Pre-implantation Genetic Diagnosis (PGD)

Pre-Implantation Genetic Diagnosis (PGD) is a technique used in conjunction with In Vitro Fertilization (IVF) to test embryos for specific genetic disorders PRIOR to their transfer to the uterus.

Genetic screening may help identify couples who have an increased risk of age-related or familial genetic disorders and birth defects. No single test, however, can accurately predict the risk of all defects in a child. Many birth defects, such as those related to environmental and toxic exposures, and those that are random and unexplained, are not genetically based and may not be detected with genetic screening.

Screening for genetic diseases that may affect offspring depends upon the racial or ethnic background of the couple, their family and medical history, and associated conditions. Various racial and ethnic groups demonstrate an increased prevalence of specific diseases, and couples from these backgrounds may have their carrier status screened by a blood test, accordingly, as described below.

One of the most common reasons to have PGD performed is the mother’s age, since the risk of having a child with a chromosomal abnormality, such as Down Syndrome, increases as a woman ages. Genetic testing of the pre-implantation embryo can determine whether the embryo could potentially be affected by a chromosomal abnormality. Therefore, the chance of conceiving a baby with a chromosomal abnormality will be reduced by more than 90% after PGD. Additionally, if both parents are carriers for a genetic condition, PGD makes it possible for couples or individuals who have or who carry serious inherited disorders to decrease the risk of passing the disorder on to their child.

For PGD to be performed, a couple undergoes a IVF cycle to obtain eggs that are subsequently inseminated and grown in the IVF Embryology laboratory for three days. At this time most of the embryos will be between the six to eight cell-stage of growth.
A highly skilled embryologist then uses a sophisticated microscope set-up to extract a single cell. Each cell is numbered and corresponds to the embryo from which it was taken. These cells are then analyzed for the particular genetic testing and the results from each cell are used by IVF determine which of the embryos are affected with the genetic trait or not. Some of the unaffected embryos can then be transferred back to the patient’s uterus to attempt a pregnancy.
There are two main types of PGD testing that can be performed on the cells extracted from each embryo.

The first type is known as aneuploidy screening utilizing CGH (a micro-array technology).
With this technology, comparative genomic hybridization (aCGH) allows for all 24 chromosomes to be screened. Aneuploidy screening appears to be most beneficial for certain women including women of advanced reproductive age (women over the age of 36), who have recurrent pregnancy loss (> 2 miscarriages) or those with chromosome translocations (abnormal combinations of chromosomes).

The second type of PGD is known as monogenic or single-disease screening. This technique involves the same components of aneuploidy screening (IVF cycle, embryo cell biopsy) but in this case a specialized test called the Polymerase Chain Reaction (PCR) is applied to the extracted cell to determine if the embryo is affected with the a particular genetic disease.
Some of the more commonly known monogenic disease includes some of the following: (with Racial / Ethnic Associations to specific diseases)

Sickle Cell Disease. Anyone with African-American ancestry should be screened via hemoglobin electrophoresis for carrier status of this disease, as one in 10 may be a carrier.
Cystic fibrosis (CF). It is estimated that 3% to 10% of Caucasians carry a defective CF gene, but do not have symptoms because a person must inherit two defective CF genes, one from each parent, to develop the disease. CF is the most common, serious, inherited disease in Caucasians, and is more common in those of northern or central European background and Ashkenazi Jewish background.
Thalassemia. People of Greek, Italian, Mediterranean or southern Asian descent experience a high incidence of this disease. Patients can have a complete blood count (CBC) with mean corpuscular volume (MCV) to rule out the possibility of thalassemia. An MCV of <80 should be evaluated further by hemoglobin electrophoresis. About 3% of the world’s population carries a gene for thalassemia.
Tay Sachs. This disease has a high incidence in Eastern European Jews and French Canadians.

Familial Associations with Specific Diseases:
A family history of any of the following disorders should prompt genetic counseling, and when relevant, screening or testing for associated gene abnormalities or carrier status:

Down syndrome
Muscular Dystrophy
Tay Sachs
Chromosomal syndromes
Neurofibromatosis
Recurrent miscarriage
Cystic Fibrosis
Hemophilia or other bleeding disorders
Mental retardation
Familial dysautonomia

Indicators for Pre-Implantation for Genetic Screening:
Advanced Maternal Age (women over 35 years of age), those with a previous affected child, and those with a positive family history have a higher risk of chromosomal problems and miscarriage.

Prior to attempting pregnancy, women of Advance Maternal Age and those with high risk histories may wish to consult their physician or a genetic counselor about their chances of having a child with a chromosomal problem, such as Down Syndrome

Medical History/Conditions Associated with Genetic Conditions:

Recurrent miscarriages. This may be due to chromosomal or genetic abnormalities. Women who experience two or more consecutive miscarriages are frequently screened to see if they carry abnormal chromosomes that predispose to miscarriage.
Congenital Bilateral Absence of Vas Deferens (CBAVD) or the absence of the two muscular tubes that carry sperm from the epididymis to the urethra. CBVAD is associated with CF. The majority of men with CBAVD have CF. For couples where the man has CBAVD, the CF carrier status of the female partner must be determined.
Azoospermia or absence of sperm in semen, and severe Oligospermia, which is having very low sperm counts, have been associated with chromosomal and genetic abnormalities. Blood tests, including a karyotype (which looks at the number and structure of the chromosomes) and Y chromosome micro-deletion analysis (which looks for missing pieces of the Y chromosome), may be helpful in selected cases. If abnormalities are identified, genetic counseling is indicated.

PGD is now developed to the point where it can be safely and reliably used to aid, not only couples who are already seeking infertility treatment, but also couples who are at genetic risk for passing along an inherited trait to their offspring.