General imprinting status is stable in assisted reproduction-conceived offspring

Objective: To evaluate whether the genomic imprinting status of assistant reproductive technology (ART)conceived offspring is stable. Design: Prospective clinical observational study. Setting: In vitro fertilization (IVF) center, university-affiliated teaching hospital. Patient(s): Sixty ART-conceived babies (30 IVF and 30 intracytoplasmic sperm injection [ICSI]) and 60 naturally conceived babies. Intervention(s): Collection of umbilical cord blood and peripheral blood samples. Main Outcome Measure(s): Expression profile was examined by microarray and real-time reverse-transcription polymerase chain reaction (PCR), allele-specific expression was studied by direct sequencing after PCR, and DNA methylation status was investigated by sodium bisulfite sequencing. Result(s): Hierarchic clustering demonstrated no obvious clustering between the ART-and naturally conceived offspring, suggesting similar genomic imprinting expression between the two groups. Three differentially expressed genes were identified in ART-conceived offspring, with PEG10 and L3MBTL up-regulated and PHLDA2 down-regulated. Allele-specific expression of the differentially expressed imprinted genes was maintained in the majority of the ART-and naturally conceived offspring. However, in one ICSI case, monoallelic expression of L3MBTL was disrupted and all CpGs were completely unmethylated. These were not inherited from the parents. Conclusion(s): The global profile of imprinting is stable in children conceived through ART. However, imprinting of a few specific imprinted genes may be vulnerable in a fraction of ART-conceived children. (Fertil Steril (R) 2011; 96: 1417-23. (C) 2011 by American Society for Reproductive Medicine.)