宫腔粘连导致无反应性薄型子宫内膜采用脐带间充质干细胞复合胶原支架治疗的初步研究。
Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study.
机构信息
Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, NO.3 Qingchun East Road, Shangcheng District, Hangzhou, 310016, People's Republic of China.
Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Hangzhou, People's Republic of China.
出版信息
Stem Cell Res Ther. 2021 Jul 22;12(1):420. doi: 10.1186/s13287-021-02499-z.
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/.
背景
由 Asherman 综合征（AS）引起的无反应性薄型子宫内膜是子宫性不孕的主要原因。然而，目前的治疗方法并不有效。本研究旨在评估胶原支架/脐带间充质干细胞（CS/UC-MSCs）移植对此种难治性疾病的疗效。
方法
本前瞻性自身对照研究纳入了 18 名因子宫内膜厚度（ET≤5.5mm）减少而取消冷冻胚胎移植（FET）的无反应性薄型子宫内膜不孕妇女。宫腔镜检查确认宫腔内无粘连，然后将 2000 万个 UC-MSCs 加载到 CS 上，在两个连续的月经周期内移植到子宫腔。两次移植后通过宫腔镜评估子宫腔。在下一个周期进行 FET。随访妊娠结局。比较治疗前后的子宫内膜厚度、子宫容受性和子宫内膜血管生成、增殖及激素反应。
结果
16 名患者完成了研究。无治疗相关严重不良事件发生。移植 3 个月后，平均 ET 从 4.08±0.26mm 增加到 5.87±0.77mm（P<0.001）。15 名接受 FET 的患者中有 3 人怀孕，其中 2 人成功分娩，1 人在 25 周妊娠时流产。2 名未接受 FET 的患者中有 1 人自然妊娠，移植后正常分娩。免疫组化分析显示微血管密度增加，Ki67、雌激素受体α和孕激素受体表达上调，表明子宫内膜血管生成、增殖和对激素的反应得到改善。
结论
CS/UC-MSCs 是治疗 AS 引起的无反应性薄型子宫内膜的一种有前途和潜在的方法。
试验注册
ClinicalTrials.gov NCT03724617。于 2018 年 10 月 26 日注册-前瞻性注册，https://register.clinicaltrials.gov/。
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