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Bioethic information and analysis newsletter

Following Letter

N°41 - May 2003

USA : 400 000 deep-frozen embryos

There are some 400 000 deep-frozen embryos stored in the 430 medically assisted reproduction clinics in the United States according to the first national survey on the subject, reported in the Washington Post for 8th May 2003. This figure is far higher than previous estimates according to which the number of deep-frozen embryos varied between several tens of thousands and 200 000.

87% of the embryos conceived in the context of medically assisted reproduction are used for "treating infertility", 4% are used for research and for quality studies, 2% are donated and at least 2% are destroyed.

According to the study, couples who have "supernumerary" embryos in reserve, find it difficult to resolve to destroy them.

Ordering the sex of your baby

Last September, Dr Frank Comhaire, an andrologist at Ghent University (Belgium), announced that he had a method by which couples could choose the sex of their child, for a sum of 6 300 €. Now, he is announcing the birth of the first child resulting from this technique. The birth took place in February in southern Europe. It was a girl. Three other European women have become pregnant using this technique.

Sorting of chromosomes
Developed some ten years ago by the American Ministry of Agriculture, for selecting animals by their sex, this technique has been named MicroSort. It was adapted to humans in 1998 by research scientists working on behalf of the Genetics and In-Vitro Fertilisation Institute in Virginia. It then formed the subject of clinical tests under the supervision of the Food and Drug administration, with the contribution of numerous American, Canadian and Belgian doctors.

The method consists in sorting the sperms by identifying those bearing the X chromosome (female) and those bearing the Y chromosome (male). The team uses a laser which is able to differentiate between these two chromosomes in order to distribute them into two tubes. The sperm thus obtained and "enriched" is either inseminated in the womb of the mother or fertilised in-vitro.

A technique under test
The effectiveness of the method is somewhat limited, since the eradication of the undesirable sperms is particularly difficult to achieve. The technique has been tested on a thousand couples in the United States and produced 400 births. The success rates so far achieved are 88% for girls and 73% for boys. To prove its reliability, it is intended to test a further 3 500 couples.

Towards family balancing ?
In France, the selection of the sex of an embryo is possible in order to avoid a serious genetic disease, such as Duchenne's myopathy or X fragile disease, etc.
The 1994 bioethics laws do not allow couples to choose the sex of their child for any other reasons. Similarly, in Belgium, article 5 of the law governing research on embryos in-vitro, prohibits research or treatments aimed at selecting an embryo unless the intention is to avoid a serious genetic disease. But Professor Comhaire does not consider he has done anything illegal, since he believes that his work is not covered by that law which merely regulates the manipulation of embryos in vitro. "We in fact perform selection on the sperms, before any embryos are yet formed." He is taking advantage of a legal loophole, which is shortly to be eradicated by a draft law currently being elaborated.

The Belgian bioethics committee is divided on the question of sexual selection of embryos. Certain of them are not opposed to the principle of "family-balancing", i.e. the possibility for a couple to choose the sex of their child in order to balance the number of girls or boys in their offspring.

Production of ovocytes from embryonic cells

Cultivated embryonic stem cells (ES cells) are generally considered as multi-purpose, in other words, capable of generating multiple types of cells, but no experiment had been able to demonstrate their ability to differentiate in vitro as sexual cells. A Franco-American team has just shown that these cells are in fact totally potent, in other words, capable of providing all types of cells under appropriate differentiation conditions.

Production of ovocytes
The authors of this study, which was recently published in the on-line version of Science magazine¹, obtained cells having the same characteristics as ovocytes, by cultivating embryonic cells from male or female mice. Part of the cultivated cells adopted the structure of ovocyte precursors then entered meiosis (specific cellular division during which the reproductive cells lose a batch of chromosomes). The development of these cells could be monitored visually thanks to a fluorescent marker identifying the expression of a gene which is specific to germinal cells. Additionally, these ovocytes produce large quantities of oestradiol, which is a female hormone.
However, although these cells obtained in vitro exhibit the characteristics of ovocytes, the study does not show whether the chromosomic reorganisation occurred correctly during the meiosis. It must now be demonstrated that these ovocytes can be fertilised and give rise to mice without any anomalies.

The expected fallout
The obtaining in vitro of germinal cells, opens up interesting prospects for fundamental research, in particular with respect to studying meiosis and the interactions between somatic and germinal cells. It would also facilitate genetic engineering.

Beyond these scientific benefits, these results have been very widely broadcast in the popular press, due to the applications to mankind, which such a discovery allows us to imagine :
- the production in vitro of a large number of ovocytes would make human cloning easier. It would in particular remove the practical and political barriers to human cloning by avoiding the need to resort to women for obtaining the ovocytes required.
- for those who accept the principle of therapeutic cloning, it would enable sterile women to have children. It would be possible to obtain embryonic cells after cloning a cell from the mother, and differentiate them into ovocytes, which in turn could be fertilised by the father's sperm. The same would do away with the age limit for women to reproduce.
- finally, this in vitro production of ovocytes from embryonic cells would allow homosexuals to have children by sexual reproduction, one of the fathers donating his sperm, the other ova by cloning one of his cells.

The scientific and ethical limits
However, these extrapolations are way beyond the published results. The authors of the study have not demonstrated that the ovocytes obtained in a culture box from embryonic cells are functional and free of chromosomic anomalies. And if that were the case, nothing proves that such a discovery can read across to human cells.

Finally, the suggested approaches do not avoid any of the ethical problems. This in vitro production of ovocytes initially requires the obtaining of human embryonic cells, taken either from supernumerary embryos or cloned embryos and their use as a laboratory product.

1 : K. Hubner et al. Derivation of ovocytes from mouse embryonic stem cells. Science 2003 May

Hope for the use of adult cells in the treatment myopathy

A French team at the Inserm neuro-genetic laboratory, together with a Belgian team at the Catholic University of Louvain, have shown the protective effect of adult muscle stem cells, known as satellite cells, in the case of genetic type degenerative muscular diseases. Judith Melki who was leading this study, together with her team in 2000, managed to isolate a survival gene for motor neurones, directly responsible for spinal amyotrophy. Moreover, a mutation of this gene, the Smn gene, may cause different types of myopathy. A severe modification may cause gradual paralysis and eventually cause death.
Research scientists have demonstrated the positive influence of muscular stem cells on the improvement in motor performance and the survival of mice exhibiting a genetic type of chronic myopathy. These cells, which were first identified a few years ago, have enabled highly active muscular regeneration in affected animals. These cells showed that they have the ability to counter the advance of a progressive myopathy.
According to the research team, these results are promising for the development of a therapeutic strategy for myopathies.
This study demonstrates once again the tremendous therapeutic potential of the stem cells present in adult organs. 

S. Nicole et coll., "The Journal of Cell Biology" dated 12thMay 2003