www.genethique.org

Bioethic information and analysis newsletter

Following Letter

N°42 - June 2003

Iris : The first French baby born using IVM (in vitro maturation of the ovocyte)

A few days ago, the press announced the birth of Iris, the first French baby conceived using the in vitro maturation technique (IVM).

A new method of MAR
In vitro maturation is a new technique in medically assisted reproduction, based on the same principle as conventional in vitro fertilisation (IVF) : biopsy of the ovocytes or ova, collection of sperm, in vitro fertilisation followed by re-implantation in the uterus. But with IVM the ovocytes (immature ova) are allowed to mature into ova in the test-tube. With IVF, maturation of the ovule takes place in the ovary by injection of hormones. IVM thus avoids the mother from the constraint of repetitive injections of hormones to stimulate the ovaries.

For 20 years in animals
In vitro maturation is far from new : biologists have been using it for 20 years in animal reproduction, using this technique in place of in vivo maturation of the ovocyte. As early as 1982 American research scientists were able to produce a calf in this way. Since then, IVM has been used successfully for sheep, goats, pigs and horses, but the move from one species to the next has proved difficult, because each time the environment has had to be adjusted : hormones, maturation period, temperature...

And what about humans ?
Up till now, a few births have been achieved using this technique in Australia and in Canada. Out of some 700 women who have tried this technique world-wide, only 200 have successfully achieved childbirth since 1991. The technique is little used due to its high rate of failure.

According to René Frydman, IVM is only applicable to certain women, suffering from polycystic ovaries, and has never been tried for "a standard woman".

It would appear to be still too unreliable and less effective than conventional IVF for women who are able to produce mature ova. A study published in Gynaecology Obstetrics in October 2002 comparing the results achieved by IVM and those achieved by IVF is very clear: 26 % of women having used IVM achieved pregnancy and only 16% achieved childbirth, whereas 38 % of women having used IVF became pregnant and 26% achieved childbirth. The success rate for IVM is therefore much lower than for IVF which is already quite low.

When questioned about this birth, Jacques Testart, the "father" of Amandine, the first test-tube baby, considers that maturation in vitro directly for humans, without any preliminary experimentation on monkeys, is dangerous. "There is a risk of perhaps causing anomalies in these children. And by thus facilitating the creation of ova, the way is laid open to cloning, because what is difficult for would-be cloners, is to obtain available ova". Other IVM babies, are due to be born in the coming weeks at the Hôpital Béclère.

The dangers of medically assisted reproduction (MAR)

The risks
In February 2002, The Lancet medical journal published a study on the neurological risks for children born through in vitro fertilisation (IVF). A month later, two studies published in the New England Journal of Medicine evaluated the consequences of the neonatal risk following medically assisted reproduction. These techniques are artificial insemination and stimulation of ovulation, as well as the more intrusive techniques such as in vitro fertilisation or cytoplasmic injection of sperm cells (ICSI). The use of these techniques doubles the number of babies who are underweight at birth and which exhibit congenital anomalies. The authors of the study attribute these risks to the use of these technologies more than to the causes of the infertility. The rate of occurrence of serious congenital malformations, diagnosed before the age of 1 year, which is 4.2% for babies conceived naturally reaches 9% for babies conceived through MAR. The most common malformations concern the uro-genital system, the cardio-vascular system and the musculo-skeletal system. According to Professor Mitchell (Boston) « These risks are not admissible for all couples and must now be considered by both doctors and patients ».

The figures in France
In France some 110 000 children have been born through medically assisted reproduction. Currently some 9 000 births are recorded per year, of which 50% in the context of ICSI. The rate of success varies from 20% for IVF to 23% for ICSI. In the last few years, by restricting the number of embryos transferred at the same time into the uterus, the rate of multiple pregnancies has decreased : from 6 to 8% a few years ago, it has dropped to 1.5% today. Dr Mouzon, a specialist in the field of reproduction at Inserm considers that MAR accounts for some 120 million Euro per year.
Treatment for sterility is covered 100% by the Social Security, all attempts being fully refunded. France holds the pole position world-wide for such expenditure, and is the only nation world-wide which refunds the cost of MAR.

An appeal for responsibility
L'Express magazine in January 2003 opened a debate on : "Relentless reproduction: what about the child's interest ?"

Prof. Didier Sicard, president of the national consultancy committee on ethics, and Marie-Hélène Mouneyrat, general secretary, put out a "cry of alarm". They are concerned about the blindness which drives certain parents to a veritable "relentless reproduction" and certain doctors to implement under-evaluated reproductive techniques. For them it is urgent to consider if one should continue to satisfy all desires for parenthood in spite of the fact that the techniques employed involve a risk for the children.

On 22^nd January 2003, in an interview for Le Monde, the minister of health, Jean-François Mattéi, denounced the deviations of medically assisted reproduction: "We must recover reason and common sense" he said. He deplores that certain techniques are used despite the fact that the consequences for the unborn child are far from being mastered : "nobody thinks of defending the child". The minister considers that children "are going to have to pay heavily for the desires of their parents and the complicity of doctors ".

Carthagenous protocol on biosafety : Should one fear GMO ?

On 11^th September 2003 the Carthagenous protocol on biosafety will come into force : from that date, any State will be able to reject any cargo of cereals or other genetically modified products.

Traceability
This protocol involves "prior agreement in full awareness of the facts", which compels exporters to provide a detailed list of the composition of farm produce, enabling the importer to accept or reject the delivery. For this protocol to be applicable, it must be ratified by 50 of the United Nations member states. To achieve this, more than 3 years' negotiations were required. The European Union ratified it in June 2002, and France did so in September 2002. The United States, who are major producers of genetically modified organisms (GMO), fiercely fought this text against Europe and Africa who support it in with a view to commercial transparency. The recent ratification by the state of Palau, in the Pacific, finally enabled the protocol to be adopted.

The fear of GMO
For several years, genetically modified organisms (GMO) have unleashed unprecedented reactions from all and sundry, but when one questions these people, it is soon clear that their technical knowledge of GMO is extremely superficial, or even non-existent. This is regrettable, since it is all too often forgotten that GMO provide considerable services, particularly in the manufacture of medicines. Insulin is a fine example. It forms the basis for treating diabetic patients, and for the last fifteen years, has been produced by GMO bacteria. A book recently reprinted (2003) and written by L.-M. Houdebine, a specialist in biotechnologies, presents the theoretical bases of GMO in clear and understandable terms, and also calmly discusses the advantages and disadvantages of these new tools which modern biology has made available to us. As far as the author is concerned, GMO should be used with care, but should not be demonised.

GMO : what are the risks ?
The various fears generated by GMO should be analysed clearly and fully.

- The transfer of genes from a GMO to man or to nature must be put in perspective with what happens every day in our plates. Every day, we eat foods which contain ADN, for example, beef ADN when we eat a steak. This ADN is then broken down in our intestine, and has little chance of transforming us into beef, or even to transfer to us a beef gene. The transfer of ADN from food, as opposed to viruses, is particularly inefficient.

- The same applies to the increased risk of contracting cancer through GMO. Even if it is true that GMO are more resistant to weed killers (Round Up) and that this is likely to result in increased use of such weed killers by farmers, it is difficult to see how they can have any direct effect on the number of cases of cancer. On the other hand, weed killers do cause cancer...

- The argument of economic dependence with respect to major companies and industrialised nations, is also frequently used to denounce GMO. This argument is not to be ignored, as it has an impact on the world which we are preparing for future generations, in particular concerning the developing countries, which do not have the means for agricultural research enjoyed by the industrialised nations. However, it is not the GMO which are at fault, but rather the people who use them. Certain GMO in fact enable wheat to be grown under much more severe conditions than normal wheat. These GMO under the control of the UNO could represent an extraordinary opportunity for nations where climatic conditions are unfavourable. On 2^nd July 2003, the European Parliament is due to adopt two rules concerning the labelling and traceability of transgenic products. 

OGM : The truths and the untruths . L-M. Houdebine. Ed.  Le Pommier. 2^nd Edition : March 2003.