Preimplantation Genetic Screening for Aneuploidy
Introduced in the mid 90's, preimplantation genetic screening (PGS) for aneuploidy involves embryo biopsy, using the same techniques as for PGD, followed by analysis of single nuclei generally by fluorescence in situ hybridisation (FISH) using combinations of chromosome specific DNA probes fluorescently labelled in a range of different colours (multicolour FISH).
PGS is now well established as a powerful diagnostic tool particularly for women in their late 30's and 40's (advanced maternal age). It is practised in many clinics especially in the US and thousands of babies have been born.
Recently, there have been several reports of randomised clinical trials which have demonstrated that there is no improvement in clinical pregnancy rates when PGS is used for embryo selection in all women of advanced maternal age. Our data on follow up analysis of screened embryos indicates that this is not because of errors but simply because it is impossible to predict which women may benefit on the basis of age alone. Follow up analysis is therefore recommended in the first PGS cycle to determine the level of risk.
Bridge Genoma is unique in offering not only single cell testing for screening purposes but also follow up analysis of screened embryos to confirm that PGS is of benefit to the patient.
Follow up analysis of an embryo by sequential multicolour FISH in the first hybridisation for 22, 21, 18, 16 and 13 (top row) and X, Y and 18 in the second hybridisation (bottom row).
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The result of the first hybridisation indicated trisomy 22 (three gold signals) in the nucleus from the single biopsied cell (left hand panels) which was confirmed in all nuclei of the biopsied embryo after follow up analysis (three of which are shown here). (Courtesy of Dr K Chatzimeletiou, London Bridge Fertility, Gynaecology and Genetics Centre).
Indications for PGS:
- Advanced maternal age for (1) embryo selection if 3 or more good quality embryos are available for transfer (2) screening to avoid viable trisomies including Downs syndrome, or (3) diagnostic use to assess liklihood of live birth
- Previous aneuploid pregnancy
- Some male infertility
Error rates following PGS by mFISH:
Detailed follow up analysis of biopsied embryos indicate that diagnostic errors for sequential mFISH for 7 chromosomes are in the range:
- False positive (aneuploid single cell result with a grossly normal embryo) 6-15%
- False negative (normal single cell result with a grossly abnormal embryo) 1-2%