Asherman's Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman's Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman's Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.© 2023. Springer Nature Limited.

        女性育龄期一般达35年（15~49岁），我国女性法定结婚年龄为20岁，如果1次妊娠加哺乳时间为2年，在女性20～44岁这段生育力旺盛期间可以生育12个孩子。我国1979—2013年实行 “一孩”为主的计划生育政策，2014—2015年放宽至“单独二孩”，2016年始实施“全面二孩”的计划生育政策。因此，在不考虑婚前性行为的情况下，中国妇女避孕时间长达20年或以上。浏览更多请关注本刊微信公众号及当期杂志。

Approximately 15-20% of all clinically confirmed pregnancies end in a miscarriage. Intrauterine adhesions (IUAs) are a possible complication after miscarriage, but their prevalence and the contribution of possible risk factors have not been elucidated yet. In addition, the long-term reproductive outcome in relation to IUAs has to be elucidated.We systematically searched the literature for studies that prospectively assessed the prevalence and extent of IUAs in women who suffered a miscarriage. To be included, women diagnosed with a current miscarriage had to be systematically evaluated within 12 months by hysteroscopy after either spontaneous expulsion or medical or surgical treatment. Studies that included women with a history of recurrent miscarriage only or that evaluated the IUAs after elective abortion or beyond 12 months after the last miscarriage were not included. Subsequently, long-term reproductive outcomes after expectant (conservative), medical or surgical management were assessed in women with and without post-miscarriage IUAs.We included 10 prospective studies reporting on 912 women with hysteroscopic evaluation within 12 months of miscarriage and 8 prospective studies, including 1770 women, reporting long-term reproductive outcome. IUAs were detected in 183 women, resulting in a pooled prevalence of 19.1% [95% confidence interval (CI): 12.8-27.5%]. The extent of IUAs was reported in 124 women (67.8%) and was mild, moderate and severe respectively in 58.1, 28.2 and 13.7% of cases. Relative to women with one miscarriage, women with two or three or more miscarriages showed an increased risk of IUAs by a pooled OR of 1.41 and 2.1, respectively. The number of dilatation and curettage (D&C) procedures seemed to be the main driver behind these associations. A total of 150 congenital and acquired intrauterine abnormalities were encountered in 675 women, resulting in a pooled prevalence of 22.4% (95% CI: 16.3-29.9%). Similar reproductive outcomes were reported subsequent to conservative, medical or surgical management for miscarriage, although the numbers of studies and of included women were limited. No studies reported long-term reproductive outcomes following post-miscarriage IUAs.IUAs are frequently encountered, in one in five women after miscarriage. In more than half of these, the severity and extent of the adhesions was mild, with unknown clinical relevance. Recurrent miscarriages and D&C procedures were identified as risk factors for adhesion formation. Congenital and acquired intrauterine abnormalities such as polyps or fibroids were frequently identified. There were no studies reporting on the link between IUAs and long-term reproductive outcome after miscarriage, while similar pregnancy outcomes were reported subsequent to conservative, medical or surgical management. Although this review does not allow strong clinical conclusions on treatment management, it signals an important clinical problem. Treatment strategies are proposed to minimize the number of D&C in an attempt to reduce IUAs.

Cesarean scar defects (CSD) are caused by cesarean sections and cause various symptoms. Although there has been no previous consensus on the name of this condition for a long time, it has been named cesarean scar disorder (CSDi).

Uterine perforation is a potential, not rare complication of all intrauterine procedures and may be associated with injury of surrounding organs and structures. The incidence, risk factors, possible prevention, dia-gnosis, management and impact on future reproduction is reviewed here.Systematic review of available sources on the topic was carried out using the PubMed database and textbooks of Czech authors.Some risk factors that make access to the uterine cavity difficult may be prevented, however, others remain unpreventable. For patients in whom the perforation occurred during sondage, dilatation or insertion of blunt and cold instrument, without significant bleeding and who are hemodynamically stable, observation is recommended rather than immediate abdominal exploration. The exception are young women planning pregnancy in whom endoscopic suture is indicated. Abdominal exploration is required in patients who have been injured by electrosurgical or sharp device, laser, vacuum curette, who are hemodynamically unstable or show signs of severe bleeding or visceral injury.

The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.

A Cesarean Scar Pregnancy (CSP) is a variant of uterine ectopic pregnancy defined by full or partial implantation of the gestational sac in the scar of a previous cesarean section. The continuous increase of Cesarean Deliveries is causing a parallel increase in CSP and its complications. Considering its high morbidity, the most usual recommendation has been termination of pregnancy in the first trimester; however, several cases progress to viable births. The aim of this systematic review is to evaluate the outcome of CSP managed expectantly and understand whether sonographic signs could correlate to the outcomes. An online-based search of PubMed and Cochrane Library Databases was used to gather studies including women diagnosed with a CSP who were managed expectantly. The description of all cases was analysed by the authors in order to obtain information for each outcome. 47 studies of different types were retrieved, and the gestational outcome was available in 194 patients. Out of these, 39 patients (20,1%) had a miscarriage and 16 (8,3%) suffered foetal death. 50 patients (25,8%) had a term delivery and 81 (41,8%) patients had a preterm birth, out of which 27 (13,9%) delivered before 34 weeks of gestation. In 102 (52,6%) patients, a hysterectomy was performed. Placenta Accreta Spectrum (PAS) was a common disorder among CSP and was linked to a higher rate of complications such as foetal death, preterm birth, hysterectomy, haemorrhagic morbidity and surgical complications. Some of the analysed articles showed that sonographic signs with specific characteristics, such as type II and III CSP classification, Crossover Sign - 1, "In the niche" implantation and lower myometrial thickness could be related to worse outcomes of CSP. This article provides a good understanding of CSP as an entity that, although rare, presents with a high rate of relevant morbidity. It is also understood that pregnancies with confirmed PAS had an even higher rate of morbidity. Some sonographic signs were shown to predict the prognosis of these pregnancies and further investigation is necessary to validate one or more signs so they can be used for a more reliable counselling of women with CSP.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

The purpose of this article is to elucidate the current role of saline infusion sonohysterosalpingography (SIS) in evaluation of various uterine pathologies. SIS improves visualization of the endometrium and pathologies related to endometrial cavity, as well as it can simultaneously assess tubal patency. SIS provides high-resolution images, and three-dimensional (3D) reformatted images provide excellent orientation for radiologists as well as the clinicians about the underlying pathologies. This article will discuss imaging technique, indications, pearls, and pitfalls in imaging, diverse disease pathologies, and ultimately compare performance of SIS among other different imaging modalities. SIS as an adjunct imaging modality results in a greater diagnostic yield for diverse uterine pathologies.© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

To develop a multimodal learning application system that integrates electronic medical records (EMR) and hysteroscopic images for reproductive outcome prediction and risk stratification of patients with intrauterine adhesions (IUAs) resulting from endometrial injuries.EMR and 5014 revisited hysteroscopic images of 753 post hysteroscopic adhesiolysis patients from the multicenter IUA database we established were randomly allocated to training, validation, and test datasets. The respective datasets were used for model development, tuning, and testing of the multimodal learning application. MobilenetV3 was employed for image feature extraction, and XGBoost for EMR and image feature ensemble learning. The performance of the application was compared against the single-modal approaches (EMR or hysteroscopic images), DeepSurv and ElasticNet models, along with the clinical scoring systems. The primary outcome was the 1-year conception prediction accuracy, and the secondary outcome was the assisted reproductive technology (ART) benefit ratio after risk stratification.The multimodal learning system exhibited superior performance in predicting conception within 1-year, achieving areas under the curves of 0.967 (95% CI: 0.950-0.985), 0.936 (95% CI: 0.883-0.989), and 0.965 (95% CI: 0.935-0.994) in the training, validation, and test datasets, respectively, surpassing single-modal approaches, other models and clinical scoring systems (all P<0.05). The application of the model operated seamlessly on the hysteroscopic platform, with an average analysis time of 3.7±0.8 s per patient. By employing the application's conception probability-based risk stratification, mid-high-risk patients demonstrated a significant ART benefit (odds ratio=6, 95% CI: 1.27-27.8, P=0.02), while low-risk patients exhibited good natural conception potential, with no significant increase in conception rates from ART treatment (P=1).The multimodal learning system using hysteroscopic images and EMR demonstrates promise in accurately predicting the natural conception of patients with IUAs and providing effective postoperative stratification, potentially contributing to ART triage after IUA procedures.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

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?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.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).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.Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Numerous treatment strategies have so far been proposed for treating refractory thin endometrium either without or with the Asherman syndrome. Inconsistency in the improvement of endometrial thickness is a common limitation of such therapies including tamoxifen citrate as an ovulation induction agent, acupuncture, long-term pentoxifylline and tocopherol or tocopherol only, low-dose human chorionic gonadotropin during endometrial preparation, aspirin, luteal gonadotropin-releasing hormone agonist supplementation, and extended estrogen therapy. Recently, cell therapy has been proposed as an ideal alternative for endometrium regeneration, including the employment of stem cells, platelet-rich plasma, and growth factors as therapeutic agents. The mechanisms of action of cell therapy include the cytokine induction, growth factor production, natural killer cell activity reduction, Th17 and Th1 decrease, and Treg cell and Th2 increase. Since cell therapy is personalized, dynamic, interactive, and specific and could be an effective strategy. Despite its promising nature, further research is required for improving the procedure and the safety of this strategy. These methods and their results are discussed in this article.© 2022. The Author(s).

Disruption of endometrial regeneration, fibrosis formation, and intrauterine adhesions underlie the development of “thin” endometrium and/or Asherman’s syndrome (AS) and are a common cause of infertility and a high risk for adverse obstetric outcomes. The methods used (surgical adhesiolysis, anti-adhesive agents, and hormonal therapy) do not allow restoration of the regenerative properties of the endometrium. The experience gained today with cell therapy using multipotent mesenchymal stromal cells (MMSCs) proves their high regenerative and proliferative properties in tissue damage. Their contribution to regenerative processes is still poorly understood. One of these mechanisms is based on the paracrine effects of MMSCs associated with the stimulation of cells of the microenvironment by secreting extracellular vesicles (EVs) into the extracellular space. EVs, whose source is MMSCs, are able to stimulate progenitor cells and stem cells in damaged tissues and exert cytoprotective, antiapoptotic, and angiogenic effects. This review described the regulatory mechanisms of endometrial regeneration, pathological conditions associated with a decrease in endometrial regeneration, and it presented the available data from studies on the effect of MMSCs and their EVs on endometrial repair processes, and the involvement of EVs in human reproductive processes at the level of implantation and embryogenesis.

What is the efficacy of platelet-rich plasma (PRP) in reducing adhesion reformation in women with moderate to severe intrauterine adhesions (IUA)?In this randomized controlled trial, women with moderate-to-severe IUA were recruited between November 2019 and June 2021 from a university hospital and randomized into the PRP or control group. The PRP group was treated using an intrauterine-suitable balloon combined with PRP infusion following hysteroscopic adhesiolysis, whereas the control group received only the former intervention. The reductions in adhesion scores from before to after surgery and the adhesion reformation rate were analysed.A total of 123 participants successfully completed the study (PRP group, 63; control group, 60). Age, pregnancy history, menstrual score and American Fertility Society score before surgery were not significantly different between the two groups. At the second-look hysteroscopy, the PRP group had a significantly greater reduction in adhesion score than the control group (7 versus 6, respectively; P = 0.027). The postoperative adhesion reformation rates in the PRP group and the control group were 20.6% and 30.0%, respectively (risk ratio 0.69, 95% confidence interval 0.27-1.38, P = 0.232; number needed to treat 10.6).Intrauterine PRP infusion seems to be beneficial in reducing postoperative adhesion reformation following hysteroscopic adhesiolysis.Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.