Preimplantation Genetic Screening

WHAT IS PGS?

Pre-implantation genetic screening (PGS) is a laboratory procedure performed as part of an IVF cycle where a genetic assessment (or screening) of the embryos is carried out. This information is used to exclude from transfer to the uterus, embryos carrying certain genetic errors.

In some cases PGS involves examining the chromosomes of the embryo for numerical or structural errors, in other cases PGS involves testing for a known single abnormal gene.

WHAT ARE CHROMOSOMES AND GENES?

Chromosomes are structures found in the centre, or nucleus, of all cells. They are made up of ‘genes’ that code all the instructions and information needed for the development and function of all the cells of the body.

A human typically has an identical set of 46 (23 pairs) chromosomes in every cell. One set of 23 is inherited from the father’s sperm, the other from the mother’s egg. The two sets come together at fertilization and a copy of the full set is inherited by all of the cells of the developing embryo and subsequently by all the cells of the body.

Although all the cells of the body contain a copy of the same set of chromosomes, different instructions (genes) are read from the chromosomes depending on what functions are required of that cell (e.g. liver, bone etc). Together the genes control the development and the characteristics of each individual cell; the developing embryo; and subsequently the individual.

WHY DO WE CHECK THE CHROMOSOMES IN THE EMBRYOS OF SOME PATIENTS?

If there are errors in the number or structure of the chromosomes in the cells of an embryo, the chances of progressing to a normal pregnancy may be significantly reduced.

One condition that PGS may be used to detect is called aneuploidy. This is where there are missing or extra chromosomes present in the cells of the embryo. Aneuploidy tends to occur with increasing incidence in the eggs (and subsequently the embryos) of women as their age increases. This is thought to be one of the reasons that women’s fertility declines with age.

While there is conflicting evidence as to the benefit of PGS to generally screen for aneuploidy, some couples may elect to use PGS to help identify which of their embryos has a normal number of chromosomes and hence has the best chance of pregnancy.

Some patients seeking fertility treatment may themselves have particular errors in their chromosomes called translocations. This is where a section of one chromosome has broken off and attached to another, or has perhaps even been swapped with a section somewhere else. The translocation may not affect the patient themselves at all, but it may mean that not all of their sperm or eggs have an intact set of 23 chromosomes. This may affect their fertility as the majority of their embryos may not then have the normal intact set of 46 chromosomes. The abnormal embryos may not develop beyond the early stages; may not implant; or may miscarry early in the pregnancy. By using PGS to test a couple’s embryos for the presence of these translocations, we can identify and avoid transferring embryos that carry the translocation and which we know

WHY DO WE CHECK SPECIFIC GENES IN THE EMBRYOS OF SOME PATIENTS?

The genes that provide the instructions controlling the function and characteristics of cells can come in various forms (or alleles). Alternate forms of many genes give rise to the normal variation that we see among individuals. The gene that codes for the pigment in the human eye, for example, codes either for pigment (brown/green) or no pigment (blue) etc and as a result humans have different eye colours. Sometimes however, one form of a gene actually results in a malfunction of a particular cellular activity and a disease condition results. Cystic fibrosis and Huntington’s disease for example are diseases that are ‘single gene disorders’.

Couples who know that they are at risk of passing on a single gene disorder to their offspring may elect to have IVF and to use PGS to screen their embryos for the presence of the ‘mutant’ allele and to thereby choose not to transfer the affected embryos.

SO WHAT HAPPENS IN THE LAB DURING A PGS CYCLE?

For a couple undergoing an IVF cycle including PGS, the process is very similar to a normal blastocyst cycle. However, what happens in the laboratory from the time between fertilization and embryo transfer on day 5 is more complex.

To test the genetic status of each embryo, one or two cells are removed or ‘biopsied’ from each embryo on day 3 after insemination when most embryos are somewhere between 5 and 8 cells. This is performed at Life Fertility Clinic by an experienced embryologist using a high powered microscope and specialist micromanipulation tools. The cells are then sent to a specialist pathology laboratory for examination of the chromosomes or testing for a particular gene as appropriate.

The test results generally take 24-48 hours to be returned from the pathology lab. In the meantime, the biopsied embryos are maintained in culture in the IVF laboratory and continue developing to the blastocyst stage. Once the results of the chromosome or gene analysis are received, the doctor and embryologist will use these and the embryology observations to decide which embryos are suitable for transfer or freezing.

WHAT SHOULD WE BE AWARE OF BEFORE STARTING PGS?

The Biopsy procedure:

It is possible that some or all of a couple’s embryos may fail to reach a stage of development where they are considered suitable for embryo biopsy. Those embryos which are not suitable for biopsy will not be tested.

While every possible measure is taken to optimise the biopsy procedure, it is possible that embryos may be damaged by the procedure or fail to survive after it. Furthermore, as is the case for all blastocyst cycles, irrespective of the genetic testing results, some (or all) embryos may fail to develop to a stage that is suitable for either embryo transfer or freezing.

The Genetic Test Results:

Even if the embryos are successfully biopsied, it is possible that technical or embryo related limitations may prevent results being obtained for some or all of the embryos tested. In addition, PGS results can sometimes be inconclusive for some or all of the embryos tested. In either of these circumstances, couples need to consider what to do with such embryos with regard to embryo transfer, cryopreservation or allowing them to succumb.

PGS results are not 100% accurate and therefore despite favourable screening results, it is still possible that an affected embryo may be transferred following PGS, potentially resulting in a pregnancy and birth of an affected child.

When PGS is used for single gene disorders, it will only screen for the single gene disorder in question and does not guarantee that any child resulting from a screened embryo will be free from any other abnormalities.

When PGS is used for aneuploidy or translocation screening, only a subset of chromosomes is tested (13, 16, 18, 21, 22, X, Y and any specific translocation previously identified as relevant). A result of ‘no abnormality detected’ does not therefore exclude the possibility of abnormalities related to chromosomes which have not been tested which may result in a failed implantation, miscarriage, pregnancy and birth of an affected child.

It is strongly recommended that patients consider undertaking either amniocentesis or chorionic villi sampling (CVS) to confirm the early embryo diagnosis if a pregnancy is established following treatment involving PGS.

HOW DO WE GET STARTED ON A PGS CYCLE?

PGS is carried out as part of an IVF/ICSI cycle so the first step is to speak to a fertility specialist who will organise all aspects of the IVF and PGS treatment.

As part of the preparation for treatment, patients are likely to need a number of blood tests and all patients must see a Genetic counsellor.

Depending on the type of genetic testing, required the preparation time for PGS can range from one to nine months. This time is required by the pathology lab to tailor the testing for each couple and to ensure that the testing procedure is as accurate as possible.

 


 

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