Letrozole stimulates the growth of human endometrial explants cultured in three-dimensional fibrin matrix

Objective: To investigate the effects of an aromatase inhibitor, letrozole, on the growth of human endometrium in a three-dimensional fibrin matrix model of endometriosis. Design: Experimental study of human endometrial biopsies in a three-dimensional fibrin matrix culture system. Setting: Academic research center. Patient(s): Eight normal women with benign gynecologic problems. Intervention(s): Endometrial biopsy samples were washed, cut into small pieces, and placed between two layers of fibrin gel in the presence or absence of letrozole in the culture medium. Tissue changes were assessed by histological and immunohistochemical staining using an inverted microscope, image analysis, and a semiquantitative scoring system. Main Outcome Measure(s): Stromal and epithelial cell outgrowth into the fibrin matrix and angiogenesis comprising endothelial cell invasion of the matrix. Result(S): Letrozole (0.1 mu mol/L, 1 mu mol/L, and 10 mu mol/L) exerted a significant growth stimulation effect on endometrial tissue in this model. Conclusion(s): In contrast to our expectations, letrozole stimulated growth of normal human endometrium in an in vitro model of endometriosis. Normal endometrium may respond differently than endometriotic lesions to therapeutic agents. Our findings should be kept in mind when considering future research to explore new clinical treatments for endometriosis. (Fertil Steril (R) 2009;91.:2172-6. (C)2009 by American Society for Reproductive Medicine.)