Gothenburg, Sweden: Couples considering undergoing assisted reproductive technology (ART辅助生殖技术) treatment should be informed about the increased risk of congenital malformation（先天畸形） posed by the use of ART, the annual conference of the European Society of Human Genetics will hear today (Monday). Dr. Géraldine Viot, a clinical geneticist at the Maternité Port Royal hospital, Paris, France, will say that she believed that most doctors working in ART clinics in France only told couples about such risks if they were asked specific questions. Dr. Viot and colleagues conducted a survey in 33 French centres registered for ART, around one third of the total number of clinics registered to perform ART procedures in France. All ART births from these clinics from 2003 to 2007 were included; 15 162 children in total. The study was the largest to date on this subject. Questionnaires（问卷，调查表） were completed both by the parents and the paediatrician（儿科专家） and the prevalence（流行，普遍） of malformations found compared with the data obtained from national registers and in published papers.

"We found a major congenital malformation in 4.24% of the children", said Dr. Viot, "compared with the 2-3% that we had expected from previous published studies. This higher rate was due in part to an excess of heart diseases and malformations of the uro-genital system. This was much more common in boys. Among the minor² malformations, we found a five times higher rate of angioma（血管瘤） , benign³（良性的） tumours⁴ made up of small blood vessels⁵ on or near the surface of the skin. These occurred more than twice as frequently in girls than boys."

However, the scientists say, their results are a long way from the 11% of major malformations that have been reported by some studies. "Given that our study is the largest to date, we think that our data are more likely to be statistically⁶ representative of the true picture", said Dr. Viot.

The average age of the parents of children born with malformations was not statistically different from the other parents in the ART group. The origins of the malformations are probably multiple, says Dr. Viot. "We need more research in order to understand the relationship between embryo⁷ culture media, timing⁸ of embryo transfer, the effects of ovarian（卵巢的，子房的） stimulation⁹, the use of ICSI, where sperm¹⁰ is injected directly into the egg, freezing of gametes（配子） and embryos¹¹ and these disorders¹³.

"We estimate that in France some 200 000 children have been born after ART and therefore a malformation rate of this magnitude is a public health issue. It is important that all doctors and also politicians are informed about this. We also need to follow up all children born after ART and to put much more effort into trying to understand which of the procedures involved is implicated¹⁴ in this problem."

Dr. Viot and colleagues intend to follow up their work analysing a further 4000 questionnaires, from children born in 2008, and to look at the motor development of children born in 2003, who are now aged¹⁵ 7. "By following all these children we hope to understand more about not only what can go wrong after ART, but why it goes wrong", she said. "At a time when infertility¹⁶（不毛，贫瘠） is increasing and more and more couples need to use ART to conceive, it is vitally important that we find out as much as we can about what is causing malformations in these children, not only so that we can try to counteract¹⁷ the problem but also in order for health services to be able to plan for their future needs."

The scientists are now trying to find out the origin of parental¹⁸ infertility for each child born after ART who has been affected¹⁹ by major malformation or epigenetic（外成的，后生的）disorders. "With this knowledge, we can better establish the origin of the malformation and whether it is more likely to be related to parental infertility or the ART procedure itself", said Dr. Viot. "We already know that imprinting²⁰ disorders – where the mechanism²¹ in which gene¹ expression depends on parental origin – are clearly more frequent in our cohort（支持者，同生群） than in the general population."

Imprinting disorders are all acquired because of either a maternal²² or paternal²³ deletion on a chromosome²⁴（染色体） , through inheritance of both chromosomes²⁵ of a pair from only one parent, through mutations in some imprinted²⁶ genes²⁷, or because of loss or gain of methylation（甲基化） (a process which is normally removed during zygote受精卵 formation and re-established through successive cell divisions during development. "The prevalence of the imprinting disorder¹² Beckwith Wiedemann syndrome²⁸ in our cohort is six times higher than we would expect in the general population, and for retinoblastoma（成视网膜细胞瘤） the prevalence among ART children is 4.5 higher than in the general population", said Dr. Viot.

"These results could be due to the effect of a number of different mechanisms²⁹. They could be due to the infertility itself, the ovarian stimulation for supernumerary（多余的，后备的） oocyte（卵母细胞） production, the in vitro maturation（成熟，化脓） of oocytes, the use of ICSI (direct injection of sperm), the culture media, the cryopreservation of gametes and embryos – we just don't know at present. Finding this out will be a major step towards improving the health of children born after ART."