Atosiban in Women With Previous Implantation Failure and Abnormal Uterine Contractions

Official title

Atosiban in Women With Previous Implantation Failure and Abnormal Uterine Contractions Undergoing Single Blastocyst-Stage Embryo Transfer: A Randomised Triple-Blind, Placebo-Controlled Trial

Overview

This study aims to evaluate the efficacy of atosiban in patients with previous pregnancy failure and abnormal uterine contractions during the peri-embryo transfer period in assisted reproductive technology. The main questions it aims to answer are: * Does the use of atosiban in patients with a history of implantation failure and abnormal uterine contractions affect the live birth rate in single blastocyst transfer cycles (fresh or frozen-thawed embryo transfer)? * Evaluate the differences in efficacy of atosiban regarding perinatal complications and neonatal outcomes, as well as differences in safety concerning miscarriage rates and ectopic pregnancy rates. Researchers will compare atosiban with placebo (a similar substance containing no active medication) to determine whether atosiban is effective in improving live birth rates from single blastocyst transfer cycles (fresh or frozen-thawed embryo transfer) in patients with a history of implantation failure and abnormal uterine contractions. * Participants allocated to the Atosiban group will be administered Atosiban (37.5 mg/5 mL, Tractocile®, Ferring Pharma, Geneva, Switzerland) as an intravenous (IV) bolus of 6·75 mg/0.9 mL in 1 minute at 30 minutes prior to the ET procedure, followed by an IV infusion at a rate of 18 mg/h for 1 hour; after 1 hour, the dose of Atosiban will be reduced to 6 mg/h, with a total dose of 37.5 mg. Participants allocated to the placebo group will receive identical-looking saline infusions for the same duration. * One hour post-embryo transfer, all randomized participants will be invited to have a reevaluation of uterine wave patterns via ultrasound, performed by the same examiner. * Women who had a clinical pregnancy will be subsequently contacted by nurses to document pregnancy events and outcomes at 12 and 24 weeks of gestation, completion of pregnancy, with a follow-up approximately 6 weeks post-delivery. Those participants who had a negative pregnancy test will not be followed up any further as part of this trial.

Interventions

• Drug Atosiban
  Participants allocated to the Atosiban group will be administered Atosiban (37.5 mg/5 mL, Tractocile®, Ferring Pharma, Geneva, Switzerland) as an intravenous (IV) bolus of 6·75 mg/0.9 mL in 1 minute at 30 minutes prior to the ET procedure, followed by an IV infusion at a rate of 18 mg/h for 1 hour; after 1 hour, the dose of Atosiban will be reduced to 6 mg/h, with a total dose of 37.5 mg.
• Drug Placebo Control
  Participants allocated to the placebo group will receive identical-looking saline infusions for the same duration.

Primary outcome measures

• Live birth [Time frame: After 24 weeks of gestation]

Secondary outcome measures (12)

• Biochemical pregnancy [Time frame: 12 days after blastocyst transfer]
• Clinical pregnancy [Time frame: 6-8 weeks after blastocyst transfer.]
• Ongoing pregnancy [Time frame: After 12 weeks of gestation]
• Miscarriage [Time frame: before 20 weeks of gestation.]
• Stillbirth [Time frame: after 20 weeks of gestation]
• Ectopic pregnancy [Time frame: After 4 to 6 weeks of embryo transfer]
• Multiple pregnancy [Time frame: 7 weeks of gestation]
• Gestational diabetes mellitus [Time frame: At 28 weeks of pregnancy]
• hypertensive disorders of pregnancy [Time frame: From 20 weeks of gestation up to at birth]
• preterm birth [Time frame: At birth]
• low birth weight [Time frame: At birth]
• Very low birth weight [Time frame: At birth]

Eligibility criteria

Participants/eligibility criteria

Infertile women who fulfill all of the following inclusion criteria, based on the results and findings of the Atosiban 1 study are eligible for participation:

• Scheduled for single blastocyst-stage embryo transfer, either in a fresh or frozen transfer cycle;
• Have a history of one or more episodes of implantation failures in previous embryo transfer cycles;
• Age between 20 and 40 years (inclusive);
• Exhibit abnormal uterine peristalsis on transvaginal ultrasound performed on the morning of the scheduled blastocyst transfer, defined as either: high-frequency peristalsis (>4 contractions per minute), or a negative wave pattern (fundus-to-cervix direction) at any frequency.
• Each woman could only participate in one transfer cycle.

Exclusion criteria

• Immunologic or endocrine disorders including thyroid dysfunction, antiphospholipid syndrome, hyperprolactinemia and other severe systematic diseases (e.g., hypertension, diabetes, etc.)
• Uterine malformations (e.g., intrauterine adhesions; unicornuate, bicornuate or septate uterus)；
• Untreated hydrosalpinx or endometrial polyp；
• Cycles that included in-vitro maturation or oocyte donation；
• Prior participation in Atosiban 1 study；
• Current participation in any other clinical trial；
• Inability to provide informed consent to the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Center for Reproductive Medicine, Northwest Women's and Children's Hospital — Xi'an

Publications

• Cai H, Li W, Mol BWJ, Liu D, Lei D, Ran X, Zhang D, Xue X, Gao L, Shi J. Randomised, triple-blind, placebo-controlled trial of atosiban in women with previous embryo implantation failure and abnormal uterine contractions undergoing single blastocyst-stage embryo transfer: a study protocol. BMJ Open. 2026 Jun 2;16(6):e114029. doi: 10.1136/bmjopen-2025-114029. PMID 42229962

Identifiers

NCT: NCT07185230 · 2025-058-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗