Use of Atosiban in in Vitro Fertilization (IVF) Treatment

This study has been completed.
Sponsor:
Collaborators:
Vietnam National University
Nanfang Hospital of Southern Medical University
Information provided by (Responsible Party):
The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01501214
First received: December 20, 2011
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Subfertility
Drug: Atosiban
Drug: Normal saline
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double Blind Comparison of Atosiban in Patients Undergoing in Vitro Fertilization Treatment

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • live birth rate [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ongoing pregnancy rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 800
Study Start Date: December 2011
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Atosiban Drug: 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.
Other Name: Tractocile
Placebo Comparator: Placebo
Normal saline
Drug: Normal saline
Normal saline given

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 43 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01501214

Locations
China, Guangdong
Reproductive Medical Center of Nanfang Hospital
Guangzhou, Guangdong, China, 510515
Vietnam
CGRH, School of Medicine
Ho Chi Minh City, Vietnam
Sponsors and Collaborators
The University of Hong Kong
Vietnam National University
Nanfang Hospital of Southern Medical University
Investigators
Principal Investigator: Ernest HY Ng, MD The University of Hong Kong
  More Information

Publications:
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.

Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01501214     History of Changes
Other Study ID Numbers: HKUQMHCARE001
Study First Received: December 20, 2011
Last Updated: January 6, 2014
Health Authority: Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
atosiban
in vitro fertilization
subfertility

Additional relevant MeSH terms:
Infertility
Genital Diseases, Male
Genital Diseases, Female
Atosiban
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Tocolytic Agents
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014