The Role of Growth Hormone in Ovulation Induction

Abstract

During the last few years the potential importance of intraovarian regulators of follicular development has been recognized, and the effects of various growth factors on granulosa cell responses to gonadotrophins 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 predicted by estimated GH reserve. However, the results of different studies of GH/hMG cotreatment were equivocal. Therefore, a randomized, prospective, 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 succeeding one (5), no benefit was detected in 8 Clonidine-positive patients from the GH/hMG combination.

The recently described GH-binding protein (BP) may reflect the GH-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 correlated with E₂, and progesterone (P₄) concentrations. The FF GH-BP correlated with serum GH-BP levels. Lower FF GH-BP levels were measured in older compared to younger women, while increased values were obtained both in patients with elevated E₂ concentrations in serum and in FF, or when more than five oocytes were retrieved. Primary increased GH-BP in unexplained infertility may suggest a new mechanism whereby excessive GH-BP levels may deprive GH from its receptor and thus decrease the intraovarian IGF-I production. Whereas the GH-BP significantly increased in correlation with moderately (1100-5500 pmol/l), or with severely increased (>5500 pmol/l) E₂ concentrations, the serum IGF-I levels increased with moderately elevated but decreased at severely increased E₂ concentrations, as measured in ovarian hyper-stimulation (OHSS). This observation may suggest an IGF-I involved mechanism explaining why OHSS is detrimental to the early conception. Clonidine test may identify patients who may benefit from this combination, during GH/hMG cycle and possibly during the succeeding cycle as well.

Key Words:

• growth hormone (GH)
• GH-binding protein
• GH receptor
• ovarian physiology
• oogenesis
• folliculogenesis