OOCYTE MATURATION IN HUMANS - THE ROLE OF GONADOTROPINS AND GROWTH-FACTORS

Objective: To determine the effect of FSH/LH in vivo and epidermal gro wth factor (EGF) and insulin-like growth factor I(IGF-I) in vitro on h uman oocyte maturation. Design: Oocyte-cumulus complexes were harveste d from three different groups of patients: [1] unstimulated ovaries fr om women undergoing surgery; [2] multifollicular development achieved with a combination of FSH and LH in the absence of an ovulatory dose o f hCG; and [3] oocyte-cumulus complexes retrieved after appropriate ov arian stimulation with FSH/LH and hCG for IVF purposes. Setting, Patie nts: In vitro fertilization program and patients undergoing surgery fo r benign disorders at the Instituto Valenciano de Infertilidad, Valenc ia, Spain. Interventions: Oocyte-cumulus complexes from unstimulated o varies collected at surgery by follicular puncture and washing. Oocyte -cumulus complexes from stimulated cycles obtained by ultrasound-guide d transvaginal aspiration. Oocyte-cumulus complexes cultured in vitro in the absence or presence of different concentrations of EGF and IGF- I. Main Outcome Measure: Germinal vesicle breakdown and metaphase-II s tage after 24 and 48 hours. Results: Comparison of the spontaneous res umption of meiosis and metaphase II oocytes among groups showed signif icant differences between unstimulated and stimulated ovaries after 24 and 48 hours in culture. Administration of hCG accelerated the percen tage of maturation by 24 hours. Further incubation of unstimulated ooc yte-cumulus complexes with EGF and IGF-I significantly increased the p ercentage of metaphase-II oocytes after 24 and 48 hours in culture. Co nclusions: Epidermal growth factor and IGF-I are able to augment spont aneous maturation in immature human oocytes. Because spontaneous matur ation is mainly observed when follicles have been exposed to pharmacol ogical doses of hMG, it is suggested that increasing FSH levels within the follicle is coincident with the generation of a positive signal n ecessary to complete oocyte maturation in humans. This signal may be l inked to the dynamics of growth factors within the follicle itself.