A cost-effectiveness analysis of intrauterine spacers used to prevent the formation of intrauterine adhesions following endometrial cavity surgery.

AIM: To assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery. MATERIALS AND METHODS: A decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results. RESULTS: In this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan. LIMITATIONS: There are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided. CONCLUSION: This analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

Every year, women in the United States (US) undergo surgery to treat intrauterine abnormalities to maintain or improve the uterus' ability to support fetal development and result in a term delivery. Despite the benefits of these procedures, damage caused to the endometrium (uterine lining) is associated with a risk of adherence of the endometrial cavity surfaces with scar tissue known as intrauterine adhesions (IUAs).Damage to the endometrium and the resulting IUAs may be associated with infertility, light or absent menstruation, pregnancy loss, and other pregnancy-related complications. Treating these conditions within the US healthcare system consumes resources and adds costs for healthcare payers (public and private insurance providers).To facilitate endometrial repair and to reduce or prevent IUAs, researchers have developed materials to place within the endometrial cavity following surgery to separate the endometrial surfaces during the early healing period. These intrauterine "spacers" are intended to improve patients' subsequent clinical outcomes and save money for healthcare payers. It is unknown whether these improved clinical outcomes offset the cost of the routine use of spacers following "at-risk" procedures that involve the endometrial cavity.We developed a model designed to determine the cost-effectiveness of an intrauterine spacer by quantifying improvements in clinical outcomes and the resultant cost savings for patients undergoing uterine surgeries with or without spacers. Our model predicted that routinely using such spacers following at-risk procedures would improve patient outcomes and reduce costs to US payers.

Hydrometrocolpos: a Contemporary Review of the Last 5 Years.

PURPOSE OF REVIEW: The goal of this review is to provide a comprehensive overview of hydrometrocolpos, covering disease etiology, pathophysiology, clinical presentation, and diagnostic and management techniques, and known outcomes. RECENT FINDINGS: This narrative review presents the literature on hydrometrocolpos in the pediatric population from the past 5 years. We highlight the 69 reported cases of hydrometrocolpos and classify them based on type of obstruction or associated anomaly, discuss new diagnostic algorithms based on imaging, and present novel and underutilized surgical techniques for definitive management. Hydrometrocolpos, a condition characterized by retained fluid causing a distended vagina and uterus in the setting of a distal vaginal outflow obstruction, has a wide range of presentation severity based on the type of obstruction. Whether hydrometrocolpos is due to an isolated condition like imperforate hymen, a complex abnormality like cloacal malformation, or a part of a large congenital syndrome, the mainstay of treatment is decompression of the dilated vagina and surgical correction of the outflow obstruction. Imaging-based diagnostic algorithms and new treatment techniques reported in the literature, as well as longitudinal and patient-reported outcome research, can improve the lives of children affected by this condition.

HPV infection and vaginal microecological disorders in women with intrauterine adhesion: cross-sectional study in a Chinese population.

BACKGROUND: The purpose of this study was to evaluate the vaginal microecology and the distribution of human papillomavirus (HPV) subtypes in patients with uterine adhesions and explore the correlation between HPV infection and vaginal microecology imbalance and the occurrence of intrauterine adhesion (IUA). METHODS: A total of 479 women were enrolled in the study, including 259 in the normal group and 220 in the IUA group. Vaginal microecological and HPV analyses were performed on all participants. Significant differences between the two groups were analyzed, and Spearman correlation analysis was performed. RESULTS: The incidence of IUA in patients between 31 and 40 years of age was high. The I-II degree of vaginal cleanliness in the IUA group was significantly lower than that in the normal group, and the number of III-IV degree was significantly higher than that in the normal group. Moreover, the incidences of VVC (vulvovaginal candidiasis) and vaginal disorders and infections with HPV 16 and HPV 52 subtypes were significantly higher in the IUA group than in the normal group. The incidence of high-risk HPV infection combined with vaginal disorders in the IUA group was higher than that in the normal group. Correlation analysis showed that the occurrence of IUAs was positively correlated with HPV infection and negatively correlated with PH and vaginal microecological imbalance. CONCLUSION: The HPV infection rate and vaginal microecology disorders affect the occurrence of IUAs. For patients with IUAs, control of the HPV infection rate and the prevention of vaginal microecological disorders should be improved.

Vesicouterine Fistula After Cesarean Delivery at Full Cervical Dilation.

IMPORTANCE: Vesicouterine fistula (VUF) is an iatrogenic consequence of cesarean section in the vast majority of cases. The worldwide increase of cesarean delivery rates is likely to be accompanied by a rise of this complication, and surgery is the mainstay treatment. OBJECTIVE: The aim of the study is to assess current evidence on VUF pathogenesis and management. STUDY DESIGN: The study is a case report and literature review on PubMed and Embase spanning over the past 2 decades. RESULTS: An early VUF developed after a cesarean section at full cervical dilation and concurrent incidental bladder injury. A transabdominal extravesical repair was performed 3 months after cesarean delivery. Both the cystotomy and hysterotomy were repaired in a double-layer fashion with no interposition flap. A contemporary literature review including 25 patients showed that VUF was repaired transabdominally in 21 patients (84%), and an open approach was adopted in 18 patients (85.7%). In most patients, the uterine side was closed with a single-layer suture and an interposition flap was used to reinforce the repair. Concomitant hysterectomy was performed in 6 patients (24%). Overall, successful term pregnancies were reported in 2 patients after VUF repair. CONCLUSIONS: Vesicouterine fistula is a rare event and is commonly associated with cesarean sections, especially those with a concurrent bladder injury. Careful and meticulous surgical technique may prevent the occurrence of this condition. Delayed repair and double-layer closure of both bladder and uterus, with or without an interposition flap, are recommended.

Reproductive outcomes and risk factors of women with septate uterus after hysteroscopic metroplasty.

Background: Hysteroscopic metroplasty of the uterine septum has been the standard treatment strategy to improve reproductive outcomes, but there are still controversies about the appropriateness of metroplasty. In addition, there have been few studies of the factors related to reproductive outcomes of women after surgery. The study aimed to evaluate the reproductive outcomes and the associated risk factors that influence reproductive outcomes after hysteroscopic metroplasty of women with septate uterus and the desire to conceive. Methods: This study was an observational study. Cases were screened by searching electronic patient files, and demographic factors were collected. We conducted telephone follow-ups to collect the postoperative reproductive outcomes. The primary outcome of this study was live birth, and secondary outcomes were ongoing pregnancy, clinical pregnancy, early miscarriage, and preterm birth. Demographic variables included patients' age, body mass index (BMI), the type of septum, infertility and miscarriage history, and complications including intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were collected to perform univariate and multivariate analyses to predict the risk factors of reproductive outcomes after surgery treatment. Results: In total, 348 women were evaluated and followed up. There were 95 cases (27.3%, 95/348) with combined infertility, 195 cases (56.0%, 195/348) with miscarriage history, and cases combined with intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were 107 (30.7%, 107/348), 53 (15.2%, 53/348), 28 (8.0%, 28/348), and 5 (1.4%), respectively. Following surgery, the live birth rate and clinical pregnancy rate were significantly higher than prior to surgery (84.6% vs 3.7%, p= 0.000; and 78.2% vs 69.5%, p= 0.01, respectively), early miscarriage rate and preterm delivery rate were significantly lower (8.8% vs 80.6%, p= 0.000; and 7.0% vs 66.7%, p=0.000, respectively). After adjusting for body mass index, miscarriage history, and complications, multivariable logistic regression analysis revealed age ≥ 35 years and primary infertility as independent factors that affected postoperative clinical pregnancy (OR 4.025, 95% CI 2.063-7.851, p= 0.000; and OR 3.603, 95% CI 1.903-6.820, p= 0.000; respectively) and ongoing pregnancy (OR 3.420, 95% CI 1.812-6.455, p= 0.000; and OR 2.586, 95% CI 1.419-4.712, p= 0.002; respectively). Conclusions: Hysteroscopic metroplasty could lead to improved reproductive outcomes of women with septate uterus. Both age and primary infertility were independent factors for postoperative reproductive outcomes. Trial registration: Chi ECRCT20210343.

An XGBoost predictive model of ongoing pregnancy in patients following hysteroscopic adhesiolysis.

RESEARCH QUESTION: What are the factors influencing the fertility of patients with intrauterine adhesions (IUA) after hysteroscopic adhesiolysis and which assessment system is more efficient in predicting post-operative ongoing pregnancy? DESIGN: The clinical information of 369 individuals diagnosed with and treated for IUA were obtained from the Multicentre Prospective Clinical Database for the Construction of Predictive Models on Risk of Intrauterine Adhesion (NCT05381376) and randomly divided into the training and validation cohorts. A univariate analysis was performed to identify relevant clinical indicators, followed by a least absolute shrinkage and selection operator (LASSO) regression for regularization and SHapley Additive exPlanation (SHAP) for extreme gradient boosting (XGBoost) predictive model visualization. Finally, receiver operating characteristic (ROC) curves were constructed to assess the model's efficiency. RESULTS: Univariate analysis and LASSO regression demonstrated that 12 clinical indicators were significantly associated with post-operative ongoing pregnancy in IUA patients. SHAP visualization indicated that post-operative Fallopian tube ostia, blood supply, uterine cavity shape and age had the highest significance. The area under the ROC curve (AUC) of the XGBoost model in the training and validation cohorts was 0.987 (95% CI 0.979-0.996) and 0.985 (95% CI 0.967-1), respectively. These values were significantly higher than those of the American Fertility Society (AFS) classification, the Chinese Society for Gynecological Endoscopy (CSGE) classification and endometrial thickness (all P < 0.001). CONCLUSIONS: The XGBoost model had higher accuracy in predicting post-operative reproductive outcomes in IUA patients. Clinically, the model may be useful for managing and categorizing IUA and determining optimal action to aid in pregnancy.

Chitosan combined with intrauterine device prevents intrauterine adhesions after hysteroscopic adhesiolysis: A target trial emulation study.

AIM: To compare the efficacy of chitosan and intrauterine device (IUD) combination with an IUD alone in patients with intrauterine adhesions (IUAs) who underwent hysteroscopic adhesiolysis. METHODS: This retrospective study assessed 303 patients with moderate-to-severe IUA (American Fertility Society [AFS] score ≥5) who underwent hysteroscopic adhesiolysis between January 2018 and December 2020. Using observational data under a cohort design, we emulated a target trial with two treatment arms: chitosan plus IUD and IUD alone groups. Second-look hysteroscopy was performed in all patients 3 months after the initial hysteroscopy. The primary outcome was improved adhesion assessed using the AFS scoring system. RESULTS: The baseline characteristics were balanced between the two groups. The second hysteroscopy revealed significantly better AFS scores in group A than in group B (values: 3 [1-4] vs. 4 [2-6], p < 0.001; change: 63% [50%-80%] vs. 44% [33%-67%], p < 0.001, respectively). Significantly better menstruation conditions (improved rate: 66% vs. 49%, p = 0.004) and endometrial thickness (mean: 7.0 mm vs. 6.0 mm, p < 0.001) were also observed in group A than in group B. Moreover, group A showed a significantly higher 1-year clinical pregnancy rate (40% vs. 28%, p = 0.037) and better quality of life (p < 0.001) than group B. CONCLUSIONS: Chitosan and IUD combination showed better efficacy in reducing adhesions and improving clinical outcomes in patients with moderate-to-severe IUA after hysteroscopic adhesiolysis.

Endometrial Stem Cells and Their Applications in Intrauterine Adhesion.

Intrauterine adhesion (IUA), resulting from pregnancy or nonpregnant uterine trauma, is one of the major causes of abnormal menstruation, infertility, or repeated pregnancy loss. Although a few methods, including hysteroscopy and hormone therapy, are routinely used for its diagnosis and treatment, they cannot restore tissue regeneration. Stem cells, which have self-renewal and tissue regeneration abilities, have been proposed as a promising therapy for patients with severe IUAs. In this review, we summarize the origin and features of endometrium-associated stem cells and their applications in the treatment of IUAs based on animal models and human clinical trials. We expect that this information will help to elucidate the underlying mechanism for tissue regeneration and to improve the design of stem cell-based therapies for IUAs.

Study on Risk Factors Related to Intrauterine Adhesion Based on Meta-Analysis.

Objective: Intrauterine adhesion (IUA) is a severe complication that occurs following abortion. To evaluate the related risk factors of uterine cavity adhesion by meta-analysis. Methods: The research literature on the influencing factors of patients with intrauterine adhesions published from January 2010 to December 2020 in PubMed, EMBASE, Cochrane Library, web of science, CNKI, Wanfang Data, VIP, and CBM were retrieved by computer. Two evaluators independently screened the literature, extracted the data, and evaluated the treatment according to the inclusion and exclusion criteria and then analyzed it with revman5.3 software. Results: Finally, 12 literatures were included, with a total sample size of 2341 cases. The results of meta-analysis showed that pelvic inflammation (p = 0.05), negative pressure during uterine suction (p < 0.0001), and uterine suction time (p < 0.00001) were the risk factors for uterine cavity adhesion. The combined or and 95% CI of each factor were 2.05 (1.24, 3.38), 125.61 (67.35, 183.87), and 4.52 (4.21, 4.84), respectively. However, the number of pregnancies, the number of curettages, the average number of births, abortion, myomectomy, menstrual abnormalities, and infertility have little impact on the occurrence of intrauterine adhesions (p > 0.05). Conclusion: Pelvic inflammatory disease, negative pressure during uterine suction and uterine suction time are the risk factors leading to uterine cavity adhesion.

Characteristics of fetal physiological and pathological uterine effusion observed on prenatal ultrasonography: a case report.

BACKGROUND: The prenatal detection rate of fetal uterine effusion is very low, and current case reports mainly focus on pathological hydrometrocolpos. We presented two cases of fetal physiological uterine effusion with different ultrasonic characteristics and compared them with one case of hydrometrocolpos with the hope of identifying strategies to reduce misdiagnosis of fetal uterine effusion. CASE PRESENTATION: This paper reports the cases of two female fetuses with abnormal pelvic echoes in the third trimester, referred to a tertiary center to be screened for suspected pelvic teratoma and cystic mass, respectively. Ultrasound consultation revealed fetal uterine effusion. The two fetuses were delivered at our hospital after a full term. Re-examining the uterus and adnexa of the neonates revealed that the uterine effusion had subsided naturally. Another female fetus had a large cystic mass in the pelvic cavity in the third trimester, and prenatal examination indicated fetal hydrometrocolpos. The fetus was delivered at our hospital after a full term. The hydrometrocolpos existed even after birth. After consultation with a neonatal surgeon and gynecologist, the newborn was diagnosed with congenital imperforate hymen with hydrometrocolpos. Hymen puncture and open drainage led to a good prognosis. CONCLUSIONS: Prenatal ultrasonography plays an important role in diagnosing and differentiating between physiological and pathological fetal uterine effusion. It can help reduce misdiagnoses that can lead to incorrect clinical decisions.

Postsurgical Intrauterine Adhesions after Hysteroscopic Myomectomy Using the Myoma Pseudocapsule Preservation Technique Evaluated bv Second-look Hysteroscopy: A Retrospective Comparative Study.

STUDY OBJECTIVE: To analyze the frequency and risk factors of postsurgical intrauterine adhesions (IUAs) using second-look hysteroscopy (SLH) in patients undergoing hysteroscopic myomectomy performed using the myoma pseudocapsule preservation technique for submucosal myoma. DESIGN: Retrospective cohort study. SETTING: University hospital from January 2017 to December 2019. PATIENTS: A total of 124 patients underwent hysteroscopic myomectomy and SLH. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surgical duration, intraoperative blood loss, number of enucleated myomas, volume of specimen, and postsurgical IUA evaluated by SLH. Postsurgical IUA were found in 5 of 124 cases (4.0%) at SLH. There were no cases of IUA formation in cases in which a single myomas was resected (0 of 83 cases, 0%); all cases were multiple myomas (5 of 41 cases, 12.2%), and IUA significantly occurred more frequently in cases of multiple myoma (p = .003). Univariate analyses showed that the IUA group contained a significantly larger number of enucleated uterine myoma (p <.001), required a longer operation (p = .003), and displayed an increased volume of intraoperative bleeding (p = .007), and the heavier the specimen, the greater the number of patients that had inserted an intrauterine device than the group that did not display postsurgical IUA. Multivariate logistic regression analysis of the risk factors of postsurgical IUA showed that the number of enucleated myomas was strongly associated with IUA (odds ratio, 1.45; 95% confidence interval, 1.06-1.97). CONCLUSION: The frequency of postsurgical IUA after hysteroscopic myomectomy was high in cases of multiple myoma and may be a risk factor. SLH should be actively pursued in cases where the patient desires to bear children, and an informed consent should be attained before performing surgery.

Short- and Long-term Outcomes of Postoperative Intrauterine Application of Hyaluronic Acid Gel: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically evaluate the role of hyaluronic acid (HA) gel and its derivatives in the postoperative prevention of intrauterine adhesions (IUA) and to assess whether HA gel could improve the pregnancy rate. DATA SOURCES: A structured search was performed in PubMed, Cochrane, Scopus, Web of Science, and Embase on February 2, 2022. METHODS OF STUDY SELECTION: We chose medical subject headings and relevant terms from other articles for the database search. The following intervention was selected: HA gel or related derivatives vs placebo in randomized controlled trials (RCTs). The following outcomes were selected: the rate and severity of IUA after intrauterine operations and pregnancy rate. After the full-text screening, 12 articles were included in the final analysis. The study quality and risk of bias were assessed with the Cochrane tool (www.training.cochrane.org/handbook). TABULATION, INTEGRATION, AND RESULTS: Data from 12 articles on 1579 patients were extracted and analyzed by 2 independent reviewers. According to the meta-analysis, HA gel could decrease the risk of IUA (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.37-0.67; p = .005; I2 = 59%) after intrauterine operations. Subgroup analysis revealed a significant positive impact of HA gel on both groups receiving dilatation and curettage (RR, 0.42; 95% CI, 0.30-0.59; p = .86; I2 = 0) or hysteroscopic surgery (RR, 0.55; 95% CI, 0.38-0.80; p = .007; I2 = 66%). The sensitivity analysis showed that heterogeneity could be improved significantly by removing one study. The severity of IUA (mean difference = -0.92; 95% CI, -1.49 to -0.34; p <.00; I2 = 89%) was lower in the intervention group. Subgroup and sensitivity analyses did not significantly improve the heterogeneity. When the studies are classified by the volume of HA gel, 10 mL (RR, 0.40; 95% CI, 0.27-0.60; p = .96; I2 = 0) and 5 mL (RR, 0.34; 95% CI, 0.14-0.82; p = .36; I2 = 0) were effective in treating IUA. In contrast, HA gel <5 mL was not sufficient to prevent IUA (RR, 0.66; 95% CI, 0.43-1.01; p = .02; I2 = 71%; p = .05). The pregnancy rate was also improved by the use of HA gel (RR, 1.39; 95% CI, 1.13-1.72; p = .37, I2 = 0). CONCLUSION: HA gel helps prevent IUA and decreases the severity of IUA after intrauterine surgery. A greater volume (≥5 mL) of HA gel is recommended to prevent IUA, according to this analysis. Moreover, HA gel can increase the pregnancy rate after intrauterine surgery. However, these conclusions should be interpreted with caution because of the inadequate quality of some RCTs with relatively small sample sizes and sample heterogeneity. Large RCTs are required to verify these conclusions in the future.

Observation of the Auxiliary Treatment Effect of Low-Frequency Nerve Therapy Instrument after Hysteroscopy for Moderate and Severe Intrauterine Adhesions Based on Intelligent Medical Treatment.

Uterine adhesions are mainly manifested as menstrual changes in women of childbearing age and affect fertility. Resection of uterine adhesions can well restore the shape of the patient's uterine cavity and improve the patient's menstruation. However, how to promote the growth of the endometrium and prevent the recurrence of adhesions after the operation is still a major problem. This article aims to study the use of traditional treatment methods as a control and use low-frequency nerve therapy device to assist in the treatment of posterior intrauterine adhesions recurrence rate, menstrual recovery effective rate, adverse reaction rate, liver function, etc. to study the low-frequency nerve therapy device auxiliary treatment method to prevent the postoperative effect of intrauterine adhesions. This article proposes an image processing algorithm based on intelligent medical related algorithms such as deep learning, Apriori algorithm, and an improved algorithm that introduces the degree of interest and details of 140 patients diagnosed with moderate to severe intrauterine adhesions who underwent hysteroscopic TCRA surgery in a certain affiliated hospital. The medical records were followed up by hysteroscopy and electric resection, and they were randomly divided into a control group and an observation group, with 70 cases in each group. Both groups of patients were closely monitored postoperatively, followed by postoperative review, and recorded menstrual recovery and pregnancy. At the same time, we performed hysteroscopy for recurrence of endometrial adhesions. The experimental results of this article show that the actual treatment rate of the control group is 65.7%, which is much lower than the 95.7% of the experimental group. The probability of returning to normal after 3 months of menstruation in the control group was 34.0%, much lower than the 69% in the experimental group. Three months after operation, the endometrial thickness of the experimental group was much higher than that of the control group, and the RI was lower than that of the control group. The difference was statistically significant (P < 0.05). The clinical treatment results are satisfactory and worthy of clinical screening.

Efficacy of hyaluronic acid on the prevention of intrauterine adhesion and the improvement of fertility: A meta-analysis of randomized trials.

BACKGROUND: and purpose:Intrauterine adhesion (IUA) and re-adhesion were common problems in women of childbearing age. The aim of our research was to evaluate the efficacy of hyaluronic acid gel on preventing IUA and improving the fertility. METHODS: A systematic search for randomized controlled trial (RCT) articles that tested the effectiveness of using hyaluronic acid gel during intrauterine surgery in prevention of IUA and improvement of fertility was performed in PubMed, Medline, Embase, the Cochrane Library and clinicaltrials.gov until December 2020. Data were extracted independently and analyzed using RevMan statistical software version 5.3. RESULTS: Twelve articles (11 studies) were deemed eligible for inclusion. There was a significantly reduced proportion of IUA after using hyaluronic acid gel during intrauterine operation (OR 0.39, 95% CI 0.29 to 0.52). It has significantly reduced the incidence of moderate-to-severe IUA after using hyaluronic acid gel, but no effect on the mild IUA. In addition, our analysis showed that the hyaluronic acid gel group was associated with a significant increased incidence of pregnancy (OR 1.64, 95% CI 1.08 to 2.50). CONCLUSION: Our analysis confirmed that using hyaluronic acid gel during intrauterine operation seemed to be more helpful for patients with high risk of IUA. However, larger and well-designed studies would be desired in the future to confirm its efficacy and safety in protecting fertility.

Local renin-angiotensin system molecular mechanisms in intrauterine adhesions formation following gynecological operations, new strategy for novel treatment.

It has recently been proposed that local tissue renin-angiotensin system activation has a role in post-surgical adhesion. Intrauterine adhesions are scar tissues that form in the endometrial cavity causing the walls of the uterine to adhere together. Women, undergoing major gynecological surgery, are exposed to a high risk of adhesion formation. Post-operative uterine adhesion is associated with chronic pain and infertility that are important problems following post-operation uterine adhesion. A local renin-angiotensin system has been found in the organs of the female reproductive system, for example in the endometrium. Data about the physiological roles of local RAS in the gynecological tract are largely unknown, but dysfunctional local RAS in the endometrium may contribute to this pathological condition. Local AngII/AT1R may be over-activated after surgical injury or hypoxia leading to an up-regulation of the molecular mechanisms that may lead to a chronic immune response, oxidative stress, and increase the expression of fibrotic molecules like TGF-ß to induce the risk of connective fibrotic tissues. Based on AngII/AT1R pathological potential to induce pelvic and uterine adhesions, using angiotensin receptor blockers could be a therapeutic strategy for the prevention and treatment of post-surgical adhesions.IMPACT STATEMENTWhat is already known on this subject? Intrauterine adhesions are described as fibrotic scar tissues following gynecological surgeries. It's reported that 55-100% of women are at risk of intrauterine adhesion after gynecological surgeries. Injury to tissues and hypoxia during the surgery, promote molecular mechanisms to contribute post-surgical adhesion. Recently evidence supports the existence of renin-angiotensin system components in the gynecological tract. Abnormal expression of local angiotensin II and AT1R in uterus tissue following gynecological surgeries up-regulate molecular mechanisms to induce post-operative adhesions.What do the results of this study add? Recently there has been an increased focus on the role of the local renin-angiotensin system in organ fibrosis. The results of this Mini-review article refer to the pathological roles of the local renin-angiotensin system in fibrotic bands formation after gynecological operations. Over-activation of local renin-angiotensin systems up-regulate molecular mechanisms such as inflammation and the TGF-ß1 signalling pathway. TGF-ß as a profibrotic molecule strongly induces the expression of some fibrotic molecules such as PAI and TIMP to increase the risk of intrauterine adhesions.What are the implications of these findings for clinical practice and/or further research? According to the biological roles of local renin-angiotensin system and AT1R following injuries to develop post-operative adhesion, the administration of ARBs may be considered as a new therapeutic strategy for the prevention of IUA.

Vesico-uterine Fistula Following C-section - A Case Report and Literature Review.

BACKGROUND/AIM: Vesico-uterine fistulas represent a rare type of genito-urinary fistulas; however, due to the increasing incidence of Caesarean section (C-section) in the last decade, this abnormal communication between the urinary and genital tracts has been reported more often after such surgical procedures. The aim of the current article was to report the case of a 28-year-old patient who was submitted to surgery for a vesico-uterine fistula seven years after a C-section. CASE REPORT: The 28-year-old patient with a previous history of four vaginal deliveries and one C-section was self-presented to the Gynecology Department for cyclic hematuria and diagnosed with a vesico-uterine fistula after injecting methylene blue in the uterine cavity during hysteroscopy. The patient was further submitted to surgery, and a parcelar myometrectomy en bloc with parcelar cystectomy, cystography, and prophylactic salpingectomy was performed. The postoperative outcome was uneventful. CONCLUSION: Although vesico-uterine fistulas represent rare events, they should be considered, especially in young patients with a previous history of C-section.

EndMT: New findings on the origin of myofibroblasts in endometrial fibrosis of intrauterine adhesions.

BACKGROUND: Intrauterine adhesion (IUA) is one of the leading causes of infertility and the main clinical challenge is the high recurrence rate. The key to solving this dilemma lies in elucidating the mechanisms of endometrial fibrosis. The aim of our team is to study the mechanism underlying intrauterine adhesion fibrosis and the origin of fibroblasts in the repair of endometrial fibrosis. METHODS: Our experimental study involving an animal model of intrauterine adhesion and detection of fibrosis-related molecules. The levels of molecular factors related to the endothelial-to-mesenchymal transition (EndMT) were examined in a rat model of intrauterine adhesion using immunofluorescence, immunohistochemistry, qPCR and Western blot analyses. Main outcome measures are levels of the endothelial marker CD31 and the mesenchymal markers alpha-smooth muscle actin (α-SMA) and vimentin. RESULTS: Immunofluorescence co-localization of CD31 and a-SMA showed that 14 days after moulding, double positive cells for CD31 and a-SMA could be clearly observed in the endometrium. Decreased CD31 levels and increased α-SMA and vimentin levels indicate that EndMT is involved in intrauterine adhesion fibrosis. CONCLUSIONS: Endothelial cells promote the emergence of fibroblasts via the EndMT during the endometrial fibrosis of intrauterine adhesions.

Transvaginal repair of vesicouterine fistulae: our experience of three cases.

INTRODUCTION AND HYPOTHESIS: Surgical repair of vesicouterine fistula (VUF) can be performed through transvaginal and transabdominal routes. Transvaginal repair of VUF has been rarely reported. This study is aimed at demonstrating the feasibility and experience of transvaginal repair of VUF, and presents a step-by-step concrete surgical technique. METHODS: We presented a video of a 36-year-old woman who developed VUF after a second cesarean section. The patient underwent a transvaginal surgical repair in the prone jackknife position. We also presented the clinical data of another two patients with VUF, and summarized the experience of all three patients in whom the same technique was performed. RESULTS: The operative times of the three patients were 120, 200, and 180 min respectively. No surgical complications were observed. After a follow-up of 2-3.5 years, none of the patients had vaginal leakage. CONCLUSION: Transvaginal repair of VUF in the prone jackknife position is a feasible and effective procedure for restoring the anatomy. However, there is still a need for well-designed studies with a large number of patients to identify the most promising approach.

Supplementation with Spirulina platensis Prevents Uterine Diseases Related to Muscle Reactivity and Oxidative Stress in Rats Undergoing Strength Training.

Strength training increases systemic oxygen consumption, causing the excessive generation of reactive oxygen species, which in turn, provokes oxidative stress reactions and cellular processes that induce uterine contraction. The aim of this study was to evaluate the possible protective effect of Spirulina platensis (SP), an antioxidant blue algae, on the contractile and relaxation reactivity of rat uterus and the balance of oxidative stress/antioxidant defenses. Female Wistar rats were divided into sedentary (CG), trained (TG), and T + supplemented (TG50, TG100) groups. Reactivity was analyzed by AQCAD, oxidative stress was evaluated by the malondialdehyde (MDA) formation, and the antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Strength training increased contractile reactivity and decreased the pharmaco-mechanical component of relaxing reactivity in rat uterus. In addition, training decreased oxidation inhibition in the plasma and exercise increased oxidative stress in the uterine tissue; however, supplementation with algae prevented this effect and potentiated the increase in antioxidant capacity. Therefore, this study demonstrated that food supplementation prevents changes in reactivity and oxidative stress induced by strength training in a rat uterus, showing for the first time, that the uterus is a target for this exercise modality and antioxidant supplementation with S. platensis is an alternative means of preventing uterine dysfunction.

Uterine niche after cesarean section: a review of diagnostic methods.

The consequence of each cesarean section is the uterine scar formation. In some patients, uterine scar after cesarean section heals incompletely and as a result, the uterine niche is formed. Most of the small niches are asymptomatic, but the large cesarean scar niches in nonpregnant women may cause a cesarean scar syndrome, which manifest itself as abnormal uterine bleeding, dysmenorrhea and secondary infertility. Among pregnant women, the presence of large niches may be associated with potentially life-threatening consequences, such as cesarean scar dehiscence and uterine rupture, placenta accreta spectrum disorders, placenta previa, cesarean scar pregnancy. Due to the possibility of dangerous consequences related to the occurrence of a uterine niche, in recent years many studies have focused on the term of cesarean scar niche, its risk factors, diagnostic methods and treatment options. Uterine niche can be examined using two- or three-dimensional transvaginal ultrasonography, as well as two- and three-dimensional sonohysterography, hysterosalpingography, hysteroscopy or magnetic resonance imaging. However, neither of the above diagnostic method is considered as the "gold standard". There are no unambiguous guidelines on some aspect concerning the diagnosis of cesarean scar niche. The aim of this study is to analyze and describe the diagnostic methods of cesarean section niche.