Science and Technology Committee

Frozen Eggs (or sperm for that matter) are a different ethical consideration to frozen embryos, as the former can be disposed of without any need to get involved in beginning of life ethical discussions.
However - the harvesting of eggs does make serious physical demands on a woman, and her body resources might be best directed towards fighting the cancer which, unlike fertility treatment, is life threatening.
I have personal experience of both a young man and a young woman (not related) each undergoing chemotherapy for cancer. The young man stored sperm as a safeguard for the future, but has not needed to use it. He is in fact getting married shortly (and in a hurry) in what used to be known as a shot-gun wedding. No need to go back to the freezer!
The woman decided not to store her eggs or ovarian tissue because she felt her life expectancy was threatened anyway and that she felt she could not morally accept the responsibility of children knowing that she might die at any stage. Her cancer is extremely rare and very aggressive, but appears to have been cured by autologous stem cell therapy (using her own harvested adult stem cells), and to the surprise of her doctors she has now recommenced ovulation and menstruation.
Anybody wishing further information about both these stories is welcome to contact me.

"Could a prebuscent girl have an ovary removed and donate eggs to an infertile relative, possibly even her mother. What issues does this raise?"

This is obviously unethical because the girl is not old enough to consent to such a procedure and will not fully understand its implications. It would also lead to a scenario whereby she has a sibling who is genetically her child, a situation which is very likely to have an adverse effect on the family.

Some additional comments regarding the effect of culturing the cells: It is known that in vitro culture can induce abnormal epigenetic regulation (e.g. Dean et al., 1998; Feil, 2001), and that abnormal epigenetic status can affect both developmentally important genes and genes that cause cancer (e.g. Falls et al., 1999; Paulsen and Ferguson-Smith, 2001).

In vitro maturation involves long periods of culture, and not surprisingly, it has recently been found that in vitro maturation of mouse oocytes affects DNA methylation and gene imprinting (Kerjean et al., 2003). Although only three imprinted genes were examined, this was sufficient to identify some abnormal DNA methylation patterns.

At this stage, in vitro maturation of oocytes would therefore be liable to greatly increase the incidence of imprinting diseases, and possibly cancer, of children produced in this way.

Dean, W. et al. (1998). Development 125: 2273-2282. “Altered imprinted gene methylation and expression in completely ES cell-derived mouse fetuses: association with aberrant phenotypes.”

Falls, J.G. et al. (1999). Am. J. Pathol. 154:635-647. “Genomic Imprinting: Implications for Human Disease.”

Feil, R. (2001). Trends in Molecular Medicine 7 (6):245-246. “Early Embryonic Culture and Manipulation Could Affect Genomic Imprinting.”

Kerjean, A. et al. (2003). Eur. J. Hum. Genet. 11(7):493-496. “In-vitro Follicular Growth Affects Oocyte Imprinting Establishment in Mice.”

Paulsen, M. and Ferguson-Smith, A.C. (2001). J. Pathol. 195:97-110. “DNA Methylation in Genomic Imprinting, Development and Disease.”

I concur with the comments by Dr Elizabeth Allan. Although this procedure would seem to obviate the ethical concerns associated with the destruction of "unwanted" embryos, at present the safety of the approach seems highly questionable. We are still only beginning to understand how genomic DNA methylation patterns are erased and established during oogenesis (Human Reproduction Update, 10: 3-18). So far, it appears that various genes are maternally imprinted throughout oogenesis at different stages and at least one gene, known as "Impact", is known to be imprinted as late as the antral follicle stage (Journal of Biological Chemistry, 277: 5285-5289). Consequently, it does not appear to be feasible to faithfully replicate the natural process of oocyte maturation in vitro using the limited information that is presently available.

Of the three loci from mouse oocytes matured in vitro that were examined by Antoine Kerjean et al., it is particularly interesting that the IgF2r locus showed the greatest abnormality in DNA methylation (European Journal of Human Genetics, 11: 493-449). Abnormally reduced methylation and expression of this gene are associated with foetal overgrowth after culture of sheep embryos, reminiscent of the large offspring syndrome observed with cloning by nuclear transfer (Nature Genetics 27: 153-154). Similarly, mice that inherit a mutant IgF2r allele from their mothers are up to 30% larger than their normal siblings (Genes and Development 8: 2953-2963). In addition, loss of IgF2r gene function has been associated with hepatocellular tumours in humans (Oncogene 10: 1725-1729, Nature Genetics 11: 447-449). Taken together, these data suggest that prolonged culture of oocytes in vitro may increase the chance of abnormally large offspring, perhaps necessitating delivery by Caesarean section, and additional increased risks of cancer for the offspring themselves.

The only apparently successful case of in vitro oocyte maturation that I have come across involved serial nuclear transfer of immature oocyte nuclei into enucleated, fully grown oocytes from adult mice (Nature 418: 497). However, if this approach is to be used in humans, an even greater supply of already mature eggs would be required.