Preimplantation Genetic Diagnosis (PGD) of embryos to detect abnormal numbers of chromosomes (aneuploidy), or to detect heritable disorders, is a rapidly growing field in

assisted reproductive technology. The first reports of PGD successfully used in conjunction with human in vitro fertilization (IVF) appeared in the early 1990’s. Since then, hundreds of normal infants who were at risk for genetic diseases have been born through use of this exciting new technology.

How Is PGD Performed?

PGD requires patients to undergo a cycle of IVF in order to have embryos available for this procedure. In IVF, a women takes medication (FSH)designed to mature several eggs during one of her monthly cycles. The mature eggs are removed vaginally by a minor aspiration procedure and inseminated with her partner’s sperm in the IVF laboratory.

In about three days the fertilized eggs have divided to the point where one or two cells called blastomeres can be safely removed from each one.

The number of fertilized eggs varies from patient to patient, but typically there are 7-8 of these embryos available for PGD evaluation. The blastomeres are then individually evaluated to see if the embryo each was taken from is normal for the traits being tested.

What Can Be Determined About an Embryo by the PGD Procedure?

PGD is currently used for determining the number of specific chromosomes present in embryos, as well as for detection of individual genes responsible for many heritable disorders.

Human beings have 23 pairs of chromosomes, one pair being those that determine sex: X-X is female, X-Y is male. Some chromosomes are more likely than others to become “unpaired” which can lead to early embryonic demise (chromosomes 13, 16, 18, 22) or term births affected by Down’s syndrome (Trisomy) or other abnormalities. Numerical mistakes in the sex chromosomes can lead to Turners Syndrome (XO), or Kleinfelters Syndrome (XXY).

Checking for normal chromosome pairing is done using a technique called Fluorescent In Situ Hybridization, or FISH. Using this technique, five or more specific chromosomes from a blastomere can be evaluated at a time. Sometimes, chromosomes can break apart and attach to other chromosomes, a condition known as translocation. Couples who have had blood tests that indicate they are at risk for passing on this trait may also have their pre-embryos evaluated by PGD-FISH to identify unaffected ones for establishing a pregnancy.
Examples of heritable conditions caused by “gene” disorders are Cystic Fibrosis, Tay-Sachs Disease, Duchenne Muscular Dystrophy, Sickle Cell Anemia as well as X chromosome-linked disorders.

Analyzing for gene disorders in embryos requires the removal of a blastomere from each embryo, just like what is done for chromosome analysis. The difference lies in the method of analysis – techniques that greatly multiply the genetic code contained in a single blastomere are employed so that the specific gene, or genes, being looked for may be detected. The process involved is the polymerase chain reaction (PCR) which causes the creation of several copies of the target DNA.  The entire procedure takes about the same amount of time as chromosomal evaluation by PGD-FISH does.

Can PGD of Embryos Improve The Chance Of Conceiving Through In Vitro Fertilization?

Before the advent of PGD, assisted reproductive technology laboratories had to rely on the “appearance” of embryos to decide which ones to put back into the patient’s uterus to establish a pregnancy. PGD has proven that normal appearing embryos frequently have abnormal numbers of chromosomes, rendering them incompatible with the development of a normal pregnancy.

This is no doubt a big part of the reason why, after twenty years and almost 1,000,000 births from assisted reproductive technology, there is probably no higher incidence of birth defects in IVF-derived births than that found in naturally conceived children, despite the replacement of these chromosomally unbalanced embryos. This is also the reason why multiple pregnancy isn’t almost 100% in IVF – many of the embryos chosen for replacement just by their appearance are actually chromosomally unbalanced, and do not “take”.

PGD allows embryologists to select embryos balanced for the chromosomes tested. This knowledge should increase the chance of pregnancy per embryo placed in the patient’s uterus, and fewer embryos will need to be replaced.

What Does The Future Hold For Genetic Testing of Embryos?

About two years ago it was announced that the entire human genetic code had been sequenced, or “mapped”. The completion of this tremendous effort will allow scientists to continue to discover sequences of the code that comprise specific units of information called genes.

Genes are responsible for directing the business of constructing our bodies down to the tiniest molecular detail. It is logical to believe that, eventually, the functions of all genes (and the detection of abnormal ones) comprising the human genome will be categorized. This knowledge may in turn be used to deliver humankind from almost all disease; heritable, infectious, and cancerous.

In ART application, a single embryo may be all that is needed to establish a pregnancy, and it will be a healthy pregnancy. Almost monthly, a new marker for genetic disorders is being reported in the literature. The future, it seems, arrives faster every day.