HUMAN FOLLICULAR-FLUID LEVELS OF ENDOTHELINS IN RELATION TO OOCYTE MATURITY STATUS

The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined i n 415 follicular fluids of 57 women participating in the IVF-ET progra mme in the University Women's Hospital, Marburg, in relation to the mo rphological appearance (''maturity'') and fertilizability of harvested oocytes as well as to the levels of inhibin, FSH, IGF-1, estradiol an d progesterone. Follicular aspiration was done transvaginally in all p atients after down regulation with nafareline and ovarian stimulation using urofollitropin and menotropin. Ovulation was induced by hCG. ETs were measured by RIA using commercial kits supplied by Peninsula Labo ratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalid ated. Immunoreactive ET-1 was detectable in all follicular samples, th e average level being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67 .5% of the samples, the average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in the average levels of ET-1 in the fl uids of small, medium and large follicles. However, there was a signif icantly higher level of ET-2 in the fluids of medium compared to large follicles and there was a negative correlation of the ET-2 levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could p lay a role during the maturation of the ovarian follicles. Unlike ET-1 , the mean concentrations of ET-2 were significantly higher in the flu ids with oocytes which could be fertilized and cleaved than in those w ith oocytes which did not fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte maturation. No correlations of ET le vels were found with the levels of inhibin, FSH, estradiol and progest erone. However, ET-2 levels significantly correlated with the levels o f IGF-1 (p < 0.001) indicating a possible synergistic effect of endoth elins and IGF-system. In conclusion, this study is further evidence fo r a physiological role of the ETs in the human ovary.