Chloé S Fortin1, Arthur Leader2, Neal Mahutte3, Scot Hamilton4, Marie-Claude Léveillé2, Marc Villeneuve5, Marc-André Sirard6. 1. Centre de recherche en reproduction, développement et santé intergénérationnelle (CRDSI), Université Laval, 2440 Boulevard Hochelaga, Québec, QC, G1V 0A6, Canada. 2. Ottawa Fertility Centre, 100-955 Green Valley Crescent, Ottawa, ON, K2C 3V4, Canada. 3. Montréal Fertility Centre, 5252 de Maisonneuve Boulevard West Suite 220, Montréal, QC, H4A 3S5, Canada. 4. Reproductive Care Centre, 2180 Meadowvale Boulevard, Toronto, ON, L5N 5S3, Canada. 5. PROCREA Cliniques, 5600 Boulevard des Galeries, Québec, QC, G2K 2H6, Canada. 6. Centre de recherche en reproduction, développement et santé intergénérationnelle (CRDSI), Université Laval, 2440 Boulevard Hochelaga, Québec, QC, G1V 0A6, Canada. Marc-Andre.Sirard@fsaa.ulaval.ca.
Abstract
PURPOSE: Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. Not every patient has the same response to the same treatment and many fail for unknown reasons. Knowing why a cycle has failed and how the follicles were affected would allow clinicians to adapt the treatment accordingly and improve success rate. This study examines the hypothesis that transcriptomic analysis of follicular cells from failed IVF cycles reveals potential reasons for failure and provides new information on the physiological mechanisms related to IVF failure. METHODS: Follicular cells (granulosa cells) were obtained from IVF patients of four Canadian fertility clinics. Using microarray analysis, patients that did not become pregnant following the IVF cycle were compared to those that did. Functional analysis was performed using ingenuity pathway analysis and qRT-PCR was used to validate the microarray results in a larger cohort of patients. RESULTS: The microarray showed 165 differentially expressed genes (DEGs) in the negative group compared to the pregnancy group. DEGs include many pro-inflammatory cytokines and other factors related to inflammation, suggesting that this process might be altered when IVF fails. Overexpression of several factors, some of which act upstream from vascular endothelial growth factor (VEGF), also indicates increased permeability and vasodilation. Some DEGs were related to abnormal differentiation and increased apoptosis. CONCLUSIONS: Our results suggest that failure to conceive following IVF cycles could be associated with an imbalance between pro-inflammatory and anti-inflammatory mediators. The findings of this study identify potential failure causes and pathways for further investigation. Stimulatory protocols personalized according to patient response could improve the chances of later success.
PURPOSE: Hormonal stimulation prior to IVF influences the ovarian environment and therefore impacts oocytes and subsequent embryo quality. Not every patient has the same response to the same treatment and many fail for unknown reasons. Knowing why a cycle has failed and how the follicles were affected would allow clinicians to adapt the treatment accordingly and improve success rate. This study examines the hypothesis that transcriptomic analysis of follicular cells from failed IVF cycles reveals potential reasons for failure and provides new information on the physiological mechanisms related to IVF failure. METHODS: Follicular cells (granulosa cells) were obtained from IVFpatients of four Canadian fertility clinics. Using microarray analysis, patients that did not become pregnant following the IVF cycle were compared to those that did. Functional analysis was performed using ingenuity pathway analysis and qRT-PCR was used to validate the microarray results in a larger cohort of patients. RESULTS: The microarray showed 165 differentially expressed genes (DEGs) in the negative group compared to the pregnancy group. DEGs include many pro-inflammatory cytokines and other factors related to inflammation, suggesting that this process might be altered when IVF fails. Overexpression of several factors, some of which act upstream from vascular endothelial growth factor (VEGF), also indicates increased permeability and vasodilation. Some DEGs were related to abnormal differentiation and increased apoptosis. CONCLUSIONS: Our results suggest that failure to conceive following IVF cycles could be associated with an imbalance between pro-inflammatory and anti-inflammatory mediators. The findings of this study identify potential failure causes and pathways for further investigation. Stimulatory protocols personalized according to patient response could improve the chances of later success.
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