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

Severe refractory Asherman syndrome 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.

The 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.

Results showed that LPO-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.

These 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.