Clinical trial NCT06741748: Direct Warming Frozen Embryo Transfer Outcomes in Assisted Reproductive Technology
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2024-12-19
Enrollment: 578
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical Pregnancy Rate
timeFrame: 6-8 weeks post embryo transfer
measure: Ongoing Pregnancy Rate (OPR)
timeFrame: 12 weeks post embryo transfer
measure: Live Birth Rate (LBR)
timeFrame: At delivery, approximately 9 months post embryo transfer
measure: Cost-Effectiveness
timeFrame: At the end of the study, approximately 4 years.
Secondary outcomes:
measure: Subgroup Analysis of Warming Medium
timeFrame: Throughout the study period, approximately 4 years.
measure: Subgroup Analysis of Storage Devices
timeFrame: Throughout the study period, approximately 4 years.
Other outcomes:
Locations:
city: Shatin, New Territories
country: Hong Kong
facility: The Chinese University of Hong Kong
state: Hong Kong SAR
city: Shatin,NT
country: Hong Kong
facility: The CUHK Medical centre
state: Hong Kong SAR
city: London
country: United Kingdom
facility: The Homerton Hospital
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.