Nathalie Lédée1, Laura Prat-Ellenberg2, Marie Petitbarat3, Lucie Chevrier3, Cynthia Simon2, Elie El Irani2, Dominique Vitoux4, Armand Bensussan5, Gérard Chaouat5. 1. MatriceLAB Innove SARL, Pépinière Paris Santé Cochin, 29 rue du Faubourg Saint Jacques, 75014 Paris, France; Centre d'assistance médical à la procréation Bluets-Drouot, Hospital Les Bluets, 4 rue Lasson 75012 Paris, France. Electronic address: nathalie-ledee@orange.fr. 2. Centre d'assistance médical à la procréation Bluets-Drouot, Hospital Les Bluets, 4 rue Lasson 75012 Paris, France. 3. MatriceLAB Innove SARL, Pépinière Paris Santé Cochin, 29 rue du Faubourg Saint Jacques, 75014 Paris, France. 4. Centre d'assistance médical à la procréation Bluets-Drouot, Hospital Les Bluets, 4 rue Lasson 75012 Paris, France; Plateforme AP-HP, Saint-Louis Hospital, 1 Avenue Claude Vellefaux, 75010 Paris, France. 5. Institut National de Santé et de Recherche Médicale, INSERM UMR-976, Saint-Louis Hospital, Research Center, 1 Avenue Claude Vellefaux, 75010, Paris, France.
Abstract
INTRODUCTION: Corticotherapy is the leading medication worldwide for patients with history of repeated implantation failures (RIF) after IVF/ICSI. Nevertheless, we still do not know its local mechanism of action, hence its precise indication. Our objective is to document the impact of prednisone on the endometrial expression of immune biomarkers (CD56 cells count, IL-18/TWEAK, IL-15/Fn-14 mRNA ratio) at the time of uterine receptivity in a RIF population. MATERIALS AND METHOD: An endometrial biopsy was realized in the mid luteal phase for immune profiling: IL-15/Fn-14 and IL-18/TWEAK mRNA ratios were determined by quantitative RT-PCR and CD56 mobilization per IHC. Fifty-five patients with a RIF history were diagnosed to have local over-immune activation [high IL-18/TWEAK mRNA ratio, and/or high IL-15/Fn-14 mRNA ratio] likely to impair the implantation process. They underwent a second immune profiling with supplementation of prednisone. A paired comparison of the immune profile before and under prednisone was performed in the subset of patients subsequently pregnant under prednisone. FINDING: In 54.5% of the cases, both immune biomarkers were normalized and in 16.5%, only one was normalized under prednisone. In 29% we observed a paradoxical increase of both immune biomarkers. The IL-18/TWEAK mRNA ratio reflecting the Th-1/Th-2 local equilibrium was significantly reduced (0.29 versus 0.10, p = .004), through very significant increase of TWEAK expression, in patients who were subsequently pregnant under prednisone. CONCLUSION: Testing the response to prednisone in a RIF context may be very useful. Less than half of RIF patients with immune deregulation may be prednisone responders and would benefit from its administration.
INTRODUCTION: Corticotherapy is the leading medication worldwide for patients with history of repeated implantation failures (RIF) after IVF/ICSI. Nevertheless, we still do not know its local mechanism of action, hence its precise indication. Our objective is to document the impact of prednisone on the endometrial expression of immune biomarkers (CD56 cells count, IL-18/TWEAK, IL-15/Fn-14 mRNA ratio) at the time of uterine receptivity in a RIF population. MATERIALS AND METHOD: An endometrial biopsy was realized in the mid luteal phase for immune profiling: IL-15/Fn-14 and IL-18/TWEAK mRNA ratios were determined by quantitative RT-PCR and CD56 mobilization per IHC. Fifty-five patients with a RIF history were diagnosed to have local over-immune activation [high IL-18/TWEAK mRNA ratio, and/or high IL-15/Fn-14 mRNA ratio] likely to impair the implantation process. They underwent a second immune profiling with supplementation of prednisone. A paired comparison of the immune profile before and under prednisone was performed in the subset of patients subsequently pregnant under prednisone. FINDING: In 54.5% of the cases, both immune biomarkers were normalized and in 16.5%, only one was normalized under prednisone. In 29% we observed a paradoxical increase of both immune biomarkers. The IL-18/TWEAK mRNA ratio reflecting the Th-1/Th-2 local equilibrium was significantly reduced (0.29 versus 0.10, p = .004), through very significant increase of TWEAK expression, in patients who were subsequently pregnant under prednisone. CONCLUSION: Testing the response to prednisone in a RIF context may be very useful. Less than half of RIF patients with immune deregulation may be prednisone responders and would benefit from its administration.