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Assisted reproductive technologies do not enhance the variability of DNA methylation imprints in human
  1. Sascha Tierling1,*,
  2. Nicole Yvonne Souren2,
  3. Jasmin Gries1,
  4. Christina Lo Porto1,
  5. Marco Groth3,
  6. Pavlo Lutsik1,
  7. Heidemarie Neitzel4,
  8. Isabelle Utz-Billing5,
  9. Gabriele Gillessen-Kaesbach6,
  10. Heribert Kentenich5,
  11. Georg Griesinger6,
  12. Karl Sperling4,
  13. Eberhard Schwinger6,
  14. Jörn Walter1
  1. 1 Saarland University, Germany;
  2. 2 Maastricht University, Netherlands;
  3. 3 Leibniz Institute for Age Research, Germany;
  4. 4 Charite, Universitätsmedizin Berlin, Germany;
  5. 5 DRK-Kliniken Westend, Germany;
  6. 6 Universitätsklinikum Schleswig-Holstein, Germany
  1. Correspondence to: Sascha Tierling, FR 8.3 Life Sciences, Genetics/Epigenetics, Saarland University, Campus, building A2 4, Saarbrücken, 66123, Germany; s.tierling{at}


Background: Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are believed to destabilize 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: The aim of this study was 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 bisulphite-based technologies we analysed ten differentially methylated regions (DMRs) 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: In conclusion our 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.

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