In Vitro Fertilisation (IVF) Treatment Clinical Trial
Official title:
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
The main purpose of this clinical research trial was to evaluate the effects of barusiban compared to placebo on uterine contractions on luteal phase uterine contractions in oocyte donors supplemented with progesterone.
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.
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 frequency was the
inverse of period converted to contractions per minute.
The period was the average time it took to complete one contraction during the studied time
interval. It was calculated from both the peaks and the troughs at the anterior and
posterior endometrial /myometrial interfaces. The period was measured in seconds per
contraction.
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, manifest 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 clinically 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 clinical 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.
The direction of wave propagation was classified as one of the following:
- Fundal (from cervix to fundus)
- Cervical (from fundus to cervix)
- Convergent (opposing) starting simultaneously from cervix and fundus
- Focal local contractions (which are not involving the whole uterine walls)
- No activity
- NE: not evaluable At each assessment time point, the most predominant type of direction
of wave propagation was recorded.
Dispersion of the ultrasound contrast agent bolus after release from the catheter was
recorded as yes/no and number of dispersed fragments, if applicable.
Location of the ultrasound contrast agent bolus was categorised as follows:
- Upper 1/3 (fundal) part of uterine cavity
- Central 1/3 of uterine cavity
- Lower 1/3 (cervical) part of the uterine cavity
- Intralumenal part of Fallopian tube
- Intra-cervical
- Vaginal
- NE: not evaluable Distance from the apex of the fundus at the myometrial-endometrial
interface to the position of the microdroplet of ultrasound contrast agent was recorded
in mm.
Velocity of the bolus of ultrasound contrast agent was assessed from distance and time, and
was recorded in mm/hour.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00587327 -
Effect of Oxytocin and Vasopressin Antagonists on Uterine Contractions
|
Phase 2 |