LAUSR

What is the effect of nolasiban on the uterine contractility of in-vitro fertilisation (IVF) patients prior to embryo transfer (ET) ? A single oral dose of nolasiban 900 mg administered 4 h before ET significantly decreased contraction frequency and increased coordination compared to placebo. Nolasiban is an investigational oral oxytocin receptor antagonist (OTRa) being developed to improve the chance of pregnancy following ET. Increased uterine contraction frequency can influence embryo implantation, and the coordination of these uterine contractions is equally important. OTRa have been shown to decrease uterine contractions and increase endometrial perfusion. Recently, an automated and quantitative measurement tool using transvaginal ultrasound (TVUS) to better characterise uterine contractility has been developed which can be used to quantify the effect of nolasiban on uterine contractility. This study is part of a completed multi-centre randomised placebo-controlled trial (IMPLANT 1 – NCT02310802) in IVF patients (n = 247) carried out in 2015. Our study retrospectively assessed a sub-set of patients with good quality TVUS recordings to evaluate their mechanical uterine motion that were randomised to receive either nolasiban 900mg (n = 39) or placebo (n = 42). Subjects were < 37 years, undergoing ET on Day 3 following IVF/ICSI and with evidence of uterine contractions 4 h before ET. Nolasiban was administered 4 h before ET. Patients underwent TVUS immediately before drug administration and again immediately before ET. Uterine contraction frequency, amplitude, power and coordination were measured by applying dedicated speckle tracking and strain analysis. The Shapiro–Wilk test, followed by the Wilcoxon rank-sum test were applied to compare features between treatment groups. The mean (SD) frequency of uterine contractions was 1.54 (0.25) in the nolasiban group versus 1.57 (0.12) in the placebo group (p = 0.016). The mean (SD) coordination was 0.10 (0.17) in the nolasiban group versus 0.02 (0.16) in the placebo group (p = 0.034). The coordination feature was measured by assessing the presence of simultaneous movements of the anterior and posterior uterine walls, a higher value reflects increased coordination. There was no difference in contraction amplitude or power. This was a retrospective analysis of TVUS videos. The small sample size limits the generalisability of the findings. Furthermore, our initial results do not show how the changes in uterine motion may affect pregnancy rate after ET, meaning that the clinical relevance of our results remains to be proven. Wider implications of the findings: Our results show that in patients taking one 900mg dose of nolasiban prior to ET, beneficial uterine contractions are seen, which could be promising for embryo implantation and pregnancy in IVF patients. Our quantitative TVUS measurement tool can be applied to different patient populations to accurately quantify uterine motion. NCT02310802