Objectives: To determine the relationship of ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity to the outcome of IVF-ET and to establish whether 11 beta-HSD activities vary for a given patient between consecutive treatment cycles. Design: Retrospective correlation analysis. Setting: Patients were treated and ovarian 11 beta-HSD activities were measured at independent fertility and biochemistry departments, respectively. Patients: Random series of 137 women undergoing a total of 172 treatment cycles for IVF-ET. Interventions: Subcutaneous buserelin acetate plus IM hMG and hCG for controlled ovarian hyperstimulation; blood samples were collected for plasma LH and steroid determinations. Main Outcome Measures: Presence or absence of detectable ovarian 11 beta-HSD activity, oocyte fertilization rates, and the identification of clinical pregnancies. Results: None of the 101 cycles associated with 11 beta-HSD positive granulosa-lutein cells resulted in clinical pregnancies, whereas the pregnancy rate for the 71 patients with undetectable ovarian 11 beta-HSD activity was 63.4% per cycle. The incidence of total fertilization failure was lower and the median oocyte fertilization rate was higher in cycles characterized by 11 beta-HSD-negative cells. Plasma concentrations of LH and E(2) were higher in cycles yielding 11 beta-HSD-negative cells, whereas plasma P, patient age, and the number of oocytes retrieved did not relate to ovarian 11 beta-HSD activity. For the 35 patients studied in repeat cycles, ovarian 11 beta-HSD activities did not relate to those in the initial cycles. Conclusions: Ovarian 11 beta-HSD activity is associated with failure to conceive by IVF-ET. For a given patient, ovarian 11 beta-HSD activity varies between consecutive treatment cycles. Hence, ovarian 11 beta-HSD activities may predict the outcome of this assisted reproduction protocol independently in each treatment cycle.