Circulating inhibins and activin A during GnRH-analogue down-regulation and ovarian hyperstimulation with recombinant FSH for in-vitro fertilization-embryo transfer

OBJECTIVE: We have investigated serial changes in plasma concentrations of inhibin A, inhibin B, pro alpha C and activin A in women undergoing stimulation with recombinant FSH in 'long-protocol' down-regulated cycles of IVF treatment. DESIGN: Blood samples were collected during the entire IVF treatment cycle at points coinciding with the early follicular phase of the cycle preceding treatment, pituitary down-regulation, stimulation with recombinant FSH, ovulatory triggering, and the luteal phase of the cycle. In patients who achieved conception, blood samples were also taken during the first 2 weeks of pregnancy. All samples were analysed for inhibin A, inhibin B, pro alpha C, activin A and oestradiol. PATIENTS: Fifteen women with normal ovarian function undergoing IVF treatment with tubal factor, mild endometriosis or idiopathic infertility. RESULTS: During pituitary desensitization, both inhibin A and inhibin B were significantly (P < 0.001, P = 0.002, respectively) reduced whereas levels of pro alpha C and activin A were largely unaltered. Levels of both inhibins rose markedly (P < 0.01) during FSH stimulation and a further rise in inhibin A was detected on the day after ovulatory trigger. Levels of both inhibin A and inhibin B then fell during and after oocyte pickup and continued to fall during the luteal phase. Activin A levels rose less markedly during gonadotrophin stimulation. Statistical analysis showed a high degree of correlation between the number of follicles (> 10 mm) and serum inhibin A (r = 0.65, P < 0.01) and pro alpha C (r = 0.65, P < 0.01) concentrations during the late follicular phase. CONCLUSIONS: These results indicate that ovarian production of dimeric inhibin A and B are gonadotrophin dependent, whereas activin A may have a significant gonadotrophin independent or extra-gonadal source. Inhibin A and pro alpha C may be useful markers for monitoring the effects of gonadotrophin stimulation.