Direct Warming Frozen Embryo Transfer Outcomes in Assisted Reproductive Technology

NCT06741748 | Not Yet Recruiting DMC

• 1 other identifier: 2024.132-T
• Study Type: interventional
• Target: 578
• Locations: 2 countries
• Sites: 3

Brief Summary

The goal of this clinical trial is to evaluate whether the direct warming method for frozen embryo transfers (FET) can improve live birth and pregnancy outcomes in women aged 18-45 undergoing IVF treatments. The main questions it aims to answer are:

• Does the direct warming method achieve a similar or higher clinical success rate for FET compared to the conventional multi-step method?
• Is the direct warming method more cost-effective than the conventional method? Researchers will compare the direct warming method to the conventional multi-step method to see if the former leads to better pregnancy outcomes and reduced procedural time. Participants will:
• Undergo either the one-step or conventional embryo thawing procedure.
• Complete standard clinical follow-ups for pregnancy, including ultrasound scans and pregnancy tests.

Conditions

Frozen Embryo Transfer (FET); Assisted Reproductive Techniques; In Vitro Fertilization (IVF); Cryopreservation of Embryos; Pregnancy Outcome After in Vitro Fertilization (IVF)

Keywords

Direct Warming Method; Frozen Embryo Transfer; Assisted Reproductive Technologies; Cryopreservation; Cost-effectiveness in ART; Embryo Warming; In Vitro Fertilization

Outcome Measures

Primary Outcomes (4)

• Clinical Pregnancy Rate

  Number of participants with at least one intrauterine gestational sac observed on ultrasound at 6-8 weeks of gestation following embryo transfer.

  6-8 weeks post embryo transfer

• Ongoing Pregnancy Rate (OPR)

  Number of participants with a viable intrauterine pregnancy observed on ultrasound at 12 weeks of gestation.

  12 weeks post embryo transfer

• Live Birth Rate (LBR)

  Number of participants who deliver a live infant after 24 weeks of gestation.

  At delivery, approximately 9 months post embryo transfer

• Cost-Effectiveness

  A comparative analysis of the total costs, including costs of consumables (e.g., warming mediums, storage devices) and staff labor hours, associated with the direct warming method compared to the conventional multi-step thawing method. Costs will be measured in USD and analyzed at the end of the study period.

  At the end of the study, approximately 4 years.

Secondary Outcomes (2)

• Subgroup Analysis of Warming Medium

  Throughout the study period, approximately 4 years.

• Subgroup Analysis of Storage Devices

  Throughout the study period, approximately 4 years.

Study Arms (2)

Direct Warming method

EXPERIMENTAL

The blastocyst designated for thawing will be placed in a pre-warmed, direct warming medium for one minute. Afterward, the embryo is transferred into an embryo culture medium within a time-lapse system, where it remains until the patient is ready for the embryo transfer procedure. This direct warming method significantly reduces the total procedure time to approximately 3 minutes, making it about ten times faster than the conventional multi-step thawing method.

Other: Direct Warming Method

Conventional multi-step thawing method

PLACEBO COMPARATOR

In the conventional multi-step thawing method, vitrified blastocysts are sequentially thawed using a series of pre-warmed thawing, dilution, and washing solutions. The blastocyst is first placed in a thawing solution for 1-3 minutes, followed by immersion in a dilution solution for 4-6 minutes to reduce cryoprotectant concentration. Finally, the blastocyst is transferred to a washing solution for 5-10 minutes for rehydration. The entire process takes approximately 30 minutes, after which the embryo is placed into an embryo culture medium in a time-lapse system until it is ready for embryo transfer.

Other: Conventional Multi-step Thawing Method

Interventions

Direct Warming Method OTHER

This intervention involves thawing vitrified blastocysts using a simplified, one-step direct warming method. The blastocyst is placed in a pre-warmed embryo culture medium for approximately one minute, then transferred directly into the embryo culture medium within a time-lapse system until ready for uterine transfer. The total thawing process takes approximately three minutes, reducing the duration and complexity of the procedure compared to conventional methods.

Also known as: One-step thawing

Direct Warming method

Conventional Multi-step Thawing Method OTHER

This intervention involves thawing vitrified blastocysts using a standard, multi-step process. The procedure includes sequential exposure of the blastocyst to different thawing solutions containing varying concentrations of cryoprotectants, followed by its transfer into an embryo culture medium in a time-lapse system. The overall process takes approximately 10-30 minutes.

Conventional multi-step thawing method

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Plan to undergo single embryo transfer (SET) during the FET cycle.
• Age between 18 and 45 years.
• Patients with at least one high-quality blastocyst available for transfer.
• Patients who have provided informed consent to participate in the study.

You may not qualify if:

• Patients with repeated implantation failure (RIF) or recurrent miscarriage (RM).
• Patients with known uterine anomalies or significant uterine pathology (e.g., fibroids, polyps).
• Patients who are unwilling or unable to provide informed consent.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (3)

The Chinese University of Hong Kong

Shatin, New Territories, Hong Kong SAR, Hong Kong

Location

The CUHK Medical centre

Shatin,NT, Hong Kong SAR, Hong Kong

Location

The Homerton Hospital

London, London, United Kingdom

Location

Related Publications (10)

• Canosa S, Parmegiani L, Charrier L, Gennarelli G, Garello C, Granella F, Evangelista F, Monelli G, Guidetti D, Revelli A, Filicori M, Bongioanni F. Are commercial warming kits interchangeable for vitrified human blastocysts? Further evidence for the adoption of a Universal Warming protocol. J Assist Reprod Genet. 2022 Jan;39(1):67-73. doi: 10.1007/s10815-021-02364-1. Epub 2021 Nov 30.

  PMID: 34845576 BACKGROUND

• Wang SF, Seifer DB. Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT. Reprod Biol Endocrinol. 2024 Apr 13;22(1):42. doi: 10.1186/s12958-024-01210-0.

  PMID: 38615016 BACKGROUND

• Parmegiani L, Beilby KH, Arnone A, Bernardi S, Maccarini AM, Nardi E, Cognigni GE, Filicori M. Testing the efficacy and efficiency of a single "universal warming protocol" for vitrified human embryos: prospective randomized controlled trial and retrospective longitudinal cohort study. J Assist Reprod Genet. 2018 Oct;35(10):1887-1895. doi: 10.1007/s10815-018-1276-4. Epub 2018 Aug 3.

  PMID: 30074129 BACKGROUND

• Schiewe MC, Anderson RE. Vitrification: the pioneering past to current trends and perspectives of cryopreserving human embryos, gametes and reproductive tissue. Journal of Biorepository Science for Applied Medicine. 2017;5:57-68.

  BACKGROUND

• Jiang VS, Cherouveim P, Naert MN, Dimitriadis I, Souter I, Bormann CL. Live birth outcomes following single-step blastocyst warming technique - optimizing efficiency without impacting live birth rates. J Assist Reprod Genet. 2024 May;41(5):1193-1202. doi: 10.1007/s10815-024-03069-x. Epub 2024 Mar 13.

  PMID: 38472563 BACKGROUND

• Liebermann J, Hrvojevic K, Hirshfeld-Cytron J, Brohammer R, Wagner Y, Susralski A, Jasulaitis S, Chan S, Takhsh E, Uhler M. Fast and furious: pregnancy outcome with one-step rehydration in the warming protocol for human blastocysts. Reprod Biomed Online. 2024 Apr;48(4):103731. doi: 10.1016/j.rbmo.2023.103731. Epub 2023 Nov 23.

  PMID: 38359734 BACKGROUND

• Manns JN, Katz S, Whelan J, Patrick JL, Holt T, Merline AM, et al. VALIDATION OF A NEW, ULTRA-FAST BLASTOCYST WARMING TECHNIQUE REDUCES WARMING TIMES TO 1 MIN AND YIELDS SIMILAR SURVIVAL AND RE-EXPANSION COMPARED TO BLASTOCYSTS WARMED USING A STANDARD METHOD. Fertility and Sterility.

  BACKGROUND

• Yan G, Yao Y, Yang W, Lu L, Wang L, Zhao D, Zhao S. An all-37 degrees C thawing method improves the clinical outcomes of vitrified frozen-thawed embryo transfer: a retrospective study using a case-control matching analysis. Arch Gynecol Obstet. 2023 Jun;307(6):1991-1999. doi: 10.1007/s00404-023-07029-1. Epub 2023 Apr 12.

  PMID: 37041370 BACKGROUND

• Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.

  PMID: 27827818 BACKGROUND

• Trounson A, Mohr L. Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. Nature. 1983 Oct 20-26;305(5936):707-9. doi: 10.1038/305707a0.

  PMID: 6633637 BACKGROUND

Central Study Contacts

Yiu Leung D Chan, DPhil

CONTACT

(852) 3505 3199; drdcyl16@cuhk.edu.hk

Waner Wu, MPhil

CONTACT

(852) 3505 1764; wanerwu@link.cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: In this trial, participants and outcomes assessors will be masked to ensure unbiased results. The embryologists performing the thawing procedures will not be masked, as they are directly involved in applying the assigned thawing method (either the direct warming method or the conventional multi-step method). Additionally, the research staff responsible for enrolling participants will also remain blinded to group assignments to maintain allocation concealment. However, participants who are determined not to be pregnant after embryo transfer may be informed of their group assignment at that time. However, if a pregnancy is confirmed, participants will not be informed of their group assignment until after delivery or in the event of pregnancy loss.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This study uses a parallel assignment model where participants are randomized into two groups: one group will receive the novel direct warming method, and the other group will undergo the conventional multi-step thawing method. Both groups will be followed to compare clinical outcomes such as pregnancy rates, live birth rates, and cost-effectiveness.

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: December 19, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: March 11, 2025

Record last verified: 2025-03

Locations

HK (2); GB (1)