Women who experienced repeated IVF/ICSI implantation failures show a relative excess of soluble VEGF-R1 before conception

Abstract

OBJECTIVE: To document simultaneously the microvessels density through a local vascular mapping of the endometrium in the luteal phase and to confront data with the documentation of VEGF and its receptor both at protein and mRNA level among patients which failed to implant compared to fertile ones. Local angiogenesis occurring in the middle luteal phase appears as essential to prepare the endometrium to uterine receptivity.DESIGN: Analytic study, European Network of researchMATERIALS AND METHODS: 38 women participated to this protocol, 13 were fertile control women and 25 were women with repeated and unexplained failures of in vitro fertilization (IVF) attempts. Three-dimensional ultrasound with power angiography was performed to record the sub-endometrial vascular flow index (Sub-VFI) before an endometrial biopsy at day 21-23 of a monitored natural cycle. Datation, semi-quantitative evaluation of spiral arteries section, immunostaining of VEGF, VEGF-R1 and R-2 and quantitative Real time PCR for mRNA expression VEGF-A, VEGF-R1, VEGF-R2 and sVEGF-R1 were performedRESULTS: The Sub-VFI was significantly lower in case of implantation failures. Quantification of spiral arteries sections confirmed the ultrasonographic vascular imaging data. For VEGF, IF patient showed a stronger staining for VEGF and VEGF-R1 than observed in control group and a slightly lower VEGF-R2 immunostaining. The mRNA levels for VEGF, VEGFR-1 and VEGFR-2 were significantly lower in the IF group and the ratio sVEGFR-1/VEGFR-1 significantly higher in context of implantation failure. The Sub-endometrial VFI did not correlate with the mRNA expressions of either VEGF and/or its receptors VEGF-R1 and -2.CONCLUSIONS: The endometrial VEGF system is dysregulated before conception in patients with history of implantation failure and show a preconceptional relative excess of the mRNA expression of sVEGF-R1. OBJECTIVE: To document simultaneously the microvessels density through a local vascular mapping of the endometrium in the luteal phase and to confront data with the documentation of VEGF and its receptor both at protein and mRNA level among patients which failed to implant compared to fertile ones. Local angiogenesis occurring in the middle luteal phase appears as essential to prepare the endometrium to uterine receptivity. DESIGN: Analytic study, European Network of research MATERIALS AND METHODS: 38 women participated to this protocol, 13 were fertile control women and 25 were women with repeated and unexplained failures of in vitro fertilization (IVF) attempts. Three-dimensional ultrasound with power angiography was performed to record the sub-endometrial vascular flow index (Sub-VFI) before an endometrial biopsy at day 21-23 of a monitored natural cycle. Datation, semi-quantitative evaluation of spiral arteries section, immunostaining of VEGF, VEGF-R1 and R-2 and quantitative Real time PCR for mRNA expression VEGF-A, VEGF-R1, VEGF-R2 and sVEGF-R1 were performed RESULTS: The Sub-VFI was significantly lower in case of implantation failures. Quantification of spiral arteries sections confirmed the ultrasonographic vascular imaging data. For VEGF, IF patient showed a stronger staining for VEGF and VEGF-R1 than observed in control group and a slightly lower VEGF-R2 immunostaining. The mRNA levels for VEGF, VEGFR-1 and VEGFR-2 were significantly lower in the IF group and the ratio sVEGFR-1/VEGFR-1 significantly higher in context of implantation failure. The Sub-endometrial VFI did not correlate with the mRNA expressions of either VEGF and/or its receptors VEGF-R1 and -2. CONCLUSIONS: The endometrial VEGF system is dysregulated before conception in patients with history of implantation failure and show a preconceptional relative excess of the mRNA expression of sVEGF-R1.