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 i nvolved in the low response to gonadotrophins in women with normal bas al serum follicle stimulating hormone (FSH) concentrations, stimulated for assisted reproduction. Nine of these patients with normal basal s erum FSH and 22 normal controls (five of whom had had a normal respons e to previous gonadotrophin stimulation) were prospectively subjected to: (i) transvaginal pulsed colour Doppler ultrasound evaluation of th e vessels surrounding the dominant follicle for blood flow impedance a nalysis, (ii) the clonidine test to explore the ability of the pituita ry to release growth hormone, and (iii) detection of anti-granulosa ce ll auto-antibodies in blood using an enzyme-linked immunosorbent assay (ELISA). The pulsatility and resistance indices (PI, RI) were signifi cantly (P < 0.01) higher in the women with low responses as compared t o 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 i n the secretion of growth hormone 60-90 min after clonidine ingestion was observed in the low responders as compared to five controls with p revious normal response to ovarian stimulation. Six out of the nine lo w responders showed a negative clonidine test. No increase in anti-gra nulosa cell auto-antibodies was observed in the low responders as comp ared to the controls, including normal responders. In conclusion, an a bnormal follicular blood flow impedance in the natural cycle may be re lated to low responses to gonadotrophins in patients with normal serum FSH concentrations. Simultaneously, a decreased growth hormone pituit ary reserve has been identified in most of these patients, suggesting that the insulin-like growth factors system might be related to the va scularization of the ovarian follicle.