OBJECTIVE: To determine the effect of thiazolidenedione derivatives (TZDs) on vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells and the morphologic development of murine embryos. DESIGN: Prospective, experimental, in vitro and in vivo study. SETTING: Research laboratory. PATIENT(S): Follicular aspirates from 10 women undergoing oocyte retrieval. INTERVENTION(S): Isolated human granulosa cells were treated with a dimethyl sulfoxide (DMSO) control or ciglitazone, in the presence and absence of an hCG stimulus. Embryos extracted from superovulated B6C3F1 female mice were cultured in the presence of DMSO or pioglitazone. MAIN OUTCOME MEASURE(S): Vascular endothelial growth factor concentrations at 24 and 48 hours. Morphologic development of murine embryos at 96 hours. RESULT(S): Following an hCG stimulus, treatment with 20 microM or 40 microM ciglitazone decreased VEGF production in a statistically significant manner at both time intervals. Blastocyst development at 96 hours did not significantly differ between untreated zygotes and those treated with pioglitazone. CONCLUSION(S): Ciglitazone significantly decreased VEGF production by human granulosa cells in an in vitro model. Pioglitazone did not adversely impact the development of cultured murine embryos. Although mechanistic evidence is not provided, the pivotal role of VEGF in ovarian hyperstimulation syndrome prompts investigation of TZDs as a novel treatment for this condition. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
OBJECTIVE: To determine the effect of thiazolidenedione derivatives (TZDs) on vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells and the morphologic development of murine embryos. DESIGN: Prospective, experimental, in vitro and in vivo study. SETTING: Research laboratory. PATIENT(S): Follicular aspirates from 10 women undergoing oocyte retrieval. INTERVENTION(S): Isolated human granulosa cells were treated with a dimethyl sulfoxide (DMSO) control or ciglitazone, in the presence and absence of an hCG stimulus. Embryos extracted from superovulated B6C3F1 female mice were cultured in the presence of DMSO or pioglitazone. MAIN OUTCOME MEASURE(S): Vascular endothelial growth factor concentrations at 24 and 48 hours. Morphologic development of murine embryos at 96 hours. RESULT(S): Following an hCG stimulus, treatment with 20 microM or 40 microM ciglitazone decreased VEGF production in a statistically significant manner at both time intervals. Blastocyst development at 96 hours did not significantly differ between untreated zygotes and those treated with pioglitazone. CONCLUSION(S): Ciglitazone significantly decreased VEGF production by human granulosa cells in an in vitro model. Pioglitazone did not adversely impact the development of cultured murine embryos. Although mechanistic evidence is not provided, the pivotal role of VEGF in ovarian hyperstimulation syndrome prompts investigation of TZDs as a novel treatment for this condition. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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