DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures

In vitro maturation (IVM) of human oocytes offers cost efficiency and minimal invasiveness, serving as a valuable supplementary tool in assisted reproduction for fertility preservation, ovarian hyperstimulation syndrome prevention, and other reproductive strategies. Despite its availability for three decades, the clinical use of IVM remains limited due to efficacy and safety concerns. This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing. Results indicate IVM oocytes exhibit a higher global methylation level. Differentially methylated regions (DMR) analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group. Additionally, the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group. However, no significant correlation between methylation levels and transcriptional activity in these oocytes is found, especially for those specific imprinted genes or genes related to embryonic development. These findings shed light on the epigenetic landscape of IVM oocytes, contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.