Intrauterine infusion of autologous platelet-rich plasma (PRP) versus granulocyte colony-stimulating factor (G-CSF) prior to single frozen blastocyst transfer in women with thin endometrium: a study protocol for a multicentre sequential multiple assignment randomised trial.

INTRODUCTION: A thin endometrium (TE) is associated with reduced reproductive potential, including lower implantation rates and increased obstetric risks. While intrauterine infusion of autologous platelet-rich plasma (PRP) or granulocyte colony-stimulating factor (G-CSF) is commonly used, robust evidence for their efficacy remains lacking. This trial aims to compare the effectiveness of PRP versus G-CSF in women with TE using a sham-controlled, sequential multiple assignment randomised trial (SMART) design. METHODS AND ANALYSIS: This is a triple-blind, multicentre SMART study conducted at four tertiary fertility centres in China. We will recruit 440 women undergoing single frozen blastocyst transfer with a history of TE (endometrial thickness <8 mm). Participants will be randomly assigned (1:1:2) to receive intrauterine infusion of PRP, G-CSF or a sham procedure (stage 1). Infusions are performed twice per cycle: when the leading follicle reaches 13-14 mm in natural frozen embryo transfer (FET) cycles or stimulated FET cycles, or on day 8 of oestradiol administration in artificial FET cycles, repeated 48 hours later. The primary outcome is the live birth rate from the first embryo transfer (Stage 1). Secondary outcomes include changes in endometrial thickness, clinical pregnancy rates and neonatal outcomes. Participants in the sham group who do not achieve a live birth will be re-randomised (1:1) to receive either PRP or G-CSF for their subsequent transfer (Stage 2). Data analysis will follow the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committees of The First Affiliated Hospital of Sun Yat-sen University ((2025)211-1), Boai Hospital of Zhongshan (AF/SC-07/03.1), The First People's Hospital of Foshan ((2026)146) and Foshan Maternity and Child Healthcare Hospital (FSFY-MEC-2026-161). All participants will provide written informed consent. Results will be published in peer-reviewed journals and presented at scientific congresses. TRIAL REGISTRATION NUMBER: ChiCTR2500108620.