Association of Uterine Tissue Innervation and Peripheral Nerve Density with Adenomyosis Related Pain. A Systematic Review.

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.

Abnormal uterine bleeding: The well-known and the hidden face.

Abnormal uterine bleeding (AUB) is a bleeding from the uterine corpus that is abnormal in regularity, volume, frequency or duration. It encompasses heavy menstrual bleeding, irregular menstrual bleeding and intermenstrual bleeding, which are common symptoms among women of reproductive age, impacting their overall well-being. Menstruation involves interactions between endometrial epithelial and stromal cells, immune cell influx, and changes in endometrial vasculature. These events resemble an inflammatory response with increased vessel permeability, tissue breakdown, and the arrival of innate immune cells. However, the mechanisms of menstrual cessation are poorly understood. AUB can be related to structural causes (polyp, adenomyosis, leiomyoma, malignancy/hyperplasia) and nonstructural conditions (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic). While transvaginal ultrasound is the primary method for the screening of intracavitary lesions, saline infusion sonohysterography is more accurate to detect endometrial polyps and submucous leiomyomas, while hysteroscopy with biopsy remains the reference method for a definitive diagnosis. The main goals in managing AUB are addressing and correcting the underlying primary cause, if possible, and establishing a regular bleeding pattern or amenorrhea, which can be done with antifibrinolytic agents, progestins, gonadotropin-releasing hormone agonists and antagonists, or surgical interventions, each one with specific indications and limitations. Further research is necessary to assess the effectiveness and the long-term effects of various medical and surgical treatments. Meanwhile, the availability of diagnostic methods such as transvaginal ultrasound and hysteroscopy and the universal distribution of medical treatments for AUB should be prioritized by policymakers to minimize the diagnostic and treatment delay and thus reduce the risk of AUB-related anemia and the need of hysterectomy.

Transforming growth factor beta-1 (TGF-ß1) expression in patients with adenomyosis.

Objective: To compare Transforming growth factor beta-1 (TGF-ß1) expression in patients with and without adenomyosis. Methods: A prospective design was performed including 49 patients submitted to hysterectomy. Immunohistochemistry was performed on anatomopathological samples staged in paraffin blocks from patients with and without adenomyosis. The sample contained 28 adenomyosis cases and 21 controls. Student's t-test and multivariate logistic regression tests were used for statistical analysis. Associations were considered significant at p < 0.05. Results: We found no significant association between adenomyosis and: smoking (p = 0.75), miscarriage (p = 0.29), number of previous pregnancies (p = 0.85), curettage (p = 0.81), pelvic pain (p = 0.72) and myoma (p = 0.15). However, we did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (p = 0.02) and previous cesarean section (p = 0.02). The mean TGF-ß1 intensity (mean ± SD) in the ectopic endometrium of women with adenomyosis showed no significant association (184.17 ± 9.4 vs.184.66 ± 16.08, p = 0.86) from the topic endometrium of women without adenomyosis. Conclusion: TGF-ß1 expression was not increased in the ectopic endometrium of women with adenomyosis.

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.

Transforming growth factor beta -1 (TGF-β 1) expression in patients with adenomyosis

Abstract Objective: To compare Transforming growth factor beta-1 (TGF-β1) expression in patients with and without adenomyosis. Methods: A prospective design was performed including 49 patients submitted to hysterectomy. Immunohistochemistry was performed on anatomopathological samples staged in paraffin blocks from patients with and without adenomyosis. The sample contained 28 adenomyosis cases and 21 controls. Student's t-test and multivariate logistic regression tests were used for statistical analysis. Associations were considered significant at p < 0.05. Results: We found no significant association between adenomyosis and: smoking (p = 0.75), miscarriage (p = 0.29), number of previous pregnancies (p = 0.85), curettage (p = 0.81), pelvic pain (p = 0.72) and myoma (p = 0.15). However, we did find a relationship between adenomyosis and abnormal uterine bleeding (AUB) (p = 0.02) and previous cesarean section (p = 0.02). The mean TGF-β1 intensity (mean ± SD) in the ectopic endometrium of women with adenomyosis showed no significant association (184.17 ± 9.4 vs.184.66 ± 16.08, p = 0.86) from the topic endometrium of women without adenomyosis. Conclusion: TGF-β1 expression was not increased in the ectopic endometrium of women with adenomyosis.

Deep infiltrating endometriosis: cine magnetic resonance imaging in the evaluation of uterine contractility.

Objective: To evaluate uterine function by using cine magnetic resonance imaging to visualize the contractile movements of the uterus in patients with and without deep infiltrating endometriosis (with or without associated adenomyosis). Materials and Methods: This was a prospective case-control study. The study sample comprised 43 women: 18 in the case group and 25 in the control group. We performed cine magnetic resonance imaging in a 3.0 T scanner, focusing on the presence, direction, and frequency of uterine peristalsis. Results: The frequency of uterine peristalsis was higher in the case group than in the control group, in the periovulatory phase (3.83 vs. 2.44 peristaltic waves in two minutes) and luteal phase (1.20 vs. 0.91 peristaltic waves in two minutes). However, those differences were not statistically significant. There was a significant difference between the patients with adenomyosis and those without in terms of the frequency of peristalsis during the late follicular/periovulatory phase (0.8 vs. 3.18 peristaltic waves in two minutes; p < 0.05). Conclusion: The frequency of uterine peristalsis appears to be higher during the periovulatory and luteal phases in patients with deep infiltrating endometriosis, whereas it appears to be significantly lower during the late follicular/periovulatory phase in patients with adenomyosis. Both of those effects could have a negative impact on sperm transport and on the early stages of fertilization.

Objetivo: Avaliar a função uterina mediante visualização dos movimentos contráteis do útero por meio de cine-ressonância magnética em pacientes com e sem endometriose infiltrativa profunda (com ou sem adenomiose associada). Materiais e Métodos: Estudo caso-controle prospectivo. A amostra foi composta por 43 mulheres, sendo 18 mulheres no grupo caso e 25 mulheres no grupo controle. A cine-ressonância magnética foi realizada com magneto 3.0 T, com foco na presença, direção e frequência do peristaltismo uterino. Resultados: O peristaltismo uterino foi mais frequente nas pacientes do grupo endometriose do que no grupo controle na fase periovulatória (3,83 × 2,44 peristalses em dois minutos) e lútea (1,20 × 0,91 peristalse em dois minutos). No entanto, esses resultados não foram estatisticamente significantes. Nas pacientes com adenomiose, observou-se redução significativa na frequência de peristaltismo durante a primeira fase do ciclo menstrual (3,18 × 0,8 peristalses; p < 0,05). Conclusão: A frequência de peristaltismo uterino parece estar aumentada durante a fase periovulatória e lútea em pacientes com endometriose infiltrativa profunda e significativamente reduzida em pacientes com adenomiose durante a primeira fase do ciclo menstrual. Ambos os efeitos têm potencial de interferir negativamente no transporte de espermatozoides e nos primeiros estágios de fecundação.

Importância do diagnóstico por imagem em pacientes com sangramento uterino anormal / Importance of diagnostic imaging in patients with abnormal uterine bleeding

O sangramento uterino anormal é diagnóstico sindrômico comum no consultório do ginecologista e pode comprometer substancialmente a qualidade de vida. O objetivo no diagnóstico de sangramento uterino anormal é distinguir pacientes com causas estruturais (anatômicas), como pólipo, adenomiose, leiomioma, malignidade e hiperplasia, de pacientes que apresentam anatomia normal, nas quais o sangramento pode ser devido a alteração dos mecanismos de coagulação, distúrbios ovulatórios, distúrbios primários do endométrio, iatrogenia, ou ter outra causa não classificada. O diagnóstico se inicia a partir de anamnese detalhada e exame físico geral e ginecológico completos, seguidos da solicitação de exames complementares (laboratoriais e de imagem), conforme indicado. O exame de imagem de primeira linha para identificação das causas estruturais inclui a ultrassonografia pélvica. Histerossonografia, histeroscopia, ressonância magnética e amostragem endometrial para exame de anatomia patológica são opções que podem ser incluídas no diagnóstico a depender da necessidade. O objetivo deste artigo é apresentar a relevância dos exames de imagem na investigação das causas de sangramento uterino anormal.

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office and may substantially affect quality of life. The aim in the diagnosis of abnormal uterine bleeding is to distinguish women with anatomic causes such as polyp, adenomyosis, leiomyoma, malignancy and hyperplasia from women with normal anatomy where the cause may be coagulopathy, ovulatory disorders, endometrial, iatrogenic and not otherwise classified. Diagnosis begins with a thorough history and physical examination followed by appropriate laboratory and imaging tests as indicated. The primary imaging test for the identification of anatomic causes include ultrasonography. Saline infusion sonohysterography, magnetic resonance, hysteroscopy, endometrial sampling are options that can be included in the diagnosis depending on the need. The aim of this article is to present the relevance of imaging exams in the investigation of the causes of abnormal uterine bleeding.

Deep infiltrating endometriosis: cine magnetic resonance imaging in the evaluation of uterine contractility / Endometriose infiltrativa profunda: cine ressonância magnética na avaliação da contratilidade uterina

Abstract Objective: To evaluate uterine function by using cine magnetic resonance imaging to visualize the contractile movements of the uterus in patients with and without deep infiltrating endometriosis (with or without associated adenomyosis). Materials and Methods: This was a prospective case-control study. The study sample comprised 43 women: 18 in the case group and 25 in the control group. We performed cine magnetic resonance imaging in a 3.0 T scanner, focusing on the presence, direction, and frequency of uterine peristalsis. Results: The frequency of uterine peristalsis was higher in the case group than in the control group, in the periovulatory phase (3.83 vs. 2.44 peristaltic waves in two minutes) and luteal phase (1.20 vs. 0.91 peristaltic waves in two minutes). However, those differences were not statistically significant. There was a significant difference between the patients with adenomyosis and those without in terms of the frequency of peristalsis during the late follicular/periovulatory phase (0.8 vs. 3.18 peristaltic waves in two minutes; p < 0.05). Conclusion: The frequency of uterine peristalsis appears to be higher during the periovulatory and luteal phases in patients with deep infiltrating endometriosis, whereas it appears to be significantly lower during the late follicular/periovulatory phase in patients with adenomyosis. Both of those effects could have a negative impact on sperm transport and on the early stages of fertilization.

Resumo Objetivo: Avaliar a função uterina mediante visualização dos movimentos contráteis do útero por meio de cine-ressonância magnética em pacientes com e sem endometriose infiltrativa profunda (com ou sem adenomiose associada). Materiais e Métodos: Estudo caso-controle prospectivo. A amostra foi composta por 43 mulheres, sendo 18 mulheres no grupo caso e 25 mulheres no grupo controle. A cine-ressonância magnética foi realizada com magneto 3.0 T, com foco na presença, direção e frequência do peristaltismo uterino. Resultados: O peristaltismo uterino foi mais frequente nas pacientes do grupo endometriose do que no grupo controle na fase periovulatória (3,83 × 2,44 peristalses em dois minutos) e lútea (1,20 × 0,91 peristalse em dois minutos). No entanto, esses resultados não foram estatisticamente significantes. Nas pacientes com adenomiose, observou-se redução significativa na frequência de peristaltismo durante a primeira fase do ciclo menstrual (3,18 × 0,8 peristalses; p < 0,05). Conclusão: A frequência de peristaltismo uterino parece estar aumentada durante a fase periovulatória e lútea em pacientes com endometriose infiltrativa profunda e significativamente reduzida em pacientes com adenomiose durante a primeira fase do ciclo menstrual. Ambos os efeitos têm potencial de interferir negativamente no transporte de espermatozoides e nos primeiros estágios de fecundação.

Ultrasound Elastography for the Diagnosis of Endometriosis and Adenomyosis: A Systematic Review with Meta-analysis.

Elastography is capable of measuring tissue mechanical properties and elasticity. It is used to help diagnose various diseases, although its use in pelvic endometriosis remains to be established. A systematic review and meta-analysis were conducted to assess transvaginal ultrasound elastography for the diagnosis of different manifestations of endometriosis and adenomyosis. PRISMA guidelines were used for a Medline, PubMed, Embase, BVS/Bireme, Scopus, Cochrane Library and Escudos database search. Studies indexed until March 2021 that evaluated elastography compared with histopathological results (gold standard), ultrasound or magnetic resonance imaging for diagnosis of pelvic endometriosis and adenomyosis were eligible. The Rayyan platform was used to select studies. Sensitivity (S), specificity (Ps), positive and negative predictive values and receiver operating characteristic curves were calculated for elastographic diagnosis of endometriosis. A meta-analysis using Review Manager 5 and Open Meta Analyst was performed. Bias risk in the studies was analyzed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. This systematic review was prospectively registered in the PROSPERO database: CRD42021244555. Among the 163 identified citations, 10 studies were eligible for review (5 for diagnosis of adenomyosis, 2 for endometrioma, 3 for deep intestinal endometriosis and rectovaginal septum [deep pelvic endometriosis], N = 744 women). In deep pelvic endometriosis, lesions diagnosed by elastography were found to correlate with histopathology results. Increased "stiffness" (elastography) was associated with a higher fibrotic component, with S = 78%-100% and Ps = 100%, according to the authors. On elastography, endometriomas were stiffer than hemorrhagic cysts (S = 82%, Ps = 79%) and malignant tumors (S = 86%, Ps = 100%). For these lesions, a meta-analysis could not be performed because the small number of studies and insufficient data. In adenomyosis, meta-analysis and receiver operating characteristic curve analysis revealed that elastography had good sensitivity and specificity. Studies indicated a low bias risk by QUADAS-2. Elastography had high sensitivity and specificity for deep pelvic endometriosis diagnosis, and its findings correlated with histopathology results. For adenomyosis, the meta-analysis confirmed the sensitivity and specificity results of the studies. Given these results, elastography may be a promising imaging test, contributing to non-invasive diagnosis of endometriosis and adenomyosis.

Effect of adenomyosis on prognosis of patients with endometrial cancer

SUMMARY OBJECTIVE: Our goal was to contrast the prognoses of patients with endometrial cancer who had adenomyosis against those that did not. METHODS: All patients who had received surgical staging for hysterectomy-based endometrial cancer had their medical data retrospectively examined. The analysis covered 397 patients, who were split into two groups depending on the presence of adenomyosis. Comparisons were made between patients covering type of surgery, histopathology, endometrial cancer stage, lymphovascular space invasion, presence of biochemical or histochemical markers, adjuvant therapy, presence of adenomyosis in the myometrial wall, and outcomes in terms of overall survival and disease-free survival. RESULTS: There is no statistically significant difference in the 5-year disease-free survival or overall survival rates between endometrial cancer patients with and without adenomyosis. This is based on comparisons of tumor stage, tumor diameter, histological type and grade of tumor, myometrial invasion, lymphovascular space invasion, and biochemical markers that affect the course of the disease. The median follow-up times were 61 months for the adenomyosis-positive group and 56 months for the group without adenomyosis. CONCLUSION: Coexisting adenomyosis in endometrial cancer has no bearing on survival rates and is not a prognostic factor.

Uterine volume, menstrual patterns, and contraceptive outcomes in users of the levonorgestrel-releasing intrauterine system: A cohort study with a five-year follow-up.

OBJECTIVE: The aim of our study was to evaluate the effects of the LNG-IUS on uterine volume, bleeding patterns, and LNG-IUS-related outcomes among women using the device to treat abnormal uterine bleeding caused by fibroids, adenomyosis, HMB (without structural cause), or contraception. STUDY DESIGN: This was a 5-year cohort study with LNG-IUS users. We selected 147 women, who were allocated to four groups: a) control (contraception indication); b) fibroids; c) adenomyosis; d) HMB. The visits for clinical and ultrasound evaluations were made at baseline and at 3, 6, 12, 24, 36, 48, and 60 months postinsertion. All data are expressed as mean and standard deviation (SD) or absolute and relative (%) frequency. Differences among groups were established by using the χ2 (chi-square) test and Fisher's exact tests for categorical outcomes, as well as the Mann-Whitney and the Kruskal-Wallis tests and Friedman's ANOVA for continuous variables. We used the 5% significance level as an indication of statistical significance. Logistic regression analyses were performed to study the association between predictors and outcomes. Results are expressed as odds ratios (ORs) with a 95% confidence interval (CI 95%). RESULTS: Although all groups had real rates of bleeding patterns, troublesome bleeding appeared to be more frequent in the fibroid group (∼15%). Also, along the 60 months of follow-up, uterine volume slightly decreased in the groups of HMB, adenomyosis, and fibroids, but not in the contraception group. However, the isolated volume of fibroids remained unchanged. In this cohort, we observed high continuation rates among LNG-IUS users. The uterine volume ≥200 cm3 was the main predictor of hysterectomy or IUS expulsion in the adenomyosis and fibroid groups. CONCLUSION: The LNG-IUS may control uterine menstrual bleeding as well as uterine volume in adenomyosis, fibroids, and HMB. An initial uterine volume smaller than 200 cm3 is an important predictor of adherence to treatment and better outcomes.

Laparoscopic Fluorescence Guided Detection of Uterine Niche-The Next Step in Surgical Diagnosis and Treatment.

(1) Background: Uterine niche is a frequent condition in patients with a history of cesarean section. Although the relation to uterotomy seems to be clear, the exact pathogenesis is not fully understood. Uterine niche can easily be diagnosed by transvaginal ultrasound. It can be related to symptoms like dysmenorrhea, bleeding disorders, dysuria and dyspareunia. Uterine niche can be the cause of scar pregnancy, a rare form of ectopic pregnancy which can be related to severe complications; (2) Methods: We present a series of nine cases with different uterine niche related findings and discuss the diagnostic and therapeutic options reviewing the current literature and introduce a novel intrauterine ICG use for laparoscopic niche detection in one case; (3) Results: Most of uterine niche related symptoms and complications can be treated by a minimally invasive approach. Laparoscopic fluorescence guided niche detection is feasible; (4) Conclusions: Hysteroscopic and laparoscopic techniques allow the treatment of uterine niche related symptoms and complications. Intrauterine ICG application during fluorescence guided laparoscopy may allow easy niche detection.

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signed-rank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9±3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6±3.2% vs 69.9±3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

Adenomyosis and in vitro fertilization impacts - A literature review.

Adenomyosis is a gynecological condition, which is characterized by stromal and glandular endometrial tissue infiltration inti the myometrium, resulting in an increase of uterine volume. The etiology of adenomyosis is presently unknown, but some theories assist us in understanding its pathogenesis and natural history. Clinical manifestations are increased menstrual flow and dysmenorrhea, abnormal uterine bleeding, chronic pelvic pain, and dyspareunia. The signs and symptoms suggestive of adenomyosis are complemented by diagnostic methods such as transvaginal ultrasound (TVUS), ideally with intestinal preparation, magnetic resonance imaging (MRI) and surgery; although currently, there are no precise criteria for the classification of findings on imaging studies. The clinical and surgical therapeutic approach must be individualized, taking into account the patient's characteristics, for instance, age, parity, depth and number of adenomyotic foci, uterine volume and, mainly, clinical manifestations. A causal relation between adenomyosis and infertility has been repeatedly suggested, mostly due to the anatomo-physiopathological conditions originated by the adenomyosis on the female genital tract; however, definitive conclusions are still lacking. This pathology is found in approximately 25% of infertile women, especially those who have had recurrent pregnancy loss (RPL), recurrent implantation failure, older women seeking In Vitro fertilization (IVF) treatment, and those with concomitant endometriosis. To determine whether adenomyosis per se affects fertility, several researchers have focused on women who are affected by the condition and underwent IVF/intracytoplasmic sperm injection (ICSI); for this model provides more accurate data about the influence of adenomyosis on embryo implantation. Therefore, our objective was to analyze, through a systematic literature review, the effect of uterine adenomyosis on the probability of pregnancy by IVF / ICSI, as well as trying to point out the main difficulties and gaps to establish a standard protocol for the management of these patients, since most of the patients with adenomyosis have other associated gynecological pathologies, mostly endometriosis; in addition to the heterogeneity of the studies still remaining as an obstacle to precise conclusions.

Association of 2D and 3D transvaginal ultrasound findings with adenomyosis in symptomatic women of reproductive age: a prospective study

OBJECTIVE: To evaluate the association of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound (TVUS) findings with adenomyosis symptoms. METHODS: This prospective study conducted between January and December 2018 enrolled 78 women aged 18 to 40 years with abnormal uterine bleeding (AUB), infertility, and/or pelvic pain. All patients underwent 2D and 3D TVUS. Signs of adenomyosis on TVUS were identified according to the consensus of the Morphological Uterus Sonographic Assessment group. RESULTS: The prevalence of adenomyosis on TVUS was 55.12%. Patients with adenomyosis were older (p=0.002) and had more dysmenorrhea, AUB, and endometriosis than those without adenomyosis. When comparing the presence of symptoms with each adenomyosis feature, on 2D TVUS, severe dyspareunia was significantly associated with the presence of a poorly defined junctional zone (JZ) (p=0.023) and on 3D TVUS, patients with AUB had a more irregular (p=0.003), poorly defined (p=0.028), and interrupted JZ (p=0.011). After logistic regression analysis, signs of adenomyosis on TVUS remained significantly associated only with age over 30 years (OR: 1.2; 95% CI: 1.0-1.2) and AUB (OR: 7.65; 95% CI: 2-29). Patients with diffuse adenomyosis were older and presented with more infertility and AUB than patients with focal or no adenomyosis. CONCLUSION: The findings of adenomyosis by 2D and 3D TVUS showed association with age and AUB. 3D TVUS alterations in the JZ were associated with AUB and dyspareunia. Diffuse adenomyosis was associated with older age, a greater prevalence of infertility, and AUB.

PIWIL2 is overexpressed in adenomyotic lesions of women with diffuse adenomyosis.

PURPOSE: Adenomyosis has been studied throughout the years, however, its aetiology and physiopathology are still unknown. The aim of this study was to identify the presence of PIWI proteins in women with adenomyosis. METHODS: We included 72 participants to be part of this study and were divided into two groups based on their anatomopathological diagnosis, control (n = 36) or adenomyosis (n = 36). All samples were tested for PIWIL1, PIWIL2 and PIWIL4 proteins by immunohistochemistry. The evaluation of protein expression was performed by the digital histological score (DHSCORE) and by the pathologist's analysis. RESULTS: The participants had a mean age of 44.28 ± 5.76 years and 45.81 ± 4.86 years in the control and adenomyosis groups, respectively (p ≥ 0.05). Other clinical characteristics of the participants showed no statistical difference as well. PIWIL2 is highly expressed in the adenomyosis in comparison to the control group (p = 0.0001). The PIWIL1 is downregulated in the adenomyosis (p = 0.003) and PIWIL4 showed no difference in its expression (p = 0.05). CONCLUSION: PIWIL2 might be involved in cellular survival and PIWIL1 may be downregulated due to the loss of tissue's function and response to the hostile environment of the myometrium. This is the first time that PIWI proteins are studied in the adenomyosis.

Pharmacological treatment for symptomatic adenomyosis: a systematic review / Tratamento farmacológico para adenomiose sintomática: revisão sistemática

Abstract Objective To assess the efficacy of non-surgical treatment for adenomyosis. Data Sources A search was performed by two authors in the Pubmed, Scopus, and Scielo databases and in the grey literature from inception to March 2018, with no language restriction. Selection of Studies We have included prospective randomized studies for treating symptomaticwomen with adenomyosis (abnormal uterine bleeding and/or pelvic pain) diagnosed by ultrasound or magnetic resonance imaging. Data Collection Studies were primarily selected by title and abstract. The articles that were eligible for inclusion were evaluated in their entirety, and their data was extracted for further processing and analysis. Data Synthesis From567retrieved records only 5 remained for analysis. The intervention groups were: levonorgestrel intrauterine system (LNG-IUS)(n= 2), dienogest (n= 2), and letrozole (n= 1). Levonorgestrel intrauterine system was effective to control bleeding when compared to hysterectomy or combined oral contraceptives (COCs). One study assessed chronic pelvic pain and reported that LNG-IUS was superior to COC to reduce symptoms. Regarding dienogest, it was efficient to reduce pelvic pain when compared to placebo or goserelin, but less effective to control bleeding than gonadotropin-releasing hormone (GnRH) analog. Letrozolewas as efficient asGnRHanalog to relieve dysmenorrhea and dyspareunia, but not for chronic pelvic pain. Reduction of uterine volumewas seen with aromatase inhibitors, GnRH analog, and LGN-IUD. Conclusion Levonorgestrel intrauterine system and dienogest have significantly improved the control of bleeding and pelvic pain, respectively, in women with adenomyosis. However, there is insufficient data from the retrieved studies to endorse eachmedication for this disease. Further randomized control tests (RCTs) are needed to address pharmacological treatment of adenomyosis.

Resumo Objetivo: Avaliar a eficácia de tratamento não cirúrgico para adenomiose. Fontes de dados: Uma pesquisa foi realizada por dois autores nas bases de dados Pubmed, Scopus, Scielo e na literatura cinzenta desde o início de cada base de dados até março de 2018, sem restrição de idioma. Seleção de estudos: Incluímos estudos prospectivos randomizados para tratamento de mulheres sintomáticas com adenomiose (sangramento uterino anormal e/ou dor pélvica) diagnosticadas por ultrassonografia ou ressonância magnética. Coleta de dados: Os estudos foram selecionados principalmente por título e resumo. Os artigos que preencheram os critérios de inclusão foram avaliados na íntegra, e seus dados foram extraídos para posterior processamento e análise. Síntese dos dados: De 567 registros recuperados, somente 5 permaneceram para análise. Os grupos de intervenção foram: sistema intrauterino de levonorgestrel (SIU-LNG) (n= 2), dienogest (n= 2), e letrozol (n= 1). O SIU-LNG foi efetivo no controle do sangramento quando comparado à histerectomia ou aos contraceptivos orais combinados (COCs).Umestudo avaliou a dor pélvica crônica e relatou que o SIU-LNGfoi superior ao COC para reduzir os sintomas.Emrelação ao dienogest, este foi eficienteemreduzir a dor pélvica quando comparado ao placebo ou à goserelina, mas foi menos eficaz no controle do sangramento do que o análogo do hormônio liberador de gonadotropina (GnRH). O letrozol foi tão eficiente quanto o análogo do GnRH para aliviar a dismenorreia e a dispareunia, mas não para a dor pélvica crônica. Redução do volume uterino foi observada com inibidores de aromatase, análogo de GnRH, e SIU-LNG. Conclusão: O SIU-LNG e dienogest apresentaram bons resultados para o controle de sangramento e dor pélvica, respectivamente, em mulheres com adenomiose. No entanto, não há dados suficientes para endossar cada medicação para tratar essa doença. Futuros estudos randomizados são necessários para avaliar o tratamento farmacológico da adenomiose.

Use of Uterine Characteristics to Improve Fertility-Sparing Diagnosis of Adenomyosis.

Objective: To describe patient demographics, determine accuracy of clinical diagnosis, and evaluate reliability of laparoscopic uterine characteristics in the diagnosis of adenomyosis. Materials and Methods: Enrollment included 117 patients undergoing laparoscopic hysterectomy for benign indications. Intraoperatively, the attending surgeon predicted uterine weight; evaluated the presence of fibroids; and commented on the uterus' shape, color, and consistency while probing it with a blunt instrument. A prediction was also made about whether final pathology would reveal adenomyosis. Standardized video recordings were obtained at the start of the case. Each video was viewed retrospectively twice by three expert surgeons in a blinded fashion. Uterine characteristics were reported again with a prediction of whether or not there would be a pathologic diagnosis of adenomyosis. These data were used to calculate inter-and intrarater reliability of diagnosis. Results: Women with adenomyosis were more likely to complain of midline pain as opposed to lateral or diffuse pain (p = 0.048) with no difference in the timing of the pain (p = 0.404), compared to patients without adenomyosis. Uterine tenderness on examination was not an accurate predictor of adenomyosis (p = 0.566). Preoperative diagnosis of adenomyosis by clinicians was poor, with an accuracy rate of 51.7%. None of the intraoperative uterine characteristics were significant for predicting adenomyosis on final pathology, nor was any combination of the features (p = 0.546). Retrospective video reviews failed to reveal any uterine characteristics that generated consistent inter- or intrarater reliability (Krippendorff's α < 0.7) in making the diagnosis of adenomyosis. Conclusions: Clinical and video diagnosis of adenomyosis have low accuracy with no uterine characteristics consistently or reliably predicting adenomyosis on final pathology. (J GYNECOL SURG 34:183).

Fertility-Sparing Treatment of Adenomyosis in Patients With Infertility: A Systematic Review of Current Options.

Adenomyosis is a benign gynecological disease observed in women in their reproductive age. Recent studies have shown that adenomyosis might be a relevant factor for infertility, either impairing implantation or leading to early miscarriage. However, conservative treatment of infertility related to adenomyosis is still unclear. This study systematically reviews the literature for the reproductive outcomes of the available conservative treatments for patients with adenomyosis-associated infertility. We conducted a search in PubMed/Medline for studies in English published in the last 7 years and included 16 studies. Six studies evaluated surgical treatments of adenomyosis. When considering only spontaneous pregnancies, the overall clinical pregnancy rate was very low (18.2%). However, when using GnRH analogues for 24 weeks after surgery, the pooled spontaneous pregnancy rate was higher (40.7% vs 15.0%; P = .002). No significant difference was observed in the other outcomes. Ten studies evaluated exclusive assisted reproductive techniques for infertility related to adenomyosis and showed that the long stimulation protocol had better outcomes compared to short stimulation protocol in pregnancy rate (43.3% vs 31.8%; P = .0001), live birth (43.0% vs 23.1%; P = .005), and miscarriage (18.5% vs 31.1%; P < .0001).

Surgery in adenomyosis.

INTRODUCTION: Adenomyosis is defined as the presence of endometrial glands and stroma within the myometrium. The true prevalence is unknown and has been reported to range from 1 to 70%. It has a significantly negative impact on women's quality of life, causing abnormal uterine bleeding, dysmenorrhea, and chronic pelvic pain. The definitive treatment for adenomyosis is hysterectomy, although it does not contemplate patients who wish to preserve their fertility. The aim of this paper is to discuss the latest evidence on the surgical techniques for the treatment of adenomyosis published in medical-scientific databases. METHOD: A comprehensive literature search for articles published from 1996 to 2017 related to surgery for adenomyosis was made in Pubmed, Medline, the Cochrane Library, and Google Scholar, in English, by the following MeSH terms: adenomyosis, surgery, pathogenesis, dysmenorrhea and infertility. RESULTS: There is extensive evidence on several surgical approaches for the improvement of adenomyosis-related symptoms; however, there is no robust evidence that they are effective for infertility. CONCLUSION: The management of adenomyosis is quite complex and controversial. Complications after extensive uterine reconstruction, such as uterine rupture, should be considered and discussed with the patient. There are still limited data to support surgery effectiveness, especially for infertility, and further well-designed studies are required.