Ernest Hung Yu Ng1, Raymond Hang Wun Li2, Leining Chen3, Vuong Thi Ngoc Lan4, Ho Manh Tuong5, Song Quan6. 1. Department of Obstetrics & Gynaecology, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China nghye@hku.hk. 2. Department of Obstetrics & Gynaecology, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China. 3. Center for Reproductive Medicine, Guangdong No.2 Provincial People's Hospital Guangzhou, Guangzhou, China. 4. Department of Obstetrics & Gynaecology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam. 5. Research Center for Genetics and Reproductive Health, School of Medicine, Vietnam National University-Ho Chi Minh, Ho Chi Minh City, Vietnam. 6. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract
STUDY QUESTION: Does atosiban (oxytocin/vasopressin V1A receptor antagonist), given around embryo transfer improve the live birth rate of women undergoing IVF treatment? SUMMARY ANSWER: The use of atosiban around embryo transfer did not improve the live birth rate in a general population of IVF patients. WHAT IS KNOWN ALREADY: Uterine contractions in IVF cycles were significantly increased following ovarian stimulation and women with frequent uterine contractions had a lower pregnancy rates. A few observational studies suggested that the use of atosiban around embryo transfer resulted in higher pregnancy rates in women with repeated implantation failure (RIF). A non-randomized trial of IVF patients also reported higher implantation and clinical pregnancy rates after the use of atosiban. STUDY DESIGN, SIZE, DURATION: This multi-centre randomized double blind study recruited 800 general subfertile women undergoing IVF treatment between November 2011 and March 2013. Subjects were randomized into the atosiban (n = 400) and placebo (n = 400) groups according to a computer-generated randomization list. PARTICIPANTS/MATERIALS, SETTING, METHODS:Subjects were recruited and randomized in the three IVF units in Guangzhou, Hong Kong and Ho Chi Minh City. Women in the atosiban group received i.v. atosiban 30 min before embryo transfer with a bolus dose of 6.75 mg, and the infusion was continued at 18 mg/h for ∼1 h. The dose of atosiban was then reduced to 6 mg/h continued for another 2 h. Those in the placebo group received i.v. normal saline only. The primary outcome measure was the live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the live birth rate between the atosiban and placebo groups (39.8 versus 38.0%, P = 0.612, rate ratio 1.051, 95% confidence interval: 0.884-1.251). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy rates and implantation rate per woman. Similar results were found between the groups at different IVF centres, with a repeated cycle, presence of uterine fibroids or a serum estradiol level on the day of hCG above the median level. LIMITATIONS, REASONS FOR CAUTION: Limitations include the transfer of early cleavage embryos, no measurement of uterine contractions, no documentation of adenomyosis and incomplete tracking of congenital abnormalities in newborns. WIDER IMPLICATIONS OF THE FINDINGS: This randomized double blind study demonstrated that the use of atosiban given around embryo transfer did not improve the live birth rate in a general population of IVF patients; therefore atosiban should be given only in the context of clinical research. STUDY FUNDING/COMPETING INTERESTS: Centres in Hong Kong and Vietnam received research funding from Ferring, which was not involved in study design, execution, data analysis and manuscript preparation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01501214.
RCT Entities:
STUDY QUESTION: Does atosiban (oxytocin/vasopressin V1A receptor antagonist), given around embryo transfer improve the live birth rate of women undergoing IVF treatment? SUMMARY ANSWER: The use of atosiban around embryo transfer did not improve the live birth rate in a general population of IVFpatients. WHAT IS KNOWN ALREADY: Uterine contractions in IVF cycles were significantly increased following ovarian stimulation and women with frequent uterine contractions had a lower pregnancy rates. A few observational studies suggested that the use of atosiban around embryo transfer resulted in higher pregnancy rates in women with repeated implantation failure (RIF). A non-randomized trial of IVFpatients also reported higher implantation and clinical pregnancy rates after the use of atosiban. STUDY DESIGN, SIZE, DURATION: This multi-centre randomized double blind study recruited 800 general subfertile women undergoing IVF treatment between November 2011 and March 2013. Subjects were randomized into the atosiban (n = 400) and placebo (n = 400) groups according to a computer-generated randomization list. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects were recruited and randomized in the three IVF units in Guangzhou, Hong Kong and Ho Chi Minh City. Women in the atosiban group received i.v. atosiban 30 min before embryo transfer with a bolus dose of 6.75 mg, and the infusion was continued at 18 mg/h for ∼1 h. The dose of atosiban was then reduced to 6 mg/h continued for another 2 h. Those in the placebo group received i.v. normal saline only. The primary outcome measure was the live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the live birth rate between the atosiban and placebo groups (39.8 versus 38.0%, P = 0.612, rate ratio 1.051, 95% confidence interval: 0.884-1.251). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy rates and implantation rate per woman. Similar results were found between the groups at different IVF centres, with a repeated cycle, presence of uterine fibroids or a serum estradiol level on the day of hCG above the median level. LIMITATIONS, REASONS FOR CAUTION: Limitations include the transfer of early cleavage embryos, no measurement of uterine contractions, no documentation of adenomyosis and incomplete tracking of congenital abnormalities in newborns. WIDER IMPLICATIONS OF THE FINDINGS: This randomized double blind study demonstrated that the use of atosiban given around embryo transfer did not improve the live birth rate in a general population of IVFpatients; therefore atosiban should be given only in the context of clinical research. STUDY FUNDING/COMPETING INTERESTS: Centres in Hong Kong and Vietnam received research funding from Ferring, which was not involved in study design, execution, data analysis and manuscript preparation. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01501214.
Authors: Rosa B Gutarra-Vilchez; Xavier Bonfill Cosp; Demián Glujovsky; Andres Viteri-García; Fernando M Runzer-Colmenares; Maria José Martinez-Zapata Journal: Cochrane Database Syst Rev Date: 2018-10-12