A Randomized Double Blind Comparison of Atosiban in Patients With RIF Undergoing IVF Treatment

NCT02893722 | Unknown Phase 1

• 1 other identifier: FERRING-001
• Study Type: interventional
• Target: 200
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study intends to carry out a prospective, randomized, double blind and controlled study to compare the influence of Atosiban and placebo on uterine contraction frequency, endometrial blood flow perfusion, oxytocin and serum concentration of PGF2α, embryo implantation rate and clinical pregnancy rate on the RIF population after fresh embryo transfer, so as to further clarify the curative effect of Atosiban in the treatment of RIF and provide evidence-based basis for Atosiban for application in RIF population.

Conditions

Repeated Implantation Failure

Keywords

ivf ,atosiban,repeated implantation failure,RCT

Outcome Measures

Primary Outcomes (1)

• Clinical pregnancy rate

  cases of clinical pregnancies / number of transplantation cycles(per patient)

  4 weeks after embryo transfer

Secondary Outcomes (4)

• implantation rate

  4 weeks after embryo transfer

• abortion rate

  6 weeks after embryo transfer

• ectopic pregnancy rate

  6 weeks after embryo transfer

• frequency of uterine contraction (4 minutes)

  1 hour before and 1 hour after intervention

Other Outcomes (2)

• uterine artery blood flow index

  1 hour before and 1 hour after intervention

• oxytocin and PGF2 α serum concentration.

  1 hour before and 1 hour after intervention

Study Arms (2)

atosiban

EXPERIMENTAL

Give drugs 30 minutes before the start of the embryo transfer. First step: give a 37.5 mg Atosiban (Ferring, Germany) to take 0.9 ml, that is, 6.75 mg, conduct intravenous injection in one minute. Second step: for the remaining 4.1 ml, namely 30.75 mg, dilute to 41 ml, use the venous pump to adjust to 24 ml/h, infuse for 1 hour, namely 18 mg. Third step: for the remaining 17 ml, use the venous pump to adjust to 8 ml/h, infuse 2.1 hours, namely 12.75 mg. Total administration time is 3 hours, total dose is 37.5 mg.

Drug: atosiban

0.9% salain

PLACEBO COMPARATOR

intravenous injection of 0.9% saline in one minute before transfer. Then use the same dose of normal saline for intravenous infusion to set the same infusion rate with experimental group, complete the infusion in 3 hours.

Drug: 0.9% saline

Interventions

atosiban DRUG

give drugs 30 minutes before the start of the embryo transfer,and intravenous infusion in total dose of 37.5 mg is set in certain infusion rate, and complete the infusion in 3 hours.

Also known as: oxytocin antagonist

atosiban

0.9% saline DRUG

give drugs 30 minutes before the start of the embryo transfer,and intravenous infusion is set in the same rate with experimental group, complete the infusion in 3 hours.

Also known as: Nacl

0.9% salain

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• or more than 3 embryo implantation failure histories previously (or the number of high-quality embryos transplanted is \>4);
• Age \<40 years；
• Ultrasound or HSG showed normal uterine cavity, endometrium on transplantation day is ≥ 8mm;
• There's at least one good quality embryo on transplantation day.

You may not qualify if:

• Patients using donor sperm or donor eggs;
• Patients have obvious uterine cavity abnormalities;
• There was a clear hydrosalpinx;
• Natural cycles or IVM patients;
• Patients who cancel the due to the transfer due to various reasons, such as the failure of fertilization, or ovarian transitional stimulus syndrome (OHSS);
• Abnormal karyotype;
• Blastocyst transplantation patients.

Sponsors & Collaborators

• Shanghai First Maternity and Infant Hospital: lead

Related Publications (22)

• Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, Cutting R, Ong K, Sallam H, Li TC. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014 Jan;28(1):14-38. doi: 10.1016/j.rbmo.2013.08.011. Epub 2013 Sep 14.

  PMID: 24269084 RESULT

• Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril. 2012 May;97(5):1039-43. doi: 10.1016/j.fertnstert.2012.03.010. Epub 2012 Mar 30.

  PMID: 22464086 RESULT

• Margalioth EJ, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod. 2006 Dec;21(12):3036-43. doi: 10.1093/humrep/del305. Epub 2006 Aug 12.

  PMID: 16905766 RESULT

• Knutzen V, Stratton CJ, Sher G, McNamee PI, Huang TT, Soto-Albors C. Mock embryo transfer in early luteal phase, the cycle before in vitro fertilization and embryo transfer: a descriptive study. Fertil Steril. 1992 Jan;57(1):156-62.

  PMID: 1730311 RESULT

• 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.

  PMID: 9740459 RESULT

• Lesny P, Killick SR, Robinson J, Raven G, Maguiness SD. Junctional zone contractions and embryo transfer: is it safe to use a tenaculum? Hum Reprod. 1999 Sep;14(9):2367-70. doi: 10.1093/humrep/14.9.2367.

  PMID: 10469712 RESULT

• 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.

  PMID: 15044599 RESULT

• 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.

  PMID: 18958771 RESULT

• Zhu L, Li Y, Xu A. Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women. Hum Reprod. 2012 Sep;27(9):2684-9. doi: 10.1093/humrep/des257. Epub 2012 Jul 14.

  PMID: 22798632 RESULT

• 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.

  PMID: 12738502 RESULT

• Pierzynski P, Reinheimer TM, Kuczynski W. Oxytocin antagonists may improve infertility treatment. Fertil Steril. 2007 Jul;88(1):213.e19-22. doi: 10.1016/j.fertnstert.2006.09.017. Epub 2007 May 3.

  PMID: 17481622 RESULT

• Moraloglu O, Tonguc E, Var T, Zeyrek T, Batioglu S. Treatment with oxytocin antagonists before embryo transfer may increase implantation rates after IVF. Reprod Biomed Online. 2010 Sep;21(3):338-43. doi: 10.1016/j.rbmo.2010.04.009. Epub 2010 Apr 18.

  PMID: 20638340 RESULT

• Song XR, Zhao XH, Bai XH, Lu YH, Zhang HJ, Wang YX, Lu R. [Application of oxytocin antagonists in thaw embryo transfer]. Zhonghua Fu Chan Ke Za Zhi. 2013 Sep;48(9):667-70. Chinese.

  PMID: 24332133 RESULT

• 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.

  PMID: 25336707 RESULT

• He Y, Wu H, He X, Xing Q, Zhou P, Cao Y, Wei Z. Administration of atosiban in patients with endometriosis undergoing frozen-thawed embryo transfer: a prospective, randomized study. Fertil Steril. 2016 Aug;106(2):416-22. doi: 10.1016/j.fertnstert.2016.04.019. Epub 2016 Apr 30.

  PMID: 27143518 RESULT

• Lan VT, Khang VN, Nhu GH, Tuong HM. Atosiban improves implantation and pregnancy rates in patients with repeated implantation failure. Reprod Biomed Online. 2012 Sep;25(3):254-60. doi: 10.1016/j.rbmo.2012.05.014. Epub 2012 Jun 16.

  PMID: 22818095 RESULT

• Chou PY, Wu MH, Pan HA, Hung KH, Chang FM. Use of an oxytocin antagonist in in vitro fertilization-embryo transfer for women with repeated implantation failure: a retrospective study. Taiwan J Obstet Gynecol. 2011 Jun;50(2):136-40. doi: 10.1016/j.tjog.2011.04.003.

  PMID: 21791296 RESULT

• Zhang Yue, Zhu Yujing, Luo Haining, et al. Clinical observation on the effect of the patients using Atosiban for frozen thawed embryo transfer after repeated failure of implantation. Chinese Journal of Family Planning,2016,22 (05): 325-328.

  RESULT

• Romero R, Sibai BM, Sanchez-Ramos L, Valenzuela GJ, Veille JC, Tabor B, Perry KG, Varner M, Goodwin TM, Lane R, Smith J, Shangold G, Creasy GW. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol. 2000 May;182(5):1173-83. doi: 10.1067/mob.2000.95834.

  PMID: 10819855 RESULT

• 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.

  PMID: 17224148 RESULT

• Tang CL, Li QY, Chen FL, Cai CT, Dong YY, Wu YY, Yang JZ, Zhao M, Chi FL, Hong L, Ai A, Chen MX, Li KM, Teng XM, Chen ZQ. A randomized double blind comparison of atosiban in patients with recurrent implantation failure undergoing IVF treatment. Reprod Biol Endocrinol. 2022 Aug 19;20(1):124. doi: 10.1186/s12958-022-00999-y.

  PMID: 35986323 DERIVED

• Craciunas L, Tsampras N, Kollmann M, Raine-Fenning N, Choudhary M. Oxytocin antagonists for assisted reproduction. Cochrane Database Syst Rev. 2021 Sep 1;9(9):CD012375. doi: 10.1002/14651858.CD012375.pub2.

  PMID: 34467530 DERIVED

MeSH Terms

Interventions

atosiban; Saline Solution; Sodium Chloride

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Zhi Qin Chen, master

CONTACT

86-21-54035206; ptchen1@hotmail.com

Chuan Ling Tang, docter

CONTACT

86-021-20261157; ttangirl56@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: associated clinical professor

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 8, 2016
• Study Start: January 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 8, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share