Hyaluronic Acid-enriched Transfer Medium in Single Blastocyst Transfer

Use of Hyaluronic Acid-enriched Transfer Medium in Women Undergoing Single Blastocyst Transfer : a Multicenter, Randomized Controlled Trial

The purpose of this study is to compare the live birth rates of high concentration of Hyaluronic Acid (0.5 mg/ml) transfer medium (EmbryoGlue®) to those containing low Hyaluronic Acid concentrations (0.125 mg/ml) (G2 medium) in women undergoing single fresh and frozen blastocyst transfer.

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Biological: High Hyaluronic Acid concentrations (0.5 mg/ml); Biological: Low Hyaluronic Acid concentrations (0.125 mg/ml)

Detailed Description

The single blastocyst-stage embryo transfer cycles will be randomised in a 1:1 allocation, with block sizes of 2 and 4 on the day of Embryo Transfer (ET). This randomisation process will be centrally managed via a web-based electronic data capture system and will be stratified according to the treatment center. The allocation sequence and the designated treatment will be completely concealed from the participating couples, clinicians - including those conducting the transfer procedures - and outcome assessors. Given the intrinsic viscous nature of EmbryoGlue, embryologists, who who are responsible for the procedures in the laboratory will not be subjected to blinding. Only at the end of the study, when data collection is completed, the allocation sequence will be revealed to the primary investigators.

• Study Type: Interventional
• Enrollment (Estimated): 858
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: He Cai, Doctor; Phone Number: 13581613908; Email: caihe@bjmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710003
      • Recruiting
      • IVF laboratory
      • Contact: Juanzi Prof Shi, MD; Phone Number: +8613581613908; Email: juanzishiart@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All cycles with single blastocyst transfer will be considered eligible
2. Both fresh and cryopreserved embryo transfer cycles utilizing autologous oocytes
3. No age restriction will be applied
4. Informed consent was signed

Exclusion Criteria:

1. Uterine anatomic anomalies
2. Women with untreated hydrosalpines
3. Once couples have been enrolled in the trial, subsequent cycles will not be incorporated.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyaluronic Acid(EmbryoGlue®); High HA concentrations (0.5 mg/ml)	Biological: High Hyaluronic Acid concentrations (0.5 mg/ml); Hyaluronic Acid(EmbryoGlue®)
Active Comparator: Hyaluronic Acid (G2 medium); Low HA concentrations (0.125 mg/ml)	Biological: Low Hyaluronic Acid concentrations (0.125 mg/ml); Hyaluronic Acid (G2 medium)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	The primary outcome was Live birth rate per embryo transfer.	Live birth is defined as the birth of at least one live baby after 24 weeks of gestation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
low birth weight	Weight of baby born < 2500 g	At birth
Very low birth weight	Weight of baby born < 1500 g	At birth
Biochemical pregnancy	Biochemical pregnancy is defined as serum beta-human chorionic gonadotropin β-hCG > 20 IU/L 12 days after embryo transfer.	12 days after embryo transfer.
Clinical pregnancy	Clinical pregnancy is defined as the presence of at least one gestational sac confirmed by ultrasonography (ectopic pregnancy is included as a clinical pregnancy).	6-8 weeks after embryo transfer
Ongoing pregnancy	Ongoing pregnancy is defined as the presence of a gestational sac and fetal heartbeat after 12 weeks of gestation.	after 12 weeks of gestation.
Miscarriage	Miscarriage is defined as spontaneous loss of an intrauterine pregnancy before 20 completed weeks of gestation.	20 weeks of gestation.
Ectopic pregnancy	Ectopic pregnancy is defined as a pregnancy implanted outside the uterine cavity, diagnosed by ultrasonography, surgical visualization, or histopathology.	After 4 to 6 weeks of embryo transfer
Multiple pregnancy	Multiple pregnancy is defined as a pregnancy with two or more gestational sacs or fetal heartbeats at 7 weeks of gestation.	7 weeks of gestation.
hypertensive disorders in pregnancy	Comprising essential hypertension; pregnancy induced hypertension; pre-eclampsia and eclampsia.	From 20 weeks of gestation up to at birth
Placental implantation disorders	Placental implantation disorders encompass placenta previa, placenta accreta spectrum, placental abruption and/or abnormal cord insertion	From 20 weeks of gestation up to at birth
Preterm birth	Delivery of a fetus at less than 37 and more than 28 weeks gestational age	At birth
Preterm premature rupture of membranes	Preterm premature rupture of membranes is defined as the leakage of amniotic fluid through the cervical os before 37 weeks of gestation and before the onset of labor	Before 37 weeks of gestation and before the onset of labor
Mode of delivery	Vaginal delivery or cesarean delivery	At birth
Gestational age	Gestational age recorded at delivery	At birth
Birth weight	Weight of baby born (grams)	At birth
Mean birth weight	By checking medical records	1 year after embryo transfer
Macrosomia	Weight of baby born > 4000 g	At birth
Large for gestational age	Birthweight > 90th percentile	At birth
Small for gestational age	Birthweight < 10th percentile	At birth
Neonatal intensive care unit admission	Safety outcome. Number of pregnancies for which newborn is admitted to the NICU	Birth up to 1 year
Stillbirth or late fetal death	Fetal death at 20 or more weeks' gestation	At birth
Early neonatal death		Up to 28 days after birth
Congenital anomaly or birth defect	Any congenital anomalies detected in baby born	Birth to first year of life

Collaborators and Investigators

• Sponsor: Northwest Women's and Children's Hospital, Xi'an, Shaanxi
• Collaborators: Huazhong University of Science and Technology; Jiangxi Maternal and Child Health Hospital; Gansu Provincial Maternal and Child Health Care Hospital
• Investigators: Study Chair: Juanzi Shi, Doctor, Center for Reproductive Medicine, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China

Publications and helpful links

General Publications

• Cai H, Xu D, Wang Z, Huang B, Xue X, Bai H, Man Y, Lei D, Wu Q, Ni Y, Lei J, Shi J. Efficacy and safety of hyaluronic acid-enriched transfer medium in women undergoing single blastocyst transfer: a study protocol for a multicentre randomised controlled trial. BMJ Open. 2025 Nov 19;15(11):e104571. doi: 10.1136/bmjopen-2025-104571.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 1, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: live birth; Hyaluronate-enriched medium; Single blastocyst transfer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Immunologic Factors; Physiological Effects of Drugs; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: 2024-127

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