Endometrial vascularity by three-dimensional power Doppler ultrasound and cytokines: a complementary approach to assess uterine receptivity

Abstract

Introduction Uterine receptivity was assessed simultaneously by measurement of vasoactive cytokines possibly involved in development of spiral arteries and by assessment of endometrial and uterine arterial blood flow. The objective was to explore the relationship between cytokine-related dysregulation and endometrial vascularisation in women with repeated implantation failures after in vitro fertilisation embryo transfer (IVF-ET). Materials and methods We studied 40 women with recurrent IVF/ICSI-ET failures, despite replacement of more than 10 embryos of ‘good quality’, and 8 fertile controls. Three-dimensional ultrasound with power angiography was performed to record the sub-endometrial vascular flow index (VFI) and uterine artery pulsatility index prior to endometrial biopsy at day 21–23 of a monitored natural cycle. Endometrial IL-18, IL-18BP and IL-15 mRNA expression was assessed by real-time PCR, and the number of CD56 + cells determined by immunochemistry. Results IL-18 and IL-15 mRNA expression was significantly different between the two groups. The range of variation in vascular imaging data was increased in the implantation failure (IF) group. The mRNA ratio for IL-15, but not the other cytokines, correlated with sub-endometrial vascular flow ( r = 0.65; p < 0.001). This ratio correlated also with the mean number of CD56 + cells per high-power field ( r = 0.41; p = 0.005). Both IL-18 and IL-18BP mRNA expression was significantly negatively correlated with mean uterine artery pulsatility index ( r = −0.37 and −0.43; p = 0.02 and 0.01, respectively). Conclusion Comprehensive ultrasonographic indicators appear to be related to various mechanisms, including insufficient or excessive uterine NK cell recruitment and inadequate endothelial vascular remodelling. New molecular tools may be useful in providing greater precision of uterine receptivity than ultrasonic indicators alone.