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Purpose To investigate and compare the clinical characteristics and risk factors between intrinsic and extrinsic adenomyosis (AM), as well as the differences in their perioperative management and findings in the two subtypes. Methods This observational study included women who were diagnosed with either intrinsic or extrinsic AM based on magnetic resonance imaging (MRI) and who underwent a hysterectomy with a subsequent pathological examination. Demographic characteristics, clinical features, treatment outcomes and associated factors were evaluated. Results 77 patients were classified in the intrinsic group and 54 in the extrinsic group. The results show that gravidity (P < 0.001), parity (P < 0.001), abortion (P < 0.001) and endometrial curettage (P = 0.017) were significantly higher in the intrinsic group, while the education level was lower in the intrinsic group (P = 0.012). Women in the extrinsic group had an earlier age of menarche (P = 0.026) and more commonly associated ovarian endometrioma (OMA) (P < 0.001) and deep infiltrating endometriosis (DIE) (P < 0.001). Dysmenorrhea was more severe in the extrinsic group (P = 0.009), whereas women in the intrinsic group had heavier menstrual blood loss (P < 0.001). Surgery time (P < 0.001), operative blood loss (P < 0.001), hospitalization cost (P < 0.001), and the intensity of postoperative medical treatment (P < 0.001) were significantly higher in the extrinsic group. Multivariate analysis showed that lower education level, higher gravidity and more endometrial curettage were significantly associated with intrinsic AM. OMA and DIE were more commonly associated to extrinsic AM. Conclusion These results suggest that intrinsic and extrinsic AM exhibit specific clinical profiles, perioperative characteristics and associated risk factors.

This study aimed to elucidate the role of microRNA-92a-3p (miR-92a-3p) in the pathogenesis of adenomyosis. We examined how miR-92a-3p, found in exosomes derived from ectopic lesions, influences the behaviour of endometrial cells, dorsal root ganglion (DRG), and human umbilical vein endothelial cells (HUVECs) and explored its potential as a non-invasive biomarker. Our findings revealed that miR-92a-3p was significantly upregulated in exosomes derived from ectopic adenomyotic lesions. This upregulation correlated with enhanced migration and invasion of eutopic endometrial cells, DRG, and HUVECs. Furthermore, this study demonstrated a significant correlation between miR-92a-3p levels in urinary exosomes and the clinical symptoms of adenomyosis, suggesting its potential as a non-invasive biomarker for the disease. This study elucidated an exosomal signalling process involving miR-92a-3p that drives pathological infiltration and angiogenesis to promote adenomyosis progression. Our findings highlight upregulated miR-92a-3p in biofluid exosomes as a promising non-invasive biomarker for diagnosing and monitoring adenomyosis and unveil novel targets and strategies for improved clinical management.

The current knowledge on adenomyosis as a risk factor for RPL is very scant. Overall 120 women were included in this retrospective observational study. They were divided in three groups each of which consisted of 40 subjects: Group 1: women with RPL who were diagnosed to have adenomyosis on transvaginal ultrasound (TVS); Group 2: patients with RPL without ultrasonographic findings of adenomyosis; Group 3: patients with ultrasound diagnosis of adenomyosis without RPL and at least one live birth pregnancy. The copresence of endometriosis was also investigated. Among women with RPL, patients with adenomyosis (Group 1) had higher number of pregnancy losses ( p = 0.03) and lower age at first pregnancy loss ( p = 0.03) than women without adenomyosis (Group 2). Moreover, they had more frequently primary RPL ( p = 0.008). Adenomyosis of the inner myometrium was found more frequently ( p = 0.04) in patients of Group 1 than in patients of Group 3 in which adenomyosis was mainly in the outer myometrium ( p = 0.02). No differences were found in the severity of adenomyosis between these two groups of women. TVS findings for endometriosis were observed more frequently in women with adenomyosis without RPL (Group 3) than in the other two groups of patients. Adenomyosis can be a factor involved in RPL. Differences in adenomyosis localization are associated with different risks for RPL. Patients with RPL should be investigated for the presence of adenomyosis and also for the type and localization of the disease in the different myometrial layers.

Purpose In a series of publications, we had developed the concept that uterine adenomyosis and pelvic endometriosis as well as endometriotic lesions at distant sites of the body share a common pathophysiology with endometriosis constituting a secondary phenomenon. Uterine auto-traumatization and the initiation of the mechanism of tissue injury and repair (TIAR) were considered the primary events in the disease process. The present MRI study was undertaken (1) to corroborate this concept by re-visiting, in view of discrepant results in the literature, the association of adenomyosis with endometriosis and (2) to extend our views concerning the mechanisms of uterine auto-traumatization. Patients and methods MRI was performed in 143 women attending our center, in whom, on the basis of transvaginal sonography (TVS) and historical data, such as documented endometriosis and dysmenorrhea of various degrees of severity, the presence of uterine adenomyosis was suspected. In addition to the measurement of the diameter of junctional zone (JZ) of the anterior and posterior walls in the mid-sagittal plane, the diagnosis of adenomyosis was based on visualization, in that all planes were analyzed with scrutiny. By this method of “visualization” all transient enlargement of the JZ, such as peristaltic waves of the archimyometrium and sporadic neometral contractions that might mimic adenomyotic lesions could be excluded. At the same time, this method allowed to lower the limit of detection in terms of thickness of the JZ for assured diagnosis of adenomyosis. Furthermore, the localizations of the individual lesions, their shapes and patterns were described. Results With the method of ‘visualization’, the diagnosis of uterine adenomyosis could be verified in 127 of the 143 patients studied. The prevalence of endometriosis in adenomyosis was 80.6 % and the prevalence of adenomyosis in endometriosis was 91.1 %. As concluded from their localization within the uterine wall, the adenomyotic lesions predominantly developed in the median region of the upper two-thirds of the uterine wall. Cystic cornual angle adenomyosis was a distinct phenomenon that was only observed in patients suffering from extreme primary dysmenorrhea. Aside from this, the majority of the patients complained of primary dysmenorrhea (80 %). On the basis of these findings and the fact that particularly extreme primary dysmenorrhea is associated with high intrauterine pressure, menstrual ‘archimetral compression by neometral contraction’ has to be considered as an important cause of uterine auto-traumatization in addition to uterine peristalsis and hyperperistalsis. Both mechanical functions of the non-pregnant uterus exert their strongest power in the upper region of the uterus, which is compatible with the predominant localization of the adenomyotic lesions. Conclusions The data confirm our previous results of a high association of adenomyosis with endometriosis and vice versa. Our view of the mechanism of uterine auto-traumatization by mechanical functions of the non-pregnant uterus has to be extended, in that ‘archimetral compression by neometral contractions’ could be realized as the predominant cause of mechanical strain to the non-pregnant uterus. The data of this study confirm our concept of the etiology and pathophysiology of adenomyosis and endometriosis in that the process of chronic proliferation and inflammation is induced at the level of the archimetra by chronic uterine auto-traumatization. Furthermore, with respect to the diagnosis of uterine adenomyosis (and consequently endometriosis) this study shows a high degree of accordance between the findings in real-time TVS and MRI.

Background Despite proposed mechanisms hypotheses, the etiology of adenomyosis remains unclear. The limited efficacy of current therapeutic approaches may stem from insufficient understanding of its pathobiological underpinnings and the pronounced heterogeneity in clinical presentation and treatment responsiveness among subtypes. This study seeks to compare clinical and sonographic profiles of adenomyosis subtypes to elucidate distinct disease mechanisms and inform subtype-specific management strategies. Methods In this retrospective cohort of 1,350 surgically treated and pathologically confirmed adenomyosis cases (2017–2022), patients were categorized into diffuse versus focal and anterior versus posterior lesion groups according to sonographic features. Comparative analyses of demographics, symptomatology, concurrent gynecological conditions, and laboratory profiles were conducted to delineate subtype-specific patterns. Results 1074 (79.56%) had a definitive adenomyotic sonographic signs, with 329 (30.63%) focal adenomyosis and 745 (69.37%) diffuse adenomyosis. Multivariate logistic regression analysis revealed that, compared with focal adenomyosis, diffuse adenomyosis were older (OR, 1.09; 95%CI: 1.06–1.12), had more pregnancies (OR, 1.22; 95%CI: 1.11–1.33), higher BMI (OR, 1.05; 95%CI: 1.00-1.09), long course of disease (OR, 1.06; 95%CI: 1.02–1.11) and higher risk of moderate to severe dysmenorrhea (OR, 1.88; 95%CI: 1.36–2.60). Divided to the location of adenomyosis lesion indicated by sonographic, patients in the posterior wall group ( n  = 418) have higher risk of moderate to severe dysmenorrhea (OR, 1.88; 95% CI: 1.36–2.60), more endometriosis combination (OR, 3.24; 95%CI: 1.85–5.68) and intraoperative blood loss (OR, 1.001; 95%CI: 1.001–1.003). Conclusion By stratifying adenomyosis into diffuse/focal and anterior/posterior subtypes, we identified distinct clinical-pathological profiles: (1) Diffuse adenomyosis was independently associated with older age, higher gravidity, and severe dysmenorrhea, suggesting a progressive phenotype driven by tissue injury mechanisms; (2) Posterior lesions exhibited a 3.24-fold risk of concurrent endometriosis and increased surgical complexity, implicating shared pathways with deep infiltrating endometriosis. These findings redefine adenomyosis as a heterogeneous disorder with subtype-specific pathophysiology, advocating for tailored therapeutic strategies.

Cellular senescence is known to be involved in tissue repair, but its role in adenomyosis remains unclear. This study was tasked to evaluate the expression of Klotho, a well-known aging-suppressing protein, as well as PPARγ and DNMT1 in adenomyotic lesions (AD) in comparison with that of control endometrium (CT). We performed immunohistochemistry analysis of markers of cellular senescence p16 and p21, along with Klotho, PPARγ and DNMT1 in CT and AD samples, followed by the quantification of gene expression of Klotho, PPARγ and DNMT1 in epithelial organoids derived from AD and CT samples and methylation-specific PCR to evaluate promoter methylation status. The effect of forced expression and knockdown of DNMT1 on Klotho and PPARγ expression in ectopic endometrial epithelial cells was evaluated. We found that both p16 and p21 immunoreactivity in AD was significantly higher while that of Klotho and PPARγ was significantly lower than CT samples, which was concomitant with elevated immunoexpression of DNMT1. The results were confirmed by transcriptional analysis using epithelial organoids derived from AD and CT samples. In addition, the promoter regions of both Klotho and PPARγ genes were hypermethylated in AD as compared with CT, and treatment with HDAC and DNMT inhibitors reactivated the expression of both Klotho and PPARγ. Forced expression of DNMT1 resulted in downregulation of both Klotho and PPARγ but its knockdown increased their expression. Thus, overexpression of DNMT1 seems to facilitate the promoter hypermethylation of both Klotho and PPARγ in AD, resulting in their reduced expression that is suggestive of the role of senescence in adenomyosis.

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers’ presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.

Aim To investigate the clinical characteristics, diagnosis, and clinical treatment of submucosal cystic adenomyosis. Methods The clinical data of five cases of patients with submucosal cystic adenomyosis in our hospital from January 2020 to June 2023 were retrospectively analyzed. Results The average age of the patients was 37.8 ± 4.5 years old, three of them experienced prolonged menstruation and heavy menstrual bleeding. All patients had a history of abnormal uterine bleeding and mild to moderate dysmenorrhea, with a VAS score of 2.8 ± 1.6. The average Carbohydrate antigen 125 (CA125) value was 29.9 ± 23.6U/ml. Two out of the five patients (40%) had CA125 values above the upper limit of normal. The nodules had a diameter of 3.2 ± 1.3 cm and a cavity size of 1.3 ± 0.7 cm. Color ultrasound revealed hypo or iso or anechoic echoic cysts, and blood flow signals were detected. The magnetic resonance imaging (MRI) findings varied among each patient. All the patients underwent hysteroscopy and resection of uterine cavity-occupying lesions, and no recurrence was observed. Conclusions The clinical features of submucosal cystic adenomyosis include abnormal uterine bleeding and menstrual changes, and the degree of dysmenorrhea is generally not severe. The diagnostic utility of CA125 in submucosal cystic adenomyosis may be limited. The three-dimensional ultrasound and MRI are valuable preoperative examination methods currently. Hysteroscopy can not only diagnose submucosal cystic adenomyosis, but also treat it, and preserve the fertility function of the patient.

Spontaneous uterine rupture outside of pregnancy is exceptionally rare, with adenomyosis potentially acting as a structurally weakening substrate. Most reports involve gravid patients, underscoring the unusual nature of nongravid presentations. We report the case of a 26-year-old nongravid, nulliparous woman who presented with sudden, diffuse abdominal pain and hemorrhagic shock. Imaging revealed a markedly enlarged, heterogeneous uterus with hemoperitoneum. Emergency laparotomy evacuated approximately 3000 mL of blood. Multiple transmural ruptures precluded repair, necessitating total hysterectomy with adnexal preservation. Histopathology confirmed diffuse adenomyosis with extensive hemorrhagic necrosis. This case highlights that in reproductive-age women presenting with an acute abdomen, a negative pregnancy test, and an enlarged heterogeneous uterus, spontaneous rupture secondary to adenomyosis should be considered. Early resuscitation and definitive surgical management are critical, and proactive counseling is recommended for patients with severe adenomyosis who may be at risk for catastrophic decompensation.

Alterations in the microbiome composition have been identified in common gynecologic pathologies such as endometriosis carving a new frontier in diagnosis and treatment. We aimed to examine the existing literature on perturbations in the reproductive tract microbiome of individuals with adenomyosis informing future therapeutic targets. To examine the association between the reproductive tract microbiome composition among individuals with adenomyosis when compared to controls that can lead to new research evaluating novel mechanisms of action and treatment modalities. A systematic literature search identified studies that compared differences in microbiome composition using culture-independent microbiome analysis between individuals with adenomyosis when compared to controls. Five observational cross-sectional studies characterizing the lower and upper reproductive tract in humans were included. The diagnostic criteria of adenomyosis included surgical and imaging-based criteria. All studies used a 16S rRNA sequencing method. All individuals were recruited from either China or Thailand. An association between adenomyosis and alterations in the microbiome composition included relative deficiencies in Lactobacillus and relative enrichment of anaerobic and gram-negative bacteria when compared to control participants. Comparative studies suggest that there are significant perturbations in the microbiota composition of individuals with adenomyosis when compared with controls. Limiting conclusions include relative small sample sizes, a homogeneous population, and scant clinical phenotypic data. This systematic review identified significant alterations in the bacterial composition of adenomyosis cases that can be leveraged to design mechanistic studies and future innovative approaches to diagnose and manage this pathology. Trial registration: PROSPERO (CRD42023494563). Registered December 28, 2023.