First-in-human pilot trial of G-CSF–mobilised platelet–leukocyte concentrate for severe refractory Asherman syndrome

IntroductionSevere refractory Asherman syndrome (SRAS) remains difficult to treat, and the benefit of regenerative blood-derived therapies remains uncertain. This study evaluated whether systemic granulocyte colony-stimulating factor (G-CSF) mobilisation combined with targeted intrauterine delivery of autologous peripheral blood platelet–leukocyte concentrate (PBPLC) could improve endometrial thickness in women with SRAS.MethodsThis prospective, single-centre, single-arm pilot study enrolled 10 women with infertility for at least 3 years, severe intrauterine adhesions, poor endometrial development, and failure of previous adhesiolysis, hormonal therapy, and platelet-rich plasma treatment. After G-CSF mobilisation, autologous PBPLC was injected into the endometrial–myometrial junction under hysteroscopic guidance without concurrent formal adhesiolysis. The primary outcome was the change in late pre-ovulatory endometrial thickness (LPO-EMT), analysed using the exact Wilcoxon signed-rank test and Hodges–Lehmann estimates.ResultsLPO-EMT increased from 4.6 mm (SD 0.7) to 5.8 mm (SD 1.3), with a Hodges–Lehmann paired difference of 1.08 mm (95% CI 0.45–2.50; p = 0.0039). Hysteroscopic cavity restoration, reduced adhesion severity, and subjective menstrual improvement were observed in all participants, and the AFS score decreased from 10.8 to 4.5. No grade 3 or higher treatment-related adverse events occurred. Among nine women who attempted conception, pregnancy was detected in six (66.7%; exact 95% CI 29.9–92.5), including four clinical pregnancies (44.4%; exact 95% CI 13.7–78.8). However, all clinical pregnancies ended in first-trimester miscarriage, and no ongoing pregnancies or live births were achieved during follow-up.DiscussionThese preliminary findings suggest that G-CSF-mobilised autologous PBPLC may be a feasible approach for improving endometrial thickness and uterine cavity restoration in women with SRAS. However, the findings do not establish reproductive efficacy, and larger controlled studies are warranted.Clinical trial registrationhttps://cris.nih.go.kr/, identifier KCT0004208.