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Assisted reproductive technologies do not enhance the variability of DNA methylation imprints in human
  1. Sascha Tierling1,
  2. Nicole Y Souren2,3,
  3. Jasmin Gries1,
  4. Christina LoPorto1,
  5. Marco Groth4,
  6. Pavlo Lutsik5,
  7. Heidemarie Neitzel6,
  8. Isabelle Utz-Billing7,
  9. Gabriele Gillessen-Kaesbach8,
  10. Heribert Kentenich7,
  11. Georg Griesinger9,
  12. Karl Sperling6,
  13. Eberhard Schwinger8,
  14. Jörn Walter1
  1. 1Universität des Saarlandes, Biowissenschaften, Genetik/Epigenetik, Postfach, Saarbrücken, Germany
  2. 2Department of Complex Genetics, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Universiteitssingel, Maastricht, The Netherlands
  3. 3Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham, UK
  4. 4Leibniz Institute for Age Research – Fritz Lipmann Institute, Beutenbergstrasse, Jena, Germany
  5. 5Universität des Saarlandes, Zentrum für Bioinformatik, Postfach, Saarbrücken, Germany
  6. 6Institut für Humangenetik, Charité – Universitätsmedizin Berlin, Augustenburger Platz, Berlin, Germany
  7. 7DRK-Kliniken Westend, Spandauer Damm 130, D-14050 Berlin, Germany
  8. 8Universitätsklinikum Schleswig-Holstein, Institut für Humangenetik, Ratzeburger Allee, Lübeck, Germany
  9. 9Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Abteilung für Gynäkologische Endokrinologie und Reproduktionsmedizin, Ratzeburger Allee, Lübeck, Germany
  1. Correspondence to Dr Sascha Tierling, Universität des Saarlandes, FR 8.3 Biowissenschaften, Genetik/Epigenetik, Postfach 151150, D-66041 Saarbrücken, Germany; s.tierling{at}


Background Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are believed to destabilise genomic imprints. An increased frequency of Beckwith–Wiedemann syndrome in children born after ART has been reported. Other, mostly epidemiological, studies argue against this finding.

Objective To examine the effect of ART on the stability of DNA methylation imprints, DNA was extracted from maternal peripheral blood (MPB), umbilical cord blood (UCB) and amnion/chorion tissue (ACT) of 185 phenotypically normal children (77 ICSI, 35 IVF, and 73 spontaneous conceptions). Using bisulfite based technologies 10 differentially methylated regions (DMRs) were analysed, including KvDMR1, H19, SNRPN, MEST, GRB10, DLK1/MEG3 IG-DMR, GNAS NESP55, GNAS NESPas, GNAS XL-alpha-s and GNAS Exon1A.

Results Methylation indices (MI) do not reveal any significant differences at nine DMRs among the conception groups in neither MPB, UCB nor in ACT. The only slightly variable DMR was that of MEST. Here the mean MI was higher in UCB and MPB of IVF cases (mean MI±SD: 0.41±0.03 (UCB) and 0.40±0.03 (MPB)) compared to the ICSI (0.38±0.03, p=0.003 (UCB); 0.37±0.04, p=0.0007 (MPB)) or spontaneous cases (0.38±0.03, p=0.003 (UCB); 0.38±0.04, p=0.02 (MPB)). Weak but suggestive correlations between DMRs were, however, found between MPB, UCB and ACT.

Conclusion This study supports the notion that children conceived by ART do not show a higher degree of imprint variability and hence do not have an a priori higher risk for imprinting disorders.

  • imprinting
  • ART
  • IVF
  • ICSI
  • DNA methylation

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  • Funding Deutsche Forschungsgemeinschaft, grant no. DI 836/1-1 and NE 531-6-1.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committees Lübeck No. 06-029/2006, Berlin No. 14/2004.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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