Treatment - Pre Implantation Genetic Diagnosis
What is Preimplantation Genetic Diagnosis?
This is a technique for discovering whether a baby will be born with a serious inherited disorder before the pregnancy has even started. This means that the parents do not have to face the possibility of terminating a wanted pregnancy after an unfavourable result has been obtained after chorionic villus sampling (CVS) or amniocentesis.Preimplantation Genetic Diagnosis (PGD) involves making a small hole in the zona pellucida (the shell-like coating surrounding the egg and embryo through which the sperm must travel) of the 8 cell embryo and removing a single cell from the embryo. Removing one cell does not harm the embryo at this stage and as the cell is identical to the rest of the embryo it can be used to make a genetic diagnosis. This tells us whether the embryo from which the cell was taken, is free of the genetic disease, is a carrier for that disease or is affected by the disease. Embryos that are unaffected by the disease are placed into the uterus to establish pregnancy.
The technique involves amplifying the genetic information within the cell millions of times so that it can be analysed in the laboratory. It is therefore at risk of being contaminated by any extraneous sperm. Therefore we require that people wishing to have Preimplantation Genetic Diagnosis undergo conventional IVF (in vitro Fertilisation) and ICSI (Intracytoplasmic Sperm Injection) even if they are able to conceive pregnancies naturally (that is naturally fertile people).
Preimplantation Genetic Diagnosis is specifically aimed at detecting the condition that we are concerned about. Of course other fetal abnormalities would not be excluded even if they were genetically determined (such as Down's Syndrome) and the risk would be the same as any other pregnancy.
Definition of Terms.
- Embryo: After an egg is fertilized, it often becomes a progressively dividing embryo prior to implanting in the uterus and becoming a pregnancy. On the third day after fertilisation, it should be at the 8-cell stage that is the most suitable for the biopsy of 1 or 2 cells from it. These cells are known as blastomeres.
- Biopsy: The removal of one of the live cells from the embryo. Cells in an embryo are undifferentiated at this stage. This has no significant adverse effect on the potential of the embryo to create a normal pregnancy.
- X & Y Chromosomes: Female embryos have two X-chromosomes. Male embryos have one X and one Y chromosome.
- FISH: Fluorescent In-Situ Hybridization. The use of a fluorescent genetic probe for a specific chromosome (e.g.) X, Y & chromosomes 13, 18, & 21) to identify the number of chromosomes present and hence determine the sex of the cell or the presence of abnormal chromosome numbers.
What types of diseases or disorders can we analyse by PGD?
In theory we should be able to diagnose any inherited disorder. Unfortunately the procedure is technically demanding and only one cell is available for diagnosis. For this reason testing is only established for some of the more common genetic conditions. These are cystic fibrosis, thalassemia, Huntingtons disease, Duchenne Muscular Dystrophy, haemophilia and sex determination for many sex-linked disorders (these are disorders where often one gender is unaffected). It is important that the mutation(s) present in each partner are well defined. We are willing to work up tests for less common mutations and disorders including family specific disorders.What are the chances of a successful outcome?
As this technology requires undergoing IVF, the chances of pregnancy depend largely on the age of the female partner. As maternal age increases fewer eggs can be collected. If there are fewer eggs the chances of obtaining an unaffected embryo are reduced, thus reducing the chance of pregnancy.The percentage of unaffected embryos for a particular person depends entirely on the disorder in question and on the number and type of mutation(s) carried by the person. Therefore some cycles are likely to yield more embryos suitable for transfer than others. It is quite possible that No embryos are found to be unaffected by the disorder and therefore no embryos will be transferred in that cycle.
Why do couples request to have PGD performed?
People can avoid their children having the inherited disorder by the antenatal tests already available. These procedures remove fetal tissue from the placenta (CVS or chorionic villus sampling at 10-12 weeks) or the amniotic fluid (amniocentesis at 16 weeks). This carries a degree of risk of miscarriage of an otherwise healthy pregnancy. More significantly diagnosis in an established pregnancy means making a decision to terminate the pregnancy or not in the second three month period of the pregnancy.What can go Wrong?
PGD is still considered an experimental procedure worldwide and is continually being refined. As such there are some risks with this procedure:- Destruction of the embryos during the biopsy procedure. The outer covering of the embryo shatters and the embryo loses its integrity. Failure of any embryos to develop to the 8-cell stage. Depending upon the female age, a number of embryos may have internal errors, which results in the cessation of division between the 4 and 8 cell stage. The more embryo's there are, the more likely that there will be embryos reaching the 8 cell stage.
- Destruction of Blastomeres. To perform FISH it is necessary to place the cell nucleus on a glass slide. Chromosomes are contained within the nucleus, in 5-10% of cases the results may be unreadable. All embryos are found to be abnormal. Around 1/3 of embryos lacking the male Y chromosome will have an abnormal number of X-chromosomes and cannot be transferred. Females over the age of 40 years have an increased chance that the embryos will have abnormal numbers of chromosomes 13, 18 & 21. The more embryos available for testing the greater likelihood that normal embryos will be found.
- Incorrect embryo diagnosis. The various blastomeres within an embryo may not all have the same chromosome numbers. If the blastomere that is biopsied is abnormal it could lead to the discarding of an otherwise normal embryo. If we were to inadvertently biopsy the only normal blastomere from an embryo, it could result in the transfer of an abnormal embryo. For this reason patients becoming pregnant from the transfer of embryos diagnosed by this procedure may still wish to have pre-natal diagnosis of the baby around 14-16 weeks or pregnancy.
What are the chances that a misdiagnosis occurs?
A misdiagnosis could occur from this technique. Conventional prenatal diagnosis methods have large amounts of material available for analysis and therefore errors are considered extremely rare. We perform our analysis on a single cell obtained from the 8-cell embryo and thus the diagnosis is very difficult. Contamination of the genetic analysis tests is possible as well as one or more if the genes failing to amplify.
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