What is PGD, or pre-implantation genetic testing?

Pre-implantation genetic diagnosis involves testing done on in vitro fertilization(IVF) embryos prior to transferring them to the mother’s uterus. The testing is done either to check for a specific genetic abnormality (such as a disease like cystic fibrosis), or it can be done to determine if the embryos are chromosomally normal (also called aneuploidy screening). It can also be used to identify gender.
PGD is done by removing multiple cells, usually at the blastocyst stage (day 5 after fertilization). A hole is made in the shell of the embryo, and then a pipette is used to suck the cell(s) away from their neighbors – removing them from the embryo so that testing can be done. This process is called embryo biopsy or blastomere biopsy.


Fluorescence in situ hybridization is a technique that is used to identify specific chromosomes by utilizing fluorescent probes. The labeled probes are a colored dye that bind to chromosomes and can be visualized under a fluorescent microscope. Currently, the technique enables up to 5 chromosomes (X, Y, 13, 18 and 21) to be detected simultaneously in a single cell. This technique is used for sex determination in sex linked diseases and family balancing cases and for numerical and structural chromosomal abnormalities e.g. aneuploidy screening. Embryos can be tested on day 3 after fertilization and transferred back to the woman on day 5 after the results are back.


Natera is a newer PGS analysis process that has the capability of analyzing all 23 chromosomes in addition to the sex chromosomes, X and Y. Natera began offering its 24 Chromosome Aneuploidy Screening with Parental Support test to IVF clinics in October 2008 and over sixty IVF clinics are now offering the test in the United States and Europe. Natera has the capability to analyze all chromosomes to provide a complete picture of each embryo and provide the ability for parents to choose the embryo that has the best chance for a live birth. Natera also affords the possibility of retesting a day 3 ”abnormal” embryo again on day 5. This capability has shown that embryos have the capability of self-correction that would have otherwise been discarded.

The issue with FISH analysis is the chance of false positives based on the timing of where the embryo is with cell division at the time of biopsy. The fear is that normal embryos are being labeled as abnormal with FISH. Natera is attempting to correct this.

“Test accuracy with PGS has historically been a chronic problem due to the inherent difficulties associated with testing the tiny amount of genetic material present in a single cell. GSN overcomes the technical limitations of previous technologies to provide more comprehensive and accurate testing for patients,” said Dr. Barry Behr, Co-Director of the REI/IVF Program at Stanford Fertility and Reproductive Medicine Center.

The first report of PGD in humans with pregnancy resulting was published in 1990 – major improvements in these technologies have occurred since then.


Aneuploidy is a condition where cells have the wrong number of chromosomes. An example of aneuploidy is trisomy 21 in which there are 46 normal chromosomes and one extra chromosome number 21 for a total of 47.

Polyploidy is a condition where cells have an extra set of chromosomes. For example, triploid embryos have 3 sets of 23 for a total of 69 instead of the normal 2 sets of 23 for a total of 46.

Mosaicism is a condition where some cells in a tissue have a different chromosomal complement as compared to other cells in the same tissue or organism. For example, a 4-cell embryo can have 2 cells that have 46 normal chromosomes and 2 cells that have 46 normal chromosomes and an extra chromosome number 18 for a total of 47.

Some things to consider:

  • It is known that in vitro cultured human embryos have a high incidence of abnormal chromosomal content. Most embryos will be abnormal.
  • The older the woman is, the more abnormal embryos
  • Proven fertility doesn’t necessarily reduce the incidence of abnormal embryos
  • There are no reports of increased fetal abnormalities following PGD. However, long-term consequences on the fetus is unknown at present. It is important to note that there is a possibility that none of the embryos tested will be normal, in this case none would be suitable to transfer. Furthermore, as with all tests there is a possibility of a false positive result (10% false positive rate PER PROBE). This is because many embryos display inconsistency in chromosomes from cell to cell (mosaicism) and thus the cell taken for biopsy may not be a representative of the other cells of the embryo. For gender identification purposes, PGD analysis is 99% accurate. The 1% is reserved for human error only.