hUC-MSCs loaded collagen scaffold for refractory thin endometrium caused by Asherman syndrome: a double-blind randomized controlled trial

In this single-center, double-blinded, randomized controlled trial, we investigated whether human umbilical cord-derived mesenchymal stromal cells loaded collagen scaffolds (hUC-MSC/CS) could improve the cumulative live-birth rate (cLBR) in infertile women with refractory thin endometrium (RTE). We randomly assigned 25 subfertile women with RTE, in a 1:1 ratio, to receive hysteroscopic adhesiolysis and plowing plus either hUC-MSC/CS or saline/CS (control) for intrauterine implantation. Uterine fluid was collected on the embryo transfer day for RNA-sequencing to explore the potential mechanisms by which hUC-MSCs exert their effects. The primary outcome was the cLBR. Live births occurred in 3 out of 11 women in the hUC-MSC/CS group and in 1 out of 13 women in the control group (27.3% vs 7.7%; relative risk [RR], 3.55; 95% confidence interval [CI], 0.43 to 29.42; P = .30). The cumulative frequencies of clinical pregnancy were 5/11 and 1/13 in the hUC-MSC/CS group and control group, respectively (45.5% vs. 7.7%; RR, 5.91; 95% CI, 0.81-43.28; P = .06). Two of 11 participants developed urticaria in the hUC-MSC/CS group. Enrichment analysis showed that T-cell activation had the largest proportion in the biological process category. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that most genes were related to cytokine-cytokine receptor interaction. In conclusion, there was a non-significant trend toward a higher cLBR with hUC-MSC/CS compared to controls, potentially through the cytokine-cytokine receptor interaction pathway. hUC-MSCs appeared to be relatively safe in a 1-year follow-up. Therefore, this novel therapy can be proposed to patients with RTE.