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Background Unresponsive thin endometrium caused by Asherman 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. Methods Eighteen infertile women with unresponsive thin endometrium, whose frozen–thawed embryo transfers (FETs) 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 twenty 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. FETs 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. Results Sixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 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 and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones. Conclusion CS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS. Trial registration ClinicalTrials.gov NCT03724617. Registered on 26 October 2018—prospectively registered, https://register.clinicaltrials.gov/

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This study means to investigate a combination of noninvasive methods in diagnosis of minimal or mild endometriosis expecting to narrow down the range of laparoscopic exploration for female infertility. It is a retrospective case control study of totally 447 patients suspected unexplained infertility before surgery were eligible from May 2012 to February 2017. Of these, 299 patients were laparoscopy-proved minimal or mild endometriosis group, the remaining 148 patients served as control group (normal pelvis). Preoperative age, duration of infertility, type of infertility, body mass index, baseline follicle-stimulating hormone, anti- Müllerian hormone, serum CA 125 , clinical symptoms, findings on vagino-recto-abdominal examinations and pregnancy prognosis had been recorded. Every variable and their combinations were evaluated. Any single factor had limited diagnostic value. The cut-off value for CA 125 was 19.25 IU/L. Parallel testing had a higher sensitivity at 81.3%. Serial tests of vagino-recto-abdominal examination combined with dysmenorrhea or positive CA 125 got reasonable sensitivity (51.4% and 49%), remarkable high specificities (95.7% and100%) and Positive Predictive Value (96.4% and 100%). Multivariate logistic regression identified the following factors in decreasing order of importance: (1) vagino-recto-abdominal examinations, (2) CA 125 , (3) dysmenorrhea, their ORs being 16.148, 3.796, and 2.809, respectively. The spontaneous pregnancy rate (50.8%) in minimal or mild endometriosis was higher than control (35.6%, P = .043). A combination of noninvasive diagnostic methods had certain preoperative diagnostic value of minimal or mild endometriosis, which might benefit some patients from avoiding laparoscopic surgery.