John Libbey Eurotext

Médecine Thérapeutique / médecine de la reproduction

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HLA typing and preimplantation genetic diagnosis Volume 8, issue 4, Juillet-Août 2006

Authors
Clinical embryologist at the Centre for Reproductive Medicine, Medical School and University Hospital, Vrije Universiteit Brussel (VUB, Free University of Brussels), Laarbeeklaan 101, 1090 Brussels, Belgium, Molecular biologist at the Centre for Medical Genetics, Medical School and University Hospital, Vrije Universiteit Brussel (VUB, Free University of Brussels), Laarbeeklaan 101, 1090 Brussels, Belgium, Director of the Centre for Medical Genetics, Medical School and University Hospital, Vrije Universiteit Brussel (VUB, Free University of Brussels), Laarbeeklaan 101, 1090 Brussels, Belgium

Typing of human leukocyte antigens (HLA) on preimplantation embryos is legally allowed and ethically accepted in Belgium. The ‘Vrije Universiteit Brussel’ (VUB) has five years of experience with technical and clinical aspects of HLA typing on single cells. Setting up and running a programme for HLA typing is labour intensive, in particular when it has to be combined with preimplantation genetic diagnosis (PGD) for distinct inherited genetic diseases, and time is always pressing because of the need for transplantation of the affected sibling. A general technique for HLA typing using short tandem repeats (STRs) linked to the HLA locus in multiplex PCR has been developed at our centre. At present, the overall clinical success rate is low: the ongoing pregnancy rate per oocyte retrieval cycle is 9.8%. This is not due to the technique because a conclusive HLA diagnosis can be assured in 91.9% of the embryos. The low success rate is correlated with a low transfer rate per cycle (35.5%). This is due to the genetic constitution of the embryos (in theory 1/4 for HLA, 1/8 for HLA in combination with sexing for X-linked recessive diseases and 3/16 for HLA in combination with autosomal recessive disorders) and clinical restrictions (in particular the reproductive age of the mother). The current ongoing pregnancy rate and implantation rate per transfer are acceptable (27.2% and 20.8% respectively). The results may be improved by selecting younger patients and by optimizing hormonal stimulation protocols and/or embryo culture systems.