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Growth and Metabolism in In Vitro Fertilization Children« Back to Volume 24, Issue 1, May 2008 - Table of Contents In vitro fertilization (IVF) singleton children have an increased risk of malformations and low birth weight. They also face an increased risk of disorders with overgrowth partly due to abnormal methylation patterns of imprinted genes. Nutritional manipulation early in fetal life has also been shown to reduce methylation and over expression of non imprinted genes. Miles et al conducted a study regarding the long-term outcome of IVF children, an area in which there is still a lack of information. The authors investigated growth and changes in the metabolic and hormonal profile of this population. Healthy prepubertal children aged 4 to 10 years, born at term, after singleton pregnancy, were recruited into IVF and control groups. All subjects had been breastfed. There were 69 IVF children (5.9 years) and 71 control children (6.9 years). Anthropometric measurements and BMI were recorded, focusing on fat and glucose metabolism, and insulin-like ratio. There was no difference in body composition. The authors speculated that IVF results in epigenetic changes altering genes involved in growth and metabolism that could be similar to the changes shown in specific syndromes like Beckwith-Wiedemann. Editor’s CommentSince this technique was introduced, IVF has accounted for a growing number of births.1 Only recently have follow-up studies focused on the postnatal outcome of these children. A few informative and elegant studies have already drawn our attention to epigenetic changes that induced major malformations. The most investigated area is the overgrowth disorder of Beckwith- Wiedemann with a variable clinical expression from the full syndrome to isolated overgrowth. It has been shown that there are imprinting disorders observed in humans and animals born after the use of assisted reproductive technology. The genomic imprinting defects relate to an epigenetic marking of certain genes, resulting in monoallelic expression in a parent-of-origin-dependent manner. Imprinting control elements are characterized by differentially methylated regions in which the imprinted allele is methylated and the other parental allele is unmethylated. Imprinting is established during the development of the germ cells and must be maintained at a critical stage of pre-implantation development when the rest of the genome is subjected to a wave of demethylation. These imprinted genes have a major role in fetal growth and development. All imprinting disorders observed after assisted reproductive technology involve the maternal side inducing a maternal to paternal switch, with activation of non-coding RNA on the maternal side. The cause of association with IVF is unknown. One can only suggest that nutritional and environmental factors, or periconceptional or preimplantation conditions could result in these alterations. Furthermore, we do not know whether the clinical changes already observed are reversible. Hence their significance remains unclear. Miles et al described an increased incidence of tall stature in prepubertal children which was accompanied by increased levels of IGF-I and IGF-II. It was suggested that this “overgrowth” might be the consequence of programmed endocrine changes related to the IVF process. Remarkably, in this group of children the body composition and the lipid profile were normal. However, in another recent study the offspring of those conceived by IVF presented significantly higher peripheral adipose tissue.2 It is difficult to compare the metabolic status of the 2 populations because of age differences and methods used in both studies. Appropriate follow-up should be established for all IVF children. Raphaël Rappaport, MD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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