Preimplantation Genetic Diagnosis (PGD)

Pre-implantation Genetic Diagnosis

Pre-implantation genetic diagnosis, also known as PGD, is a groundbreaking assisted reproductive technique for screening eggs or embryos for genetic diseases and chromosomal abnormalities like balanced translocations. PGD is used when couples know they are carriers of a genetic disorder, such as cystic fibrosis, Tay-Sachs, Turner syndrome or other diseases or when they have suffered pregnancy losses due to chromosomal problems.

PGD can screen for the following conditions:

  • Cystic fibrosis
  • Down syndrome
  • Hemophilia
  • Huntington’s disease
  • Muscular dystrophy
  • Sickle cell anemia
  • Marfan syndrome
  • Tay-Sachs disease
  • Turner syndrome


One of the most significant uses of PGD is to identify balanced translocations. Often patients will discover they have this genetic disorder after suffering multiple miscarriages and undergoing genetic testing to rule out a genetic link. A balanced translocation results when two chromosomes exchange parts. Normally during fertilization, each parent contributes 23 pairs of chromosomes, or genetic packages, to the developing embryo. A balanced translocation has the correct number of chromosomes, but there is a rearrangement of chromosomal material.

There are several possible outcomes for balanced translocations: the child may inherit normal chromosomes from both parents; the child may inherit the same balanced translocation and be normal; the child may inherit an abnormal chromosome pattern that results in either too much or too little information transmitted, which may result in severe birth defects; or the pregnancy ends in miscarriage.


The first part of the PGD process is similar to routine in vitro fertilization. After stimulation with fertility medications to increase the number of eggs a woman normally produces, the female partner undergoes an egg retrieval while the male partner contributes a sperm sample. The next step is dependent on whether the source of the translocation is male or female.


If the translocation is inherited from the mother, the embryologist performs a polar body biopsy. Polar bodies are extruded by mature eggs and contain one set of chromosomes from the previously diploid eggs. An embryologist carefully inserts a small hole in each egg’s zona (outer shell), and removes the polar body for analysis. The polar body is put on a slide fixed and a FISH probe (see description below) is applied. The sperm and the normally growing eggs then are combined in the laboratory via ICSI, enabling fertilization, growth of the embryos and transfer into the female partner’s uterus.


When there is a male balanced translocation, a blastomere biopsy is performed. Before the embryo transfer, single blastomeres (cells) from each embryo are removed and analyzed for abnormal chromosome complement. Normally, human embryos are cultured in a special medium for several days before transfer. Typically after approximately three days in culture, most high quality embryos reach the eight to ten cell stage and are amenable to PGD. PGD is achieved by creating a small hole in the zona pellucida of single embryos and removing carefully one or two cells. The aspirated cells are then used for genetic analysis. At this early stage of embryo development, all cells are equivalent and removal of one or two does not affect viability, the cleavage rate, or further development. After the cell removal, the biopsied embryos are returned to the culture pending the diagnosis based on the genetic analysis of the single cell biopsies.


Fluorescent In Situ Hybridization (FISH) is the method of genetic analysis of polar bodies and blastomeres from couples with a balanced translocation. FISH uses chromosome-specific probes labeled with different colored fluorescent tags to detect the number of copies of a given chromosome in a non-dividing cell. The tags glow when they are exposed to fluorescent light of the correct wavelength and bind or “hybridize” to the target DNA. When a DNA FISH probe binds with its genetic target, a brightly colored signal can be observed allowing the embryologist to detect chromosomal aneuploidies, thus permitting the identification of embryos with a normal chromosome complement.


The PCR, polymerase chain reaction, technique is used to analyze embryos for genetic disorders such as cystic fibrosis and sickle cell disease. PCR is a primer extension reaction for amplifying specific nucleic acids in vitro. It amplifies a short stretch of DNA to about a million fold so that its size, sequence and other factors can be determined. This sequence can be used to determine if a particular embryo is “affected” or has the particular sequence identified as being responsible for the genetic abnormality.