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In Vitro Fertilization Improves Childhood Growth and Metabolism

The National Research Centre for Growth and Development and Liggins Institute (H.L.M., P.L.H., M.H., D.W., P.D.G., W.S.C.) and Department of Community Health (E.M.R.), University of Auckland, Auckland 1010, New Zealand; and Fertility Associates (J.P.), Auckland 1051, New Zealand

Address all correspondence and requests for reprints to: Associate Professor Wayne Cutfield, The Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: w.cutfield{at}auckland.ac.nz.

Background: There is limited information regarding the long-term outcome of children born after in vitro fertilization (IVF), although an increase in rare imprinted gene disorders such as Beckwith-Wiedemann syndrome has been reported.

Methods: We recruited healthy, prepubertal children born at term after singleton pregnancy. The children in the study group were conceived using IVF with fresh embryo transfer, whereas controls were naturally conceived. Anthropometric measurements, bone age, dual-energy x-ray absorptiometry, fasting serum glucose, insulin, lipid profile, IGF-I and -II, and IGF-binding proteins 1, 2, and 3 were performed.

Results: There were 69 IVF children aged 5.9 ± 0.2 yr and 71 control children aged 6.9 yr. IVF children were taller than controls when corrected for parents’ heights (height SD score of 1.05 ± 0.1 vs. 0.51 ± 0.11, P = 0.001) with higher levels of serum IGF-II (850 ± 24 vs. 773 ± 24 µg/liter, P = 0.03), higher IGF-I to IGF-binding protein 3 ratio (P = 0.04), and a trend toward higher IGF-I (105 ± 4 vs. 92 ± 4 µg/liter, P = 0.06). IVF children had higher high-density lipoprotein (1.67 ± 0.04 mmol/liter vs. 1.53 ± 0.04 mmol/liter, P = 0.02), lower triglycerides (0.65 ± 0.04 mmol/liter vs. 0.78 ± 0.04 mmol/liter, P = 0.02), and a lower total to high-density lipoprotein cholesterol ratio (2.58 vs. 2.86, P = 0.01). There were no differences in body composition.

Conclusions: IVF children are taller with higher IGF-I and IGF-II levels and have a slightly more favorable lipid profile. We speculate that IVF results in epigenetic change through altered methylation of genes involved in growth and metabolism. IVF programs should consider long-term longitudinal follow-up of IVF offspring.

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