A fertilin-derived peptide improves in vitro maturation and ploidy of human oocytes

Abstract Objective To analyze the effect of a fertilin-derived peptide (cFEE) on in vitro maturation of human oocytes. Design Randomized study. Setting Fertility center in an academic hospital. Patients Not applicable. Intervention Human immature germinal vesicle-stage oocytes (n=1629), donated for research according to French bioethics laws were randomly allocated to groups treated with 1 μM, 100 μM cFEE or to a control group. They were incubated at 37° C in 6% CO2 and 5% O2 and their maturation was assessed using time-lapse microscopy over 24 hours. In vitro-maturated metaphase II oocytes were analyzed for chromosomal content using microarray-comparative genomic hybridization (CGH-array) and their transcriptomes were analyzed using Affymetrix Clariom D microarrays. Main outcome measures The percentage of oocytes undergoing maturation in vitro was observed. Aneuploidy and euploidy were assessed for all chromosomes, and differential gene expression was analyzed in oocytes treated with cFEE compared to the control to obtain insights into its mechanism of action. Results cFEE significantly increased the percentage of oocytes that matured in vitro and improved euploidy in meiosis II oocytes by upregulation of FMN1 and FLNA genes, both of which encode proteins involved in spindle structure. Conclusion cFEE improves human oocyte maturation in vitro and reduces aneuploidy. It might prove useful for treating oocytes prior to fertilization in Assisted Reproduction Technology and for in vitro maturation in fertility preservation programs to improve oocyte quality and the chances for infertile couples to conceive.