Proposed classification of adenomyosis in Infertile women to simplify management options undergoing ART.

OBJECTIVE: Adenomyosis associated with subfertility is a situation of a dilemma for the treating clinician as the treatment is highly controversial and there remains an overall lack of consensus regarding the value of conservative surgery with or without medical management to improve reproductive out-comes. Hence we proposed this classification based on mapping of the size of adenomyoma, its location, distance from the endometrial cavity, and any associated endometriosis by studying 100 women with adenomyosis undergoing IVF. METHODS: We did a prospective study over 2 years in 100 women with adenomyosis who underwent IVF. They were classified into 4 categories based on our management-based proposed classification and the pregnancy outcomes were studied in each group. RESULTS: According to our classification, 56% of women belonged to grade 1, 24% to grade 2, 8% to grade 3, and 12% to Grade 4 Adenomyosis. The Pregnancy rates were 71% in Grade 1, 66% with Medical management, and 33% with surgical management in Grade 2, Grade 3 were offered surrogacy, and 66% in Grade 4 Adenomyosis. CONCLUSIONS: Our classification is simple and allows cost-effective management based on the location and ex-tent of the disease with the help of ultrasonography.

Adenomyosis and infertility: the role of the junctional zone.

OBJECTIVE: Adenomyosis is a benign uterine disorder characterized by the invasion of the endometrium within the myometrium, starting from the junctional zone (JZ), the inner hormone dependent layer of the myometrium that plays an important role in sperm transport, implantation and placentation. The resulting histological abnormalities and functional defects may represent the pathogenic substrate for infertility and pregnancy complications. The objective of this paper is to review the literature to evaluate the correlation between inner myometrium alterations and infertility and to assess the role of JZ in the origin of adverse obstetric outcomes of both spontaneous and in vitro fertilization (IVF) pregnancies. METHODS: we searched Pubmed for all original and review articles in the English language from January1962 until December 2019, using the MeSH terms of 'adenomyosis', 'junctional zone', combined with 'infertility', 'obstetrical outcomes', 'spontaneous conception', 'in vitro fertilization' and 'classification'. The review was divided into three sections to assess this pathogenic correlation, evaluating also the importance of classification of the disease. RESULTS AND CONCLUSIONS: Absent or incomplete remodeling of the JZ can affect uterine peristalsis, alter vascular plasticity of the spiral arteries and activate inflammatory pathways, all related to adverse obstetric outcomes. Despite these observations, there is still limited evidence whether adenomyosis is a cause of infertility. However, it is reasonable to screen patients for adenomyosis, to consider pregnant women with diffuse adenomyosis at high risk of adverse obstetric outcomes, and to evaluate the importance of a noninvasive validated classification in the management of women with adenomyosis.

Transvaginal Sonographic Imaging and Associated Techniques for Diagnosis of Ovarian, Deep Endometriosis, and Adenomyosis: A Comprehensive Review.

Imaging of endometriosis and in particular deep endometriosis (DE) is crucial in the clinical management of women facing this debilitating condition. Transvaginal sonography (TVS) is the first-line imaging method and magnetic resonance imaging (MRI) may provide supplemental information. However, the delay in diagnosis of up to 10 years and more is of concern. This problem might be overcome by simple steps using imaging with emphasis on TVS and referral to tertiary care. Finally, TVS is crucial in mapping extent and location of disease in planning surgical therapy and counseling women regarding various therapeutic options. This review presents the available data on imaging of endometriosis with a focus on TVS and MRI for DE, adenomyosis, and ovarian endometriomas including endometriomas in pregnancy as well as the use of "soft markers." The review presents an approach that is in accordance with the International Deep Endometriosis Analysis (IDEA) group consensus statement.

Exploring the challenges for a new classification of adenomyosis.

The availability of non-invasive diagnostic tests is an important factor in the renewed interest in adenomyosis, as the disease can now be more accurately mapped in the uterus without a need for hysterectomy. An agreed system for classifying and reporting the condition will enhance our understanding of the disease and is envisaged to enable comparison of research studies and treatment outcomes. In this review, we assess previous and more recent attempts at producing a taxonomy, especially in view of the latest proposal for subdivision of adenomyosis into an internal and an external variant. In this context, we also explore the uncertainties linked to classifying involvement of the uterovesical pouch, the pouch of Douglas and lesions in the outer myometrium. Two opposing hypotheses are forwarded to explain the pathogenesis of these variants, namely that disease localized in these areas originates from an invasion by uterine adenomyosis of peritoneal organs; alternatively, that lesions present in the outer myometrium originate from peritoneal endometriosis. At the root of debates around these opposing theories of pathogenesis is fragmentary evidence. Because of the limitations of currently available evidence, and until this issue is resolved, broad agreement on a hypothesis to underpin any proposed classification is unlikely.

A Classification Proposal for Adenomyosis Based on Magnetic Resonance Imaging.

There is a lack of an international consensus on adenomyosis classification that is useful for clinical practice and research. This article reviews advancements in the classification of adenomyosis, and the existing limitations. We collected a literature search from PubMed and Embase database up to March 2019. The proposed adenomyosis classification is based on magnetic resonance imaging and clinically relevant parameters. Adenomyosis is not a disease of homogeneity but is composed of multiple heterogeneous subtypes. Adenomyosis represents a spectrum of lesions, ranging from increased thickness of the junctional zone to focal or diffuse lesions involving the entire uterine wall. Potentially important parameters to be included in the classification could be affected area (internal or external adenomyosis), pattern (focal or diffuse), size or volume (myometrial involvement <1/3, <2/3, or >2/3 of uterine wall), concomitant pathologies (none, peritoneal endometriosis, ovarian endometrioma, deep infiltrating endometriosis, uterine fibroids, or others) and localization (anterior, posterior, left lateral, right lateral, or fundal). We propose a simplified classification system to monitor symptom severity against morphological types or extent of adenomyosis using the combination of previously published classifications as a starting point. More studies are needed to investigate whether this classification represents a useful tool for disease assessment in clinical practice and research.

New Sonographic Classification of Adenomyosis: Do Type and Degree of Adenomyosis Correlate to Severity of Symptoms?

STUDY OBJECTIVE: To correlate the type and degree of adenomyosis, scored through a new system based on the features of transvaginal sonography, to patients' symptoms and fertility. DESIGN: This is a multicenter, observational, prospective study. SETTING: Two endometriosis tertiary referral centers (University of Rome "Tor Vergata" and University of Siena). PATIENTS: A total of 108 patients with ultrasonographic signs of adenomyosis. INTERVENTIONS: A new ultrasonographic scoring system designed to assess the severity and the extent of uterine adenomyosis was used to stage the disease in correlation with the clinical symptoms. Menstrual uterine bleeding was assessed by a pictorial blood loss analysis chart, painful symptoms were evaluated using a visual analog scale, and infertility factors were considered. MEASUREMENTS AND MAIN RESULTS: A total of 108 patients with ultrasonographic signs of adenomyosis (mean age ± standard deviation, 37.7 ± 7.7 years) were classified according to the proposed scoring system. Women with ultrasound diagnosis of diffuse adenomyosis were older (p = .04) and had heavier menstrual bleeding (p = .04) than women with focal disease; however, no statistically significant differences were found regarding the presence and severity of dyspareunia and dysmenorrhea. Higher values of menstrual bleeding were found for severe diffuse adenomyosis, with the highest values being found in those with adenomyomas. In patients trying to conceive, the presence of ultrasound findings of focal disease was associated with a higher percentage of infertility than in those with diffuse disease, and the focal involvement of the junctional zone showed a higher percentage of at least 1 miscarriage than in those with diffuse adenomyosis. CONCLUSION: The ultrasonographic evaluation of the type and extension of adenomyosis in the myometrium seems to be important in correlation to the severity of symptoms and infertility.

Classification and Reporting Systems for Adenomyosis.

OBJECTIVE: To conduct a review of the available histologic and image-based classification systems to determine which of these systems, if any, provide clinical utility for prognosis or the selection of appropriate therapeutic interventions. DATA SOURCES: PubMed in addition to the bibliographies of identified publications. METHODS OF STUDY SELECTION: One investigator searched PubMed using Medical Subject Headings terms that included "Adenomyosis," "Classification," "Ultrasound Classification," "MRI Classification," and "Diagnosis," TABULATION, INTEGRATION AND RESULTS: Search results were tabulated in a Microsoft Excel workbook that facilitated the identification of duplicate entries. Publications were allocated into separate categories that included histopathologic, ultrasound, and MRI classifications. Identified systems associated with clinical outcomes were separately tabulated. Abstracts of 1669 articles were reviewed and 278 were identified for review of full text. Twenty-five were considered potentially relevant from the PubMed review and an additional 17 were found in bibliographies. In the 42 full-text articles that were reviewed in detail, 9 histologic classifications were identified, 4 of which were accompanied by an attempt at clinical correlation, 1 of which described a correlation with the outcome of medical, procedural, or surgical intervention. There were 9 image-based reporting or classification systems, 2 using transvaginal ultrasound and 7 using MRI, 3 of which included correlations with intervention outcomes, although these were surrogate (imaging) and not clinical outcomes. CONCLUSION: There is inconsistency in histopathologic definitions, and there is no uniformly accepted or validated system of image-based reporting or classification that can inform clinical decision making. There exists a need for harmonized classification systems for both ultrasound and MRI that agree with the histopathologic features of the disorder.

Uterine adenomyosis: pathogenesis, diagnostics, symptomatology and treatment.

OBJECTIVE: To summarize the current knowledge about pathogenesis, diagnostics, symptomatology and the treatment of adenomysis. DESIGN: Review article. SETTING: The Centre of Assisted Reproduction, ISCARE I.V.F., Prague. METHODS: Analysis of literature and current studies. RESULTS: This article reviews etiology, diagnostics and classification of adenomyosis, medical and surgical management options and the fertility implication of adenomyosis. CONCLUSION: Uterine adenomyosis is characterized by the presence of endometrial glands in myometrium and usually manifests by pelvic pain, abnormal uterine bleeding or infertility. Although adenomyosis and endometriosis share a number of features, they are considered to be two different entities. Recent improvements of imaging techniques such as transvaginal ultrasound and magnetic resonance imaging have affected the detection of adenomyosis. Adenomyosis has a negative impact on IVF results.

A critical review of recent advances in the diagnosis, classification, and management of uterine adenomyosis.

PURPOSE OF REVIEW: The purpose of this review is to summarize and highlight recent critical advances in the diagnosis, classification, and management of adenomyosis. RECENT FINDINGS: Recent studies have clarified the specific mechanism through which adenomyotic lesions invade the underlying myometrium by epithelial-mesenchymal transition. Correlation studies using diagnostic MRI also strongly support the hypothesis of a different pathogenesis between the inner and outer myometrium forms of adenomyosis. Given advances in diagnostic imaging, several international organizations have also highlighted the importance of classification systems for adenomyosis. Finally, selective progesterone receptor modulators and gonadotropin-releasing hormone antagonists have demonstrated significant promise for treating pelvic pain and bleeding associated with adenomyosis, whereas novel fertility-preserving surgical techniques have been introduced to excise diffuse adenomyotic pathology while maintaining adequate uterine integrity. SUMMARY: Recent attempts at a uniform and reproducible classification system likely represent the first step for the development of a staging system for adenomyosis that can be correlated with the severity of clinical symptoms and promote an individualized therapeutic approach. Simultaneously, further insights into the etiology and pathogenesis as outlined in this review may also help in the development of targeted medical therapies.

A sonographic classification of adenomyosis: interobserver reproducibility in the evaluation of type and degree of the myometrial involvement.

OBJECTIVE: To study the interobserver reproducibility of our new ultrasonographic mapping system to define the type and extension of uterine adenomyosis. DESIGN: Interobserver study involving two observers with different medical backgrounds and gynecological ultrasound experience. SETTING: University hospital. PATIENTS: Seventy consecutive women who underwent transvaginal ultrasound for suspected endometriosis, pelvic pain, heavy menstrual bleeding, and infertility. INTERVENTION: Two operators (observers A and B), who were blinded, independently reviewed the ultrasound videos offline, assessing the type of adenomyosis and the severity of the disease. Diagnosis of adenomyosis was made when typical ultrasonographic features of the disease were observed at the examination. Adenomyosis was defined as diffuse, focal, and adenomyoma according to the ultrasonographic characteristics. The severity of adenomyosis was described using a new schematic scoring system that describes the extension of the disease considering all possible ultrasound adenomyosis features. MAIN OUTCOME MEASURES: Reproducibility of the new mapping system for adenomyosis and rate agreement between two operators. RESULTS: Multiple rate agreements to classify the different features and the score of adenomyosis (diffuse, focal adenomyoma, and focal or diffuse alteration of junctional zone) ranged from substantial to almost perfect (Cohen κ = 0.658 - 1) except for adenomyoma score 4 (one or more adenomyomas with the largest diameter >40 mm) in which interobserver agreement was moderate (κ = 0.479). CONCLUSION: Our new scoring system for uterine adenomyosis is reproducible and could be useful in clinical practice. The standardization of the transvaginal approach and of the sonographer training represent a crucial point for a correct diagnosis of myometrial disease.

Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis.

Where histology used the presence of glands and/or stroma in the myometrium as pathognomonic for adenomyosis, imaging uses the appearance of the myometrium, the presence of striations, related to the presence of endometrial tissue within the myometrium, the presence of intramyometrial cystic structures and the size and asymmetry of the uterus to identify adenomyosis. Preliminary reports show a good correlation between the features detected by imaging and the histological findings. Symptoms associated with adenomyosis are abnormal uterine bleeding, pelvic pain (dysmenorrhea, chronic pelvic pain, dyspareunia), and impaired reproduction. However a high incidence of existing comorbidity like fibroids and endometriosis makes it difficult to attribute a specific pathognomonic symptom to adenomyosis. Heterogeneity in the reported pregnancy rates after assisted reproduction is due to the use of different ovarian stimulation protocols and absence of a correct description of the adenomyotic pathology. Current efforts to classify the disease contributed a lot in elucidated the potential characteristics that a classification system should be relied on. The need for a comprehensive, user friendly, and clear categorization of adenomyosis including the pattern, location, histological variants, and the myometrial zone seems to be an urgent need. With the uterus as a possible unifying link between adenomyosis and endometriosis, exploration of the uterus should not only be restricted to the hysteroscopic exploration of the uterine cavity but in a fusion with ultrasound.

Uterine Cystic Adenomyosis: A Disease of Younger Women.

PURPOSE OF REVIEW: We adopted a life-cycle approach to further our understanding of the natural history of the cystic forms of uterine adenomyosis first described by Cullen in 1908. SEARCH STRATEGY: Scopus and PubMed were searched for all terms referring to cystic variant of adenomyosis or adenomyoma. References found in major publications were also included in the review. MAIN FINDINGS: With the introduction of non-invasive imaging techniques, a number of cases of cystic variants of adenomyosis have been reported. Progressive, severe, medication-resistant dysmenorrhea is the main clinical feature but delay in diagnosis remains problematic. The life-cycle approach demonstrates that cystic adenomyosis is more relevant to adolescent and young adulthood. Congenital müllerian and wolffian cysts and the uterus-like masses are more frequent in women >30 years of age. The latter is frequently located outside the uterus and may represent a form of endometriosis rather than adenomyosis. Differential diagnosis includes ovarian cysts and congenital uterine anomalies. Menstruation suppression with continuous oral contraceptive pill with ultrasonographic monitoring of cyst regression may prove successful in the young woman, but surgical excision using minimally invasive endoscopy is highly effective. The various terms used in literature to describe these lesions cause considerable confusion. Here we propose a classification into 3 subtypes and standardized reporting criteria to enable comparison. CONCLUSIONS: Endometrial lined myometrial cysts are almost specific to adolescent and young women. We propose a new classification system.

Intravascular adenomyomatosis: expanding the morphologic spectrum of intravascular leiomyomatosis.

Intravascular leiomyomatosis (IVL) is characterized by the presence of smooth muscle in venous and lymphatic spaces within the myometrium. Although the intravascular component usually consists solely of typical smooth muscle or variants of smooth muscle differentiation, we report 5 cases in which the intravascular component also included endometrioid glandular and stromal elements. We propose the term "intravenous adenomyomatosis" to describe this unusual variant of IVL. The mean age of the patients in this series was 50.2 years, slightly older than that of patients with conventional IVL. In addition to intravenous adenomyomatosis, both adenomyosis and leiomyomas were identified in all of our cases, supporting the hypothesis that the intravascular smooth muscle component in IVL is derived from associated myometrial pathology rather than from vessel walls. In our series, intravenous adenomyomatosis had a similar benign clinical behavior to most cases of IVL with no metastatic or recurrent disease identified at follow-up in 4 cases for which follow-up information was available. The main differential diagnoses are adenomyosis with vascular involvement, low-grade endometrial stromal sarcoma (ESS), including ESS with smooth muscle and glandular differentiation, and adenosarcoma with lymphovascular invasion. The possibility of intravenous adenomyomatosis should be borne in mind when considering these diagnoses, particularly ESS and adenosarcoma, which have different implications for patient management and prognosis.