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改善宫腔粘连预后的临床和动物实验研究

The Clinical Animal Research in Improving the Prognosis of Asherman Syndrome

【作者】 林小娜

【导师】 张松英;

【作者基本信息】 浙江大学 , 生殖微创(专业学位), 2015, 博士

【摘要】 第一部分短期多次宫腔镜下粘连分离术用于宫腔粘连治疗的队列分析目的:通过中重度宫腔粘连患者疗效的回顾性队列分析,寻找影响疗效的相关因素,比较不同复查期限对粘连复发和妊娠结局的影响,从中寻找有利于术后恢复正常官腔形态、提高妊娠分娩率的临床治疗路径。方法:2010年1月至2013年7月初次在浙江大学医学院附属邵逸夫医院因中重度宫腔粘连行宫腔镜下粘连分离术的患者纳入本研究。纳入标准:(1)初次宫腔镜术中粘连评分符合中重度宫腔粘连(AFS评分≥5分);(2)年龄≤40岁;(3)至少在术后一定时间内进行过一次宫腔镜复查;(4)术前病史记录完整,包括经量改变情况、既往孕产史、宫腔操作史等。所有患者在静脉麻醉下行宫腔镜下剪刀锐性宫腔粘连分离手术,必要时B超监护。术后常规给予抗生素和雌孕激素序贯人工周期疗法,一定时间内行二次宫腔镜探查,术后定期门诊或电话随访。记录手术并发症,二次宫腔镜复查距初次手术的时间,每次宫腔镜检查时AFS评分评级,宫腔粘连分离次数,最终宫腔形态恢复情况,妊娠时间,分娩时间,不良妊娠情况,孕产期并发症。结果:1.总体情况:2010年1月20日-2013年7月24日,共205例完成初次宫腔镜手术及二次宫腔镜探查。纳入者平均年龄29.7±4.3岁。术后随访时间11-55个月,中位随访时间27个月。32例失访,17例无生育打算,随访成功且有生育意愿者156例。156例有生育要求的患者114例获得妊娠,总体妊娠率73.1%。114例妊娠患者中早期流产13例(11.4%),晚期流产8例(7.0%),异位妊娠3例(2.6%),总妊娠丢失率21.0%;3例目前继续妊娠至孕中期;已分娩87例,分娩率78.4%(87/111),总活产率56.9%(87/153)。2.宫腔形态恢复正常的相关因素分析2.1术后不同复查期限对官腔恢复正常形态的影响将所有患者按照二次宫腔镜复查距初次手术时间长短分成2组:A组为≤2个月,155例;B组为>2个月,50例。两组一般临床特征无明显差异。二次复查时A组AFS下降中位数为7分,B组下降6分,相比差异有显著性意义(P<0.05)。205例患者中136例(66.3%)形态恢复正常,45例(23.9%)好转,20例(9.8%)无改变。A组中76.8%(119例)恢复正常,B组仅52.0%(26例)。比较两组二次宫腔镜复查宫腔形态恢复程度,差异也有显著性意义(P<0.05)。205例患者中6例在形态恢复正常前失访,186例经过1-7次分离均恢复正常宫腔形态。A组中位恢复时间为1个月,B组3个月,两组患者恢复正常宫腔形态的累积比例比较,差异有显著性意义(P<0.001)。2.2不同粘连程度对宫腔形态恢复正常的影响将所有患者分成中度和重度粘连2个亚组。中度粘连患者A组中位恢复时间为1个月,B组3个月;重度粘连患者A组中位恢复时间为2个月,B组中位恢复时间为7个月。2个亚组比较恢复正常宫腔形态的总趋势在复查时间小于等于2个月组均较有利,差异有显著性意义(P均<0.001)。3.妊娠率相关因素分析3.1基本疾病特征与妊娠率的关系妊娠和非妊娠组年龄、月经性状、既往妊娠相关病史和既往宫腔操作史无差异;重度粘连组妊娠率57.8%(26/45),显著低于中度粘连组(79.3%)(P<0.05)。3.2不同干预措施与妊娠率的关系:比较复查期限≤2月与>2月的患者,前者妊娠率达到77.9%,与后者63.4%有显著性差异(P<0.05)。使用不同的防粘连方式和不同的粘连分离次数,妊娠率的差异均无统计学意义。3.3影响妊娠率的多因素综合分析3.3.1logistic回归分析试将前面比较有差异的不同复查期限、不同粘连程度联合年龄一起比较,得出不同复查期限、不同粘连程度和年龄均对妊娠率有影响,OR值分别是0.413,0.283和0.893。3.3.2累积妊娠率分布曲线的影响因素分析≤2月组术后中位妊娠时间8个月,>2月组为19个月,2组累积妊娠率曲线分布比较有显著性差异(P<0.01)。按粘连程度进行分层分析,中度粘连患者中,复查期限≤2月者累积妊娠率分布曲线优于>2月的患者(P<0.01),而重度粘连患者两者无差异。3.4子宫内膜厚度与妊娠率的关系采用行IVF-ET治疗方式者40例,妊娠29例,妊娠率72.5%。妊娠组平均内膜厚度7.5±0.9mm,非妊娠组5.8±1.5mm,相比有显著性差异(P<0.05)。4.活产率相关因素分析4.1基本疾病特征与活产率的关系活产和未获活产组在年龄、月经性状、既往妊娠相关病史和既往宫腔操作史比较均无统计学差异。中度粘连组活产率62.2%,重度组46.7%,组间差异无显著性意义(P=0.076)。4.2不同干预措施与活产率的关系复查期限≤2月组活产率61.9%,>2月组46.5%,差异无显著性意义(P=0.081)。使用不同的防粘连方式和不同的粘连分离次数,活产率的差异均无统计学意义。4.3影响活产率的多因素综合分析:4.3.1logistic回归分析不同粘连程度和年龄对妊娠率有影响,OR值分别是0.463和0.850。4.3.2累积活产率分布曲线的影响因素分析≤2月组有活产者中位妊娠时间10个月,>2月组为27个月。2组累积活产率曲线分布比较有显著性差异(P<0.05)。按粘连程度进行分层分析,中度粘连患者中,复查期限≤2月者累积活产率分布曲线优于>2月的患者(P<0.05),而重度粘连患者两者无差异。4.4子宫内膜厚度与活产率的关系:IVF-ET患者中剔除1例妊娠中患者,共39例,19例活产,活产率48.7%。活产组平均内膜厚度7.5±0.9mm,未获活产组6.6±1.5mm,相比有显著性差异(P<0.05)。结论:宫腔镜下锐性粘连分离术是行之有效的宫腔粘连治疗手段。宫腔粘连程度和年龄影响妊娠率和活产率。2个月内复查宫腔镜可以加快宫腔形态恢复的进程、增加累积妊娠和活产率。包括多次分离、短期复查、雌激素治疗、辅助生殖治疗在内的综合性治疗策略可以最大限度地增进宫腔粘连患者的生育机会。子宫内膜厚度影响IVF治疗的妊娠率和活产率。第二部分物理屏障预防再粘连形成的研究第一节官内节育器、官腔球囊支架和透明质酸凝胶预防官腔镜下粘连分离术后再粘连的队列研究目的:比较COOK球囊支架、宫内节育器和透明质酸凝胶预防Asherman综合症宫腔镜术后再粘连的效率。方法:107名Asherman综合征患者在宫腔镜下宫腔粘连分离术后纳入回顾性队列研究。宫腔镜下剪刀锐性分离粘连,20例患者宫腔内置入COOK球囊支架,28例放置官内节育器(IUD),18例患者宫腔内注入透明质酸凝胶,另41例无额外治疗措施的患者作为对照组。术后1-2个月内行宫腔镜二次检查。宫腔粘连程度采用AFS评分。统计学分析采用Wilcoxon秩和检验和Kruskal-Wallis秩和检验,以P<0.05为有统计学意义。结果:4组术前评分没有差异,粘连分离后下降最多的是球囊支架组(中位数8,范围0-10),随后是IUD组(中位数6,范围0-10),透明质酸组(中位数4.5,范围0-12)和对照组(中位数3,范围2-12)。球囊支架组的下降分数与其它3组比均有显著性差异(p<0.001);IUD组的下降值也明显大于透明质酸组(P<0.001)和对照组(P=0.001);而透明质酸组和对照组之间没有显著性差异。我们用将二次宫腔镜检查时的临床转归分成正常、好转和无效三个等级,正常和好转定义为有效。有效率在4组分别为:球囊组95%,IUD组93%,透明质酸组67%和对照组71%。球囊支架组临床转归明显好于其它三组(p<0.001),IUD组也明显由于其它两组(P<0.001)。结论:宫腔镜下粘连分离术后置入球囊支架和宫内节育器是比使用透明质酸凝胶更有效的宫腔内再粘连预防措施,球囊支架的预防效率优于宫内节育器。第二节宫内节育器与官腔球囊支架预防官腔镜下粘连分离术后再发的前瞻性随机对照试验目的:比较心形子宫球囊支架与官内节育器(IUD)预防宫腔镜下粘连分离术后再粘连的效率。设计:前瞻性随机病例对照试验研究单位:大学附属医院患者:201位中重度官腔粘连妇女干预措施:研究对象被随机分成2组,分别在宫腔镜下粘连分离术毕放置心形子宫球囊支架或圆宫型宫内节育器,术后7天后取出。1-2月后二次宫腔镜检查。主要评估指标:首次宫腔镜手术前后宫腔粘连评分的下降值和宫腔粘连的复发率。结果:共募集了201例患者,39例失访,进入最终结果分析的有球囊支架组82例、IUD组80例。2组患者的粘连、月经性状、妊娠病史和术前粘连评分均无差异。粘连评分下降值中位数(球囊支架组7分,IUD组7分)和粘连复发率(球囊支架组30%,IUD组35%)无显著性差异。按照粘连程度分为中度和重度亚组再比较上述指标仍无显著性差异。结论:心形子宫球囊支架和圆宫型宫内节育器在预防宫腔镜下粘连分离术后再粘连的效率上无差异。第三节子宫球囊支架放置7天的感染风险评价目的:比较子宫球囊支架与宫内节育器放置7天后子宫颈管细菌存在的差异。方法:1.研究对象:2012年6月-2013年12月在邵逸夫医院妇产科行宫腔镜下粘连分离术的中重度官腔粘连患者,选择在本院不孕不育门诊取出子宫球囊支架和宫内节育器(IUD)的患者纳入研究。2.研究方法:门诊采集患者主诉、阳性体征和实验室结果。同时采集子宫颈管分泌物行通用细菌培养,比较两组菌落发现率和构成的差异。3.统计学分析:用SPSS16.0进行统计学分析。计量资料用t检验,计数资料用卡方检验,以P<0.05为有统计学差异。结果:共93例纳入研究,其中子宫球囊支架组59例,IUD组34例。两组基本情况无差异(P>0.05)。球囊支架组培养发现阳性例数20例,阳性率34%,IUD组阳性例数12例,阳性率35%,两者无显著性差异(P>0.05)。发现阳性的菌落有大肠埃希菌、粪肠球菌、阴道加德纳氏菌、不动杆菌、无乳链球菌、草绿色链球菌和白色念珠菌,两组的菌落分布无显著差异。球囊支架组有9位患者主诉球囊放置期间腹部轻微胀满感,2位诉阴道少量出血,2位诉外阴瘙痒。IUD组2位诉阴道少量出血,无其它不适。9位腹部不适患者取出支架后明显好转,双合诊检查无阳性体征。外阴瘙痒患者阴道分泌物涂片发现白色念珠菌感染,宫颈分泌物培养有相同发现,予以阴道外用药物治疗后好转。无中大量阴道出血或上生殖道感染发现。结论:在预防性应用抗生素的前提下,宫腔粘连分离术后放置子宫球囊支架7天的感染风险和放置IUD无差异。第三部分子宫内膜间充质干细胞修复小鼠受损子宫内膜的试验研究目的研究子宫内膜间充质干细胞(eMSC)在电热损伤后的小鼠子宫内膜的归巢效应和对受损内膜的修复作用。方法1.建立的小鼠子宫内膜电热损伤模型,所有小鼠均选损伤右侧子宫,左侧作为阴性对照。2.损伤后3日,用Dil标记的eMSC5105,经尾静脉注射进入小鼠体内,对照组用0.9%氯化钠尾静脉注射。3.注射后3天、7天、14天用小动物成像仪观察eMSC在损伤部位的归巢效应。4.比较注射后7天、14天的内膜组织学变化和微血管密度(MVD)变化。5.用SPSS16.0进行统计学分析。正态分布计量资料用t检验,非正态分布用秩和检验,以P<0.05为有统计学差异。结果1.注射后3天、7天、14天,与注射0.9%氯化钠(Nacl)组及末损伤侧相比,eMSC在小鼠受损子宫内膜侧有明显的归巢效应。2.注射后7天、14天,注射eMSC组子宫内膜厚度比Nacl组增厚,差异有显著性意义,2组子宫内膜腺体数量无明显差异。3.注射后7天,eMSC组损伤侧比非损伤侧MVD增多,NaCl组MVD略减少,左右侧差值2组比较有显著性差异。注射后14天2组MVD均增加,无显著差异。结论子宫内膜间充质干细胞可以向小鼠受损子宫归巢,促进损伤部位子宫内膜厚度增加,加速内膜血管新生,起到协助内膜修复的正向作用。

【Abstract】 Part one The value of repeating hysteroscopic adhesiolysis at short time interval in Asherman syndrome treatment:a cohort studyObjectives:To improve the pregnancy and live birth rate after operation, it is the core in the treatment of Asherman syndrome that choosing appropriate surgical intervention to reduce the uterine adhesion reformation. In this retrospective cohort study, we discuss the factors related to the uterine shape rebuilding and the pregnancy result, especially timing of second look.Methods:The patients suffered moderate to severe degree uterine adhesion were recruited during Jan.2010to Jul.2013. The including criteria are:(1) first time adhesiolysis in Sir Run Run Shaw Hospital;(2) AFS score≥5;(3)age≤40;(4) received second hysteroscopic examination some time after first surgery;(5)with completed record, including menstrual pattern, previous pregnancy history and intrauterine manipulation history, etc.All of the operation were done by sharp hysteroscopic scissors under general anesthesia. Ultrasonographic guidance were used when difficult cases were met with. Surgery ended when the normal uterine anatomy was gained or the perforation risk remarkably increased. Sometimes one of the following modalities were inserted after surgery to prevent readhesion:Cook intrauterine balloon, intrauterine contraceptive device(IUD), hyalouronic acid gel, or Foley catheter balloon.Broad spectrum antibiotics and cyclic hormone treatment were given routinely after operation. Second look hysteroscopy were conducted in certain time phase. Follow up was done in clinic and also by telephone. The following information was recorded: operation complication, the time interval between two hysteroscopic operation, AFS score in every time examination, the times of adhesiolysis, final uterine shape recovery, pregnancy time, delivery time, abnormal pregnancy procedure and pregnancy complication.Results:1. General results205cases completed primary and secondary hysteroscopic operations. The average age of the patients was29.7±4.3, average pregnancy times was2.4±1.6, and average delivery times was0.2±0.4.The main surgical complication was3cases uterine perforation,2cases repaired by laparoscopy and1by conservative therapy.Follow up time phase was between11-55months, median was27months.32cases(17.8%)dropped out;17cases had not planned to conceive;156cases reported willing to conceive.114cases(73.1%) got pregnancy after operation,79cases spontaneously,3by ovulation induction,3by artificial insemination, and the other29cases by in vitro fertilization and embryo transfer(IVF-ET). Among114pregnant women,13cases(11.4%) suffered first trimester miscarriage,8(7.0%) second trimester miscarriage and3(2.6%) ectopic pregnancy, general pregnancy lost rate21.0%.87cases had elivered until now except3woman’s pregnancy was going, live birth rate was56.9%.2. The factors related to uterine cavity shape recovery 2.1The influence of second look hysteroscopy in short time interval to the uterine shape recoveryThe patients were separated into2groups according to the different time interval between primary and secondary hysteroscopic operation, group A≤2months,155cases; group B>2months,50cases. There were no difference between2groups in age, previous uterine operation history, pregnancy related history and severity of adhesion. Group A had more oligomenorrhea patients whereas group B had more amenorrhea patients.The median AFS score reduction is7in group A at the second look, comparing to6in group B with significant difference(P=0.015).136patients (66.3%) achieved normal uterine shape at the time of second look,45improved (23.9%) and20not improved (9.8%). The ratio of normal uterine shape in group A was higher than that in group B (76.8%vs52.0%, P<0.05).186cases of205gained normal shape in the end through adhesiolysis for1-7times,93.3%in group A and94.0%in group B. The time related accumulate ratio of normal uterine shape was better in group A (50%recovery ratio group A1month vs group B3months, P<0.001).2.2The influence of adhesion degree to the uterine shape recoveryThe ratio of normalized uterine cavity was71.8%in moderate adhesion group, and54.0%in severe group (P<0.05).Comparing the recovery ratio in different second look time based on both moderate and severe group, the time related accumulate recovery ratios are both better in short time second look group(P<0.001).3. analysis of factors relating to pregnancy rateThere were no difference between pregnant or not pregnant women in age, menstrual pattern, previous pregnancy history and previous uterine manipulation history. The pregnancy rate was lower in severe group (moderate79.3%vs severe 57.8%,P<0.05). Comparing in different time second look groups, pregnancy rate in earlier second look group was77.9%, higher than later group (63.4%)(P<0.05). there were no difference between2groups in using different adhesion prevention modalities and different adhesion relaxing times.Age, second look time and adhesion degree were selected as significant effective factors for pregnancy rate by logistic regression analysis. The OR was0.893,0.413and0.283.In Kaplan-Meier model, the time related accumulate pregnancy rate was higher in earlier second look group with8months of50%PR, and19months of50%PR in the other group(P<0.01). The difference was still significant (P<0.01) in moderate adhesion subgroup, but not represent in severe subgroup.In40cases received IVF-ET treatment, the thickness of endometrium was thicker in pregnant group(7.5±0.9mm vs5.8±1.5mm in not pregnant group, P<0.05).4. analysis of factors relating to live birth rateThere was no difference between live birth or no live birth women in age, menstrual pattern, previous pregnancy history and previous uterine manipulation history. The difference of general live birth rate was not significant in different severe degree and different second look time.In logistic regression analysis, age and adhesion degree were selected as significant effective factors, OR was0.850and0.463.In Kaplan-Meier model, the time related accumulate live birth rate was higher in earlier second look group(10month vs27month of50%live birth rate, P<0.05). Comparing separately, the difference was still exist in moderate adhesion subgroup(P<0.05), but not represent in severe subgroup.As to IVF-ET patients, total live birth rate was48.7%, the thickness of endometrium was thicker in live birth group(7.5±0.9mm vs6.6±1.5mm in not pregnant group, P<0.05). Conclusion:Hysteroscopic adhesiolysis was effective intervention to treat Asherman syndrome. The age and adhesion degree affect pregnancy rate and live birth rate after operation. Performing second hysteroscopic examination in2month may speed the recovery of uterine shape, increase the accumulate pregnancy rate and live birth rate. Comprehensive treatment could improve the fertility condition after surgery. The thickness of endometrium affects the pregnancy rate and live birth rate of IVF. Part Two Research of mechanical barrier preventing adhesion reformationChapter1A comparison of intrauterine balloon stent, intrauterine contraceptive device and hyalouronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome:a cohort studyObjective:To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyalouronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Asherman’s syndromeStudy design:107women with Asherman’s syndrome who were treated with hysteroscopic division of intrauterine adhesion were enrolled in this retrospective cohort study. After hysteroscopic adhesiolysis,20patients had intrauterine balloon inserted,28patients had intrauterine contraceptive device (IUD) fitted,18patients had hyaluronic acid gel instilled into the uterine cavity, and41control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases. The effect of hysteroscopic adhesiolysis was scored by AFS. The main results were compared by Wilcoxon test and Kruskal-Wallis test. A p value of<0.05was considered as statistically significant.Results:The preoperative AFS scores among4groups are not significantly differed. The median dropping of scores after surgery were as following:balloon group8(0-10), IUD group6(0-10), gel group4.5(0-12) and control group3(2-12). Both the intrauterine balloon group and IUD group achieved significantly (P<0.001) greater amount of reductions in the adhesion score than that of the hyaluronic acid gel group and control group; the efficacy of the balloon is greater than that of the IUD(P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups.We defined the second-look hysteroscopic finding as normal, improved and no change, and named normal and improved as effective. The effective rates in4groups are:balloon group95%, IUD group93%, gel group67%and control group71%. Comparing the recovery rates of uterine shape, the balloon group was greater than all of the other groups(P<0.001),and the IUD was following (comparing to the gel and control group,P<0.001)。Conclusion:The insertion of intrauterine balloon and intrauterine device are more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation, and the intrauterine balloon performed better. Chapter2A prospective randomized controlled trial comparing the efficacy of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation following hysteroscopicadhesiolysisObjective:To compare the efficacy of heart-shaped intrauterine balloon and intrauterine contraceptive device(IUD) in the prevention of adhesion reformation after hysteroscopic adhesiolysis.Design:Prospective, randomized controlled trial.Setting:University hospitalPatients:201women with moderate to severe degree of Asherman syndromeIntervention:Women were randomised to having either a heart-shaped intrauterine balloon or an IUD fitted after hysteroscopic adhesiolysis. The devices were removed after7days. A second look hysteroscopy was carried out1to2months after the surgery.Main outcome measure:The incidence of adhesion reformation and the reduction of adhesion score before and after surgery.Results:201cases were recruited initially,39cases dropped out, resulting in82cases in the balloon group and80cases in IUD group. The age, menstrual characteristics, pregnancy history and AFS score before surgery were comparable between the two groups. The median adhesion score reduction (balloon group,7; IUD group,7) and the adhesion reformation rate (balloon group30%, IUD group35%) were not significantly different between the two groups. There are also not different between2groups in median adhesion score reduction and adhesion reformation rate when the subjects were divided into moderate and severe subgroups.Conclusion:The heart-shaped intrauterine balloon and intrauterine contraceptive device are of similar efficacy in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome.Clinical Trial Registration Number:ISRCTN69690272, Chapter3The infection risk of keeping intraterine balloon stent in the uterine cavity for7days Objective:To compare the bacteria flora in the cervical canal between the COOK intrauterine balloon stent and IUD being kept in uterine cavity for one week after the hysteroscopic adhesiolysis.Method:Women with moderate-sever Asherman syndrome were enrolled in this study from June2012to December2013. as were removed the devices one week after hysteroscopic adhesion relaxing in the infertility clinic of Sir Run Run Shaw Hospital. The patients were divided into two groups:intrauterine balloon stent subgroup, tailed intrauterine contraceptive device subgroup. Any complain was recorded and checked by physical examination and laboratory test when necessary. The sterile swabs were taken from the cervical canals for bacteria culture.Results:93subjects were enrolled into the observation,59cases in balloon group and34in IUD group. Positive microorganism in culture media were seen in20patients (34%) in the balloon group and12patients (35%) in the IUD group, and the positive rate was no different between these two groups. The positive flora include:Escherichia coli, Staphylococcus faecalis, Gardnerella vaginalis, Acinetobacter, Streptococcus agalactiae, Streptococcus viridans, and Candida albicans.The constituent ratio of bacterial culture has no difference in these two groups. No obvious pelvic infection was found in these patients.Conclusion:The sake of infection is not different between intrauterine balloon stent and IUD groups by keeping in the uterine cavity for one week after hysterocopic adhesiolysis, when the prophylactic antibiotics were given. Part3The experiment of eMSC repairing injured mouseendometriumObjective:Investigate the grafting of eMSC to heat injured mouse endometrium and positive effect in endometrial repair.Methods:Establish the mouse endometrial heat injured model, inject Dil marked eMSC through tail vein3days after injury. The control group was injected0.9%Nacl. Obeserve the homing of eMSC3,7,14days after injection. Compare the thickness of endometrium, numbers of endometrial glands between2groups in7and14days, as well as the microvessel density in endomtrium.Results:1. Dil marked eMSC presented obvious homing effect to the injured uterus comparing to the control side and control group.2. The thickness of endometrium was remarkably thicker in the eMSC injection group than the control, but the numbers of endometrial glands were not different in7and14days.3. The MVD after7days injection elevated in eMSC injection group,which has statistic significancy comparing with NaCl injection group. There is no difference of MVD between2groups after14days injection.Conclusion:The injection of eMSC could home to injured side of uterus, might help the injured endometrium repair due to increase the endometrial thickness and accelerate angiogenesis.

  • 【网络出版投稿人】 浙江大学
  • 【网络出版年期】2015年 09期
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