First Multicentre Clinical Results of Human Umbilical Cord Blood Platelet-rich Plasma for Endometrial Restoration

Research question Can human umbilical cord blood platelet-rich plasma (hUC-PRP), characterised by a distinct regenerative proteomic profile, enhance endometrial growth, vascular remodelling and tissue regeneration in patients with Asherman's syndrome (AS), endometrial atrophy (EA) or thin endometrium (TE)? Design This multicentre pilot study included 15 infertile patients with AS or EA/TE despite repeated oestrogen exposure. hUC-PRP was extensively characterised and compared with adult platelet-rich plasma (PRP) using proteomic and metabolomic analyses. Patients underwent hysteroscopic subendometrial hUC-PRP injection while continuing oestrogen administration. Endometrial thickness, ultrasound patterns, vascular markers (α-smooth muscle actin and von Willebrand factor), and transcriptomic changes were assessed pre- and post-treatment. Results hUC-PRP showed high homogeneity across donors in principal component analysis and a 1.89-fold increase in platelet concentration versus whole human umbilical cord blood. Proteomic profiling of hUC-PRP identified 138 growth factor–related proteins, and revealed enrichment of extracellular matrix (ECM) remodelling pathways compared with adult PRP. Endometrial thickness did not significantly increase after two oestrogen-only cycles ( P =0.57), but rose significantly after hUC-PRP administration from a mean±SD of 3.67±0.72 mm to 5.59±1.20 mm ( P <0.001). Seventy percent (7/10) of patients with non-trilaminar or atrophic endometrium developed a trilaminar pattern post-treatment. Immunofluorescence demonstrated an 11.86-percentage-point increase in mean neoangiogenic vascular area per patient, while transcriptomic analysis revealed activation of pathways related to proliferation, angiogenesis, immune response, hormone response, and ECM remodelling. Conclusions hUC-PRP combines a distinctive regenerative molecular profile with meaningful endometrial regeneration, supporting its potential as a novel therapeutic strategy for infertile women with compromised endometria. As a proof-of-concept study, these findings support further investigation of hUC-PRP as a potential endometrial regenerative approach, while reproductive efficacy remains to be established.