ETIOLOGIC FACTORS INVOLVED IN THE LOW RESPONSE TO GONADOTROPINS IN INFERTILE WOMEN WITH NORMAL BASAL SERUM FOLLICLE-STIMULATING-HORMONE LEVELS

This study was designed to investigate possible aetiological factors involved in the low response to gonadotrophins in women with normal basal serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal serum FSH and 22 normal controls (five of whom had had a normal response to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of the vessels surrounding the dominant follicle for blood flow impedance analysis, (ii) the clonidine test to explore the ability of the pituitary to release growth hormone, and (iii) detection of anti-granulosa cell auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were significantly (P < 0.01) higher in the women with low responses as compared to the controls on days -1 and 0 (day 0 = ovulation). Seven out of the nine low responders were out of the range calculated for normal values after evaluation of the controls. A significant (P < 0.05) decrease in the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with previous normal response to ovarian stimulation. Six out of the nine low responders showed a negative clonidine test. No increase in anti-granulosa cell auto-antibodies was observed in the low responders as compared to the controls, including normal responders. In conclusion, an abnormal follicular blood flow impedance in the natural cycle may be related to low responses to gonadotrophins in patients with normal serum FSH concentrations. Simultaneously, a decreased growth hormone pituitary reserve has been identified in most of these patients, suggesting that the insulin-like growth factors system might be related to the vascularization of the ovarian follicle.