Culture of oocytes and risk of imprinting defects

BACKROUND Follicle culture and oocyte in vitro maturation (IVM) are emerging assisted reproductive technologies with potentially important future applications in the fertility clinic. There is concern that these technologies might interfere at the epigenetic level and, in particular, with genomic imprinting. The timely acquisition of correct imprinting patterns in oocytes and the maintenance of genomic imprinting after fertilization are both required for normal embryonic development. METHODS A systematic literature search in Pubmed was performed and all publications reporting on the effects of follicle culture, IVM or ovarian tissue culture on genomic imprinting were retained. RESULTS Mouse ovarian tissue culture studies, mouse in vitro follicle culture studies and a single bovine IVM study generally showed correct imprinted DNA methylation establishment in oocytes. Influences of treatment and suboptimal culture conditions in mouse follicle culture indicate that imprinting establishment in oocytes is a robust process. This is in contrast with preimplantation embryo culture-induced epigenetic defects reported in mice. For human IVM, no definitive conclusion on imprinting establishment can be drawn as well-designed studies are currently not available. CONCLUSIONS Animal models provide reassuring data on imprinting establishment in cultured oocytes, but further studies should assess the effect of oocyte culture on imprinting maintenance. Optimized IVM procedures should be assessed in well-designed human studies. Finally, epigenetic analysis should be performed in children born from pregnancies after IVM to draw definitive conclusions on the epigenetic safety of human IVM.