Direct Warming Frozen Embryo Transfer Outcomes in Assisted Reproductive Technology

NCT ID: NCT06741748

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 578 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2027-10-31

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.

Detailed Description

This clinical trial explores a novel direct warming method for frozen embryo transfer (FET), aimed at improving both clinical and operational outcomes in assisted reproductive technologies (ART). The method was designed to simplify and accelerate the embryo thawing process, reducing the time needed for thawing while eliminating the use of cryoprotectants commonly required in conventional thawing methods. This innovation has the potential to offer a more efficient and cost-effective alternative to standard FET procedures.

The primary focus of this trial is to compare the clinical effectiveness of the direct warming method against the conventional multi-step thawing process. In particular, the study seeks to determine whether the new method yields comparable or superior outcomes in terms of clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and live birth rate (LBR), while also assessing its overall cost-effectiveness.

Study Design and Technical Details

This study employs a randomized controlled design, with participants being allocated into either the intervention group (direct warming method) or the control group (conventional multi-step thawing). The direct warming method streamlines the thawing process to just 3 minutes, in contrast to the conventional method, which requires multiple stages and takes approximately 20 minutes. By using only an embryo culture medium without cryoprotectants, the direct warming method reduces both complexity and potential risks associated with handling and cryoprotectant toxicity.

Key Objectives

• Primary Objective: To evaluate the clinical efficacy of the direct warming method in achieving comparable or higher success rates for FET as compared to conventional multi-step thawing.
• Secondary Objective: To assess the cost-effectiveness of the direct warming method by comparing the consumable and time costs across different centers.

Expected Impact and Innovation

The direct warming method challenges the traditional multi-step thawing approach, offering a faster and simpler alternative without compromising clinical outcomes. By minimizing the need for cryoprotectants and reducing the complexity of the thawing process, the new method is expected to enhance the overall efficiency of FET procedures while maintaining or improving pregnancy success rates. Additionally, the cost and time savings associated with the direct warming method may make it a viable option for IVF clinics worldwide, driving standardization and consistency across clinical settings.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Direct Warming method

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.

Group Type: EXPERIMENTAL

Direct Warming Method

Intervention Type: 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.

Conventional multi-step thawing method

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.

Group Type: PLACEBO_COMPARATOR

Conventional Multi-step Thawing Method

Intervention Type: 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.

Interventions

Direct Warming Method

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.

Intervention Type: OTHER

Conventional Multi-step Thawing Method

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.

Intervention Type: OTHER

Other Intervention Names

One-step thawing

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Yiu Leung David Chan

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Chinese University of Hong Kong

Shatin, New Territories, Hong Kong SAR, Hong Kong

The CUHK Medical centre

Shatin,NT, Hong Kong SAR, Hong Kong

The Homerton Hospital

London, London, United Kingdom

Countries

Hong Kong; United Kingdom

Central Contacts

Yiu Leung D Chan, DPhil

Role: CONTACT

drdcyl16@cuhk.edu.hk

(852) 3505 3199

Waner Wu, MPhil

Role: CONTACT

wanerwu@link.cuhk.edu.hk

(852) 3505 1764

Facility Contacts

Role: primary

(852) 3505 1764

Yiu Leung, David Chan

Role: primary

drdcyl16@cuhk.edu.hk

+852 3946 6888

Priya Bhide

Role: primary

p.bhide@qmul.ac.uk

020 8510 5555

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

2024.132-T

Identifier Type: -

Identifier Source: org_study_id