Search

Background: This prospective study aims to identify the effect of the dienogest 2 mg/day and aspirin 150 mg/day combined treatment for two months before frozen ET on the assisted reproduction outcome in women with adenomyosis and recurrent implantation failure (RIF). Methods: Patients were selected based on specific criteria and divided into two groups (with and without treatment). Preimplantation biochemical parameters and ultrasonographic features (endometrial thickness, uterine peristalsis, and junctional zone thickness) were compared with pregnancy rate in a non-natural cycle frozen embryo transfer technique. A comparison between the two study groups indicated an increased successful implantation rate and clinical pregnancy rate (25% vs. 7.4%). Results: These results were attributed to the reduced uterine peristalsis and the reduction in thickness of the junctional zone following treatment. Available data were limited due to the nature of the study though maximal effort was exerted for the selected patients between groups to be as demographically similar and free from other potential pathology that may affect the results. Conclusions: In conclusion, it appears that the above stated treatment improves outcomes in women with adenomyosis and RIF; the parameters used may provide an insight as to the reasons why this occurs, though an explanation of the molecular mechanisms is still elusive. [ABSTRACT FROM AUTHOR]

The junctional zone (JZ) is an important structure in the myometrium that maintains uterine fertility. Changes in the junctional zone are closely related to infertility and adenomyosis (ADS). As an increasing number of young women are affected by ADS, the disease is no longer considered typical of women over 40. With these changes, an increasing number of patients refuse hysterectomy and desire fertility preservation treatment. At the same time, ADS is a crucial factor causing female infertility. Therefore, the treatment of ADS-related infertility and preservation of reproductive function is one of the other major challenges facing clinicians. For these young patients, preserving fertility and even promoting reproduction has become a new challenge. Therefore, we searched and summarized these studies on PubMed and Google Scholar using keywords such as "adenomyosis", "junctional zone", and "infertility" to explore infertility causes, diagnosis, and treatment of ADS patients who wish to preserve their uterus or fertility and become pregnant, focusing on the junctional zone, to obtain a full appreciation of the new perspective on this disease. [ABSTRACT FROM AUTHOR]

Background and Objective: The prevalence of adenomyosis of the uterus varies from 5% to 70%, and there is no clear consensus on its imaging diagnostic criteria. The objective of this study was to evaluate the role of transvaginal sonography (TVS), combined TVS and color Doppler (TVS-CD), and magnetic resonance imaging (MRI) in the diagnosis of adenomyosis. Materials and Methods: This was a tertiary care hospital-based prospective study, in which 365 clinically suspected cases of adenomyosis were enrolled. All three types of imaging (TVS, TVS-CD, and MRI) were done in 233/365 patients, followed by hysterectomy in 50. Imaging features were correlated with the histopathological examination (HPE), which was taken as the gold standard for the diagnosis. The diagnostic performance of each imaging modality was assessed. Results: Among patients who underwent hysterectomy, 36/50 (72%) had adenomyosis on HPE, with or without associated benign gynecological abnormalities. Sensitivity, specificity, positive predictive value (PPV), negative PV (NPV), and diagnostic accuracy (DA) of MRI were higher than that of TVS-CD (91.67% vs. 77.78%, 85.71% vs. 78.57%, 94.29% vs. 90.32%, 80% vs. 57.89%, and 90% vs. 78%, respectively). TVS alone had lower diagnostic performance (specificity: 64.29%, PPV: 84.85%, NPV: 52.94%, and DA: 74%) than TVS-CD, but equal sensitivity (77.78%). Heterogeneous myometrium was the most sensitive (80.56%), while myometrial cyst was the most specific (92.86%) TVS feature. The maximum junctional zone thickness ≥12 mm was the most sensitive (97.22%), while the hyperintense myometrial focus was the most specific (100%) MRI feature. Conclusion: TVS-CD should be used as an initial diagnostic imaging modality in clinically suspected cases of adenomyosis; however, MRI due to better diagnostic efficacy should be the imaging modality of choice before subjecting such patients to hysterectomy.

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to (i) summarize the current literature regarding the role of magnetic resonance imaging (MRI) in diagnosing adenomyosis, (ii) examine how to integrate MRI phenotypes with clinical symptomatology and histological findings, (iii) review recent advances including proposed MRI classifications, (iv) discuss challenges and pitfalls of diagnosing adenomyosis, and (v) outline the future role of MRI in promoting a better understanding of the pathogenesis, diagnosis, and treatment options for patients with uterine adenomyosis. Recent Findings: Recent advances and the widespread use of MRI have provided new insights into adenomyosis and the range of imaging phenotypes encountered in this disorder. Summary: Direct and indirect MRI features allow for accurate non-invasive diagnosis of adenomyosis. Adenomyosis is a complex and poorly understood disorder with variable MRI phenotypes that may be correlated with different pathogeneses, clinical presentations, and patient outcomes. MRI is useful for the assessment of the extent of findings, to evaluate for concomitant gynecological conditions, and potentially can help with the selection and implementation of therapeutic options. Nevertheless, important gaps in knowledge remain. This is in part due to the lack of standardized criteria for reporting resulting in heterogeneous and conflicting data in the literature. Thus, there is an urgent need for a unified MRI reporting system incorporating standardized terminology for diagnosing adenomyosis and defining the various phenotypes. [ABSTRACT FROM AUTHOR]

Background and Objective: The prevalence of adenomyosis of the uterus varies from 5% to 70%, and there is no clear consensus on its imaging diagnostic criteria. The objective of this study was to evaluate the role of transvaginal sonography (TVS), combined TVS and color Doppler (TVS-CD), and magnetic resonance imaging (MRI) in the diagnosis of adenomyosis. Materials and Methods: This was a tertiary care hospital-based prospective study, in which 365 clinically suspected cases of adenomyosis were enrolled. All three types of imaging (TVS, TVS-CD, and MRI) were done in 233/365 patients, followed by hysterectomy in 50. Imaging features were correlated with the histopathological examination (HPE), which was taken as the gold standard for the diagnosis. The diagnostic performance of each imaging modality was assessed. Results: Among patients who underwent hysterectomy, 36/50 (72%) had adenomyosis on HPE, with or without associated benign gynecological abnormalities. Sensitivity, specificity, positive predictive value (PPV), negative PV (NPV), and diagnostic accuracy (DA) of MRI were higher than that of TVS-CD (91.67% vs. 77.78%, 85.71% vs. 78.57%, 94.29% vs. 90.32%, 80% vs. 57.89%, and 90% vs. 78%, respectively). TVS alone had lower diagnostic performance (specificity: 64.29%, PPV: 84.85%, NPV: 52.94%, and DA: 74%) than TVS-CD, but equal sensitivity (77.78%). Heterogeneous myometrium was the most sensitive (80.56%), while myometrial cyst was the most specific (92.86%) TVS feature. The maximum junctional zone thickness ≥12 mm was the most sensitive (97.22%), while the hyperintense myometrial focus was the most specific (100%) MRI feature. Conclusion: TVS-CD should be used as an initial diagnostic imaging modality in clinically suspected cases of adenomyosis; however, MRI due to better diagnostic efficacy should be the imaging modality of choice before subjecting such patients to hysterectomy. [ABSTRACT FROM AUTHOR]

Abstract Background In clinical practice it is an ongoing challenge to distinguish between angular pregnancy and interstitial pregnancy. With the three-dimensional (3D) magnetic resonance imaging (MRI) being increasingly used, it is worth exploring its role in differentiating angular pregnancy from interstitial pregnancy. This study aims to investigate how 3D MRI can help reveal the differences between these two special pregnancies in the early diagnosis. Methods We reviewed and analyzed the 3D MRI images of 50 patients with interstitial pregnancy and 55 patients with angular pregnancy retrospectively. Imaging features were identified to compare these two special pregnancies, and the ROC (Receiver Operating Characteristic) analysis was conducted to assess the diagnostic performance. Results The significant differences of the 3D MRI imaging features between interstitial pregnancy and angular pregnancy were found in the outline of uterus cavity (p

Abstract Background Let-7a is a small non-coding RNA that has been found to take part in cell proliferation and apoptosis. The hippo-YAP1 axis, known as a tumour suppressor pathway, also plays an important role in cell proliferation and apoptosis. YAP1, TAZ, and phospho-YAP1 play key roles in actions of the hippo-YAP1 axis. Adenomyosis (ADS) is a proliferative disease leading to a large uterus in patients with prolonged illness. Abnormal proliferation of smooth muscle cells (SMCs) in the uterine endometrial-myometrial junctional zone (JZ) is an important reason for developing ADS. This study aimed to explore the expression levels of let-7a and components of the hippo-YAP1 axis in SMCs in the uterine endometrial-myometrial JZ in ADS and to explore the roles of let-7a and the hippo-YAP1 axis of JZ SMC proliferation and apoptosis in ADS. Methods We collected JZ tissues for the primary culture of SMCs from 25 women diagnosed with ADS and 27 women without ADS. We used quantitative real-time polymerase chain reaction and western blotting to measure the mRNA and protein expression levels of let-7a, YAP1, TAZ, and phospho-YAP1 in ADS JZ SMCs. A CCK-8 assay and flow cytometry analysis of apoptosis were utilized to test the proliferation and apoptosis of JZ SMCs. The let-7a overexpression lentiviral vector GV280 was used to increase the expression level of let-7a. We added verteporfin to block the phosphorylation of components of the hippo-YAP1 axis. Results We found that the let-7a level was decreased, while the YAP1 and TAZ levels were increased in ADS JZ SMCs. Upregulated let-7a affected the expression levels of components of the hippo-YAP1 axis, accelerated apoptosis, and inhibited proliferation in JZ SMCs. Furthermore, accumulated YAP1 led to increasing proliferation of JZ SMCs after verteporfin treatment to block the phosphorylation of components of the hippo-YAP1 axis. If components of the hippo-YAP1 axis were unphosphorylated, upregulated let-7a could not inhibit the proliferation of ADS JZ SMCs. Upregulated let-7a could not activate the hippo-YAP1 axis in verteporfin treatment. Conclusions Our findings suggest that the let-7a and hippo-YAP1 axis may act as important regulators of JZ SMCs proliferation, and upregulated let-7a may be an effective method to treat ADS.

Abstract Background The denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis. Methods JZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation. Results We demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2. Conclusions Our results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling.

Although many studies show that patients with diffuse adenomyosis who underwent fertility-sparing surgery can have a successful pregnancy, their pregnancy outcomes are still controversial. The objective of this study was to determine long-term pregnancy outcomes and possible influencing factors after double-flap adenomyomectomy for patients with diffuse adenomyosis. A total of 137 patients with diffuse adenomyosis who underwent double-flap adenomyomectomy between January 2011 and December 2019 were studied, and correlations between pregnancy outcomes and clinical data, including age and junctional zone measured by magnetic resonance imaging (JZmax-A), were analyzed. The results show that 56 patients (40.9%, 56/137) had 62 pregnancies, including 35 natural pregnancies and 27 assisted reproduction pregnancies, after operation. A univariate regression analysis showed that the pregnancy outcomes were related to age at surgery, visual analog scale (VAS) score of preoperative dysmenorrhea, parity experience, length of infertility, and postoperative JZmax-A. A multivariate regression analysis showed that age at surgery, VAS score of preoperative dysmenorrhea, and postoperative JZmax-A were the independent indicators correlated with pregnancy outcomes. A receiver operating characteristic curve analysis showed that postoperative JZmax-A was the most valuable indicator for predicting pregnancy outcomes. Cumulative pregnancy rates during the first 3 years were 70.1% and 20.9% in the postoperative JZmax-A ≤ 8.5 mm and the postoperative JZmax-A > 8.5 mm groups, respectively. In conclusion, double-flap adenomyomectomy could improve fertility for diffuse adenomyosis, and postoperative JZmax-A might be a promising indicator for predicting pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Uterine peristalsis occurs in the endometrial–myometrial junctional zone. It is involved in sperm transport and embryo implantation in spontaneous and in vitro fertilization (IVF) cycles. We investigated the reproducibility of transvaginal assessment of peristalsis and endometrial combined thickness (ECT) as a surrogate marker for contraction frequency and directionality. Methods: We studied 74 women undergoing IVF between 2015 and 2018. On day 9 of stimulation, participants had a transvaginal ultrasound to assess follicular development and ECT. Women proceeding to fresh embryo transfer had an ultrasound preprocedure. A videoclip was analyzed for frequency (total contractions per minute) and directionality of contractions (cervical to fundal [CF] and fundal to cervical [FC]). Anonymized images were reviewed on three separate occasions by a single observer. Intraclass correlation (ICC with 95% CI) and Bland–Altman plots were constructed to assess intraobserver agreement. Secondary analysis was performed to assess peristalsis with ECT and pregnancy rates. Results: Between the first and second observations, there was suboptimal correlation between visual assessment of contraction frequency and directionality (ICC–total 0.67 (0.43–0.80) p < 0.001, ICC–CF 0.62 (0.35–0.78), p < 0.001, ICC–FC 0.74 (0.55–0.85), p < 0.001. Correlation for both frequency and directionality significantly improved between second and third viewing (ICC–total 0.97 (0.95–0.98), p < 0.001, ICC–CF 0.84 (0.73–0.91), p < 0.001, ICC–FC 0.89 (0.81–0.94), p < 0.001). Good agreement was seen on Bland–Altman plots with narrower limits of agreement on second and third viewing. Median ECT was 10 mm (interquartile range [IQR] 8–12 mm). Women with ECT ≥ 10 mm versus

Abstract Objective To analyze the interobserver and intraobserver reproducibility of the visualization and continuity of the juncional zone (JZ) by three-dimensional (3D) ultrasound in infertile women, and to evaluate the sociodemographic, hormonal, and structural factors that influence these assessments. Methods A prospective study conducted at the Assisted Reproductive Technology Unit of Hospital Senhora da Oliveira, in the city of Guimarães, Portugal. Transvaginal 3D ultrasonography was performed, and 2 volumes were generated per case. Two observers who were blinded to each other's work analyzed these volumes, choosing the best coronal section. Four months later, one of the observers performed the same methodology. The JZ visualization was classified as optimal, satisfactory, and unsatisfactory, and the JZ continuity, as continuous and discontinuous. The interobserver and intraobserver agreements were analyzed. The influence of hormonal, structural, and sociodemographic factors on the JZ was evaluated. Results In total, 65 women were included in the present study. The interobserver reproducibility was substantial for JZ visualization and continuity (k = 0.635 and 0.753 respectively), and the intraobserver reproducibility was very good for JZ visualization and continuity (k = 0.884 and 0.816 respectively). Trilaminar endometrial pattern was associated with optimal JZ visualization (p = 0.012). The increase of 1 unit in the level of serum estradiol represents a 9.9% decrease in the odds of unsatisfactory visualization of the JZ (odds ratio [OR] = 0.9; 95% confidence interval [95%CI] = 0.814–0.996; p = 0.042). Endometriosis increases the odds of unsatisfactory visualization by 24 times (OR = 23.7; 95%CI = 1.262–437.057; p = 0.034). The prevalence of discontinuous JZs was of 60%. Myomas and endometriosis were associated with discontinuous JZs (p = 0.034 and 0.016 respectively). Conclusion The assessment of JZ visualization and continuity by 3D ultrasound is reproducible enough to be used in the clinical practice.

Background: In clinical practice it is an ongoing challenge to distinguish between angular pregnancy and interstitial pregnancy. With the three-dimensional (3D) magnetic resonance imaging (MRI) being increasingly used, it is worth exploring its role in differentiating angular pregnancy from interstitial pregnancy. This study aims to investigate how 3D MRI can help reveal the differences between these two special pregnancies in the early diagnosis.Methods: We reviewed and analyzed the 3D MRI images of 50 patients with interstitial pregnancy and 55 patients with angular pregnancy retrospectively. Imaging features were identified to compare these two special pregnancies, and the ROC (Receiver Operating Characteristic) analysis was conducted to assess the diagnostic performance.Results: The significant differences of the 3D MRI imaging features between interstitial pregnancy and angular pregnancy were found in the outline of uterus cavity (p < 0.001), involvement of junctional zone (p < 0.001), the signal of surroundings (p = 0.005), the relationship with round ligament (p = 0.042), and the overlying myometrial thickness (p = 0.041). Furthermore, the multivariate logistic regression analysis identified a series of significant indicators for angular pregnancy, including the junctional zone involvement, being-surrounded by hyper/iso-intensity on 3D images, and the asymmetric outline of uterus cavity. Combining these three imaging features, the AUC (Area under the Curve) of ROC curve was 0.87 in distinguishing interstitial pregnancy from angular pregnancy.Conclusions: This study suggests that 3D MRI can help distinguish angular pregnancy from interstitial pregnancy in clinical practice, with the advantages that conventional MRI or ultrasound does not have. Through the significant image features, 3D MRI plays an important role in improving the timing of diagnosis, avoiding unnecessary interventions, and preventing hemorrhage in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate whether there is a relationship between adenomyosis and nabothian cyst (NC) in a large patient series. Material and methods: The patient’s data were scanned retrospectively and patients with a junctional zone thickness of 12 mm and above on magnetic resonance imaging were accepted as group adenomyosis (group A). Patients with a junctional zone thickness of less than 12 mm were not admitted as adenomyosis (control group). Both groups were compared for NC. Results: In group A, 176 (69.8%) patients had NC (n = 250), while in the control group (n = 202), 57 (28.2%) patients had NC. NC was significantly higher in group A than in the control group (p < 0.001). Conclusions: The aetiology of NC is still unclear. According to our results, similar factors may affect adenomyosis and NC aetiopathogenesis. [ABSTRACT FROM AUTHOR]

The use of the mouse as a model organism is common in translational research. This mouse–human similarity holds true for placental development as well. Proper formation of the placenta is vital for development and survival of the maturing embryo. Placentation involves sequential steps with both embryonic and maternal cell lineages playing important roles. The first step in placental development is formation of the blastocyst wall (approximate embryonic days [E] 3.0-3.5). After implantation (∼E4.5), extraembryonic endoderm progressively lines the inner surface of the blastocyst wall (∼E4.5-5.0), forming the yolk sac that provides histiotrophic support to the embryo; subsequently, formation of the umbilical vessels (∼E8.5) supports transition to the chorioallantoic placenta and hemotrophic nutrition. The fully mature ("definitive") placenta is established by ∼E12.5. Abnormal placental development often leads to embryonic mortality, with the timing of death depending on when placental insufficiency takes place and which cells are involved. This comprehensive macroscopic and microscopic atlas highlights the key features of normal and abnormal mouse placental development from E4.5 to E18.5. This in-depth overview of a transient (and thus seldom-analyzed) developmental tissue should serve as a useful reference to aid researchers in identifying and describing mouse placental changes in engineered, induced, and spontaneous disease models. [ABSTRACT FROM AUTHOR]

Aim. The aim is to analyze the data thus far published on the radiologic diagnosis of adenomyosis in patients with reproductive problems in order to determine promising areas for further scientifi c research.Materials and methods. An information search for subsequent analysis was performed using E-Library, PubMed and CochraneLibrary electronic bibliographic databases with the following keywords: “ultrasound diagnosis of adenomyosis”, “MRI adenomyosis”, “junctional zone adenomyosis”, “ultrasound adenomyosis”, “diagnosis adenomyosis”, “magnetic resonance imaging adenomyosis”, “adenomyosis junction”.Results. Imaging techniques are prioritized in diagnosing the initial incidence of adenomyosis. The value of such techniques increases when analyzing the causes of implantation failures. Key issues associated with the modern radiologic diagnosis and monitoring of adenomyosis during treatment have been considered on the basis of the standardization of studies, classifi cation of the disease, assessment of the diagnostic accuracy and prognostic value of imaging techniques in patients with reproductive losses and infertility.Conclusion. Promising areas of scientifi c research are found to be the specifi cation of optimal diagnostic timeframes, informativity of diagnostic criteria for 3D reconstruction, MRI, elastography, angiography, as well as the development of prediction methods for healthy childbearing and monitoring the treatment effectiveness.

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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Let-7a is a small non-coding RNA that has been found to take part in cell proliferation and apoptosis. The hippo-YAP1 axis, known as a tumour suppressor pathway, also plays an important role in cell proliferation and apoptosis. YAP1, TAZ, and phospho-YAP1 play key roles in actions of the hippo-YAP1 axis. Adenomyosis (ADS) is a proliferative disease leading to a large uterus in patients with prolonged illness. Abnormal proliferation of smooth muscle cells (SMCs) in the uterine endometrial-myometrial junctional zone (JZ) is an important reason for developing ADS. This study aimed to explore the expression levels of let-7a and components of the hippo-YAP1 axis in SMCs in the uterine endometrial-myometrial JZ in ADS and to explore the roles of let-7a and the hippo-YAP1 axis of JZ SMC proliferation and apoptosis in ADS. Methods: We collected JZ tissues for the primary culture of SMCs from 25 women diagnosed with ADS and 27 women without ADS. We used quantitative real-time polymerase chain reaction and western blotting to measure the mRNA and protein expression levels of let-7a, YAP1, TAZ, and phospho-YAP1 in ADS JZ SMCs. A CCK-8 assay and flow cytometry analysis of apoptosis were utilized to test the proliferation and apoptosis of JZ SMCs. The let-7a overexpression lentiviral vector GV280 was used to increase the expression level of let-7a. We added verteporfin to block the phosphorylation of components of the hippo-YAP1 axis. Results: We found that the let-7a level was decreased, while the YAP1 and TAZ levels were increased in ADS JZ SMCs. Upregulated let-7a affected the expression levels of components of the hippo-YAP1 axis, accelerated apoptosis, and inhibited proliferation in JZ SMCs. Furthermore, accumulated YAP1 led to increasing proliferation of JZ SMCs after verteporfin treatment to block the phosphorylation of components of the hippo-YAP1 axis. If components of the hippo-YAP1 axis were unphosphorylated, upregulated let-7a could not inhibit the proliferation of ADS JZ SMCs. Upregulated let-7a could not activate the hippo-YAP1 axis in verteporfin treatment. Conclusions: Our findings suggest that the let-7a and hippo-YAP1 axis may act as important regulators of JZ SMCs proliferation, and upregulated let-7a may be an effective method to treat ADS. [ABSTRACT FROM AUTHOR]

Abstract The onset of gestation is characterized by growth, morphological and functional changes of the placenta. We aim to evaluate the placental compartments in New Zealand rabbits by means of stereological methods. The fetal and maternal portion of placenta (12, 14, 18 and 20 gestational days) was randomly sampled for the stereological analysis. Histological sections were scanned to estimate fetal (labyrinth and junctional) and maternal (decidua) compartment volumes. The total volume of the placenta for the ages of 12, 14, 18 and 20 days was, respectively, 320 mm3, 340 mm3, 940 mm3 and 1300 mm3. The volume of the labyrinth was 56 mm3, 119 mm3, 231 mm3 and 481 mm3, respectively. The volume of junctional zone was 75 mm3, 76 cm3, 238 mm3 and 314 mm3, respectively. The volume of decidua was 174 mm3, 143 mm3, 469 mm3 and 504 mm3, respectively. We concluded that the rabbit´s placenta compartments varied according to the gestational period, increasing continuously over the 20 gestational days. However, on the onset of the development of the placenta the decidua presented faster growth, whereas after the 20 days of development, the labyrinth developed more quickly. This study represents an aid to the understanding of placentation in humans.

Diffuse leiomyomatosis is a rare condition among benign smooth muscle neoplasms of the uterus, being defined as innumerable small myomatous nodules that mainly occur in the submucosal area. Young women with this disease suffer from menorrhagia, pains, and infertility. It is essential to perform extensive myomectomy after opening the endometrial cavity by a deep, median, longitudinal incision of the uterine corpus, followed by careful suture and reconstruction of the uterus for fertility spearing and childbearing in young women with this disease. So far, there have been no experiences of the uterine rupture during pregnancy even after such myomectomy, but Caesarean section is recommended for safe delivery.

Aim. The research was designed to study the possibilities of ultrasound examination with Color Doppler imaging (CDI) and three-dimensional volumetric reconstruction (3D) in the diagnostics of adenomyosis of minimal prevalence in patients with unspecified infertility and reproductive losses at the early stages of gestation. Materials and methods. 40 patients with unspecified infertility and early pregnancy loss (the main group) and 35 healthy patients (the control group) were examined in the course of the study. All patients underwent small pelvic ultrasound in В / CDI / 3D-modes with an assessment of the junctional zone (JZ) on days 5-7 and 18-22 of the menstrual cycle (MC).Results. In the main group, there was a discrepancy between the structure of the endometrium and the phase of the cycle at 5-7 days of the MC, a decrease in vascularization of the JZ at 18-22 days of the MC, a local increase in blood flow in the endometrium in phases 1 and 2 of the MC; the fuzziness of the junctional zone, an increase in min and max thickness of the junctional zone, the difference between them, as well as the ratio of max thickness of the junctional zone to the thickness of the uterus wall regardless of the phase of the MC (p = 0.005; 0.0001; 0.005; 0.03; 0.0004; 0, 0001; 0.0001; 0.0001; 0.0001 respectively).Conclusion. Ultrasonography with the CDI and 3D reconstruction allows us to identify a high-risk group by the presence of a minimal prevalence of adenomyosis in the patients with unspecified infertility and reproductive losses at the early stages of gestation.

Background: The denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis. Methods: JZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation. Results: We demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2. Conclusions: Our results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling. [ABSTRACT FROM AUTHOR]

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Introduction: Amino acid transport across the placenta is crucial for fetal growth. In rodent models, the visceral yolk sac (referred to as yolk sac hereafter) is also likely to contribute to fetal amino acid provision. System L amino acid transporters mediate the transport of essential amino acids. System L activity is mediated by light chains LAT1 (Slc7a5) and LAT2 (Slc7a8) which form functional complexes by heterodimeric linkage to CD98 (Slc3a2). LAT4 (Slc43a2) is monomeric, possessing overlapping amino acid substrate specificity with LAT1 and LAT2.Methods: This study investigates the expression of these LAT subtypes in fetus-matched rat placenta and yolk sac.Results: Slc7a5, Slc7a8 and Slc43a2 transcripts were expressed in placenta and yolk sac with similar expression patterns between sexes. LAT1 expression was significantly higher in placenta than yolk sac. Conversely, LAT2 and LAT4 expression was significantly higher in yolk sac than placenta; CD98 expression was comparable. LAT1, LAT2, LAT4 and CD98 were distributed to rat placental labyrinth zone (LZ) and junctional zone (JZ). LAT1 and LAT4 demonstrated higher expression in LZ, whilst LAT2 was more intensely distributed to JZ. LAT1, LAT2, LAT4 and CD98 were expressed in yolk sac, with punctate LAT1 staining to endodermal cell cytoplasm, contrasting with the intense LAT2, LAT4 and CD98 endodermal cell basolateral distribution, accounting for greater LAT2 and LAT4 expression in yolk sac compared to placenta.Conclusion: LAT1, LAT2 and LAT4 are expressed in rat placenta and yolk sac implicating a combined role for these LAT subtypes in supporting fetal growth and development. [ABSTRACT FROM AUTHOR]

We investigated the role of oestrogen receptor 1 (ESR1) in regulating the [Ca2+]i concentration in the junctional zone (JZ) and its effect on adenomyosis. JZ smooth muscle cells (JZSMCs) were isolated from 17 control and 24 adenomyotic uteri, and membrane proteins were extracted from the cells. In the control group, the levels of membrane ESR1 and [Ca2+]i in the proliferative phase were significantly greater than they were in the secretory phase. While no difference was detected between the two phases, ESR1 and [Ca2+]i levels in the adenomyosis group were significantly higher in the proliferative and secretory phases than they were in the control groups. Oestradiol induced a rapid increase in [Ca2+]i in the JZSMCs of both groups. When pretreated with the ESR1 antagonist ICI 182,780, the increase in [Ca2+]i was clearly reduced in both groups compared with the control, but the differences were not significant. Filtered E-6-BSA also induced [Ca2+]i, and its actions were similar to those of oestrogen. Removal of extracellular Ca2+ did not alter the effect of oestradiol, but the phospholipase C inhibitor U73122 (10 μM) and 2-aminoethoxydiphenyl borate (5 μM) significantly reduced the oestradiol-induced [Ca2+]i flux. Oestradiol was unable to induce a [Ca2+]i flux in thapsigargin-depleted cells; this result indicated that oestradiol mediates the [Ca2+]i flux in JZSMCs through ESR1, which activates the phospholipase C pathway. ESR1 levels were assessed by Western blotting. Changes in the [Ca2+]i concentration induced by oestrogen stimulation were analysed by immunofluorescence. The ΔFCa2+ was calculated as the difference between baseline and peak fluorescence response to stimulation. We found that the abnormal intracellular [Ca2+]i response to oestrogen could account for aberrant JZ peristalsis. [ABSTRACT FROM AUTHOR]

Objective(s): To assess the association between the ultrasonographic presence of adenomyosis and recurrent miscarriage (RM).Study Design: A prospective matched case-control study was conducted between March 2018 and December 2018 at Ankara University Hospital. A total of 132 women were assessed with transvaginal ultrasonography for the presence of adenomyosis markers. The case group consisted of 66 women with RM. The control group consisted of 66 women without RM or any other gynaecologic conditions. The rates of ultrasonographic adenomyosis, using strict criteria, were compared between the groups. Other etiologic factors for RM were described in the case group. The primary outcome was the ultrasonographic diagnosis of adenomyosis.Results: The ultrasonographic diagnosis of adenomyosis, using diagnostic criteria of at least two markers, was significantly higher in the RM group when compared to the control group (19.7% vs. 6.1%, respectively; P = 0.035). The most common ultrasonographic finding in the RM group was heterogeneous myometrium (18.2%). In the RM group, there was at least one possible risk factor (including adenomyosis) for RM in 42 women (63.6%). The prevalence of adenomyosis in nine women with unexplained RM was 13.6%.Conclusion(s): The prevalence of adenomyosis was significantly increased in women with RM compared to healthy controls. Adenomyosis and uterine anomalies were the most common risk factors associated with RM. [ABSTRACT FROM AUTHOR]

Background: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging.Objective and Rationale: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed.Search Methods: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018.Outcomes: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis.Wider Implications: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research. [ABSTRACT FROM AUTHOR]

The inner myometrium, also called the junctional zone (JZ), is believed to play a major role in the development of adenomyosis. Recently, we found that the lethal-7a (Let-7a) microRNA (miRNA) was clearly downregulated in the miRNA expression profiles of JZ smooth muscle cells (JZSMCs) of patients with adenomyosis. Lin28, including Lin28A and Lin28B, is responsible for the post-transcriptional downregulation of the Let-7 miRNA family. However, the expression pattern of Lin28 and the function of the Lin28/Let-7 axis in adenomyosis have not yet been identified. In this study, we aim to explore the potential roles of the Lin28/Let-7 axis in the development of adenomyosis. Immunohistochemistry, western blot, and reverse transcription polymerase chain reaction (RT-qPCR) were used to evaluate the Lin28 expression, respectively. The correlation between Let-7a, Lin28A, and Lin28B expression was further examined using Pearson's correlation analysis. RNA interference was used to inhibit Lin28B gene, and then Cell Counting Kit (CCK-8) assay was performed to detect the cell proliferation capacity. The results revealed that the expression levels of Lin28B were upregulated in the JZ of adenomyosis whatever about proteins or mRNA (P < 0.0001); furthermore, its mRNA expression level was negatively correlated with Let-7a (r = − 0.749, P < 0.0001). After inhibiting Lin28B gene, the proliferation capacity of JZSMCs in adenomyosis group decreased after 48 h (P < 0.05). These results indicated that Lin28B may be involved in the pathogenesis of adenomyosis by promoting the proliferation capacity of JZSMCs via regulating Let-7a. [ABSTRACT FROM AUTHOR]

Study Objective: To determine if it is possible and safe to obtain adenomyosis tissue in vivo without removing the uterus in order to use it for further molecular investigations of adenomyosis, which would allow investigating the pathogenesis of the disease.Design: A prospective cohort study.Setting: A university hospital.Patients: Eighty-one premenopausal women scheduled for a hysterectomy because of various benign indications were included.Interventions: Ultrasound-guided, transvaginal uterine core biopsy samples were obtained, and the required time was registered. Any trauma to the pelvic organs, blood loss, and other complications were documented during the subsequent hysterectomy. Two biopsy samples were analyzed histopathologically to confirm the presence of adenomyosis, and another 2 were snap frozen using liquid nitrogen for use in further research. Laser microscopic dissection and RNA extraction were performed on the collected samples.Measurements and Main Results: Biopsy specimens could be obtained in 80 (99%) of the 81 cases. There was no visible trace of the biopsy retrieval in 20 women (25%), perforation of uterine serosa or peritoneum was present in 56 (70%), and ongoing minor bleeding occurred in 4 (5%). The median amount of bleeding was 2 mL (range, 0-200 mL). No serious complications were observed. The procedure took 6.1 ± 1.9 minutes (mean ± standard deviation). Adenomyosis tissue was obtained in 10 (22%) of the 45 cases with adenomyosis. The inner myometrium with the junctional zone was accessible in all cases. It was possible to produce frozen sections, extract RNA, and dissect single adenomyosis glands with laser microscopic dissection.Conclusions: No serious complications caused by the uterine biopsies were observed. This technique opens up the possibility of investigating early stages of adenomyosis and the inner myometrium containing the junctional zone independent of hysterectomy specimens. [ABSTRACT FROM AUTHOR]

A recent article supports our longstanding view that all intramural fibroids can cause disturbance of uterine function. This may be reflected in the symptom of menorrhagia or fertility-related issues, as well as pregnancy losses at all gestational stages. However, it was disappointing that there was no reference to either the mechanism by which fibroids disturb uterine function nor to the gynaecologist who described this more than 100 years ago, namely John Sampson. In fact, Sampson's findings about the unique venous drainage mechanism from the endometrium explains how menstrual loss is contained in normal physiology, but which can be excessive when the protective 'anaemic' zone is disturbed. Two more recent and pertinent observations include the hysteroscopic findings of Osamu Sugimoto, who showed in the 1970s that the endometrium overlying submucous fibroids is actually atrophic, hence the oft-cited reason of hyperplastic or excessive endometrium cannot be the cause of the associated menorrhagia. Furthermore, recent imaging techniques describe an additional 'junctional zone' adjacent to the endometrium in cases of fibroids and adenomyosis. We believe this all adds up to disturbed venous drainage as described by Sampson and needs to immediately enter the educational training of medical students, doctors and gynaecologists worldwide. [ABSTRACT FROM AUTHOR]

Abstract Research question How diagnostically accurate is two-dimensional (2D-TVS) compared with three-dimensional transvaginal ultrasonography (3D-TVS) in diagnosing adenomyosis of the inner myometrium. What is the most accurate combination of ultrasonographic features? Design Premenopausal women (n = 110) scheduled for hysterectomy or transcervical resection of the endomyometrium owing to abnormal uterine bleeding were consecutively enrolled. All participants had real-time 2D-TVS and, later, blinded off-line 3D-TVS to diagnose adenomyosis. Results were compared with a detailed histopathological examination of the inner myometrium as gold standard. Results Prevalence of adenomyosis of the inner myometrium was 29%. For 2D-TVS and 3D-TVS, respectively, the diagnostic accuracy was sensitivity 72% (95% CI 53 to 86) and 69% (95% CI 50 to 84); specificity 76% (95% CI 65 to 85) and 86% (95% CI 76–93); and area under the curve (AUC) 0.74 (95% CI 0.7 to 0.8) and 0.77 (95% CI 0.7 to 0.9). Specificity of 3D-TVS was not statistically significantly better than 2D-TVS; the difference between them almost reached statistical significance (P = 0.06). The most accurate three-dimensional feature was junctional zone irregularity (JZ max –JZ min ≥5mm) (AUC: 0.78). A combination of two or more two-dimensional and two or more three-dimensional features was highly accurate (AUC: 0.77). Conclusions For diagnosing adenomyosis of the inner myometrium, 3D-TVS offers a high accuracy similar to 2D-TVS. Identification of junctional zone irregularity with 3D-TVS may be beneficial to diagnosis. Two or more two-dimensional features and two or more three-dimensional features combined may give a more objective diagnosis, and may be useful for clinical practice and future research. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of our study was to evaluate MRI as a tool to examine placental morphology in a murine model in comparison to classical histology techniques.Methods: Assessment of placental samples (n = 24) from C57Bl/6 J mice was performed using MR imaging and histomorphological analyses. To optimize image contrast for MRI, a protocol for gadolinium-mediated enhancement of placental tissue was established. To test method sensitivity, placental zone assessment with MRI and histology was applied to a model of prenatal stress exposure known to affect placental morphology (n = 10). Mean data acquisition time for both methods was estimated. Difference between groups was calculated using the Mann-Whitney U test.Results: Tissue fixation with formaldehyde and staining with gadolinium resulted in the best image quality. Placental functional zones were identified and measured with both MRI and histology. MRI and histology were able to detect changes in the L/Jz ratio upon a prenatal stress challenge (p = 0.001; p = 0.003). Data acquisition time was shorter using MRI assessment.Conclusions: Ex vivo MRI analyses of murine placental functional morphology with MRI are feasible and results are comparable to time-consuming histology. Both MRI and histology allow the detection of experimentally induced morphological tissue alterations. [ABSTRACT FROM AUTHOR]