Pre-implantation genetic diagnosis (PGD) is essentially an alternative to prenatal diagnosis, in which genetic testing is performed on embryos produced by in vitro fertilization (IVF) before a pregnancy is established. PGD has been mostly applied to woman of advanced maternal age undergoing IVF in order to increase implantation rates and to reduce the chances of miscarriage and genetically abnormal offspring. This modality of PGD is known as PGD of aneuploidy.

PGD has also been applied to chromosomal disorders, such as translocations, in which it has proven to decrease the number of miscarriages while preventing the conception of abnormal babies.

The number of single gene disorders (disease caused by genetic defects) that can now be diagnosed with PGD continues to grow. Now, diseases such as Cystic Fibrosis, Fragile X Syndrome, Myotonic Dystrophy, Thalassemia, and Tay Sachs Disease can be prevented with PGD.

Embryo biopsy for PGD.

The advent of commercially available probes labeled with different fluorochromes (colors) has made it possible for clinical scientists to screen individual embryos for the normal number of chormosomes. There should be 2 (and only 2) chromosomes of each of 22 non-sex chromosomes (autosomes) besides the sex chromosomes (XX or XY). Any more (for example, 3 chromosomes, such as chromosome 21, which would be a trisomy [Down Syndrome]) or less than 2 chromosomes (monosomy) will result in an abnormal (aneuploid) embryo, which will ultimately either fail to develop, implant and miscarry, or will produce a genetically abnormal baby.

Normal chromosomes as demonstratrated by fluorescence in situ hybridization (FISH).

Trisomy 21 (Down Syndrome). Note the 3 blue chromosomes, consistent with Down Syndrome.
Normally, only two copies of chromosome 21 should be present.

PGD allows us to identify and separate the chromosomally normal embryos from the abnormal embryos so that only normal embryos are transferred into the woman’s uterus.

Most couples who choose PGD have one of the following conditions: recurrent miscarriages, maternal age over 38, prior unexplained IVF failures, conception of a chromosomally abnormal child or fetus, heritable medical condition in the patient or prior child (such as cystic fibrosis), or two or more children of the same gender (sex selection for family balancing).

Using PGD to select the best embryos appears to be superior to traditional methods of embryo selection. In the past, doctors selected embryos for transfer based on appearance (low fragmentation, even cell size, and tight junctions) and rate of cell division. PGD has demonstrated that many “beautiful” embryos are in fact genetically abnormal (abnormal embryos can develop “normally”), and that many moderately fragmented or slow-growing embryos are normal and highly viable. While blastocyst culture (without PGD) appears to eliminate most monosomies (embryos with a single copy of a chromosome instead of two copies), it does not eliminate all trisomies (three copies of a chromosome such as trisomy 21, Down Syndrome). With PGD, the laboratory can detect more than 90% of abnormal embryos and thus avoid the transfer of abnormal embryos.

Once the pregnancy test is positive, couples can be more optimistic that they will experience the birth of a genetically normal child. Although single digit miscarriage rates do occur after PGD, miscarriage rates will likely decrease and implantation rates will likely increase as the technology associated with PGD continues to grow. PGD and other technologies will also help us to reach the goal of transferring a single embryo and virtually assuring a singleton pregnancy.