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.

Deep Learning-Based Three-dimensional Transvaginal Ultrasound in Diagnosis of Intrauterine Adhesion

This study was aimed to enhance and detect the characteristics of three-dimensional transvaginal ultrasound images based on the partial differential algorithm and HSegNet algorithm under deep learning. Thereby, the effect of quantitative parameter values of optimized three-dimensional ultrasound image was analyzed on the diagnosis and evaluation of intrauterine adhesions. Specifically, 75 patients with suspected intrauterine adhesion in hospital who underwent the hysteroscopic diagnosis were selected as the research subjects. The three-dimensional transvaginal ultrasound image was enhanced and optimized by the partial differential equation algorithm and processed by the deep learning algorithm. Subsequently, three-dimensional transvaginal ultrasound examinations were performed on the study subjects that met the standards. The March classification method was used to classify the patients with intrauterine adhesion. Finally, the results by the three-dimensional transvaginal ultrasound were compared with the diagnosis results in hysteroscope surgery. The results showed that the HSegNet algorithm model realized the automatic labeling of intrauterine adhesion in the transvaginal ultrasound image and the final accuracy coefficient was 97.3%. It suggested that the three-dimensional transvaginal ultrasound diagnosis based on deep learning was efficient and accurate. The accuracy of the three-dimensional transvaginal ultrasound was 97.14%, the sensitivity was 96.6%, and the specificity was 72%. In conclusion, the three-dimensional transvaginal examination can effectively improve the diagnostic efficiency of intrauterine adhesion, providing theoretical support for the subsequent diagnosis and grading of intrauterine adhesion.

Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion

Intrauterine adhesion (IUA) is a common gynaecological disease that develops from infection or trauma. IUA disease may seriously affect the physical and mental health of women of childbearing age, which may lead to symptoms such as hypomenorrhea or infertility. Presently, hysteroscopic transcervical resection of adhesion (TCRA) is the principal therapy for IUAs, although its function in preventing the recurrence of adhesion and preserving fertility is limited. Pharmaceuticals such as hormones and vasoactive agents and the placement of nondegradable stents are the most common postoperative adjuvant therapy methods. However, the repair of injured endometrium is relatively restricted due to the different anatomical structures of the endometrium. Recently, the treatment outcome of IUAs has improved with the advancement of hysteroscopic techniques. In particular, the application of bioactive scaffolds combined with tissue engineering technology has proven to have high therapeutic potential or endometrial repair in IUA treatment. Herein, this review has summarized past therapeutic strategies, including postoperative adjuvant therapy, cell or therapeutic molecular delivery therapy methods and bioactive scaffold-based tissue engineering methods. Therefore, this review presented the recent therapeutic strategies for repairing endometrium treatment and pointed out the issues of clinical concern to provide alternative methods for the management of IUAs.

The Latest Developments in Immunomodulation of Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions, Both Allogeneic and Autologous

Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.

The Top 100 Most Cited Articles on Intrauterine Adhesion: a Bibliometric Analysis

Bibliometric analysis is a statistical method that attempts to assess articles by their citations, analyzing their frequency and citation pattern, which subsequently gleans direction and guidance for future research. Over the past few years, articles focused on intrauterine adhesions have been published with increasing frequency. Nevertheless, little is known about the properties and qualities of this research, and no current analysis exists that has examined the progress in intrauterine adhesion research. Web of Science Core Collection, BIOSIS Citation Index, and MEDLINE database were searched to identify articles on intrauterine adhesion published from 1950 to October 2020. The 100 most cited articles were chosen to analyze citation count, citation density, authorship, theme, geographic distribution, time-related flux, level of evidence, and network analysis. An overwhelming majority of these 100 articles were published in the 2010s (35%). Citations per article ranged from 30 to 253. Chinese authors published the most papers in the top 100, followed by the USA, France, Israel, and Italy. The most salient study themes included operative hysteroscopy and adjunctive treatments for improving reproductive outcomes. The most common level of evidence was level II, and there was no statistical difference in the number of citations between the levels. The network analysis indicated that hysteroscopy, hysteroscopic adhesiolysis, infertility, and the reproductive outcome had a great degree of centrality in the 2000s and 2010s. In comparison, placental implantation had a great degree of centrality in the 2000s, and stem cell and fibrosis had a great degree of centrality in the 2010s. The value of IUA investigation has been gradually appreciated recently. Hysteroscopic adhesiolysis was continuously explored to achieve better reproductive outcome. Over time, the main focus of research has gradually shifted from complications to postoperative adjuvant treatment. Moreover, breakthrough progress is needed in underlying mechanism and early prevention of IUA.

Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury

Intrauterine adhesion refers to endometrial repair disorders which are usually caused by uterine injury and may lead to a series of complications such as abnormal menstrual bleeding, recurrent abortion and secondary infertility. At present, therapeutic approaches to intrauterine adhesion are limited due to the lack of effective methods to promote regeneration following severe endometrial injury. Therefore, to develop new methods to prevent endometrial injury and intrauterine adhesion has become an urgent need. For severely damaged endometrium, the loss of stem cells in the endometrium may affect its regeneration. This article aimed to discuss the characteristics of various stem cells and their applications for uterine tissue regeneration.

Application of Bioactive Hydrogels for Functional Treatment of Intrauterine Adhesion

Intrauterine adhesion (IUA) is a common endometrial disease and one of the main causes of infertility in women of childbearing age. Current treatment strategies, such as hysteroscopic adhesion resection, hysteroscopic transcervical resection of adhesion (TCRA), the use of local hormone drugs, and anti-adhesion scaffold implantation, do not provide a satisfactory pregnancy outcome for moderate-severe IUA, which presents a great challenge in reproductive medicine. With the development of material engineering, various bioactive and functional hydrogels have been developed using natural and synthetic biomaterials. These hydrogels are not only used as barely physical barriers but are also designed as vectors of hormone drugs, growth factors, and stem cells. These characteristics give bioactive hydrogels potentially important roles in the prevention and treatment of IUA. However, there is still no systematic review or consensus on the current advances and future research direction in this field. Herein, we review recent advances in bioactive hydrogels as physical anti-adhesion barriers, in situ drug delivery systems, and 3D cell delivery and culture systems for seeded cells in IUA treatment. In addition, current limitations and future perspectives are presented for further research guidance, which may provide a comprehensive understanding of the application of bioactive hydrogels in intrauterine adhesion treatment.