Pre-implantation Genetic Diagnosis (PGD)/Pre-implantation Genetic Screening (PGS) are techniques used during In Vitro Fertilization (IVF) procedures to screen embryos for genetic or chromosomal disorders prior to transfer into the uterus. These tests are designed to reduce the risk of transmitting specific heritable genetic or chromosomal disorders. PGD allow couples at high risk for having a child with serious genetic disorder to screen the embryos prior to implantation, transferring only embryos that do not carry the specified genetic disorders. The development of PGS has enabled the pre-selection of embryos with normal chromosomal numbers for transfer, decreasing the chance of pregnancy loss for women of advanced maternal age or with a history of repeated miscarriage. PGD/PGS require specialized micromanipulation technology, equipment and experience. Coordination of genetic counseling, embryology/IVF technology and molecular genetic analysis is necessary. Given the need to manipulate and remove cells from the embryo as well as the cost involved, these procedures are not performed routinely but rather only for specific indications.


To accomplish PGD/PGS, embryos are derived through IVF. The first stage of the procedure involves creating an opening in the zona pellucida (shell) surrounding the embryo using micromanipulation techniques. Usually the embryo is composed of 6-8 cells 3 days after fertilization or are at the blastocyst stage 5 days after fertilization. A single cell from day-3 embryo or several trophectoderm (the outer cell layer of embryo) cells from day-5 embryo are removed at this time, and are sent for genetic evaluation. Removing a single cell from a day 3 embryo or several cells from day-5 embryo will not compromise the embryo development. The embryos are returned to the incubator for either a fresh embryo transfer or cryopreserved for future use.

Genetic Analysis

DNA from the biopsied cells is studied using the molecular technique of Polymerase Chain Reaction (PCR), Fluorescent in situ Hybridization (FISH) or Comparative Genomic Hybridization (CGH). PCR is used to detect single gene disorders. The DNA sequence in question is amplified through PCR and then studied for the presence or absence of the mutation. FISH is utilized to study chromosome number and in some cases, chromosome structural disorders (translocation). The FISH technique involves the use of differently colored fluorescent probes, which attach to specific chromosomes then the chromosome pairs are analyzed. In CGH, DNA from the test sample and DNA from normal control DNA are amplified separately using a Whole Genome Amplification (WGA) approach such as PCR. The amplified DNA is differently labeled with one of two fluorochromes (color) and allowed to compete to hybridize to either side. Specialized computer software analyses the ratio of two different colors for the deficiency or gain of certain regions or for the entire chromosome.

Practical and Ethical Issues

The goal of PGD/PGS cycle is the birth of an unaffected, healthy child. PGD/PGS has not yet been demonstrated to significantly increase the pregnancy/IVF success rate, and does add additional cost to the IVF procedure. To date, the studies of children born in association with PGD/PGS have been reassuring, with no adverse outcomes experienced in excess compared to the general population. As such, the technique should be utilized to prevent the conception of child bearing significant genetic or chromosomal abnormalities. Public concept exists about the use of PGD for social reasons, such as a sex selection. It is imperative that appropriate ethical guidelines are established and adhered to at centers offering PGD/PGS. Continuing efforts to develop methods to screen for a larger number of disorders are underway. Overall, PGD/PGS is becoming an increasingly valuable procedure offering at risk couples improved chances of carrying and giving birth to a healthy, unaffected child.