Effect of Oxytocin and Vasopressin Antagonists on Uterine Contractions
Condition: In Vitro Fertilisation (IVF) Treatment
Study type: Interventional
Phase: Phase 2

Summary: 
      The main purpose of this clinical research trial was to evaluate the effects of barusiban and
      atosiban compared to placebo on luteal phase uterine contractions in oocyte donors
      supplemented with progesterone.
    

Detailed description: 
      This was a randomised, double-blind, parallel groups, placebo-controlled, multi-centre trial.
      It was designed to evaluate the effects of a selective oxytocin antagonist (barusiban) and a
      mixed oxytocin antagonist - vasopressin V1a antagonist (atosiban) on uterine contractions
      during the luteal phase. 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 or single-dose GnRH antagonist protocols, received hCG
      for triggering of final follicular maturation and undergone oocyte retrieval (OR). The
      duration of the trial was five days and participants attended the clinic on three occasions:
      Day OR +1 (screening), Day OR +2 (randomisation and dosing of investigational medicinal
      product), and Day OR +5 (end-of-trial).

      After screening on Day OR +1, participants initiated luteal support supplementation with
      vaginal progesterone, which continued throughout the trial. On Day OR +2, participants were
      randomised to either barusiban, atosiban or placebo and participants received an intravenous
      (IV) bolus followed by an IV infusion of either barusiban, atosiban or placebo for
      approximately 4h. A mock embryo transfer was performed 3h after start of dosing.

      Uterine contractility parameters were assessed by transvaginal ultrasound. The transvaginal
      ultrasound recordings were analysed for uterine contractions by a central independent
      assessor, blinded to treatment allocation

      Definitions:

      The frequency of uterine contractions was defined as the number of uterine contractions per
      minute. A contraction was defined as one sequential upward and downward vertical displacement
      of the endometrial / myometrial interface over time.

      The external contractile measure was the mean wave amplitude in mm at the lumenal surface.
      This metric was measured at the lumenal peaks and troughs only and was a measurement designed
      to study the relationship between endometrial wave activity, manifested as bulk motion of the
      uterus, versus internal contractile strength. The external contractile measure was reported
      in mm/contraction.The external contractile measure quantified the movement of the uterus as a
      whole as measured at the lumen, i.e. the motion of the uterus relative to the body.

      The internal contractile measure was the strength of the contractions based upon the sum of
      the contraction amplitudes measured at the anterior and posterior endometrial / myometrial
      interfaces. The amplitude at each interface was defined as the average difference between the
      endometrial / myometrial-lumenal distance measured at the peaks and troughs of the
      endometrial / myometrial interfaces. The internal contractile measure was reported in
      mm/contraction. The internal contractile measure quantified the movement of the endometrium
      relative to the lumen, i.e. the motion internal to the uterus.

      The total contractile measure was the sum of the external contractile measure and the
      internal contractile measure and quantified total muscle movement in the uterus. If the waves
      at the anterior and posterior endometrial / myometrial interfaces were in phase then there
      was no endometrial motion relative to the lumen and the motion was a pure wave motion with
      the internal contractile measure equal to zero. The total contractile measure was reported in
      mm/contraction.

      Inter-subendometrial space was measured as the distance between the anterior stratum basalis
      and posterior stratum basalis layers in mid-sagittal plane at an anatomic location between 5
      and 10 mm from the fundus. All inter-subendometrial space measurements were made by selecting
      a clear image of the uterus, waiting for any contractions to pass and freezing the image.

      A linear distance measurement was then taken between the anatomic landmarks described above.
      Inter-subendometrial space was calculated from existing measurements using the mean of all
      measurements identifying the endometrial-myometrial interfaces on the superior and inferior
      surfaces in each endometrial strip when the arrows identifying endometrial contractions were
      placed for motion analysis. Inter-subendometrial space was reported in mm
    

Intervention name(s): Barusiban; Atosiban; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Solution for IV treatment. Bolus and infusion for 4 hours; Solution for IV administration. Bolus and infusion for 4 hours; Saline solution for IV administration. Bolus and infusion for 4 hours.
Intervention MeSH terms: Atosiban
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment