Medical and scientific aspects
Preimplantation Genetic Diagnosis
Last update: March 2013
Contact: Theresia Volhard
I. Medical and scientific aspects
The term "preimplantation genetic diagnosis" (PGD) (see module Preimplantation Genetic Diagnosis) describes methods of testing embryos generated by in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) (see module Intracytoplasmic Sperm Injection (ICSI)). The genome of one or two cells of a several-days-old embryo – usually during the so-called 8-cell stage (blastomere), i.e. about three days after fertilisation (see module Embryonic Development) - is tested for certain mutations (see module Application of PGD for Genetic Diseases) or chromosomal abnormalities (see module Aneuploidies) that may result in a disorder, before the embryo is transferred to the uterus. PGD can also be used to identify other than disease-relevant characteristics, such as the embryo’s sex, the "presence of a certain disability" (see module Fields of Application of PGD for Selecting Embryos with Certain Characteristics) or the embryo’s suitability as an organ or tissue donor (see module HLA Compatibility) for a living sibling affected with a disease. In "some countries" (see module Saviour Siblings) , PGD is already being applied for these purposes. More indications for the application of PGD can be found in international medical literature: “high” maternal age, i.e. over 35 years, repeated unsuccessful IVF treatments, recurrent miscarriages and ICSI. However, a study published in 2007 in the New England Journal of Medicine (see module Study of the New England Journal of Medicine) claims that IVF with subsequent PGD does not lead to higher pregnancy rates.
In the case of most of the employed techniques (see module Methods Used for PGD) the one or two cells which are removed from the embryo for testing are totipotent (see moduleTotipotency) at this stage. It can thus be assumed that, given certain conditions, they could each develop into an individual embryo. As the destruction of totipotent cells is considered as ethically and legally problematic (see below), it is being suggested that the removal of cells (biopsy) should take place five to six days after fertilisation, i.e. at the so-called blastocyst stage. According to the current state of research, these cells are no longer totipotent, but merely pluripotent (see module Pluripotency). However, since cell junctions are already much tighter at this moment (so-called compaction), there is a higher risk of damaging individual cells whose genetic material could then contaminate the test sample. In addition, removing cells at this stage more frequently leads to the destruction of the embryo than the removal of cells at the blastomere stage.
The technologies necessary to perform PGD were mostly developed in the U.S., Great Britain and Belgium at the end of the eighties/beginning of the nineties. The first child after PGD testing was born in Great Britain in 1990.
The PGD-related methods of preconception or prefertilisation diagnosis (see module Preconception / Prefertilisation Diagnosis) are less controversial than genetic testing of embryos. They involve the genetic analysis of the polar bodies of the woman’s oocytes prior to fertilisation. This method thus only provides information on the maternal genotype. It could be complemented by a preconceptional genetic analysis of the male spermatocytes. However, the main difficulty of this method lies in the fact that the spermatocytes are generally being destroyed in the procedure and are thus no longer available for later fertilisation of an oocyte. Currently, procedures aiming at artificially duplicating the spermatocytes prior to their genetic analysis are being clinically tested: thus, the genetic material of the first spermatocyte could be used for testing and the second, identical spermatocyte for fertilisation.
Physical methods allow the identification of sperms carrying Y-chromosomes, as they vary in mass to those carrying X-chromosomes due to different DNA contents. This could be used in the context of fertilisation involving sex selection to avoid X-linked genetic diseases.
If PGD and the subsequent transfer of the embryos to the maternal uterus result in a pregnancy, the diagnostic findings of PGD are usually checked by the (non-invasive and/or invasive) (see module Non-invasive Methods of Prenatal Diagnosis (PND) and/or Invasive Methods of PND) methods of prenatal diagnosis (PND).
The risks of PGD for the woman can be compared to those of extracorporeal fertilisation by IVF/ICSI without PGD. On the one hand, the removal of the oocytes and the transfer of the embryos following PGD may bring about infections. On the other hand, there is an increased risk of ovarian hyperstimulation syndrome (see module Ovarian Hyperstimulation Syndrome (OHSS)). This is due to the fact that, as a general rule, more oocytes have to be generated for PGD than for IVF/ICSI without PGD, given that many embryos are not transferred because of unsuccessful biopsies, diagnostic findings or irrelevant results of the testing. Therefore, hormonal stimulation is usually set at a higher level when PGD is used than in the context of in vitro fertilisation without subsequent PGD. In addition, there are risks related to multiple pregnancies, which increasingly occur in the context of extracorporeal fertilisation. Moreover, the woman or the couple may have to face high psychological strain, as a result of hormone treatments and also of hopes and fears related to the success of the method.
The embryo faces the risk of not being transferred and of being destroyed in the case of abnormalities discovered, irrelevant testing results or false diagnosis. Further risks include the embryo’s destruction during the removal of cells for testing and the increase in multiple pregnancies. Some studies prove that IVF embryos are more likely to develop malformations (see module Increased Risk of Malformations in IVF Embryos).