Diminished alpha-inhibin messenger ribonucleic acid in in vitro fertilization-embryo transfer poor responders reflects declining follicle reserve.

OBJECTIVES: To quantitate and compare granulosa cell alpha-inhibin messenger RNA (mRNA) levels in IVF-ET poor and good responders and thereby learn how alpha-inhibin mRNA levels change in states of diminished ovarian responsiveness. DESIGN: Ribonucleic acid analysis of stored luteinized granulosa cell samples. SETTING: Academic tertiary care institution. PATIENTS: Fifty-three women undergoing follicle aspiration for IVF-ET were studied. Patients were classified as poor responders (n = 16) or good responders (n = 37) according to their E2 concentration on the day of hCG; the E2 of poor responders was < 1,000 pg/mL (3,671 pmol/L) and that of good responders was > or = 1,000 pg/mL (3,671 pmol/L). MAIN OUTCOME MEASURES: Messenger RNA levels were measured using dot blot RNA analysis. The following parameters were determined or derived: total mRNA levels, total alpha-inhibin mRNA levels, alpha-inhibin mRNA per follicle, and proportional alpha-inhibin mRNA as the ratio of alpha-inhibin mRNA:total mRNA. RESULTS: Proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle were not significantly different between poor responders and good responders. Total mRNA and total alpha-inhibin mRNA levels, however, were diminished significantly in poor responders. CONCLUSIONS: The observations that proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle do not significantly change in poor responders, whereas total alpha-inhibin mRNA does, indicate that the decrease in total alpha-inhibin mRNA in poor responders reflects a decreased pool of total mRNA, likely because of a reduction in follicle number. These findings are in contrast to other recent reports that describe a change in granulosa cell function accompanying states of decreased ovarian responsiveness.

Enhanced expression of resident leukocyte interferon gamma mRNA in endometriosis.

PROBLEM: Previous studies have shown that the endometrial epithelial/stromal cell proliferative activity of endometriosis is significantly less than that of normal endometrium and that the concentration of resident stromal leukocytes is significantly greater in ectopic than in eutopic endometrium. Other work has shown that interferon gamma (IFN gamma), secreted by resident leukocytes, inhibits endometrial cell proliferation in vitro. Accordingly, we hypothesized that the lower proliferative activity of endometriosis may be related to enhanced resident leukocyte IFN gamma production. This study was designed to assess whether resident leukocytes in endometriosis express IFN gamma mRNA and to compare this expression to that of normal endometrium. METHODS: Biopsies of ectopic endometrium (N = 16) from women in the follicular phase and normal proliferative (N = 9) and secretory (N = 8) endometria were examined for IFN gamma expression. Using monoclonal antibodies specific for CD45 (leukocyte common antigen), CD3 (a T-cell marker) and CD11c (a macrophage marker), leukocyte types were identified immunocytochemically, followed by in situ hybridization to examine expression of IFN gamma mRNA. RESULTS: Results demonstrated that (1) the overall concentration of T cells and macrophages expressing IFN gamma mRNA is significantly greater in endometriosis as compared to eutopic endometrium, and (2) the percent of each leukocyte type expressing IFN gamma mRNA is greater in endometriosis than in normal endometrium. CONCLUSIONS: These findings support a possible paracrine role for resident leukocytes in regulating cell proliferation in endometriosis.