Who is karyomapping for?

You may know that you are a carrier of a genetic disorder because you already have an affected child or you may be aware of a family history of the disorder and have had your DNA tested to confirm that you carry a defective gene.

Karyomapping is a new technique that allows couples, known to be carriers of an inherited condition, to avoid passing on that disorder on to their offspring. The technique works by screening embryos for the problem before implantation in the womb (uterus) – a technique called preimplantation genetic diagnosis or PGD for short.

PGD greatly reduces the chance that a fetus will be affected by the genetic disorder and consequently it is much less likely that termination of a pregnancy will need to be considered or that an affected child will be born.


Why is IVF required?

In order to carry out PGD in vitro fertilisation (IVF) is essential. This process involves collecting several eggs from the ovaries and fertilising them outside the body (in vitro) to produce several embryos. Each of the embryos can then be tested to find out which is healthy.

Only the embryos that are predicted to be free of the genetic condition are transferred to the uterus and consequently any pregnancy that begins has a low risk of being affected by the disorder.


How does karyomapping work?

A blood sample is taken from the father, the mother and another relative who is affected by (or carries) the disorder. In most cases the relative tested is a child of the couple. This relative is referred to as ‘the reference’.

Karyomapping looks at the chromosomes, the rod-like structures that are found in cells and contain the genes. Karyomapping examines the chromosomes of the mother, father and the reference at 300,000 different points, looking for features characteristic of the defective chromosome. Essentially, karyomapping finds a fingerprint that is unique to the chromosome that carries the defective gene. It is then possible to test embryos produced using IVF for this presence of this fingerprint. Whenever the fingerprint is seen in an embryo it means that it has inherited the chromosome carrying the defective gene.

If the fingerprint characteristic of the chromosome carrying the defective gene is not detected then it can be inferred that the embryo has inherited normal copies of the gene and is therefore likely to be free of the disorder. Embryos of this type are good candidates for transfer to the mother’s uterus (womb).


How does karyomapping differ from other PGD tests?

Up until recently, PGD tests for disorders caused by inheritance of a defective gene had to be tailor made for each couple. This required weeks or months of work by highly skilled scientists, meaning that there was often a long wait before IVF treatment could begin. By contrast karyomapping provides a universal test for PGD of almost any gene defect. This reduces the waiting time before treatment can begin to just a couple of weeks.


Does karyomapping detect any other disorders caused by abnormal genes?

We will only use karyomapping to assess embryos for the single condition that you are known to be at risk of passing on to your children. In rare cases, a family may be at risk for two different inherited conditions. In such cases it is usually possible to screen embryos for both problems using karyomapping. The disorder(s) you want us to analyse in your embryos must be agreed upon in writing before the test is carried out and will be noted on the report issued after embryos have been tested. Additionally, please note that for IVF treatments carried out in the UK, disorders may only be tested if approved by the Human Fertilisation and Embryology Authority.


Does karyomapping detect chromosome abnormalities?

Chromosomes are tiny, rod-shaped, structures that are found in almost all of the cells of the body. The chromosomes contain the genes, the chemical instructions that control cells. There should be exactly 46 chromosomes in every cell. Unfortunately many embryos produced during IVF treatments have the wrong number of chromosomes. When these embryos are transferred to the uterus they usually fail to implant and so there is no pregnancy. On some occasions an embryo with an incorrect number of chromosomes may succeed in implanting, but the pregnancy produced usually ends with a miscarriage. More rarely, embryos with an abnormal number of chromosomes manage to produce a baby, but in such cases the child may be affected by problems such as Down syndrome. Karyomapping can detect most (although not all) embryos with an incorrect number of chromosomes and can therefore help guide doctors to the embryo most likely to produce a healthy pregnancy. Transferring embryos with the correct number of chromosomes to the uterus reduces the chance of miscarriage and Down syndrome, but cannot entirely eliminate the risk of these problems.


Accuracy and the need for prenatal testing

Karyomapping is used to test a single cell (or sometimes a small number of cells) taken from an embryo before it is transferred to the uterus. A test carried out on such a minute amount of tissue can never be 100% accurate. In most cases, the chance of karyomapping successfully detecting an embryo affected by a specific inherited disorder is better than 95%. This is as at least as good as older methods used for PGD. Because there is a small chance of an incorrect diagnosis using karyomapping, it is strongly recommended that prenatal testing (for example amniocentesis or chorionic villus sampling – CVS) is used to confirm that any pregnancy is unaffected. Amniocentesis and CVS collect many thousands of cells from the fetus and are therefore more accurate. Like all tests involving analysis of embryos, karyomapping should be considered a way of reducing the risk of having an affected pregnancy, not an absolute guarantee. The accuracy of karyomapping for the detection of chromosome abnormalities is not yet known, but it is thought that the majority of such problems are successfully detected.


Requirements for karyomapping

In order to utilise karyomapping, a sample of blood or DNA is needed from the couple undergoing IVF treatment (both the woman and the man). Additionally, a sample is needed from at least one more relative who carries the same defective gene. If the disease is recessive (in which case each of the patients carries a defective copy of the gene), a sample is needed from one additional person on each side of the family (i.e. someone on the maternal side who has the same defective gene as the mother and someone on the paternal side who shares the father’s mutant gene). The most straightforward strategy in a case like this is to obtain a DNA sample from any children that the couple have, as they are related to both of the parents, but if no children are available samples from the couple’s siblings or their parents are usually sufficient. In the case of a dominant disorder, only one side of the family carries a defective gene, so an additional sample is only needed from that side of the family – i.e. samples are needed from the couple and one child or other relative affected by the disorder.


Time required for work-up

The time required to prepare for a PGD case involving karyomapping is far less than with other methods used for the diagnosis of single gene disorders in embryos. Reprogenetics UK typically needs to spend 1-2 weeks working on the samples received before approval for the case to proceed is given and the patient can begin stimulation.