Ryan J Heitmann1, Kyle J Tobler1, Laurie Gillette2, Juan Tercero2, Richard O Burney3,4,5. 1. Department of Obstetrics and Gynecology, Madigan Army Medical Center, 9040 Jackson Ave, Tacoma, WA, 98431, USA. 2. Department of Clinical Investigation, Madigan Army Medical Center, 9040 Jackson Ave, Tacoma, WA, 98431, USA. 3. Department of Obstetrics and Gynecology, Madigan Army Medical Center, 9040 Jackson Ave, Tacoma, WA, 98431, USA. roburney@stanford.edu. 4. Department of Clinical Investigation, Madigan Army Medical Center, 9040 Jackson Ave, Tacoma, WA, 98431, USA. roburney@stanford.edu. 5. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Madigan Healthcare Systems, ATTN: MCHJ-OG, 9040A Fitzsimmons Drive, Tacoma, WA, 98431-1100, USA. roburney@stanford.edu.
Abstract
PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model. METHODS: PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development. RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.
PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model. METHODS: PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development. RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.
Authors: Sanjeev Kumar; David A Allen; Julius E Kieswich; Nimesh S A Patel; Steven Harwood; Emanuela Mazzon; Salvatore Cuzzocrea; Martin J Raftery; Christoph Thiemermann; Muhammad M Yaqoob Journal: J Am Soc Nephrol Date: 2009-09-24 Impact factor: 10.121