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• In vitro development and implantation of normal human preimplantation embryos and comparison with uni- or poly- pronucleate pre-embryos (R0026)
• Derivation of Human Embryonic Stem Cell Lines from Embryos created from Clinically Unused Oocytes or Abnormally Fertilised Embryos (R0170/171)

In vitro development and implantation of normal human preimplantation embryos and comparison with uni- or poly- pronucleate pre-embryos (R0026)

In Conjunction with Manchester Fertility Services and the University of Manchester

Licence holder: Dr Daniel Brison and Dr Sue Kimber

In spite of the fact that clinical in vitro fertilisation (IVF) has been used as a treatment for infertility for more than 20 years, human embryos created by IVF continue to develop poorly in the laboratory, and the success rate of IVF is low. Only one in every 5 or 10 embryos goes on to form a baby after transfer to the womb. 

The aim of this research is to investigate the way normal human embryos develop in the laboratory, and compare them to embryos which develop abnormally.  This will help us to improve laboratory conditions to allow normal embryo development, which will increase success rates of IVF. 

We are looking particularly at genes and proteins which control cell death in embryos, and the ability of cells in the embryo to stick to one another, and make contact to the wall of the womb, in order to implant and develop. 

We are also studying master genes which control other genes, particularly those which are involved in giving cells in the embryo the ability to go on to form any cell in the adult body.

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Derivation of Human Embryonic Stem Cell Lines from Embryos created from Clinically Unused Oocytes or Abnormally Fertilised Embryos (R0170/171)

In Conjunction with Manchester Fertility Services

Licence holder: Dr Daniel Brison

Human embryo stem (hES) cells can be made to develop into a variety of specific cell types and as such have many potential medical uses, including the treatment of degenerative diseases by the replacement of defective cells, the safety testing of new medicines and treatments, and the study of disease.

These cells can be isolated from the inner cells of early embryos produced during in vitro fertilisation treatment before they are transferred to establish a pregnancy. A variety of hES cell lines are required to understand both their biological properties and limitations. Large numbers of hES cell lines will be required for research and for their use in medical treatments, in order to provide the correct tissue match, similar to existing organ transplantation programmes.

To date hES lines have only been derived from embryos left over from IW treatment programmes. These so-called "spare" embryos are in great demand for the couples' own treatment, for donation to other couples that do not have healthy eggs, and for research into infertility and improving IW treatment.

As a result, embryos donated for hES cell derivation are very scarce and this essential research is progressing very slowly. Although the first hES cell lines were reported in 1998, so far only two additional lines have been derived in the UK.

To avoid many of the ethical and practical problems associated with the use of "spare" IW embryos, we plan to use eggs (oocytes) that cannot be used for treatment, and are currently discarded, to create embryos specifically for hES cell derivation.

Two groups of eggs will be used; those that are immature, and cannot be used safely for treatment, and those that have failed to fertilise after insemination. About 30-40% of all eggs (3-4 hi each cycle of IW treatment) fall into this category and are normally discarded. We plan to activate these eggs, or use sperm from a fertile donor, to "recover" these eggs to make embryos specifically for hES cell derivation.

Although the success rate of these procedures may be lower than from normal embryos, we anticipate that many patients will be willing to give consent as the use of these eggs/embryos for research is preferable to then- being discarded. Information gained from these studies will then help to improve methods such as in vitro maturation, to be used hi clinical IVF treatment.

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