Intrauterine adhesion(IUA) is a common gynecological disease that is difficult to treat, and there is a lack of specific effective drugs and measures to prevent endometrial fibrosis. In this study, the mechanism of endometrial oxidative stress and fibrosis regulation was studied in an IUA rat model constructed by Bushen Huoxue Formula intervention of mechanical injury combined with infection. A total of 72 SPF SD female rats aged 8-10 weeks were randomly divided into blank control group, model control group, low-dose, medium-dose, and high-dose groups of Bushen Huoxue Formula, and estrogen groups. The rats in the estrous cycle of the model control group and the positive control group were simulated with surgical injury and infection, and the sham operation group was treated with on-off abdominal treatment. After successful modeling, the model control group was administered intragastrically with purified water of 15 μL·g~(-1) every day. The low-dose group was administered intragastrically with Bushen Huoxue Formula of 7.8 g·kg~(-1); the medium-dose group was administered intragastrically with Bushen Huoxue Formula of 15.6 g·kg~(-1), and the high-dose group was administered intragastrically with Bushen Huoxue Formula of 31.2 g·kg~(-1). The estrogen group was administered intragastrically with estradiol valerate of 4.2 mg·kg~(-1). After continuous intervention for 28 days, all rats were deprived of water and killed to collect blood and tissue. Hematoxylin-eosin(HE) staining calculated the number of uterine glands; Masson staining calculated the area of uterine collagen fibers. Combined with HE and Masson staining, semi-quantitative scores were performed on the degree of endometrial fibrosis. Immunohistochemistry was performed to detect the vascular endothelial growth factor(VEGF), stromal cell-derived factor-1(SDF-1), and transforming growth factor-β1(TGF-β1) expression in rats' uterine tissue. Enzyme-linked immunosorbent assay(ELISA) dected angiopoietin 1(IFN-γ), interleukin-1α(IL-1α), TGF-β1, tumor necrosis factor-α(TNF-α), collagen type Ⅳ(Ⅳ-Col), leukemia inhibitory factor(LIF), superoxide dismutase(SOD)、glutathione peroxidase(GSH-Px);The mRNA expressions of Smad2, Smad3, adisintegrin and metalloproteinase(ADAM17) and TGF-β1 were determined by qPCR. Notch and ADAM17 protein expression in rat uterus were determined by Western blot. The results showed that the area of uterine fibrosis was significantly reduced and the conditions of edema and adhesion were effectively alleviated after high-dose intervention of Bushen Huoxue Formula. The levels of inflammatory factors and Ⅳ-Col were significantly decreased, and the levels of LIF and antioxidant enzymes were significantly increased. The mRNA expressions of Smad2, Smad3, ADAM17 and TGF-β1 were significantly down-regulated. Immunohistochemical results showed that Bushen Huoxu Formula could effectively increase the positive expression of SDF-1 and reduce the positive expression of VEGF and TGF-β1. Western blot results showed that the protein expressions of Notch and ADAM17 in high-dose, medium-dose and low-dose of Bushen Huoxu Formula groups were significantly down-regulated in a dose-dependent manner. These results suggest that Bushen Huoxue Formula may inhibit fibrosis process through ADAM17/Notch signaling pathway, suggesting that Bushen Huoxuet Formula is one of the potential therapeutic methods for IUA.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Endometrium/pathology* ; Rats ; Fibrosis/metabolism* ; Oxidative Stress/drug effects* ; Humans ; Uterine Diseases/genetics* ; Vascular Endothelial Growth Factor A/genetics*

OBJECTIVES: Endometrial tuberculosis, which commonly affects women of reproductive age, is a significant cause of intrauterine adhesions (IUA), potentially leading to hypomenorrhea, amenorrhea, and infertility. Hysteroscopic adhesiolysis is the primary treatment for IUA; however, studies specifically addressing its efficacy in tuberculosis-induced IUA remain scarce. This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis. METHODS: This retrospective cohort study included patients diagnosed with tuberculosis-induced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022. Clinical data including age, medical history, adhesion severity, surgical treatment, and reproductive outcomes were analyzed. RESULTS: Among 39 patients identified, 2 were lost to follow-up. A total of 37 patients were included, with a follow-up duration ranging from 6 months to 9 years. Hypomenorrhea was reported in 24 (64.9%) patients, secondary amenorrhea in 10 (27.0%) patients, and normal menstruation in 3 (8.1%) patients. Most patients presented with primary infertility (59.5%), and only 2 (5.4%) had secondary infertility. The median American Fertility Society (AFS) score at initial assessment was 10 (range, 8-12); 8 (21.6%) patients had moderate IUA, and 29 (78.4%) had severe IUA. A total of 86 surgical procedures were performed across 37 patients, with 27 patients undergoing 2 or more surgeries. Postoperatively, 25 (67.6%) patients achieved normalization of the uterine cavity, while 12 (32.4%) still had a reduced cavity. Only 7 (18.9%) patients had a grossly normal endometrium at the final surgery, all of whom had moderate adhesions at the initial procedure. Menstrual flow returned to normal in 12 (32.4%) patients, while 25 (67.6%) continued to experience hypomenorrhea. Of 29 patients who attempted in vitro fertilization and embryo transfer (IVF-ET), only 6 (20.7%) conceived. Among these, 4 (13.8%) delivered at term via cesarean section; one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion. CONCLUSIONS Endometrial tuberculosis can lead to severe IUA. Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions, but the overall reproductive outcomes remain suboptimal.
Humans ; Female ; Hysteroscopy/methods* ; Tissue Adhesions/etiology* ; Retrospective Studies ; Adult ; Uterine Diseases/etiology* ; Infertility, Female/surgery* ; Treatment Outcome ; Tuberculosis, Female Genital/surgery* ; Fertility ; Pregnancy

OBJECTIVES: Transcervical resection of adhesions (TCRA) under hysteroscopy is the mainstay treatment for intrauterine adhesions (IUA), but its effectiveness varies depending on the surgical approach. This study aims to investigate the impact of different surgical techniques on endometrial repair and pregnancy outcomes in patients with secondary infertility and moderate-to-severe IUA. METHODS: A retrospective analysis was conducted on 225 patients who underwent TCRA followed by in vitro fertilization and embryo transfer between January 2021 and December 2022. Patients were grouped based on the surgical method: A cold knife group (n=127) and an electrosurgical group (n=98). Adhesions were separated using either cold knife or electrosurgical instruments. Postoperative visualization of uterine angle and tubal ostia, endometrial restoration, vascular endothelial growth factor (VEGF) expression in adhesion tissues, and clinical pregnancy outcomes were compared. Univariate and multivariate Logistic regression analyses were performed to identify factors influencing pregnancy outcomes. A LightGBM model was constructed to predict pregnancy outcomes. RESULTS: Compared with the electrosurgical group, patients in the cold knife group had significantly greater postoperative endometrial thickness [(8.86±0.53) mm vs (8.10±0.87) mm, P<0.05], higher live birth rates (64.57% vs 30.61%, P<0.05), and lower VEGF expression (1.31±0.09 vs 1.53±0.16, P<0.05). Logistic regression analyses identified age, number of visible tubal ostia postoperatively, and surgical method as significant factors affecting pregnancy outcomes (P<0.05). The LightGBM model based on surgical method had an area under the curve (AUC) of 0.882 (0.838-0.926), with internal validation AUC of 0.817 (0.790-0.840). CONCLUSIONS Cold knife surgery promotes faster recovery of the endometrial microenvironment and earlier improvement of fertility in patients with secondary infertility and IUA Surgical method is a key factor influencing pregnancy outcomes, and the LightGBM model based on surgical approach shows good predictive performance for pregnancy outcomes in patients with moderate-to-severe IUA.
Humans ; Female ; Pregnancy ; Tissue Adhesions/surgery* ; Retrospective Studies ; Adult ; Pregnancy Outcome ; Uterine Diseases/surgery* ; Hysteroscopy/methods* ; Infertility, Female/etiology* ; Electrosurgery/methods* ; Fertilization in Vitro ; Endometrium/surgery* ; Embryo Transfer ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVE: To evaluate the impact of endometrial polyps (EP) on postoperative pregnancy outcomes in infertile women with endometriosis (EMs). METHODS: PubMed, Embase, The Cochrane Library, CNKI, VIP, SinoMed, and WanFang Data databases were searched to include clinical studies on the effect of EP on pregnancy outcomes in patients with EMs, published before August 31, 2020. A meta-analysis was performed using Rev Man 5.3 software after two investigators independently screened the literature, extracted information, and evaluated the risk of bias of the included studies. RESULTS: The meta-analysis included ten studies (651 and 1,040 in the combined EP and uncomplicated EP groups, respectively). The spontaneous pregnancy rate, clinical pregnancy rate, and live birth rate were significantly lower in the group with combined EPs than in the group without combined EPs [Odd's ratio ( OR) = 0.63, 95% confidence interval ( CI): 0.50-0.80, P = 0.0001; OR = 0.63, 95% CI: 0.48-0.84, P = 0.001; OR = 0.63, 95% CI: 0.42-0.96, P = 0.03], and the rate of embryonic abortion was significantly higher than that in the uncomplicated EP group [ OR = 3.10, 95% CI: 1.52-6.32, P = 0.002]. CONCLUSION EP may adversely affect pregnancy outcomes in patients with infertility and EMs. Even after surgical treatment, EP can still reduce natural pregnancy, clinical pregnancy, and live birth rates in infertile women with EMs and increase the risk of embryo arrest in these women.
Humans ; Female ; Pregnancy ; Endometriosis/complications* ; Pregnancy Outcome/epidemiology* ; Polyps/complications* ; Infertility, Female/etiology* ; Pregnancy Rate ; Uterine Diseases/complications*

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O₂) or hypoxia condition (1%O₂). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×10⁶/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×10⁶/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD₃₁], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD₃₁ showed that, the expressions of VEGFA and CD₃₁ in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD₃₁ in BMSC-exo group and CD₃₁ in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD₃₁ in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.
Rats ; Female ; Humans ; Animals ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism* ; Vascular Endothelial Growth Factor A ; Exosomes/metabolism* ; Uterine Diseases/therapy* ; Collagen ; Hypoxia/therapy* ; Fibrosis ; Mesenchymal Stem Cells/metabolism* ; Oxygen

OBJECTIVE: To depict the cell landscape and molecular biological characteristics of human intrauterine adhesion (IUA) so as to better understand its immune microenvironment and provide new inspirations for clinical treatment. METHODS: Four patients with IUA who underwent hysteroscopic treatment at Dongguan Maternal and Child Health Care Hospital from February 2022 to April 2022 were selected as the study subjects. Hysteroscopy was used to collect the tissues of IUA, which were graded based on the patient's medical history, menstrual history and status of IUA. Library construction, sequencing, single cell data comparison and gene expression matrix construction were carried out in strict accordance with the single cell RNA sequencing process. Thereafter, the UMAP dimension reduction analysis of cell population and genetic analysis were carried out based on the cell types. RESULTS: A total of 27 511 cell transcripts were obtained from four moderately graded IUA tissue samples and assigned to six cell lineages including T cells, mononuclear phagocytes, epithelial cells, fibroblasts, endothelial cells and erythrocytes. Compared with normal uterine tissue cells, the four samples showed different cell distribution, and the proportions of mononuclear phagocytes and T cells in sample IUA0202204 were significantly increased, suggesting a strong cellular immune response. CONCLUSION The cell diversity and heterogeneity of moderate IUA tissues have been described. Each cell subgroup has unique molecular characteristics, which may provide new clues for further study of the pathogenesis of IUA and heterogeneity among the patients.
Pregnancy ; Female ; Child ; Humans ; Endothelial Cells ; Uterine Diseases/complications* ; Hysteroscopy/methods* ; Tissue Adhesions/etiology* ; Sequence Analysis, RNA

OBJECTIVES: Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare female genital tract malformation, and there are few large sample studies reported at home and abroad. The clinical manifestations of this syndrome are diverse, and insufficient understanding may delay the diagnosis and treatment of the patients. This study aims to analyze the clinical characteristics of different types of HWWS patients, and to improve the diagnosis and treatment of HWWS. METHODS: The clinical data of patients with HWWS who were hospitalized in the Department of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University from October 1, 2009 to April 5, 2022 were retrospectively analyzed. The age, medical history, physical examination, imaging examination and treatment of the patients were collected for statistical analysis. The patients were divided into an imperforate oblique vaginal septum type, a perforate oblique vaginal septum type, and an imperforate oblique vaginal septum and cervical fistula type. The clinical characteristics of different types of HWWS patients were compared. RESULTS: A total of 102 HWWS patients were enrolled, with age of 10-46 years old, including 37 (36.27%) patients with type I, 50 (49.02%) type II, and 15 (14.71%) type III. All patients were diagnosed after menarche, with an average age of (20.5±7.4) years. There were significant differences in the age of diagnosis and course of disease among the 3 types of HWWS patients (both P<0.05). Patients with type I had the youngest age of diagnosis [(18.0±6.0) years] and the shortest course of disease (median course of 6 months), while patients with type III had the oldest age of diagnosis [(22.9±9.8) years] and the longest course of disease (median course of 48 months). The main clinical manifestation of type I was dysmenorrhea, and the main clinical manifestation of type II and type III was abnormal vaginal bleeding. Of the 102 patients, 67 (65.69%) patients had double uterus, 33 (32.35%) had septate uterus, and 2 (1.96%) had bicornuate uterus. The vast majority of patients had renal agenesis on the oblique septum, and only 1 patient had renal dysplasia on the oblique septum. The oblique septum located on the left side in 45 (44.12%) patients and on the right side in 57 (55.88%) patients. There were no significant differences in uterine morphology, urinary system malformation, pelvic mass, and oblique septum among the 3 types of HWWS patients (all P>0.05). Six (5.88%) patients had ovarian chocolate cyst, 4 (3.92%) patients had pelvic abscess, and 5 (4.90%) patients had hydrosalpinx. All patients underwent vaginal oblique septum resection. Among them, 42 patients underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen because they had no sexual life history, and the remaining 60 patients underwent traditional oblique vaginal septum resection. Among the 102 patients, 89 patients were followed up for 1 month to 12 years. The symptoms of vaginal oblique septum in 89 patients such as dysmenorrhea, abnormal vaginal bleeding and vaginal discharge were improved after operation. Among the 42 patients who underwent hysteroscopic incision of the oblique vaginal septum without destroying the intact hymen, 25 patients underwent hysteroscopies again 3 months after operation, and there was no obvious scar formation at the oblique septum incision site. CONCLUSIONS Different types of HWWS have different clinical manifestations, but all can be manifested as dysmenorrhea. The patient's uterine morphology can be manifested as double uterus, septate uterus, or bicornuate uterus. The possibility of HWWS should be considered if uterine malformation is combined with renal agenesis. Vaginal oblique septum resection is an effective treatment.
Pregnancy ; Humans ; Female ; Adolescent ; Young Adult ; Adult ; Child ; Middle Aged ; Male ; Dysmenorrhea ; Retrospective Studies ; Kidney Diseases ; Bicornuate Uterus ; Uterine Duplication Anomalies ; Uterine Hemorrhage

Placenta accreta is one of the most feared complications among gravid women, as it is associated with massive and potentially life-threatening intrapartum and postpartum hemorrhage. Due to its natural history, placenta accreta is only naturally seen or expected as a cause of bleeding only among obstetric patients. This case report describes a rare manifestation of profuse abnormal uterine bleeding secondary to a placenta accreta in a non-gravid patient. The non-pregnant state was evidenced by the absence of history of amenorrhea and pregnancy signs and symptoms, a negative urine pregnancy test and normal serum bhcg results. A diagnosis of placenta accreta was mainly based on a post-hysterectomy histopathological examination. Theoretical explanations to explain this phenomenon is discussed in this case report.
Pregnancy ; Female ; Placenta Accreta ; Uterine Diseases ; Uterine Hemorrhage

Uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are very rare tumors that occur mainly in the uterine fundus of women in reproductive age. These tumors can be classified into group 1 and group 2 by histological results. In group 1, epithelial-like differentiation is partially observed in the tumors. In group 2, sex-cord elements are predominant in uterine mural mass. We experienced UTROSCT group 1 in a 29-year-old woman who complained of severe abdominal pain that started one week after delivery and UTROSCT group 2 case in a 49-year-old woman who complained of dysfunctional uterine bleeding. We report two different types of UTROSCT cases that we experienced.
Abdominal Pain ; Adult ; Female ; Humans ; Metrorrhagia ; Middle Aged ; Sex Cord-Gonadal Stromal Tumors ; Uterine Diseases ; Uterine Neoplasms

Arteriovenous malformations (AVM) are vascular disorders with a mixture of arterial, venous and small capillary-like channels with fistulous connections. Uterine arteriovenous malformations are rare cause of abnormal uterine bleeding with only a few reported cases. They may arise from pregnancy, miscarriage, previous cesarean section or other uterine surgery and gestational trophoblastic disease. Diagnosis can be made through angiography or doppler ultrasonography. Traditionally, uterine AVMs are treated with hysterectomy but with the advances in technology, minimally invasive conservative approaches such as radiologic arterial embolization or laparoscopic uterine artery ligation have become available. We present a case of a 29-year-old, G2P1 (1011) who had a three- month history of heavy, intermittent vaginal bleeding from uterine arteriovenous malformation after a miscarriage. Laparoscopic bilateral uterine artery occlusion, offered a minimally invasive treatment with high symptomatic effectiveness.
Uterine Artery ; Arteriovenous Malformations ; Uterine Diseases ; Ligation ; Uterine Hemorrhage