Use of Atosiban in in Vitro Fertilization (IVF) Treatment

NCT ID: NCT01501214

Last Updated: 2014-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2013-12-31

Brief Summary

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The hypothesis of this randomized double blind study is that the live birth rates are significantly higher after the use of atosiban prior to the embryo transfer in patients undergoing in vitro fertilization (IVF) treatment. This study aims to compare the live birth rates of IVF treatment between patients receiving atosiban and placebo prior to the transfer.

Detailed Description

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In-vitro fertilization-embryo transfer (IVF-ET) treatment involves multiple follicular development following ovarian stimulation, oocyte retrieval and ET after fertilization. Despite recent advances in ovarian stimulation, the method of assisted fertilization and improved culture conditions, the implantation potential of embryos remains around 20-25% for a long time.

ET is the final step of an IVF cycle and its success depends on the embryo quality, the endometrial receptivity and uterine contractions. Uterine contractions play an important role in embryo implantation (Fanchin, 2009) as excessive uterine contractions may expel embryos from the uterus and decrease the implantation potential of embryos (Fanchin et al., 1998).

Ovarian stimulation is used in the great majority of IVF programs so that multiple embryos are available for selection and transfer. However, supraphysiological concentrations of oestradiol following ovarian stimulation may induce endometrial production of oxytocin, formation of oxytocin receptors, and indirectly formation/release of PGF2a (Richter et al., 2004; Liedman et al., 2008). It has been shown that uterine contractile activity in IVF cycles is increased by approximately 6-fold when measured before ET as compared with the situation before ovulation in the natural cycle (Ayoubi et al., 2003). Fanchin et al. (1998) have estimated that about 30% of patients undergoing ET have pronounced uterine contractions. Uterine contractions can also be triggered after excessive cervical manipulation in difficult transfer procedure (Fanchin et al., 1998).

Drugs to inhibit increased uterine contractions at the time of ET are an attractive approach to improve the IVF success. However, the use of beta agonists or non-steroid anti-inflammatory drugs has not been shown to provide sufficient benefit (Bernabeu et al., 2006; Moon et al., 2004; Tsirigotis et al., 2000). Uterine contractions involve oxytocin and therefore inhibition of oxytocin receptors may improve the IVF success by decreasing uterine contractions, interfering with PGF2a/oxytocin systems and possibly improving endometrial perfusion (Vedernikov et al., 2006).

Atosiban, a combined oxytocin/vasopressin V1A antagonist, is currently registered for clinical use in women suffering from preterm labour. In a multicentre, randomized, placebo-controlled trial, it has been shown to reduce the frequency and amplitude of uterine contractions in egg donors when compared with placebo (Blockeel et al., 2009; Pierson et al., 2009; Visnova et al., 2009). There was a lack of an embryotoxic effect of atosiban in concentrations up to 50-fold therapeutic blood concentrations (Pierzynski et al., 2007). Atosiban did not affect the survival of 1-cell rabbit embryos, nor decrease the percentage of hatched rabbit blastocysts. The human sperm motility bioassay also showed no adverse influence.

Conditions

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Subfertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Atosiban

Group Type ACTIVE_COMPARATOR

Atosiban

Intervention Type DRUG

Patients in the atosiban group will receive intravenous atosiban 30 min before the transfer with a bolus dose of 6.75 mg, and the infusion will be continued with an infusion rate of 18 mg/h. After performing ET, the dose of atosiban will be reduced to 6 mg/h and the infusion will be continued for 2 hours (total administered dose: 37.5 mg). Those in the placebo group will receive normal saline only.

Placebo

Normal saline

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type DRUG

Normal saline given

Interventions

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Atosiban

Patients in the atosiban group will receive intravenous atosiban 30 min before the transfer with a bolus dose of 6.75 mg, and the infusion will be continued with an infusion rate of 18 mg/h. After performing ET, the dose of atosiban will be reduced to 6 mg/h and the infusion will be continued for 2 hours (total administered dose: 37.5 mg). Those in the placebo group will receive normal saline only.

Intervention Type DRUG

Normal saline

Normal saline given

Intervention Type DRUG

Other Intervention Names

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Tractocile

Eligibility Criteria

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Inclusion Criteria

* Age \< 43 years
* Normal uterine cavity shown on ultrasound scanning

Exclusion Criteria

* Age \>=43
* Three previous IVF cycles
* Use of donor oocytes
* Natural IVF or IVM cycles
* Abnormal uterine cavity on ultrasound scanning
* ET canceled because of absent fertilization or risk of ovarian hyperstimulation syndrome
* Blastocyst transfer
* Undergoing preimplantation genetic diagnosis
* Recruited in the same study before
Minimum Eligible Age

18 Years

Maximum Eligible Age

43 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Vietnam National University

OTHER

Sponsor Role collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role collaborator

The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ernest HY Ng, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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Reproductive Medical Center of Nanfang Hospital

Guangzhou, Guangdong, China

Site Status

CGRH, School of Medicine

Ho Chi Minh City, Ho Chi Minh City, Vietnam

Site Status

Countries

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China Vietnam

References

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Ayoubi JM, Epiney M, Brioschi PA, Fanchin R, Chardonnens D, de Ziegler D. Comparison of changes in uterine contraction frequency after ovulation in the menstrual cycle and in in vitro fertilization cycles. Fertil Steril. 2003 May;79(5):1101-5. doi: 10.1016/s0015-0282(03)00179-1.

Reference Type BACKGROUND
PMID: 12738502 (View on PubMed)

Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. doi: 10.1093/humrep/dei343. Epub 2005 Nov 10.

Reference Type BACKGROUND
PMID: 16284067 (View on PubMed)

Blockeel C, Pierson R, Popovic-Todorovic B, Visnova HA, Garcı´a-Velasco HA, Mra´zek M, Barri PN, Pierzynski P, Kuczynski W, Devroey P, Breinholt V, Erichsen L, Klein BM, Arce JC. Effects of barusiban and atosiban on frequency of uterine contractions in the luteal phase after stimulation: a randomized placebo controlled trial. Hum. Reprod. 24 (Suppl. 1), i26, 2009.

Reference Type BACKGROUND

Fanchin R, Ayoubi JM. Uterine dynamics: impact on the human reproduction process. Reprod Biomed Online. 2009;18 Suppl 2:57-62. doi: 10.1016/s1472-6483(10)60450-6.

Reference Type BACKGROUND
PMID: 19406033 (View on PubMed)

Fanchin R, Righini C, Olivennes F, Taylor S, de Ziegler D, Frydman R. Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Hum Reprod. 1998 Jul;13(7):1968-74. doi: 10.1093/humrep/13.7.1968.

Reference Type BACKGROUND
PMID: 9740459 (View on PubMed)

Liedman R, Hansson SR, Howe D, Igidbashian S, McLeod A, Russell RJ, Akerlund M. Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects. Gynecol Endocrinol. 2008 Sep;24(9):508-13. doi: 10.1080/09513590802306218.

Reference Type BACKGROUND
PMID: 18958771 (View on PubMed)

Moon HS, Park SH, Lee JO, Kim KS, Joo BS. Treatment with piroxicam before embryo transfer increases the pregnancy rate after in vitro fertilization and embryo transfer. Fertil Steril. 2004 Oct;82(4):816-20. doi: 10.1016/j.fertnstert.2004.02.140.

Reference Type BACKGROUND
PMID: 15482753 (View on PubMed)

Pierson R, Deptuch JJ, Invik J, Klein BM, Breinholt V, Arce JC. Reproducibility of uterine contractility assessments based on transvaginal ultrasound cine-loop recordings. Hum. Reprod. 24 (Suppl. 1), i103, 2009.

Reference Type BACKGROUND

Pierzynski P, Gajda B, Smorag Z, Rasmussen AD, Kuczynski W. Effect of atosiban on rabbit embryo development and human sperm motility. Fertil Steril. 2007 May;87(5):1147-52. doi: 10.1016/j.fertnstert.2006.08.089. Epub 2007 Jan 16.

Reference Type BACKGROUND
PMID: 17224148 (View on PubMed)

Richter ON, Kubler K, Schmolling J, Kupka M, Reinsberg J, Ulrich U, van der Ven H, Wardelmann E, van der Ven K. Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri. Mol Hum Reprod. 2004 May;10(5):339-46. doi: 10.1093/molehr/gah039. Epub 2004 Mar 25.

Reference Type BACKGROUND
PMID: 15044599 (View on PubMed)

Tsirigotis M, Pelekanos M, Gilhespie S, Gregorakis S, Pistofidis G. Ritodrine use during the peri-implantation period reduces uterine contractility and improves implantation and pregnancy rates post-ivf. Hum. Reprod. 15, (Abs. Bk 1), O-024, 10, 2000.

Reference Type BACKGROUND

Vedernikov Y, Betancourt A, Shi S, Shi L, Reinheimer T, Garfield R. (2006) Oxytocin antagonistic effect of barusiban and atosiban in isolated uterine artery from late pregnant rats. In: Annual scientific meeting of the Society for Gynecologic Investigation. Toronto, Canada.

Reference Type BACKGROUND

Visnova H, Coroleu B, Piro M, Blockeel C, Mrazek M, Arce JC. Barusiban and atosiban for reduction of uterine contractions on day of embryo transfer do not alter the endocrine profile at time of implantation. Hum. Reprod. 24 (Suppl. 1), i178, 2009.

Reference Type BACKGROUND

Ng EH, Li RH, Chen L, Lan VT, Tuong HM, Quan S. A randomized double blind comparison of atosiban in patients undergoing IVF treatment. Hum Reprod. 2014 Dec;29(12):2687-94. doi: 10.1093/humrep/deu263. Epub 2014 Oct 21.

Reference Type DERIVED
PMID: 25336707 (View on PubMed)

Other Identifiers

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HKUQMHCARE001

Identifier Type: -

Identifier Source: org_study_id

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