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 a 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.