Effect of Oxytocin Antagonists on Implantation Success Rates of Frozen-thawed Embryo Transfer

Uterine contraction has a negative impact on implantation and pregnancy rates. Inhibition of oxytocin receptors decreases uterine contraction frequency both on pregnant and non-pregnant women. Atosiban has been studied as an oxytocin antagonist to decrease uterine contraction frequency in order to increase implantation and pregnancy rates in assisted reproduction. Previous studies have studied 37,5mg total dose which was used both before and during embryo transfer, and found atosiban to be effective in increasing implantation and pregnancy rates. We aim to use a single dose of 6,75mg atosiban before embryo transfer, in order to decrease the dose and cost and possibly introduce a simpler protocol. Our study will also be the first randomized clinical study which investigates the effect of atosiban on frozen-thawed embryo transfer cycles.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Atosiban

Detailed Description

Inhibition of uterine contractions in order to increase implantation rates have been studied on several agents in the last two decades. Beta-adrenergic agonists and non-steroidal anti-inflammatory drugs have been shown to have no benefit on implantation rates. Vasopressin V1a and oxytocin receptor antagonist atosiban was first studied on premature labor patients and found to be effective.

Endometrium-originated oxytocin can possibly stimulate myometrium and have a negative impact on embryo implantation. Inhibition of oxytocin receptors has been shown to reduce uterine contraction frequency in non-pregnant women. Atosiban has been studied on assisted reproductive technologies in the last decade and has been shown to be effective on increasing implantation and clinical pregnancy rates. However, previous studies have used a 37,5 mg total dose of atosiban which was used both before and during embryo transfer. We aim to use a single and low dose of 6,75mg atosiban only before embryo transfer, which is simpler and cheaper and the medication given to patient is significantly lower. If we can demostrate the positive effect of our protocol, it can be suggested to be used routinely in all in vitro fertilization cycles. Additionally, our study is an original study in terms of being the first randomized clinical trial studying the effect of atosiban on frozen-thawed embryo transfer cycles.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pinar Ozcan; Phone Number: +905414031625; Email: pinarozcan@hotmail.com
• Study Contact Backup: Name: Taha Takmaz; Phone Number: +905548707340; Email: thtkmz@hotmail.com

Study Locations

• Turkey
  • Istanbul, Turkey, 34746
    • Recruiting
    • Bezmialem University
    • Contact: Pinar Ozcan
  • Istanbul, Turkey, 34746
    • Recruiting
    • Yeditepe University
    • Contact: Mert Yesiladali; Phone Number: +905321000206; Email: yesiladali@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Infertile women applied to assisted reproduction clinic
• Follicle stimulating hormone < 12
• Body mass index < 25
• Patients whom antagonist protocol will be used
• Patients whom at least 2 good-quality embryos obtained
• Patients who are volunteer

Exclusion Criteria:

• Severe male factor (Sperm concentration <5 M/ml, progressive sperm motility <%10)
• Uterine anomaly
• Hydrosalphynx
• Difficult embryo transfer
• Patients who previously had a diagnosis of endometriosis and / or adenomyosis
• Endocrine problems (hypothyroidism, hyperthyroidism, hyperprolactinemia, premature ovarian insufficiency)
• Having more than 3 in vitro fertilization failure
• Refusing to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atosiban used before embryo transfer; the patients in this group will be administered 6,75mg atosiban intravenously.	Drug: Atosiban; 6,75mg of atosiban will be administered intravenously 30 minutes before embryo transfer
No Intervention: Control group; the patients in this group will not be administered atosiban before embryo transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy rates	Pregnancy rates of the participants	1 year

Collaborators and Investigators

• Sponsor: Bezmialem Vakif University
• Collaborators: Yeditepe University

Publications and helpful links

General Publications

• 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.
• 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.
• Bossmar T, Akerlund M, Fantoni G, Szamatowicz J, Melin P, Maggi M. Receptors for and myometrial responses to oxytocin and vasopressin in preterm and term human pregnancy: effects of the oxytocin antagonist atosiban. Am J Obstet Gynecol. 1994 Dec;171(6):1634-42. doi: 10.1016/0002-9378(94)90415-4.
• Mishra V, Agarwal H, Goel S, Roy P, Choudhary S, Lamba S. A Prospective Case-control Trial to Evaluate and Compare the Efficacy and Safety of Atosiban versus Placebo in In vitro Fertilization-embryo Transfer Program. J Hum Reprod Sci. 2018 Apr-Jun;11(2):155-160. doi: 10.4103/jhrs.JHRS_7_17.
• Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H. Structure and expression of a human oxytocin receptor. Nature. 1992 Apr 9;356(6369):526-9. doi: 10.1038/356526a0. Erratum In: Nature 1992 May 14;357(6374):176.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 21, 2020
• Primary Completion (Anticipated): July 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): December 16, 2020
• Last Update Submitted That Met QC Criteria: December 13, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: embryo transfer; atosiban; in vitro fertilization; oxytocin antagonist
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Tocolytic Agents; Atosiban
• Other Study ID Numbers: Atosiban study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No