Pre-Implantation Genetic Testing

Embryo or pre-implantation genetic testing has made tremendous advances since its introduction in 2005. Although genetic testing could be performed on human cells before 2005, techniques were developed in 2005 to perform genetic testing on a single cell removed from a developing embryo. The test not only determined if the embryo was genetically normal, but it did so within 30 hours of removing the cell. This new tool allows the prospective parent(s) undergoing in vitro fertilization (IVF) to test for a specific gene or for chromosomal abnormalities before transferring the embryo into the uterus. Thus for the first time, the parent(s) could avoid transferring an embryo with genetic diseases. But we are getting ahead of ourselves; first let’s have a short discussion about genetics.

Genetics

The human genome is the complete set of genetic information that a baby inherits from its parents. This genetic information is organized into rod-like structures called chromosomes. Each cell of an embryo, as well as in a human body, has 23 pairs of chromosomes. The first 22 pairs are called autosomes and the 23rd pair is called the sex chromosomes. Since the sex chromosomes may be composed of two different types of chromosomes (either XX or XY), there are 24 different types of chromosomes in humans.

Chromosomes are made up of DNA, which has a double-helix structure, defined by two intertwined helical backbones composed of phosphates and sugars, and connections between the helices made of 4 unique bases commonly labeled A for adenine, C for cytosine, G for guanine, and T for thymine. Each chemical base has a particular shape such that connections between the two backbones can be made of only 4 possible pairs: A-T, T-A, G-C, or C-G. So if one backbone has an A, then the corresponding backbone connection has to be a T. This feature enables cells to divide and create new cells.

The genetic information is stored in a sequence of these base units. For humans, the sequence contains roughly 3 billion base pairs. A gene is the basic unit for transmitting hereditary characteristics from parents to offspring, and each one typically contains thousands of base units. The human genome is thought to contain roughly 20,000 to 25,000 genes. Some of the base pairs do not play a role in determining hereditary characteristics and are therefore not part of any known gene.

Currently, pre-implantation genetic testing can simultaneously test for all 24 chromosomes for abnormalities within a chromosomal pair. We can also check for a limited number of structural abnormalities between chromosome pairs, called unbalanced chromosome rearrangements. Single gene testing is available only for a few hundred specific genes, representing roughly 1% of the estimated number of genes in the human genome. Testing, therefore, is limited to assessing whether the structure of all of the chromosomes are normal or testing to determine if a specific defect exists, whether it is a base pair sequence within a specific gene or unbalanced chromosomal rearrangements. Human genetics is a complicated subject, but for the sake of our discussion, it is important to remember that there are 24 different chromosomes in 23 chromosome pairs that contain many thousands of different genes.

PGD and PGS

There has been some confusion with respect to the terms Pre-Implantation Genetic Diagnosis (PGD) and Pre-Implantation Genetic Screening (PGS). We have adopted the terminology used by the American Society Reproductive Medicine (ASRM) 2008 Practice Committee Opinion on pre-implantation genetic testing:

• The term Pre-Implantation Genetic Diagnosis (PGD) applies to testing performed to determine whether a specific genetic mutation or chromosome abnormality has been transferred to the embryo when the genetic parents are known to have that specific genetic mutation or a chromosome abnormality.
• The term Pre-Implantation Genetic Screening (PGS) applies to testing performed to screen embryos for extra or missing chromosomes when the genetic parents are known or presumed to be chromosomally normal.