A Randomised, Double-blind, Parallel Groups, Placebo-controlled, Multi-centre Trial in Oocyte Donors Assessing the Effects of Barusiban, a Selective Oxytocin Antagonist, on Uterine Contractions on the Day of Embryo Transfer

This was a randomised, double-blind, parallel groups, placebo-controlled, multi-centre trial. It was designed to evaluate the efficacy of barusiban, a selective oxytocin antagonist, on reducing the frequency of uterine contractions on the day of embryo transfer.

Participants in this trial were oocyte donors who had undergone controlled ovarian hyperstimulation in the long gonadotrophin-releasing hormone (GnRH) agonist protocol or the multiple-dose GnRH antagonist protocol, had received human chorionic gonadotrophin (hCG) for triggering of final follicular maturation and had undergone oocyte retrieval (OR) with a yield of ≥ 6 cumulus-oocyte-complexes. The duration of the trial was two days: Day OR +2 (screening, randomisation and dosing of investigational medicinal product) and Day OR +3 (end-of-trial).

On Day OR +2, participants were screened and subsequently randomised to barusiban or placebo. All participants received an intravenous (IV) bolus for 1 minute followed by an IV infusion for up to 59 minutes, administered via an indwelling catheter, of barusiban or placebo. Bolus volume and infusion rate were identical for barusiban and placebo. A mock embryo transfer (MET) procedure was performed 40 minutes after start of dosing and included intrauterine administration of a non-radioactive ultrasound contrast agent (SONOVUE) via the embryo transfer catheter. Transvaginal ultrasound of around 5 minutes duration was performed at seven time points on Day OR +2 and covered a span of approximately 2.5 hours including pre-dosing, during dosing, before and after mock embryo transfer, and post-dosing. The transvaginal ultrasound recordings were analysed for frequency of uterine contractions and other uterine contractility parameters by a central independent assessor, blinded to treatment allocation. Movement of the ultrasound contrast agent after the mock embryo transfer procedure was evaluated by the central independent assessor.

As an attempt to document the impact of uterine contractions on potential embryo expulsion, an exploratory evaluation of the movement of an ultrasound contrast agent (SONOVUE)administered intrauterinely via an embryo transfer catheter during the mock embryo transfer was performed. The anatomical point of release of the ultrasound contrast agent (correct or incorrect deposition site, and estimated distance from fundus) as well as any immediate movement (yes/no) of the bolus was recorded by the central independent assessor.

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