THE ROLE OF GROWTH-HORMONE IN OVULATION INDUCTION

During the last few years the potential importance of intraovarian reg ulators of follicular development has been recognized, and the effects of various growth factors on granulosa cell responses to gonadotrophi ns have been extensively investigated. Ovarian responses to exogenous gonadotrophins were improved by adjuvant growth hormone (GH) treatment of GH-deficient patients, and responses to hMG were apparently predic ted by estimated GH reserve. However, the results of different studies of GH/hMG cotreatment were equivocal. Therefore, a randomized, prospe ctive, cross-over study protocol between GH/hMG/hCG versus hMG/hCG was undertaken. Whereas 16 pregnancies were achieved in the 26 Clonidine- negative patients (61.5%) either in the GH/hMG cycle (11) or in the su cceeding one (5), no benefit was detected in 8 Clonidine-positive pati ents from the GH/hMG combination. The recently described OH-binding pr otein (BP) may reflect the OH-receptor. GH-BP levels were evaluated in the sera and follicular fluids (FF) of patients undergoing ovulation induction with either hMG/hCG or GH/hMG/hCG. GH-BP increase in serum c orrelated with E(2), and progesterone (P-4) concentrations. The FF GH- BP correlated with serum GH-BP levels. Lower FF GH-BP levels were meas ured in older compared to younger women, while increased values were o btained both in patients with elevated E(2) concentrations in serum an d in FF, or when more than five oocytes were retrieved. Primary increa sed GH-BP in unexplained infertility may suggest a new mechanism where by excessive GH-BP levels may deprive OH from its receptor and thus de crease the intraovarian IGF-I production. Whereas the GH-BP significan tly increased in correlation with moderately (1100-5500 pmol/l), or wi th severely increased (>5500 pmol/l) E(2) concentrations, the serum IG F-I levels increased with moderately elevated but decreased at severel y increased E(2) concentrations, as measured in ovarian hyperstimulati on (OHSS). This observation may suggest an IGF-I involved mechanism ex plaining why OHSS is detrimental to the early conception. Clonidine te st may identify patients who may benefit from this combination, during GH/hMG cycle and possibly during the succeeding cycle as well.