| Preimplantation
Genetic Diagnosis and Screening at The Bridge Centre |
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Preimplantation Genetic Screening (PGS) for Aneuploidy Aneuploidy
Eggs and sperm are unique in having a half set of chromosomes - one of each pair and one sex chromsome. This results from two special cell divisions in their development. Sometimes there is an error in this process and instead of one chromosome for each pair there is either no chromosome or an extra second chromosome in the egg or the sperm Following fertilization then, the embryo inherits one too few or one extra chromosome. In rare cases, the embryo can correct this error, but in most cases, all of the cells of the embryo are affected. Because each chromosome codes for hundreds of genes this can result in failure of development, miscarriage or fetal and congenital abnormalities. In addition, chromosomal abnormalities can arise in an embryo fertilised with gametes with the correct number of chromosomes. Aneuploidy is the major known cause of miscarriage and pregnancy loss.
Preimplantation Genetic Screening (PGS) Preimplantation genetic screening (PGS) for aneuploidy is new technique. It allows the screening of the early human embryo for some of the common aneuploidies within days of fertilisation and before it attaches to the womb establishing a pregnancy.
A coloured fluorescent spot reveals the presence of the specific chromosome and up to five chromosomes can be identified at the same time in the same nucleus using the colours red, green, gold, aqua and blue. By repeating this process, more chromosomes can be identified.
What are the benefits of PGS?
As most aneuploid embryos will not survive to birth or result in congenital abnormality, PGS for aneuploidy and selection of embryos with the normal number of chromosomes for transfer should have a threefold benefit:
Several recent reports of clinical trials have confirmed these benefits. For example one well established clinic in the US reports that the implantation rate of each embryo transferred was increased in women above the age of 35 years and in women aged between 39 and 45 signficantly so. Another major clinic in Belgium reports an increase in pregnancy rates in women >37 years of age from 7.3% to 17.2% following PGS for 7 chromosomes (HFEA Annual Report, 2003). Miscarriage rates particularly in women in their late thirties are also reported to be significantly reduced. As this is a new service at The Bridge Centre accurate figures of improvement in pregnancy rates will be made available to the HFEA within one year or sooner when a sufficient number of cases have been completed. Interim data will be made available on request. The follow up of over one hundred children born following this procedure over the last ten years has confirmed that the incidence of serious congenital defects is not significantly increased when compared to the normal population (3.9%). However, we cannot be absolutely sure there is no risk of any abnormality and it is possible that there may be minor effects which may only appear later in childhood or adulthood. Please note that sex selection for non-clinical reasons using PGS is NOT permitted in the UK. The sex chromosome results will therefore not be revealed to patients. What happens to embryos that are not transferred?
Who should think about aneuploidy screening? Any couple having IVF or ICSI treatment for infertility with an increased risk of aneuploidy.
2. Some cases of
male infertility 3. Recurrent miscarriage 4. Repeated IVF failure What are the problems with PGS? The main problems to consider are: Some normal embryos will be misidentified as aneuploid and not transferred and, less frequently, some aneuploid embryos will be misidentified as normal for the chromosomes tested and may be transferred. In some cases, no diagnosis may be available. For technical or other reasons, a diagnosis may not be possible on some or all of the embryos following biopsy and chromosome analysis. Also, some embryos may be damaged by the process of embryo biopsy. Transfer of these embryos will be considered on a case by case basis. The reasons for this are partly technical; there is no way of checking the result from a single cell. More often, the embryo is aneuploid in some cells because of errors in the early divisions of the egg effectively making them chromosomal 'mosaics'. Some reports suggest that 30% of embryos could be like this and if the affected cell is sampled these embryos may not be transferred. However, just as with aneuploidies inherited in the egg or sperm and affecting the whole embryo following fertilisation, these mosaic embryo are also likely to have a reduced chance of developing normally. Because PGS is not 100% accurate we recommend that any pregnancy is monitored with ultrasound scans and that the patient has a non-invasive blood test for Down's and other syndromes. Couples should also carefully consider the optional possibility of invasive prenatal diagnosis by chorion villus sampling or amniocentesis. The Bridge Centre currently only offers PGS for 7 out of the 24 different human chromosomes We currently screen 7 chromosomes: X, Y, 22, 21, 18, 16 and 13. These have been selected on the basis that they are the ones most commonly associated with miscarriage, can cause fetal abnormality or in rare cases cause congenital abnormalities at birth. Aneuploidies for the other chromosomes are not identified and, if present, could cause problems in pregnancy. Also we cannot guarantee to eliminate the risk of miscarriage because it can be caused for reasons other than aneuploidy. Improvements in pregnancy and miscarriage rates are more likely when there are a number of embryos to select from. Women whose ovaries are difficult to stimulate and have few eggs may not be helped. 1 in 5 or 6 PGS cycles will fail to identify ANY embryos with the normal number of the chromosomes tested. This is a very difficult outcome to accept after going through an IVF or ICSI cycle. Particularly so as it is possible that follow up analysis of the embryos not transferred may show that a few were only mosaics for example. However, the redeeming feature is that at least couples then know the basis for their problem and can consider whether to choose another option to start a family, for example, through oocyte donation. PGS at the Bridge Centre The Bridge Centre is committed to providing the best treatment possible for the infertile couple. We believe that PGS is a valuable option for some patients and have invested in the equipment and resources needed to offer this service. The PGS team is led by Professor Alan Handyside, Scientific Director at the Bridge, who pioneered embryo screening for inherited disease in the late eighties at Hammersmith Hospital and has an active research programme at the University of Leeds trying to understand how aneuploidies and other genetic abnormalities arise in early human development. This enables an active clinical research programme to improve PGS by, for example, extending analysis to an increased number of chromosomes. The cost of Treatment at the Bridge Centre The cost of PGS (basic price £1950.00) is in addition to the cost of IVF/ICSI. Further details are available on request. Who should I contact at Bridge about PGS? To arrange a consultation please contact Annie Marchand by email on annie@thebridgecentre.co.uk or call direct on 020 7403 3363.
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