for prenatal diagnosis.  

By increasing the pregnancy rate this procedure will also spare the emotional and financial cost of unsuccessful treatment cycles.

Asangla Ao is Assistant Professor at McGill University, Department of Ostetrics and Gynecology in the Department of Human Genetics. She is also the Scientific Director of the PGD Program at the McGill Reproductive Centre in Montreal.

PGD has since been offered in more than 40 centres around the world and the number of diseases that can be screened by this technique has increased considerably.