Assessment of oocyte quality following repeated gonadotropin stimulation in the mouse

The present study assessed the effects of repeated ovarian stimulation on oocyte quality. Female mice were stimulated with eCG and hCG at 1-wk intervals for 4 wk. Germinal vesicle (GV)-stage oocytes were evaluated in relation to size, somatic cell association, and chromatin organization after each week of stimulation. In addition, ATP content and expression of meiotic competence were monitored in GV and in vivo (IVO) or in vitro (IVM)-matured oocytes. The developmental competence of ovulated oocytes was determined after in vitro fertilization and embryo culture, and reproductive outcome was evaluated after mating following repeated cycles of stimulation. In GV oocytes, the degree of somatic cell association, size, and timing of transcriptional repression were altered when comparing repeated with single cycle(s) of stimulation. Meiotic competence expression was unaffected for IVO oocytes while IVM oocytes exhibited a progressive decrease in meiotic competence with repeated stimulation. The ATP content of immature and IVO oocytes decreased with repeated stimulation. Although after one cycle of stimulation ATP content was lower in IVM than IVO oocytes, IVM oocytes exhibited stable levels of ATP across cycles of stimulation. Last, the in vitro developmental competence of IVO oocytes retrieved after repeated stimulation was not significantly different, and in vivo, similar implantation and resorption rates were observed following mating of animals subjected to repeated stimulation. Therefore, despite measurable consequences of repeated stimulation on specific parameters of follicular oocyte quality, compensatory mechanisms may exist in vivo to optimize the developmental competence of ovulated oocytes in the mouse.