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 insuli n-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3) concen trations in serum and ovarian follicular fluid were investigated in wo men undergoing buserelin human menopausal gonadotrophin (HMG) ovulatio n induction for in-vitro fertilization. Women (n = 40), aged 24-39 (me an 35 years), who showed poor ovarian responses to HMG, were recruited and randomly divided into two groups. Each patient received two cycle s of ovulation induction, one with GH (12 IU/day x 12 days/HMG/buserel in) and another with placebo/HMG. Serum IGF-I increased substantially during the GH treatment and remained significantly higher than the con trol 2 days after the last GH injection. Serum IGFBP-3 fell steadily d uring the placebo/HMG treatment and to a nadir on the day of oocyte re trieval (P < 0.05 compared to serum before any treatment). In contrast , IGFBP-3 was increased (P < 0.01) during the GH administration and re turned to the control level 2 days after GH injection. Serum oestradio l concentrations on the eighth day of HMG and the day of human chorion ic gonadotrophin (HCG) were not significantly different between the tw o groups. Serum IGF-I was highly correlated with IGFBP-3 before any tr eatment (r = 0.433, P < 0.001). This correlation disappeared after bus erelin, placebo/HMG treatment in the control group, but it was maintai ned during GH/HMG treatment (r = 0.343, P = 0.04). Follicular fluid co ncentrations of GH and IGF-1, not IGFBP-3 or oestradiol, were signific antly elevated in the GH-treated women. Serum IGF-1 on the day of oocy te retrieval was highly correlated to the follicular fluid IGF-1 in bo th groups. The relationships between the follicular fluid GH and IGF-1 were completely opposite in the two groups, being positive in the con trol group and negative in the GH-treated group. In the control group, significant correlations were found between follicular fluid concentr ations of IGF-I and IGFBP-3, and GH and IGFBP-3 which were not found i n the GH-treated group. There were no correlations found between folli cular fluid concentrations of GH or IGF-1 or IGFBP-3 and oestradiol. T he results clearly demonstrate that the normal GH, IGF-1, IGFBP-3 rela tionships can be altered by treatments which influence the ovarian - p ituitary axis; the significance of such changes to ovulation remains t o be discovered.