Abstract
BackgroundUnresponsive 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.MethodsEighteen 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.ResultsSixteen 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.ConclusionCS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS.Trial registrationClinicalTrials.gov NCT03724617. Registered on 26 October 2018—prospectively registered, https://register.clinicaltrials.gov/
Highlights
IntroductionThin endometrium is often found in women with Asherman syndrome (AS) because the basal layer is destroyed, and the functional layer fails to respond to hormonal stimulation, which is the major cause of uterine infertility [1, 2]
Collagen scaffold (CS)/Umbilical cord mesenchymal stem cells (UC-Mesenchymal stromal cells (MSCs)) is a promising and potential approach for treating women with unresponsive thin endometrium caused by Asherman syndrome (AS)
Thin endometrium is often found in women with Asherman syndrome (AS) because the basal layer is destroyed, and the functional layer fails to respond to hormonal stimulation, which is the major cause of uterine infertility [1, 2]
Summary
Thin endometrium is often found in women with Asherman syndrome (AS) because the basal layer is destroyed, and the functional layer fails to respond to hormonal stimulation, which is the major cause of uterine infertility [1, 2]. Adequate endometrial thickness (ET ≥ 7 mm) at the day of embryo transplantation represents the “fertile soil” for an implanting embryo, which is essential to accomplish a successful pregnancy [3]. Even with the use of these therapies, the endometrium of some patients still remained unresponsive, frozen–thawed embryo transfer (FET) cycles have to be cancelled repeatedly, or embryo implantations failed. Unresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease
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