Unresponsive Thin Endometrium Caused by Asherman Syndrome Treated With Umbilical Cord Mesenchymal Stem Cells: A Pilot Study

Abstract BackgroundUnresponsive thin endometrium caused by Asherman’s syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease.MethodsEighteen infertile women with unresponsive thin endometrium, whose frozen–thawed embryo transfers (FET) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then ten million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FET were performed in the following cycle. Pregnancy outcomes were followed-up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment.ResultsSeventeen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.11 ± 1.01 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks’ gestation. One of 2 patients without FET had a natural pregnancy at 36 weeks after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alfa and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones.ConclusionCS/UC-MSCs can promote the growth of unresponsive thin endometrium caused by AS, possibly through promoting endometrial proliferation and angiogenesis and enhancing the response of the endometrium to hormones.Trial RegistrationClinicalTrials.gov (NCT03724617). Registered 26 October 2018-prospectively registered, https://register.clinicaltrials.gov/