PGD: genetic pre-implantation diagnostics – facts and myths

PGD: genetic pre-implantation diagnostics – facts and myths

Thanks to advances in medical science we have now diagnostic tests that can be used at the very beginning of human development. It is now possible to assess not only the reproductive cells but also embryos during the first stages of in vitro culture after fertilization. Currently available technologies make the comprehensive evaluation of embryo genetic status possible. Clinics worldwide use genetic status as a criterion for embryo selection for transfer. Is preimplantation genetic diagnosis only a manifestation of possibilities associated with new diagnostic methods showing that medicine follows the latest technologies? Or does it bring real benefits to patients? Who else can benefit from this medical procedure?

Since 1989 preimplantation genetic diagnosis has been changing dynamically and new improved techniques have been introduced. It all began with one technique and with time the range of available methods has increased to more than 10. Currently, revolutionary next generation sequencing has been introduced into this field. The first diagnostic test included reading of one region of the Y chromosome whereas currently the whole genome is read. Embryos are profiled with regard to a selected genetic trait and it is a basis to prioritize them when selecting for transfer.

It is important to consider the scope of a given diagnostic test. In case of a diagnostic test for a single gene disease it means selecting an embryo that lacks the specific mutation in a specific gene. In case of a diagnostic test for chromosomal copy number changes (aneuploidy) it means selecting an embryo with a normal number of chromosomes, i.e., no additional (as in trisomy) or missing (monosomy) chromosomes. It is also possible to perform both types of tests at the same time.

Regardless of the type of tests performed, preimplantation genetic diagnosis is aimed to find an embryo without an undesirable pathogenic trait that it was tested for. Preimplantation genetic diagnosis replaces “blind” selection with selection based on knowledge. From a pool of available embryos it is possible to transfer a selected one based on the results of tests performed on several cells that have been collected from this embryo. A biopsy of embryonic cells is currently a well-developed procedure, and when performed appropriately by a trained embryological personnel it is a safe procedure.

Patients opting for preimplantation genetic diagnosis obtain real benefits such as a shorter time to a normal pregnancy. It is a result of the fact that thanks to selection based on knowledge IVF cycles are not performed with embryos lacking potential for development. Each IVF cycle is associated with more psychological burden, is time-consuming and associated with economic costs for patients. But what about patients who have time and are willing to wait for several cycles until pregnancy?  Blind selection is associated with even greater costs as it may turn out that none of embryos available in a given pool had a potential for a normal pregnancy (and it shall be known only when all current embryos have been exhausted).

Preimplantation diagnosis does not prevent creation of abnormal embryos but provides knowledge and makes informed selection possible. The rate of abnormal embryos depends on the patients’ individual situation, including their age and genetic mutation load.

Preimplantation diagnosis does not increases chances of development of a normal embryo but makes it possible to avoid side effects associated with “blind” transfers. It enables identification of genetically normal (based on the specific  test performed) embryos and optimal selection for transfer.

The consequences of a situation when PGD has not been performed despite indications are also important. Such situations still happen. Patients are then at risk of an increased psychological burden due to pregnancy termination or permanent treatment of a child with a genetic disease. This last problem also affects the national economy. Pre-implantation diagnosis is associated with costs incurred now and with great savings in the future, such as reduction of expenses covering care for chronically-ill patients. For example, thanks to preimplantation diagnosis for single gene diseases a given disease is no longer passed on to new generations in the family.

The latest technologies are also present in the reproductive medicine. Nonetheless, advances associated with procedures have not affected basic rules valid in pre-implantation diagnosis. Genetic preimplantation diagnosis is aimed at identifying the best embryo. PGD shortens time to a normal pregnancy. PGD does not increases chances of a normal embryo developing and does not reduce chances of an abnormal embryo developing. PGD is a tool for observation and makes an optimum selection possible – based on knowledge. Selection that will make it possible to enjoy future offspring.

Sebastian Pukszta, Ph.D.
Sebastian Pukszta, Ph.D.
Deputy Manager of the INVICTA Laboratory in charge of the Molecular Biology Lab. He holds a Ph.d. in Biology and is an author of numerous publications and member of the INVICTA’s scientific team. His interests include new methods of laboratory diagnostics, in particular in the field of molecular biology.