Diagnostic Accuracy of Hysterosalpingography in the Identification of Intrauterine Adhesions in Infertile Women in a Referral Centre, Southern Nigeria

Background: Examination of the endometrial cavity is crucial in the management of infertile women. This evaluation is done by Hysterosalpingography (HSG) in the University of Port Harcourt Teaching Hospital. The diagnostic value and accuracy of hysterosalpingography varies in various centres and has not been assessed in the University of Port Harcourt Teaching Hospital (UPTH), hence this study. Methodology: A prospective cross sectional study done among 101 infertile women at the gynaecology clinic of the UPTH from December 2018 to July 2019. Socio-demographic data of women who met the eligibility criteria were collected. Their hysterosalpingographic and outpatient hysteroscopic findings were statistically analyzed using IBM SPSS for windows version 20.0. The validity and reliability statistics of hysterosalpingography for the identification of endometrial adhesions were determined and significance was reported at p-value < 0.05. The analyzed data was presented in tables and figure. Result: The respondents were all married, 66.3% of them were nulliparous, while 54.5% were above 35 years of age. Most, 93.1% of the studied group had at least secondary education and had duration of infertility of more than 2 years. There was a moderate strength of agreement in the diagnostic accuracy of HSG with hysteroscopy in the diagnosis of intrauterine adhesions;showing sensitivity and specificity of 59.6% and 90.9% respectively. The accuracy of HSG in the identification of intrauterine adhesions in this study was 73.3%. The agreement in the diagnostic accuracy of HSG using Hysteroscopy as a gold standard for intrauterine adhesions was therefore moderately significant (k = 0.482). Conclusion: HSG had an overall fair strength of agreement with office hysteroscopy in the identification of intrauterine adhesions. It is a specific but not a sensitive predictor of intrauterine adhesion.

Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) and the Stem Cells Treatment: A Systemic Review and Meta-Analysis

Background: Intrauterine Adhesions (IUAs) or Asherman’s Syndrome (AS) usually contains symptoms such as decreased menstrual flow or even amenorrhea, chronic pelvic pain, recurrent abortion and infertility. The current treatment of IUAs includes hysteroscopic adhesiolysis, oral hormone and biological barriers, but each of them has limitation. Stem cell therapy may be an expanding field seeking for therapy in IUAs. Objective: We will discuss current advances in stem cell therapy as a treatment for endometrial pathophysiology. Materials and Methods: We search on PubMed, Embase and Cochrane library and select several keywords on researches, then review the cell biology theories and animal experiments, finally do meta-analysis in human clinical trials. Results: 77 articles on PubMed, 71 articles on Embase and 17 articles on Cochrane Library, as a result, 37 articles are included under the criteria, which are intrauterine adhesions (IUAs), Asherman’s Syndrome (AS), cell therapy, stem cells, bone marrow stem cells, clinical trials, recent 10 years and human or animal experiments. The included criteria: original articles, cohort study, case control study, animal experiments, human clinical trials, high quality, 10 years recent. The excluded articles are case reports, meeting reports, low quality or more than 10 years ago. Conclusion: Stem cell may be a new therapeutic schedule for IUAs in the future clinical treatment, but it is necessary to compare it with traditional therapy such as oral hormone, also the development of random clinical tests should proceed. For clinical treatment on IUAs, stem cells could be a new choice.

The Clinical Value of Ultrasound Image Texture Analysis in the Diagnosis of Uterine Adhesions

Purpose: This review examines the diagnostic value of transvaginal 3D ultrasound image texture analysis for the diagnosis of uterine adhesions. Materials and Methods: The total clinical data of 53 patients with uterine adhesions diagnosed by hysteroscopy and the imaging data of transvaginal three-dimensional ultrasound from the Second Affiliated Hospital of Chongqing Medical University from June 2022 to August 2023 were retrospectively analysed. Based on hysteroscopic surgical records, patients were divided into two independent groups: normal endometrium and uterine adhesion sites. The samples were divided into a training set and a test set, and the transvaginal 3D ultrasound was used to outline the region of interest (ROI) and extract texture features for normal endometrium and uterine adhesions based on hysteroscopic surgical recordings, the training set data were feature screened and modelled using lasso regression and cross-validation, and the diagnostic efficacy of the model was assessed by applying the subjects’ operating characteristic (ROC) curves. Results: For each group, 290 texture feature parameters were extracted and three higher values were screened out, and the area under the curve of the constructed ultrasonographic scoring model was 0.658 and 0.720 in the training and test sets, respectively. Conclusion Relative clinical value of transvaginal three-dimensional ultrasound image texture analysis for the diagnosis of uterine adhesions.

Safety of menstrual blood-derived stromal cell transplantation in treatment of intrauterine adhesion

BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.

Intrauterine transplantation of autologous bone marrow derived mesenchymal stem cells followed by conception in a patient of severe intrauterine adhesions

On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. Adult autologous bone marrow mesenchymal stem cells isolated from patient’s own bone marrow and were cultured and placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently using ultrasound. Three months later, endometrium partly recovered with improved ultrasonic echo. This resulted in spontaneous pregnancy followed by confirmation of gestational sac, yolk sac, and primitive heart tube pulse on ultrasound. Autologous bone marrow derived mesenchymal stem cells could regenerate injured endometrium not responding to conventional treatment and can be used as an alternative in females with severe Asherman’s syndrome.

Clinical and investigative correlates of etiologic risk factors on treatment outcome of intrauterine adhesion in women with infertility: A descriptive study

Background: Intrauterine adhesion is a clinical entity that may present with subfertility. However, outcome of management depends on severity of intrauterine adhesion and type of treatment intervention employed. Objective: To evaluate clinical and investigative correlation of etiologic risk factors of intrauterine adhesion on fertility and pregnancy outcome following treatment. Patients and Methods: A 5 years prospective observational study. Treatment employed includes transvaginal blind intrauterine adhesiolysis, insertion of inert intrauterine device or inflated Foley’s catheter balloon and oestrogen therapy. Inclusion criteria are intrauterine adhesion as the only identifiable cause of infertility and post treatment follows up for at least a year. Results: Over a period of 5 years, 63 patients with mean age of 31.6 years and age range of 21 to 42 years were managed. Etiologic risk factors were dilatation and curettage 33 (52.4%), vacuum aspiration 13 (20.6%), myomectomy 11 (17.5%) and caesarean section in 6 (9.5%) patients. Of the 63 patients, 28 conceived giving a pregnancy rate of 44.4%. Nine out of the 28 patients that conceived had miscarriage, giving a miscarriage rate of 32.1%. The highest pregnancy rate and lowest miscarriage rate were recorded in the subgroup that had vacuum aspiration as their etiologic risk factor. Late pregnancy complications encountered are preterm contractions 5 (26.3%), placenta praevia 4 (21.1%), morbidly adherent placenta 5 (26.3%) and preterm delivery in 2 (10.5%) patients. Route of delivery was per vaginum in 13 (68.4%) patients and by caesarean section in 6 (31.6%) patients. Live birth rate was 89.5% (17/19 deliveries). There was no maternal mortality recorded. Conclusion: Compared to other risk factors, uterine vacuum aspiration was associated with higher fertility rate and better pregnancy outcome.

Expression of miR-195 in intrauterine adhesion and its relationship with TGF-β1/Smads and FGF2/FGFR1/ERK pathways

Objective:To investigate the expression of miR-195 in intrauterine adhesion(IUA)and its relationship with TGF-β1/Smads and FGF2/FGFR1/ERK pathways.Methods:118 cases of IUA patients who underwent hysteroscopic treatment in our hospital between September 2017 and February 2019 were regarded as IUA group,80 cases of dysfunctional uterine bleeding patients who underwent hysteroscopic curettage in our hospital during the same period were regarded as control group.Differences in the expression levels of miR-195 as well as TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathway-related molecules in the focal tissues obtained by hysteroscopy were compared between the two groups.Pearson test was used to evaluate the correlation of miR-195 expression in the intrauterine adhesion tissues with TGF-β1/Smads and FGF2/FGFR1/ERK pathways in IUA patients.Results:miR-195 expression in intrauterine adhesion tissues of IUA group was higher than that in endometrial tissues of control group(P<0.05).TGF-β1,Smad2 and Smad3 mRNA expression in intrauterine adhesion tissues of IUA group were higher than those in endometrial tissues of control group;FGF2,FGFR1 and ERK mRNA expression in intrauterine adhesion tissues were higher than those in endometrial tissues of control group(P<0.05).Pearson test showed that the miR-195 expression in intrauterine adhesion tissues of IUA group was positively correlated with the TGF-β1/Smads pathway-related molecules TGF-β1,Smad2 and Smad3 mRNA expression,and positively correlated with the FGF2/FGFR1/ERK pathway-related molecules FGF2,FGFR1 and ERK mRNA expression(P<0.05).Conclusion:miR-195 is highly expressed in IUA lesion tissues and may promote disease progression by activating TGF-β1/Smads and FGF2/FGFR1/ERK signaling pathways.

Clinical Study of Changmaile II Combined with Estrogen and Progesterone in Preventing and Treating Intrauterine Adhesion

Purpose: To explore the clinical efficacy of Changmaile II combined with cyclic estrogen/progesterone therapy in treating hypomenorrhea caused by intrauterine adhesion (IUA) and its effect on the endometrium after the separation procedure for intrauterine adhesion. Methods: Sixty patients with IUA confirmed by hysteroscopy in the Second People’s Hospital of Fujian University of Traditional Chinese Medicine from March 2020 to December 2020 were selected and randomly divided into the control group and the observation group, with 30 cases in each group. After the separation procedure for intrauterine adhesion, the observation group underwent the cyclic estrogen/progesterone therapy alone, while the observation group was administered the in-hospital preparation of Changmaile II in addition to the therapy of the observation group. Menstrual recovery, endometrial thickness, and the diagnostic grading scores of IUA after 3 menstrual cycles were measured in both groups. Results: After the treatment for 3 menstrual cycles, the total effective rate was higher in the observation group (73.33%) than in the control group (53.33%) (P < 0.05). The period flow was heavier in the observation group than in the control group (P < 0.05). The endometrial thickness of both groups was thicker than before treatment (P < 0.05), nonetheless the difference between the groups was not statistically significant (P > 0.05). After treatment, the diagnostic grading scores of IUA were higher in the observation group than in the control group (P < 0.05). Conclusions: Changmaile II combined with estrogen and progesterone artificial cycle therapy could increase the menstrual volume and endometrial thickness of patients with intrauterine adhesion, while promoting the endometrial repair, with better efficacy than artificial cycle therapy alone.

Correlation of FoxF2 expression with MMPs, ADAMs and TGF-β1 pathway in intrauterine adhesions

Objective: To study the correlation of forkhead box F2 (FoxF2) expression with matrix metalloproteinases (MMPs), a disintegrin and metalloproteases (ADAMs), transforming growth factor-β1 (TGF-β1) pathway in intrauterine adhesions. Methods: The patients who underwent hysteroscopic surgery and were diagnosed with intrauterine adhesions according to postoperative pathology results in our hospital between March 2015 and January 2018 were selected as the IUA group, and the patients who underwent surgical resection and were diagnosed with uterine fibroid according to postoperative pathology results in our hospital during the same period were selected as the control group. The intrauterine adhesion tissues of the IUA group and the normal endometrial tissues of the control group were collected to measure the expression levels of FoxF2, MMPs and ADAMs-related molecules as well as TGF-β1 pathway molecules. Results: FoxF2, ADAM15, ADAM17, TIMP1, TGF-β1, Smad2, Smad3 and CTGF mRNA expression in the intrauterine adhesion tissues of IUA group were significantly higher than those of control group whereas MMP9 mRNA expression was significantly lower than that of control group;FoxF2 mRNA expression in the intrauterine adhesion tissues of IUA group was negatively correlated with MMP9 mRNA expression, and positively correlated with ADAM15, ADAM17, TIMP1, TGF-β1, Smad2, Smad3 and CTGF mRNA expression. Conclusion: The high expression of FoxF2 in intrauterine adhesions can inhibit protease activity and enhance TGF-β1 pathway function.

Correlation of the changes of TLR4/NF-κB pathway function in intrauterine adhesion tissue with the characteristics of cytokine secretion and collagen metabolism

Objective:To study the correlation of the changes of Toll-like receptor 4 (TLR4) / nuclear factorκB (NF-κB) pathway function in intrauterine adhesion (IUAs) tissue with the characteristics of cytokine secretion and collagen metabolism.Methods:The patients with IUAs who were treated in our hospital between February 2015 and March 2018 were selected as the IUAs group, and the patients who underwent hysteroscopy due to infertility and were pathologically confirmed to have normal endometrium during the same period were selected as the control group. The expression levels of TLR4/NF-κB pathway molecules and collagen metabolism genes as well as the contents of cytokines and collagen metabolism markers in the adhesion tissues of IUAs group and the normal endometrial tissue of control group were measured.Results: TLR4, NF-κB, a disintegrin and metalloproteinase 15 (ADAM15), ADAM17, matrix metalloproteinase 9 (MMP9) and plasminogen activator inhibitor 1 (PAI-1) mRNA expression as well as transforming growth factor-β1 (TGF-β1), Smad2/3, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), basic fibroblast growth factor (bFGF), periostin/osteoblast-specific factor 2 (Postn), type I collagen (Col-I) and actin-α (α-SMA) contents in the adhesion tissues of IUAs group were significantly higher than those of control group while urokinase-type plasminogen activator (uPA) mRNA expression was significantly lower than that of control group;TLR4 and NF-κB mRNA expression were positively correlated with TGF-β1, Smad2/3, IGF-1, IGF-1R, bFGF, Postn, Col-I,α-SMA, ADAM15, ADAM17, MMP9 and PAI-1, and negatively correlated with uPA.Conclusion:The excessive activation of TLR4/NF-κB pathway in IUAs is associated with the cytokine secretion and collagen metabolism abnormalities.

宫腔镜冷刀微剪分离术应用于重度IUA患者中的疗效及对其血清指标的影响

目的:分析宫腔镜冷刀微剪分离术应用于重度宫腔粘连(IUA)患者中的疗效及对其血清指标的影响。方法:采取便利抽样的方法选取2022年1月—2023年1月黄冈市黄州区人民医院妇产科收治的80例重度IUA患者作为研究对象,根据随机数表法将患者分为对照组与观察组,各40例。对照组予以宫腔镜电切手术,观察组予以宫腔镜冷刀微剪分离术,比较两组临床疗效、月经改善情况、子宫内膜动脉血流、子宫内膜厚度及血清指标。结果:观察组总有效率为95.0%,高于对照组的77.5%,差异有统计学意义(P<0.05);观察组月经恢复总有效率为90.0%,高于对照组的72.5%,差异有统计学意义(P<0.05);术后30 d、90 d,两组子宫内膜动脉血流与子宫内膜厚度较术前显著改善,两组术后90 d优于术后30 d,且观察组阻力指数(RI)、搏动指数(PI)低于对照组,而子宫内膜厚度高于对照组,差异有统计学意义(P<0.05);术后30 d、90 d,两组血清指标较术前显著改善,两组术后90 d优于术后30 d,且观察组血清转化生长因子-β_(1)(TGF-β_(1))、白细胞介素-6(IL-6)及纤溶酶原激活物抑制因子-1(PAI-1)水平均低于对照组,而基质金属蛋白酶-9(MMP-9)水平高于对照组,差异有统计学意义(P<0.05)。结论:宫腔镜冷刀微剪分离术应用于重度IUA患者可取得显著效果,不仅能提升临床疗效及月经改善效果,还能促进子宫内膜动脉血流与子宫内膜厚度恢复,有效改善血清指标。

Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.

HAMSCs移植联合G-CSF有效修复IUA大鼠子宫内膜损伤并抑制其纤维化

目的探讨人羊膜间充质干细胞(HAMSCs)联合粒细胞集落刺激因子(G-CSF)对宫腔粘连(IUA)大鼠子宫内膜损伤后的修复及纤维化抑制的影响。方法酶消化法提取HAMSCs体外培养,取P3代细胞通过生长特征、免疫荧光鉴定表面标记分子和三系分化能力进行鉴定。32只动情期SD大鼠随机均分为IUA组、HAMSCs组、G-CSF和H+G组。乙醚麻醉后行背部开口,IUA组从近卵巢端向左侧子宫腔内注射1 mL无水乙醇作用90 s,1 mL生理盐水冲刷子宫2次,右侧子宫注射等体积生理盐水作为假手术自身对照(Sham对照)。在造模后第7天和第10天进行2次治疗,每次注射体积均为0.2 mL。其中IUA组注射PBS,HAMSCs组宫腔灌注含1×106个细胞的PBS;G-CSF组灌注含20μg G-CSF的PBS;H+G组则在G-CSF灌注后再行HAMSCs灌注。各组大鼠在第2次治疗结束7 d后处死取子宫角备用。HE、Masson染色法检测各组大鼠子宫内膜的修复情况;qRT-PCR和免疫组化法检测各组大鼠子宫中TGF-β1、SMAD3、SMAD7、β-catenin、孕酮受体(PR)及雌激素受体(ER)的表达情况;另取32只大鼠同样分组造模后与正常雄鼠交配,计算其怀孕率和胚胎数。结果所获细胞经生长特性、细胞表面分子和分化能力的鉴定符合MSCs特征。IUA组大鼠子宫出现水肿、充血等现象,其余各组大鼠子宫形态均在一定程度上得以恢复,子宫内膜厚度和腺体数目从高到低依次为Sham对照、H+G组、HAMSCs组、G-CSF组、IUA组。Masson染色结果显示,在纤维化面积占整个子宫内膜面积的比例上,从高到低依次为IUA组、G-CSF组、HAMSCs组、H+G组、Sham对照。qRT-PCR结果显示,Sham对照TGF-β1、SMAD3和β-catenin mRNA最低,在IUA组中表达最高(P<0.05)。与IUA组相比,HAMSCs、G-CSF和H+G处理不同程度降低TGF-β1、SMAD3和β-catenin mRNA表达,尤其H+G组的表达水平接近于Sham对照水平(P<0.05)。SMAD7、PR和ER mRNA的表达趋势则与TGF-β1、SMAD3、β-catenin相反(P<0.05)。免疫组化结果显示,与IUA组相比,HAMSCs、G-CSF和H+G处理可以降低TGF-β1、SMAD3和β-catenin表达而升高SMAD7、PR和ER表达(P<0.05)。怀孕率和胚胎数计数结果显示,IUA组怀孕率为0,HAMSCs、G-CSF、H+G可以提高怀孕率和胚胎数(P<0.05)。结论HAMSCs移植及G-CSF宫腔灌注可能通过TGF-β1/SMAD3/β-catenin信号促进IUA大鼠子宫内膜损伤后的修复并抑制其纤维化,并且H+G处理的治疗效果优于单一的HAMSCs和单一G-CSF处理。

Engineering self-healing adhesive hydrogels with antioxidant properties for intrauterine adhesion prevention

Intrauterine adhesion (IUA) is the fibrosis within the uterine cavity. It is the second most common cause of female infertility, significantly affecting women’s physical and mental health. Current treatment strategies fail to provide a satisfactory therapeutic outcome for IUA patients, leaving an enormous challenge for reproductive science. A self-healing adhesive hydrogel with antioxidant properties will be highly helpful in IUA prevention. In this work, we prepare a series of self-healing hydrogels (P10G15, P10G20, and P10G25) with antioxidant and adhesive properties. Those hydrogels exhibit good self-healing properties and can adapt themselves to different structures. They possess good injectability and fit the shape of the human uterus. Moreover, the hydrogels exhibit good tissue adhesiveness, which is desirable for stable retention and therapeutic efficacy. The in vitro experiments using P10G20 show that the adhesive effectively scavenges ABTS+, DPPH, and hydroxyl radicals, rescuing cells from oxidative stress. In addition, P10G20 offers good hemocompatibility and in vitro and in vivo biocompatibility. Furthermore, P10G20 lowers down the in vivo oxidative stress and prevents IUA with less fibrotic tissue and better endometrial regeneration in the animal model. It can effectively downregulate fibrosis-related transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). Altogether, these adhesives may be a good alternative for the clinical treatment of intrauterine adhesion.

中重度宫腔粘连应用中医临床决策系统效果分析

[目的]探讨中医临床决策系统在治疗中重度宫腔粘连(intrauterine adhesion,IUA)中的应用及效果。[方法]采用随机对照试验进行前瞻性研究,选择2022年1月至12月在杭州市某三级甲等中医院行宫腔镜下子宫粘连松解术的中重度IUA患者,根据是否通过中医优势病种临床决策系统进行辨证论治分为对照组(51例)、决策系统组(53例)、临床医师组(54例),比较3组患者治疗前后月经量改善、美国生育协会(American Fertility Society,AFS)评分、子宫内膜厚度、子宫内膜血流参数、中医伴随症候疗效。[结果]治疗后3组患者月经量比较,决策系统组、临床医师组较对照组均有显著改善,差异有统计学意义(P<0.05),决策系统组与临床医师组差异无统计学意义(P>0.05)。治疗后3组患者宫腔AFS评分比较,决策系统组、临床医师组较对照组显著下降(P<0.01),决策系统组与临床医师组差异无统计学意义(P>0.05)。治疗后3组患者子宫内膜厚度显著增加,子宫内膜血流参数显著下降,差异有统计学意义(P<0.01),但治疗前后组间差异均无统计学意义(P>0.05)。治疗后3组患者中医伴随症候疗效比较,临床医师组较对照组、决策系统组明显改善,差异有统计学意义(P<0.05),对照组与决策系统组差异无统计学意义(P>0.05)。[结论]中医临床决策系统用于中重度IUA的治疗可显著改善患者月经量,降低术后AFS评分,防止粘连再发生。

lncRNA LUCAT1调控AREG的表达促进宫腔粘连的发生

目的探讨lncRNA LUCAT1通过调控双调蛋白(amphiregulin,AREG)对宫腔粘连发生的作用,为宫腔粘连的防治提供新的分子靶点。方法在宫腔粘连组织和经过转化生长因子-β1(transforming growth factor-β1,TGF-β1)处理的子宫内膜基质细胞(endometrial stromal cell,ESC)中采用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)方法检测lncRNA LUCAT1、AREG及纤维化标志物α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原蛋白(collagen typeⅠalpha 1 chain protein,COL1A1)的mRNA表达水平,采用Western blot法检测AREG、α-SMA、COL1A1的蛋白表达水平。si-LUCAT1、pcDNA LUCAT1、si-AREG分别转染ESC,RT-qPCR方法进一步检测lncRNA LUCAT1和AREG的mRNA表达水平。然后,si-LUCAT1和pcDNA LUCAT1分别转染入ESC中并经过TGF-β1处理48h,采用Western blot法进一步检测AREG、α-SMA、COL1A1的蛋白表达水平,细胞增殖实验和细胞凋亡实验检测细胞增殖率和细胞凋亡率。结果宫腔粘连组织和经TGF-β1处理的ESC中lncRNA LUCAT1、AREG及纤维化标志物α-SMA、COL1A1的表达水平上调。AREG随lncRNA LUCAT1的变化而变化,而下调AREG后lncRNA LUCAT1的表达无明显变化,lncRNA LUCAT1正向调节AREG。在ESC向成纤维细胞转化过程中,si-LUCAT1显著抑制AREG、α-SMA、COL1A1的蛋白表达水平,抑制细胞增殖促进细胞凋亡,差异有统计学意义(P<0.01);pcDNA LUCAT1显著诱导AREG、α-SMA、COL1A1的蛋白表达,差异有统计学意义(P<0.01)。结论lncRNA LUCAT1通过上调AREG的表达促进宫腔粘连的发生。lncRNA LUCAT1/AREG轴可能为宫腔粘连的防治提供新的分子靶点。

HEOS治疗宫腔粘连术后预防再粘连3种方法的对比研究

目的 比较3种不同方法在HEOS系统治疗不同程度宫腔粘连术后预防再粘连疗效的研究。方法 分析昆明市妇幼保健院收治的284例的轻中重度宫腔粘连患者,使用HEOS系统治疗后,分为3组,A组(节育环组)放置宫内节育环+透明质酸钠凝胶、B组(球囊组)放置Foley水囊管+透明质酸钠凝胶、C组(对照组)仅放置透明质酸钠凝胶。比较3组术后宫腔粘连恢复情况、月经改善情况、子宫内膜厚度以及术后不良反应。结果轻度宫腔粘连组,月经改善情况中3组比较,差异有统计学意义(P<0.05),A组比C组月经改善率高(对R×C卡方检验两两比较,校正显著水平,P<0.017),其他疗效指标中无显著差异(P>0.017),但A组不良反应率较C组高(P<0.017)。在中度宫腔粘连组,B组的宫腔粘连改善率与其他两组比较有显著差异(P<0.017)。在月经改善率、子宫内膜厚度、不良反应方面,A、B组均较C组增加(P<0.017)。重度宫腔粘连组中,A组各疗效指标均较其他组高(P<0.017)。结论 综合疗效指标和不良反应率分析,对轻、中、重度宫腔粘连,术后依次为放置透明质酸钠凝胶、Foley水囊管+透明质酸钠凝胶、宫内节育环+透明质酸钠凝胶为各程度粘连的最佳选择。达到个体化及分层管理,可取得良好临床效果,值得推广。

基于Smad3抑制剂SIS3对兔宫颈粘连程度影响的机制研究

目的:研究信号传导蛋白(Smad3)抑制剂SIS3对宫腔粘连模型兔血清中转化生长因子-β1(TGF-β1)、Smad3表达的影响,为宫腔粘连治疗效果提供理论依据。方法:将18只成年雌性新西兰大白兔随机分为正常组、模型组、SIS3干预组,每组6只。除正常组外,模型组和干预组采用刮宫法建立宫腔粘连模型。造模后干预组每天给予2.5μg/g SIS3注射处理,正常组(开腹未刮宫)和模型组每天给予等体积0.9%氯化钠溶液注射。注射持续14 d后取各组实验兔血清。采用ELISA酶联免疫法检测各组实验兔血清中TGF-β1、Smad3的蛋白表达量。采用实时荧光定量(RT-qPCR)法检测各组实验兔血清中TGF-β1、Smad3的mRNA表达量。结果:与正常组相比,模型组实验兔血清中TGF-β1和Smad3的蛋白及mRNA表达均显著升高(P<0.05);与模型组相比,SIS3干预组实验兔血清中TGF-β1和Smad3的蛋白及mRNA表达显著降低(P<0.05)。此外,TGF-β1蛋白和Smad3蛋白在血清中的表达水平呈显著正相关(R2=0.52),TGF-β1 mRNA和Smad3 mRNA在血清中的表达水平亦呈显著正相关(R2=0.84)。结论:SIS3能抑制宫腔粘连模型兔血清中TGF-β1、Smad3的表达,具有潜在治疗宫腔粘连的作用。

术前雌激素、孕激素水平与稽留流产清宫术后宫腔粘连发生的关系及其预测价值

目的探讨雌激素、孕激素水平与稽留流产(MA)患者清宫术后发生宫腔粘连(IUA)的关系及其预测价值。方法选取2019年1月至2022年1月在该院妇科就诊行清宫术的128例MA患者作为研究对象,根据术后6个月内宫腔检查情况分为未发生IUA组(MA组,97例)和IUA组(31例),并根据严重程度将IUA组分为轻、中和重度IUA组。比较IUA组和MA组,以及不同严重程度IUA组术前雌二醇(E 2)和孕酮(P)水平,采用多因素Logistic回归分析发生IUA的独立影响因素;分析E 2、P与IUA病情的相关性,采用受试者工作特征(ROC)曲线分析E 2、P水平对发生IUA及其病情严重程度的预测价值。结果IUA组E 2、P水平均明显低于MA组,差异均有统计学意义(P<0.05);多因素Logistic回归分析结果显示,E 2为MA清宫术后发生IUA的独立影响因素(P<0.05);术前E 2和P水平预测MA清宫术后发生IUA的曲线下面积分别为0.714和0.702。重度IUA组E 2、P水平均明显低于轻、中度IUA组,差异均有统计学意义(P<0.05),且E 2、P水平与IUA严重程度均呈负相关(P<0.05);术前E 2、P水平预测IUA轻/中度和重度的曲线下面积分别为0.845和0.923。结论E 2、P水平与MA清宫术后IUA的发生及严重程度均相关,对临床预测MA清宫术后IUA的发生及病情进展具有一定的参考价值。

防粘汤对宫腔粘连模型大鼠的治疗作用研究

目的:观察防粘汤对宫腔粘连模型大鼠炎症因子、T细胞亚群及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路关键分子蛋白表达的影响,探讨防粘汤对宫腔粘连的治疗作用。方法:首先使用HPLC法分析防粘汤各药物主要有效成分,将76只SD大鼠随机分为正常组和造模组,采用机械刮宫及感染双重损伤建立宫腔粘连大鼠模型,造模成功后,将造模组动物随机分为模型组、雌激素组及防粘汤低、中、高剂量(4.14 g·kg^(-1)·d^(-1)、8.28 g·kg^(-1)·d^(-1)、16.56 g·kg^(-1)·d^(-1))组。每天1次,连续灌胃给药21 d后处死大鼠,收集其血清、脾脏、肝脏及双侧子宫组织,采用HE及Masson染色观察其组织病理学变化;HE染色观察肝脏组织病理变化;ELISA法检测血清中TNF-α、IL-6及TGF-β1的表达;Western Blot法检测子宫组织中PI3K、p-Akt及Akt蛋白的表达;流式细胞仪检测大鼠脾淋巴细胞CD4^(+)、CD8^(+)亚群的变化。结果:防粘汤中含有金丝桃苷、甘草苷、落新妇苷、阿魏酸、丹酚酸B及淫羊藿苷。与正常组相比,模型组大鼠子宫组织明显肿胀、短缩,质硬,无弹性,子宫内膜菲薄,结构被破坏,腺体数量少,有大量炎性细胞浸润,胶原纤维增生明显;血清TNF-α、IL-6及TGF-β1表达显著升高(P<0.05,P<0.01);子宫组织中PI3K、Akt、p-Akt蛋白表达明显增多(P<0.01);CD4^(+)细胞比例下降而CD8^(+)细胞比例上升,CD4^(+)/CD8^(+)比值降低(P<0.05,P<0.01)。与模型组相比,防粘汤中、高剂量组大鼠子宫形态改善明显,炎症渗出明显减少,子宫内膜腺体数量增多,纤维化面积减少;血清TNF-α、IL-6及TGF-β1水平明显降低(P<0.05,P<0.01);子宫组织中PI3K、Akt、p-Akt蛋白表达显著减少(P<0.05,P<0.01);CD4^(+)/CD8^(+)比值升高(P<0.01)。结论:防粘汤能促进宫腔粘连大鼠子宫内膜组织修复,减少炎性浸润,改善免疫调节,抑制PI3K/Akt信号通路中关键蛋白的表达,延缓子宫内膜纤维化。