Direct Warming Frozen Embryo Transfer Outcomes in Assisted Reproductive Technology
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Direct Warming Method, Conventional Multi-step Thawing Method.
- Who it may be relevant to
- Registry conditions: Frozen Embryo Transfer (FET), Assisted Reproductive Techniques, In Vitro Fertilization (IVF), Cryopreservation of Embryos. Basic parameters: 18 years — 45 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Hong Kong, United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
A Pragmatic, Multi-centre, Double-blinded, Two-arm Randomized Controlled Trial on a Direct Warming Frozen Embryo Transfer in Assisted Reproductive Technologies Treatment Outcome
Overview
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.
Interventions
- Other 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. - 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.
Primary outcome measures
- Clinical Pregnancy Rate [Time frame: 6-8 weeks post embryo transfer]
- Ongoing Pregnancy Rate (OPR) [Time frame: 12 weeks post embryo transfer]
- Live Birth Rate (LBR) [Time frame: At delivery, approximately 9 months post embryo transfer]
- Cost-Effectiveness [Time frame: At the end of the study, approximately 4 years.]
Secondary outcome measures (2)
- Subgroup Analysis of Warming Medium [Time frame: Throughout the study period, approximately 4 years.]
- Subgroup Analysis of Storage Devices [Time frame: Throughout the study period, approximately 4 years.]
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.
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
- Double blind
- Primary purpose
- Treatment
Study locations
Hong Kong · 2 centers
- The Chinese University of Hong Kong — Shatin, New Territories
- The CUHK Medical centre — Shatin,NT
United Kingdom · 1 center
- The Homerton Hospital — London
Publications
- 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
- 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
- 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
- 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.
- 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
- 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
- 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.
- 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
Identifiers
NCT: NCT06741748 · 2024.132-T