Efficacy and safety of a novel semiautomated vitrification system for human blastocysts: a study protocol for a multicentre randomised controlled device trial with a live-birth extension study.

introductionCryopreservation, particularly vitrification, is a cornerstone of assisted reproductive technology, preventing ice crystal damage to ensure high survival rates. However, existing manual systems, such as Cryotop, depend on the embryologist's skill, which introduces procedural variability and hinders standardisation. While some semiautomated systems have been developed, issues with laboratory integration and limited throughput have prevented their widespread adoption. To address this, Biorocks (China) has created a novel semiautomated vitrification system. This study consists of a parent multicentre randomised device trial and a prospective observational live-birth extension follow-up study. The parent multicentre randomised controlled trial is designed to determine whether this novel semiautomated vitrification system is non-inferior to the established manual vitrification method in preserving postwarming human blastocyst viability. To further assess clinically relevant reproductive outcomes, a prospective multicentre observational live-birth extension study will evaluate live birth and postpartum safety outcomes among participants who complete the parent trial follow-up. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial that will enrol 176 women between the ages of 20 and 39 who are undergoing in vitro fertilisation-embryo transfer or intracytoplasmic sperm injection. The study will be carried out in China at Nanjing Drum Tower Hospital, The Second Affiliated Hospital of Air Force Medical University, Shenzhen Maternity and Child Healthcare Hospital and Guangdong Provincial Maternity and Child Healthcare Hospital. On Day 5 or Day 6 of embryo culture, high-quality blastocysts will be randomised in a 1:1 ratio to either the novel semiautomated Biorocks vitrification system or the manual gold standard Cryotop method. The blastocyst survival rate after the warming serves as the primary outcome, defined as a warmed blastocyst maintaining at least 75% cellular integrity or re-expanding within 1-2 hours. Participants who complete the 10-week post-transfer follow-up in the parent trial may enter a prospective observational live-birth extension follow-up study after separate informed consent, with live birth status, concomitant medications and adverse events assessed up to 42 days postpartum. ETHICS AND DISSEMINATION: Ethical approvals for this study were obtained from the research ethics committees of Nanjing Drum Tower Hospital (IRB approval #: 2024-529-01, 2024-529-02), The Second Affiliated Hospital of Air Force Medical University (IRB approval #: 202504-12), Shenzhen Maternity and Child Healthcare Hospital (IRB approval #: SZFYGCPLS2025001) and Guangdong Provincial Maternity and Child Healthcare Hospital (IRB approval #: 2025IRB009). This study has been registered in the Chinese Clinical Trial Registry (ChiCTR2400093517). Before any procedures, written informed consent will be obtained from all enrolled participants. Study data will be stored electronically in the electronic data capture system for interim analysis. The findings will be disseminated through presentations at international conferences and publications in peer-reviewed journals.The live-birth follow-up extension study (ChiCTR2500109209) is planned as a prospective, multicentre observational extension of the parent randomised device trial. At the time of this report, ethics approval for the extension study has been obtained from the Ethics Committee of Nanjing Drum Tower Hospital, the coordinating centre (IRB approval #: 2025-0732-01). Site-specific ethics applications for the remaining participating centres are being prepared or submitted. Each additional centre will be activated for extension follow-up only after local ethics approval has been obtained; before such approval, no extension-specific procedures at that centre, including re-consent, follow-up contact or collection of extension follow-up data beyond the parent trial, will be initiated. TRIAL REGISTRATION NUMBER AND PROTOCOL VERSION: ChiCTR2400093517 (URL: https://www.chictr.org.cn/showproj.html?proj=251859, Date of registration: 06-12-2024, Protocol version: V1.1/20-01-2025, Identifier: BELK-DHF-CRYC-426-A), ChiCTR2500109209 (Live-birth follow-up extension study, URL: https://www.chictr.org.cn/showproj.html?proj=286900, Date of registration: 15-09-2025, Protocol version: V1.0/08-07-2025, Identifier: BELK-DHF-CRYC-426-B). TRIAL REGISTRATION NUMBER: ChiCTR2400093517 and ChiCTR2500109209.