SUPPLEMENTARY GROWTH-HORMONE TREATMENT OF WOMEN WITH POOR OVARIAN RESPONSE TO EXOGENOUS GONADOTROPINS - CHANGES IN SERUM AND FOLLICULAR-FLUID INSULIN-LIKE GROWTH FACTOR-I (IGF-1) AND IGF BINDING PROTEIN-3 (IGFBP-3)

The effects of supplementary growth hormone (GH) treatment upon insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) concentrations in serum and ovarian follicular fluid were investigated in women undergoing buserelin human menopausal gonadotrophin (HMG) ovulation induction for in-vitro fertilization. Women (n = 40), aged 24-39 (mean 35 years), who showed poor ovarian responses to HMG, were recruited and randomly divided into two groups. Each patient received two cycles of ovulation induction, one with GH (12 IU/day x 12 days/HMG/buserelin) and another with placebo/HMG. Serum IGF-I increased substantially during the GH treatment and remained significantly higher than the control 2 days after the last GH injection. Serum IGFBP-3 fell steadily during the placebo/HMG treatment and to a nadir on the day of oocyte retrieval (P < 0.05 compared to serum before any treatment). In contrast, IGFBP-3 was increased (P < 0.01) during the GH administration and returned to the control level 2 days after GH injection. Serum oestradiol concentrations on the eighth day of HMG and the day of human chorionic gonadotrophin (HCG) were not significantly different between the two groups. Serum IGF-I was highly correlated with IGFBP-3 before any treatment (r = 0.433, P < 0.001). This correlation disappeared after buserelin, placebo/HMG treatment in the control group, but it was maintained during GH/HMG treatment (r = 0.343, P = 0.04). Follicular fluid concentrations of GH and IGF-1, not IGFBP-3 or oestradiol, were significantly elevated in the GH-treated women. Serum IGF-1 on the day of oocyte retrieval was highly correlated to the follicular fluid IGF-1 in both groups. The relationships between the follicular fluid GH and IGF-1 were completely opposite in the two groups, being positive in the control group and negative in the GH-treated group. In the control group, significant correlations were found between follicular fluid concentrations of IGF-I and IGFBP-3, and GH and IGFBP-3 which were not found in the GH-treated group. There were no correlations found between follicular fluid concentrations of GH or IGF-1 or IGFBP-3 and oestradiol. The results clearly demonstrate that the normal GH, IGF-1, IGFBP-3 relationships can be altered by treatments which influence the ovarian - pituitary axis; the significance of such changes to ovulation remains to be discovered.