Preimplantation Genetic Testing of Human Embryos

Preimplantation genetic testing (PGT) of embryos to detect abnormal numbers of chromosomes, or to detect heritable disorders, is a rapidly growing field in assisted reproductive technology. The first reports of PGT successfully used in conjunction with human in vitro fertilization (IVF) appeared in the early 1990s. Since then, hundreds of normal infants have been born through use of this exciting new technology.

How Is PGT Performed?

PGT requires patients to undergo a cycle of IVF in order to have embryos (actually pre-embryos) available for this procedure. In IVF, a woman takes medication 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 pre-embryos available for PGT evaluation. The blastomeres are then individually evaluated to see if the pre-embryo each was taken from is normal for the traits being tested. It takes 1-2 days for the results to be known. Once they are, only the unaffected pre-embryos are transferred into the patient’s uterus to establish a pregnancy.

What Can Be Determined About A Pre-Embryo By The PGT Procedure?

PGT in its current usage is used for determining the number of specific chromosomes present in pre-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” – this can lead to early embryonic demise (chromosomes 13, 16, 18, 22) or affected term births such as Down’s Syndrome (Trisomy 21). 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 can also have their pre-embryos evaluated by PGT-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 pre-embryos requires the removal of a blastomere from each pre-embryo, just like what is done for analysis of chromosomes. 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 entire procedure takes about the same amount of time as chromosomal evaluation by PGT-FISH does.

Can PGT of Pre-Embryos Improve The Chance Of Conceiving Through In Vitro Fertilization?

Until there was PGT, assisted reproductive technology laboratories had to rely on the “appearance” of the pre-embryo to decide which ones to put back into the patient to establish a pregnancy. PGT has proven that normal appearing pre-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 in vitro fertilization, there is no higher incidence of birth defects in IVF-derived births than that found in naturally conceived children, despite the replacement of these chromosomally unbalanced pre-embryos. This is also the reason why multiple pregnancy isn’t almost 100% in IVF – many of the pre-embryos chosen for replacement just by their appearance are actually chromosomally unbalanced, and do not “take”.

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

What Does The Future Hold For Genetic Testing of Pre-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 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, cancerous. In ART application, a single pre-embryo will be all that need be transferred to establish a pregnancy – and it will be a healthy pregnancy. Almost monthly, a new marker for heritable disorders is being reported in the literature. The future, it seems, arrives faster every day.