Search

Adenomyosis is a common benign uterine disorder in which ectopic endometrial glands extend into the myometrium. Adenomyosis is increasingly diagnosed in young women, affecting 20%-35% of women of reproductive age. Features of adenomyosis can be seen with either US or MRI, especially with newer imaging technology. With advances in reproductive endocrinology as well as a trend toward later maternal age, adenomyosis is increasingly noted during pregnancy, often while performing imaging for other reasons. Hormonal changes during pregnancy alter the appearance of adenomyosis, which includes diffuse, focal, and cystic adenomyosis. Recognizing these imaging changes in pregnancy proves essential for accurately diagnosing adenomyosis as a benign condition, as it mimics serious placental and myometrial abnormalities. Using a lower-frequency US transducer or MRI can be helpful in distinguishing among these entities. Describing the location of adenomyosis in relationship to the site of placentation is also important. Diagnosing adenomyosis is crucial because it can be associated with poor pregnancy outcomes, including spontaneous abortion, preterm birth, and fetal growth restriction. Adenomyosis is also a risk factor for preeclampsia. Intramural ectopic pregnancy is a rare but serious condition that can mimic cystic adenomyosis, and comparison with prepregnancy images can help differentiate the two conditions. The authors review the unique imaging characteristics of adenomyosis in pregnancy, focusing on accurate diagnosis of an underrecognized benign condition that can mimic myometrial and placental pathologic conditions.©RSNA, 2021.

This study aimed to relate the serum levels of energy indicators (glucose and beta-hydroxybutyrate) and calcium to the occurrence of uterine and mammary diseases in the transition period of Holstein cows. One hundred and fifteen Holstein cows from a commercial herd were monitored starting one week before calving and during the first 2 weeks after calving. The presence of subclinical mastitis was monitored for 3 weeks postpartum using the California Mastitis Test (CMT) and somatic cell counting. Positive samples of subclinical mastitis were analyzed for bacterial identification. Clinical mastitis was monitored for 6 weeks postpartum, using data that were recorded by the farmer based on some established definitions. The presence of uterine disorders was identified for 3 weeks postpartum by clinical examination. Blood collections were made from all cows for determining calcium, glucose, and β-hydroxy-butyrate (BHB) the week before calving and twice during the postpartum (days 5 and 15 postpartum). A group of 70 healthy cows was used as control. Clinical mastitis was identified in 20% of the cows, subclinical mastitis in 10.4% and clinical metritis in 8.7% of the cows. The bacterial agents with the highest occurrence in subclinical mastitis cases were coagulase-negative Staphylococcus and Streptococcus. No relationships were observed between any of the biochemical metabolite studied and the uterine and mammary diseases in the cows during the studied period. Resumen Este estudio tuvo por objetivo relacionar valores séricos de indicadores energéticos (glucosa y beta-hidroxibutirato) y calcio con la ocurrencia de trastornos uterinos y mamarios durante el periodo de transición en vacas holstein. Ciento quince vacas holstein de un rebaño comercial fueron monitoreadas en la semana previa al parto y durante las primeras dos semanas después del parto. La presencia de mastitis subclínica fue monitoreada por tres semanas posparto mediante la prueba de mastitis California (CMT) y conteo de células somáticas. Las muestras positivas a mastitis subclínica fueron analizadas para identificación bacteriana. La mastitis clínica fue monitoreada durante seis semanas posparto, usando datos registrados en el rebaño. La presencia de trastornos uterinos fue identificada durante tres semanas posparto mediante examen clínico. Se realizaron muestras de sangre de todas las vacas para determinar calcio, glucosa y β-hidroxibutirato la semana anterior al parto y dos veces en el posparto (días 5 y 15). Un grupo de 70 vacas sanas fue usado como control. Un 20% de las vacas presentó mastitis clínica, el 10,4% mastitis subclínica y el 8,7% metritis clínica. Los agentes bacterianos con mayor ocurrencia en los casos de mastitis subclínica fueron Staphylococcus coagulasa-negativos y Streptococcus. No se observó relación de ninguno de los metabolitos bioquímicos con los trastornos uterinos o mamarios en las vacas durante el periodo estudiado.

Experimental studies have demonstrated statin-induced toxicity for ovary and uterus. However, the safety of statins on the functions of ovary and uterus in real-world clinical settings remains unknown. The aim of this study was to identify ovary and uterus related adverse events (AEs) associated with statin use by analyzing data from FDA Adverse Event Reporting System (FAERS). We used OpenVigil 2.1 to query FAERS database. Ovary and uterus related AEs were defined by 383 Preferred Terms, which could be classified into ten aspects. Disproportionality analysis was performed to assess the association between AEs and statin use. Our results suggest that statin use may be associated with a series of ovary and uterus related AEs. These AEs are involved in ovarian cysts and neoplasms, uterine neoplasms, cervix neoplasms, uterine disorders (excl neoplasms), cervix disorders (excl neoplasms), endocrine disorders of gonadal function, menstrual cycle and uterine bleeding disorders, menopause related conditions, and sexual function disorders. Moreover, there are variabilities in the types and signal strengths of ovary and uterus related AEs across individual statins. According to our findings, the potential ovary and uterus related AEs of statins should attract enough attention and be closely monitored in future clinical practice.

Adenomyosis is a nonmalignant uterine disorder in which endometrial tissue exists within and grows into the myometrium. Animal models have generated limited insight into the still-unclear pathogenesis of adenomyosis, provided a platform for preclinical screening of many drugs and compounds with potential as therapeutics, and elucidated mechanisms underlying the pain and fertility issues that occur in many women with the disease. Spontaneous adenomyosis has been studied in nonhuman primates, primarily in the form of case reports. Adenomyosis is routinely experimentally induced in mice through methods such as neonatal tamoxifen exposure, pituitary engraftment, and human tissue xenotransplantation. Several studies have also reported hormonal or environmental toxicant exposures that give rise to murine adenomyosis, and genetically engineered models have been created that recapitulate the human-like condition, most notably involving alteration of β-catenin expression. This review describes the animal models for adenomyosis and their contributions to our understanding of the factors underpinning the development of symptoms. Animal models represent a unique opportunity for understanding the molecular basis of adenomyosis and developing efficacious treatment options for affected women. Herein, we assess their different potentials and limitations with regard to identification of new therapeutic interventions and reflect on future directions for research and drug validation.

Endometriosis is a gynecological disease characterized by pain and infertility. The diagnosis is very often made during the infertility work-up, together with other reproductive diseases and uterine disorders. A retrospective cohort study was conducted on infertile women with clinical or ultrasound suspect of endometriosis, undergoing an ultrasound (US) evaluation by a team of expert sonographers (

Acute pelvic pain in the nonpregnant woman is one of the most common conditions requiring emergent medical evaluation in routine clinical practice. Although clinical evaluation and laboratory testing are essential, imaging plays a central role. Although various adnexal and uterine disorders may result in acute pelvic pain of gynecologic origin, other nongynecologic disorders of the gastrointestinal and genitourinary systems may likewise result in acute pelvic pain. Ultrasound is first choice for initial evaluation of acute pelvic pain of gynecologic origin. Computed tomography is performed if pelvic sonography is inconclusive, or if a suspected disorder is nongynecologic in origin.

Benign uterine disorders, including uterine fibroids (UF) and adenomyosis (AM), can impact the life quality and fertility of women of reproductive age. Transvaginal ultrasound (TVUS) has long been used for their early identification, but its combined use with elastography seems to improve diagnostic accuracy of UF and AM. Thus, a prospective pilot study was conducted on 79 patients who underwent hysterectomy (25 microscopically diagnosed with AM and 53 with UF), with the aim of assessing the ability of TVUS combined with strain ratio elastography (SE) to accurately diagnose and distinguish UF and AM. Significantly higher mean and maximal strain ratio (SR) values were identified for patients with histologically confirmed AM as opposed to those with UF (p &lt, 0.001). Diagnostic sensitivity and specificity, calculated in comparison with histology results, were higher for UF than AM. Receiver operating characteristic (ROC) analysis was applied between the two study groups, revealing cutoff values of 7.71 for mean SR and 8.91 for maximal SR, respectively, with good sensitivity and specificity parameters (100% and 96.23%, 96% and 96.23%). Our results support the use of TVUS in combination with SE for the positive and differential diagnosis of UF and AM, through identification of their particular tissue stiffness features.

Infertility is a major social and clinical problem affecting 13–15% of couples worldwide. The pelvic causes of female infertility are categorized as ovarian disorders, tubal, peritubal disorders, and uterine disorders. Appropriate selection of an imaging modality is essential to accurately diagnose the aetiology of infertlity, since the imaging diagnosis directs the appropriate treatment to be instituted. Imaging evaluation begins with hystero- salpingography (HSG), to evaluate fallopian tube patency. Uterine filling defects and contour abnormalities may be discovered at HSG but usually require further characterization with pelvic ultrasound (US), sono-hysterography (syn: hystero-sonography/saline infusion sonography) or pelvic magnetic resonance imaging (MRI), when US remains inconclusive. The major limitation of hysterographic US, is its inability to visualize extraluminal pathologies, which are better evaluated by pelvic US and MRI. Although pelvic US is a valuable modality in diagnosing entities comprising the garden variety, however, extensive pelvic inflammatory disease, complex tubo-ovarian pathologies, deep-seated endometriosis deposits with its related complications, Mulllerian duct anomalies, uterine synechiae and adenomyosis, often remain unresolved by both transabdominal and transvaginal US. Thus, MRI comes to the rescue and has a niche role in resolving complex adnexal masses, endometriosis, and Mullerian duct anomalies with greater ease. This is a review, based on the authors’ experience at tertiary care teaching hospitals and aims to provide an imaging approach towards the abnormalities which are not definitively diagnosed by ultrasound alone.

Endometritis is an inflammation of the endometrium associated with bacterial infection. The pathogenesis of endometritis in cows is still not completely understood. The combined analysis of the markers of inflammation and oxidative stress has contributed to a better understanding of disease mechanisms, but is still unexplored in uterine disorders. Moreover, research provides evidence about an important role of the vagus nerve in regulating the innate immune function through the cholinergic anti-inflammatory pathway in response to bacterial infections. This new pathway has demonstrated a critical role in controlling the inflammatory system. The aim of this study was to evaluate the activity of cholinesterase in total blood, lymphocytes, and serum of dairy cows with clinical and subclinical endometritis. Sixty-one Holstein cows, between 30 and 45 days in milk, were classified into 3 groups of animals: presenting clinical endometritis (n = 22), subclinical endometritis (n = 17), and healthy (n = 22). Mean leukocyte counts did not differ among groups, but the neutrophil number was significantly higher in cows with clinical endometritis than those in healthy animals. Also, serum concentration of interleukin-1beta (pg/mL) was significantly higher in cows with endometritis. The activity of acetylcholinesterase in blood and lymphocytes increased in both groups with endometritis. Animals with endometritis presented an increase in lipid peroxidation, but the antioxidant enzyme activity (catalase levels) was higher in endometritis groups than in normal cows. In conclusion, the inflammatory process of clinical and subclinical endometritis leads to systemic lipid peroxidation despite the compensatory increase of the antioxidant enzyme. These data also provide evidence of an important role of the cholinergic pathway in regulating dairy cows with clinical and subclinical endometritis.

Wnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential for the development of glandular epithelia in the intestine and stomach, but their existence in the developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models to identify Lgr5-expressing cells in the developing uterus and to evaluate their stem cell identity and function. Lgr5 is broadly expressed in the uterine epithelium during embryogenesis, but becomes largely restricted to the tips of developing glands after birth. In-vivo lineage tracing/ablation/organoid culture assays identify these gland-resident Lgr5high cells as Wnt-dependent stem cells responsible for uterine gland development. Adjacent Lgr5neg epithelial cells within the neonatal glands function as essential niche components to support the function of Lgr5high stem cells ex-vivo. These findings constitute a major advance in our understanding of uterine development and lay the foundations for investigating potential contributions of Lgr5+ stem/progenitor cells to uterine disorders., Uterine gland development is essential for successful embryo implantation, decidua formation and placental development. Here the authors demonstrate that neonatal Wnt-dependent Lgr5 expressing stem/progenitor cells at the tips of developing glands are indispensable for uterine gland development.

The objective of current study was to evaluate the association of uterine health between serum glucose and beta hydroxybutyric acid (BHB) levels, body condition score (BCS), calving type (eutocia or dystocia), calving season (summer or winter) and parity in Holstein dairy cows and to determine the cut-off levels for these parameters. While cows without any reproductive problems during calving and pp 50 days enrolled into control group (n:27), cows with metritis and endometritis in the same days included the other one (n:33). BCS were recorded at dry period (-60 days), calving and pp 30 days. Blood samples were collected at d 21±3 prepartum and d 15 and d 35 for determination of glucose and BHB levels. Parity, calving type and calving season of cows were recorded and their relationship with uterine health were evaluated. Receiver operating characteristics (ROC) curves for BHB, glucose and BCS were used to determine the cow-level thresholds for the development of uterine problems. In addition, pairwise comparisons of area under the curve (AUC) of ROC curves for the thresholds of glucose, BHB, BCS predicting uterine problems were determined. While the BHB concentration were higher, glucose concentration were lower at 21±3 days prepartum and 15 days postpartum in cows with uterine problems. Serum glucose and BHB concentrations at 21±3 days prepartum and 15 days were also the best predictor for the diagnosis of uterine problems. However, BCS had no significant effect on development of uterine problems. There were also no significant effect of parity, calving season and type on development of uterine problems. In conclusion, serum glucose and BHB concentrations were the risk factors for uterine problems but BCS had no significant role on development of uterine disorders., Sunulan çalışmada Holstein ırkı ineklerde uterus enfeksiyonlarının; doğum şekli, doğum mevsimi, doğum sayısı, vücut kondisyon skoru, serum BHB ve glikoz konsantrasyonu ile ilişkisinin değerlendirilmesi ve anılan parametreler için kritik eşik değerlerin belirlenmesi amaçlandı. Doğum ve postpartum 50 gün aralığında reprodüktif sorun yaşamayan inekler kontrol grubuna (n=27), anılan süre içinde metritis ve endometritis saptanan inekler de uterus problemli inekler grubuna (n=33) dahil edildi. Gruplara ait ineklerin vücut kondisyon skorları kuruya çıkarken (-60. gün), doğum zamanında ve postpartum 30. günde belirlendi. Prepartum 21. gün, postpartum 15. ve 35. günlerde kan glikoz ve BHB konsantrasyonları belirlendi. İneklerin doğum sayıları, doğum şekli ve doğum mevsimi bilgileri toplanarak uterus durumu ile ilişkisi araştırıldı. BHB, Glikoz ve VKS değerleri ROC analizi ile değerlendirilerek her bir örnekleme zamanındaki uterus enfeksiyonlarının varlığının tahmin edilmesi amacıyla kritik eşik değerler saptandı. Uterus problemli ineklerin prepartum 21. günde ve pp 15. günde kan serum BHB düzeylerinin daha yüksek, glikoz düzeylerinin ise daha düşük olduğu gözlendi. Ayrıca, serum BHB ve glikoz konsantrasyonlarının prepartum 21. günde ve postpartum 15. günde en iyi ön belirteç oldukları gözlendi. VKS’nin uterus problemleri üzerine herhangi bir etkisi saptanmadı. Ayrıca doğum sayısı, doğum mevsimi ve doğum tipinin de uterus enfeksiyonlarının gelişimine herhangi bir etkisinin olmadığı gözlemlendi. Sonuç olarak, serum glikoz ve BHB düzeylerinin uterus problemleri açısından birer risk faktörü olduğu, ancak VKS’nin uterus enfeksiyonlarının gelişiminde belirgin bir role sahip olmadığı gözlendi.

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.

Transcriptomic approaches are increasingly used in reproductive medicine to identify candidate endometrial biomarkers. However, it is known that endometrial progression in the molecular biology of the menstrual cycle is a main factor that could affect the discovery of disorder-related genes. Therefore, the aim of this study was to systematically review current practices for considering the menstrual cycle effect and to demonstrate its bias in the identification of potential biomarkers. From the 35 studies meeting the criteria, 31.43% did not register the menstrual cycle phase. We analysed the menstrual cycle effect in 11 papers (including 12 studies) from Gene Expression Omnibus: three evaluating endometriosis, two evaluating recurrent implantation failure, one evaluating recurrent pregnancy loss, one evaluating uterine fibroids and five control studies, which collected endometrial samples throughout menstrual cycle. An average of 44.2% more genes were identified after removing menstrual cycle bias using linear models. This effect was observed even if studies were balanced in the proportion of samples collected at different endometrial stages or only in the mid-secretory phase. Our bias correction method increased the statistical power by retrieving more candidate genes than per-phase independent analyses. Thanks to this practice, we discovered 544 novel candidate genes for eutopic endometriosis, 158 genes for ectopic ovarian endometriosis and 27 genes for recurrent implantation failure. In conclusion, we demonstrate that menstrual cycle progression masks molecular biomarkers, provides new guidelines to unmask them and proposes a new classification that distinguishes between biomarkers of disorder or/and menstrual cycle progression.

The myometrium is the smooth muscle layer of the uterus that generates the contractions that drive processes such as menstruation and childbirth. Aberrant contractions of the myometrium can result in preterm birth, insufficient progression of labor, or other difficulties that can lead to maternal or fetal complications or even death. To investigate the underlying mechanisms of these conditions, the most common model systems have conventionally been animal models and human tissue strips, which have limitations mostly related to relevance and scalability, respectively. Myometrial smooth muscle cells have also been isolated from patient biopsies and cultured in vitro as a more controlled experimental system. However, in vitro approaches have focused primarily on measuring the effects of biochemical stimuli and neglected biomechanical stimuli, despite the extensive evidence indicating that remodeling of tissue rigidity or excessive strain is associated with uterine disorders. In this review, we first describe the existing approaches for modeling human myometrium with animal models and human tissue strips and compare their advantages and disadvantages. Next, we introduce existing in vitro techniques and assays for assessing contractility and summarize their applications in elucidating the role of biochemical or biomechanical stimuli on human myometrium. Finally, we conclude by proposing the translation of “organ on chip” approaches to myometrial smooth muscle cells as new paradigms for establishing their fundamental mechanobiology and to serve as next-generation platforms for drug development.

BACKGROUND Adenomyosis, characterized by the presence of islands of endometrial tissue surrounded by hypertrophic smooth muscle cells within the myometrium, is one of the most challenging uterine disorders in terms of diagnosis and management. Adenomyosis presents with pelvic pain, excessive uterine bleeding, anemia and infertility. The relative contributions of abnormal endometrial tissue and myometrial smooth muscle cells to the development and growth of adenomyosis are not well understood. Moreover, there is continuing debate on the origins of adenomyosis; two competing theories describe the invagination of basal endometrium into the myometrium or the metaplastic differentiation of remnant endometrial stem/progenitor cells within the myometrium. OBJECTIVE AND RATIONALE A recent series of next-generation sequencing (NGS) studies have provided the best scientific evidence thus far regarding the cellular origins of adenomyosis and the contributions of new signaling pathways to its pathogenesis, survival, and growth. These seminal studies on endometrium, adenomyosis and endometriosis demonstrate or support the following key points. (i) Mutations of KRAS map to both intracavitary endometrial tissue and proximally located adenomyotic samples, supporting the invagination theory of pathogenesis. Driver mutations found in smooth muscle cells of uterine fibroids are absent in adenomyosis. (ii) KRAS and other less frequent mutations are limited to endometrial-type epithelial cells. They are also observed in endometriosis, indicating that the disease process in adenomyosis is similar to that in endometriosis and distinct from that of uterine fibroids. (iii) Activating mutations of KRAS stimulate specific pathways to increase cell survival and proliferation and are associated with progesterone resistance in adenomyosis. Together, these findings suggest that distinct cell populations in eutopic endometrial tissue play key roles in the etiology of adenomyosis. Dependence on ovarian steroids and ovulatory cycles for disease severity is a unique feature of adenomyosis. In this context, common patterns of aberrant gene expression have been reported both in adenomyosis and endometriosis. These include pathways that favor increased estrogen biosynthesis, decreased estradiol metabolism, a unique estrogen receptor beta (ESR2)-driven inflammatory process, and progesterone resistance due to decreased progesterone receptor expression. Since adenomyosis exhibits a uniquely estrogen-driven inflammatory process and progesterone resistance, we discuss the interactions between these molecular characteristics and signaling pathways induced by the newly discovered KRAS mutations. SEARCH METHODS We conducted a comprehensive search using PubMed for human and animal studies published until 2020 in the following areas: adenomyosis, endometriosis, endometrium, NGS, whole-exome sequencing, whole-genome sequencing, RNA sequencing, targeted deep sequencing, epigenetics, driver mutation, KRAS, progesterone resistance, estrogen action and steroid production. OUTCOMES Targeted deep sequencing analyses of epithelial cells in adenomyosis and adjacent basalis endometrial glands demonstrated recurring KRAS mutations in both cell types. This finding suggests that adenomyosis originates from basalis endometrium. Epithelial cells of the endometrium, adjacent adenomyosis and co-occurring endometriosis also share identical KRAS mutations. These findings suggest both adenomyosis and endometriosis are oligoclonal tissues that arise from endometrial cell populations carrying a specific driver mutation that most commonly affects the KRAS gene. WIDER IMPLICATIONS Adenomyosis usually follows an event such as pregnancy that has disrupted the integrity of the endometrial–myometrial junction followed by repetitious menstrual episodes that increase the likelihood of the entrapment of the basalis endometrium within the myometrium. Glandular epithelial cells carrying KRAS mutations and located within the deep crypts of basalis endometrium may become entrapped and invade myometrial tissue to give rise to adenomyosis. Evidence suggests that KRAS mutations may be responsible, in part, for previously observed phenomena such as prolonged cell survival and progesterone resistance in adenomyosis.

PROBLEM Intrauterine adhesion (IUA) is a uterine disorder with partial or total obstruction of the uterine cavity and/or the cervical canal primarily caused by intrauterine operations and infections. It is the most common cause of uterine infertility and recurrent abortion. However, the reasons for endometrium repair disorders in patients with IUA are still unclear. While increasing evidence demonstrates that endometrial mesenchymal stem/stromal cells (EMSCs) contribute to the regeneration and repair of endometrium, the roles of EMSCs in the pathogenesis of IUA have not been reported. METHODS AND STUDY We investigated the differences of phenotype and biological characteristics between EMSCs from women with IUA and healthy women. Firstly, the fibrosis of endometrium were measured by immunohistochemistry and Masson staining. Second, we used immunofluorescence to detect the location of EMSCs in endometrial tissue, and the proportion of CD146+ CD140b+ in the two groups was compared by flow cytometry. Then, plate colony formation experiment, CCK-8 assay, flow cytometry, would-healing assay, and transwell invasion experiment were used to compare the cloning ability, proliferation, cell cycle, migration and invasion capabilities respectively. Finally, we compared the potential angiogenesis and immunosuppression capabilities. RESULTS Our results showed that there were fewer CD146+ CD140b+ cells in patients with IUA, and the clone-forming, migration, invasion, angiogenic and immunosuppressive abilities of the EMSCs of patients with IUA were significantly decreased compared with those of healthy women. CONCLUSION There are some differences between the EMSCs of IUA patients and healthy women, which may be related to the occurrence of IUA and dysfunction of endometrium.

Granulosa cell tumour is a common ovarian pathology in bitches. Depending on its hormonal production, this tumour often induces persistent oestrus signs and uterine disorders. Chronic treatment with progesterone contraceptives has been associated with endometrial mineralisation in bitches. The authors describe the case of a three-year-old female entire mastiff dog with a one-year history of chronic hyperoestrogenism signs and anorexia. Serum biochemistry and haematology revealed moderate leucocytosis. Abdominal ultrasound showed dilated uterine horns with anechoic fluid in the lumen, small cystic structures, and multiple stippled hyperechoic lesions with mild acoustic shadowing and comet tail artefact along the endometrial wall. Furthermore, cystic structures were observed in the right ovary. After surgery, histopathological study revealed the presence of endometrial hyperplasia-pyometra complex, endometrial mineralisation and a granulosa cell tumour. To the best of the authors’ knowledge, this is the first report of endometrial mineralisation associated with ovarian granulosa cell tumour in a bitch.

Endometriosis and uterine fibroids (leiomyomas) are benign gynecological disorders affecting 5-15% of women of reproductive age. They cause a wide range of symptoms including mild to severe pelvic pain and infertility. Due to a paucity of proper study models, hormonal and cellular mechanisms driving the pathology of endometriosis and fibroid development and growth remain unclear. Therefore, in the current study, we established 3D spheroid/organoid cultures from human uterine epithelial and Stro-1+/CD44+ myometrial stem cells and also from cells isolated from normal proliferative phase endometrium. Uterine organoid cultures were derived from endometrial epithelial and myometrial cells isolated from women who were not receiving exogenous hormones at the time of laparoscopy or hysterectomy. They were embedded in Matrigel, and grown in culture media. To determine whether spheroids/organoids were responsive to steroid hormones, the cultures were treated in presence or absence of estradiol (E2), progesterone (P4) or the combination (E2+P4) in serum free culture media. Time-dependent spheroid/organoid-growth curves and morphological analyses were used to define growth characteristics of endometrial and myometrial organoids. Subsequently, immunohistochemical colocalization of steroid hormone receptors (estrogen receptor alpha (ER-α) and progesterone receptor (PR-A\B), alpha smooth muscle actin (α-SMA; myometrial cell marker), vimentin (stromal cell marker) and E-cadherin (endometrial epithelial cell marker) was assessed. Epithelial organoids expressed only E-cadherin in the absence of hormonal treatment. Myometrial organoids expressed α-SMA and vimentin. No expression of E-cadherin was observed in myometrial organoids. However, we observed the expression of ER-α and PR-A\B when organoids were treated with E2+P4 in a time-dependent manner. Stro-1+/CD44+ myometrial stem cells differentiated into α-SMA and fibroblast/stromal cells and response to sex hormones. These findings suggest human uterine organoid cultures retained their characteristic cellular responses to E2+P4 and could be maintained long-term in ex vivo culture. Thus, the current 3D uterine organoid systems show high expansion capacity with retention of phenotypical and functional properties, which can be used for uterine pathophysiological studies, drug discoveries and drug repositioning.

The objective of this study was to assess how uterine disorders alter the lying behaviour and plasma biomarkers in dairy cows. 34 multiparous cows were retrospectively classified into three groups according to the first uterine disorder that cows were diagnosed with: retained placenta (RP), metritis (MET), or healthy (H; cows without any clinical disease). Lying time (LT) and duration of lying bouts (LB) were monitored between 6 weeks prior to and 8 weeks after calving via the AfiAct II pedometer. Blood samples were collected routinely between 14 days before and 28 days after calving. Data was analysed using Proc MIXED of SAS ver. 9.4. Regardless of grouping, both LT and LB were longer (P 0.01) in the prepartum period (774 ± 16.6 min/day and 89.9 ± 2.1 min/bout) than in the first 28 days after calving (DFC; 653 ± 16.7 min/day and 63.7 ± 2.1 min/bout). Cows with RP had longer LT than healthy cows during the last 3 weeks before calving (837 ± 30.9 vs. 735 ± 27.1 min/day; P 0.05). LT in cows with MET and healthy cows were not significantly different. The LB was similar among groups, averaging 76.1 ± 3.4 min/bout in healthy cows, 73.2 ± 3.8 min/bout in cows with RP, and 75.2 ± 3.7 min/bout in cows with MET (P 0.05). Compared with healthy cows, cows with RP laid down longer and stood up for shorter times (P 0.05), particularly before calving. In addition, cows with RP had increased mobilization of body stores and more pronounced inflammatory status, as demonstrated by plasma haptoglobin (P = 0.04) and albumin (P 0.01) concentrations. Our data suggest that automatic monitoring of lying behaviour could help identify cows at increased risk of developing certain disorders, such as RP.

Summary Disorders of the female genital tract are among the most common disorders in pet guinea pigs (Cavia porcellus); however, knowledge of many aspects of these disorders is sparse, especially regarding their incidence and age distribution. Ovarian cysts, as the most common genital tract disorder in guinea pigs, have been investigated in detail; however, information on the nature of these cysts is inconsistent. The present study reviewed genital tract disorders occurring within 655 full post-mortem examinations of intact female pet guinea pigs and 64 female genital tract biopsies examined over a 22.5 year period. Age distribution was determined from 550 post-mortem examinations of animals of known age. Genital tract disorders were found in 295 post-mortem examinations (45.0%) in animals with a median age of 52 months. Additionally, disorders were found in all genital tract biopsy samples from guinea pigs with a median age of 48 months. The incidence of genital tract diseases increased from 1.5% in guinea pigs ≤6 months of age to up to 77.8% in animals >6 years of age. Ovarian cysts were the most common genital tract disorder, found in 245 of the 655 post-mortem cases (37.4%) and 38 of 43 ovarian biopsy samples (88.4%). The incidence of ovarian cysts increased with advancing age, reaching 75.6% in animals >6 years. In 119 cases, histopathology and immunohistochemistry confirmed cystic rete ovarii as the only cyst type. A Fallopian tube adenoma was found in a single case, so disorders of the Fallopian tube should be considered rare. Uterine disorders were diagnosed in 17.4% of the post-mortem examinations and 98.1% of uterine biopsy samples. Uterine neoplasia, hyperplasia and inflammation were common, but occurred at different ages. The incidence of uterine neoplasia and hyperplasia was higher in older animals (>15% in guinea pigs >6 years), while the incidence of uterine inflammation was the highest (17.9%) in animals aged 7–12 months. An association between ovarian cysts and uterine neoplasia or hyperplasia was not evident. Vaginal disorders were rare and included leiomyoma, polyps and vaginitis.

Genital tract disorders, especially uterine disorders, are the most common conditions of the female pet rabbit (Oryctolagus cuniculus); however, there have been few large studies of diseases of the female genital tract of this species. The present study examined diseases of the ovaries, Fallopian tubes, uterus and vagina, retrospectively over a period of 22 years, and included 854 full post-mortem examinations of female pet rabbits and 152 female genital tract biopsy samples. The age distribution of uterine neoplasia, endometrial hyperplasia and uterine inflammation was determined in the post-mortem cases. Uterine disorders were a common finding, occurring in 26.8% of all full necropsy examinations and in almost all genital tract biopsy samples. Uterine tumours (n = 205) were the most common uterine pathology, with adenocarcinoma being the most frequent tumour type. Metastasis was found in 46.2% of rabbits with uterine adenocarcinomas diagnosed at post-mortem examination, with metastatic spread to the lung occurring in 79.1% of these animals. The second most common uterine pathology was endometrial hyperplasia, which was glandular-cystic in most cases. The incidence of uterine tumours and endometrial hyperplasia increased with age, while endometrial hyperplasia was found more commonly in slightly younger animals. In contrast, uterine inflammation, the third most common finding, was found predominately in young to middle-aged rabbits. Ovarian disorders were found rarely at post-mortem examinations (3.3% of all animals), but comprised 16.9% of biopsy samples. Of these, ovarian cysts, especially follicular cysts, and secondary tumours were found most frequently. Disorders of the Fallopian tube and the vagina were found in1% of cases and should be considered rare.

There are many reasons for sterility, and uterine malformations are of the greatest concern. Among uterine disorders, myomas play a significant role and are present in 27% of infertile women. The occurrence of myomas is frequent - 20-40% in women of reproductive age. Thus, for those infertile patients surgical treatment may be needed to preserve an opportunity to conceive. This case report refers to an uterine rupture at 28 weeks of gestation after laparoscopic myomectomy (3 months before conceiving). The myomectomy was conducted correctly and two layers of sutures on the myometrium were performed. The purpose of the myomectomy in a young woman should be well considered. In cases of infertility, removal of the lesions is usually necessary to give the patient a chance of pregnancy. At the same time, the risk of uterine rupture is increased. There are some suggestions referring to myomectomy to reduce the risk of uterine rupture in a subsequent pregnancy. It seems that the method of sewing the uterine closure is crucial. For example, multilayer uterine stitches, preservation of the endometrial cavity, and avoidance of using electrosurgery to prevent devascularization (to avoid haematoma formation) should be taken into consideration to prevent weakness of the wall of the uterus. Uterine scars differ histologically and biochemically.

Adenomyosis is a commonly diagnosed estrogen-dependent gynecological disorder that causes pelvic pain, abnormal uterine bleeding, and infertility. Despite its prevalence and severity of symptoms, its pathogenesis and etiology have not yet been elucidated. The aim of this manuscript is to review the different hypotheses on the origin of adenomyotic lesions and the mechanisms involved in the evolution and progression of the disease. Two main theories have been proposed to explain the origin of adenomyosis. The most common suggests involvement of tissue injury and the repair mechanism and claims that adenomyosis results from invagination of the endometrial basalis into the myometrium. An alternative theory maintains that adenomyotic lesions result from metaplasia of displaced embryonic pluripotent Müllerian remnants or differentiation of adult stem cells. Previous investigations performed in human adenomyotic lesions and corroborated by studies in mice supported the involvement of the epithelial-mesenchymal transition process in the early stages of progression and spread of adenomyosis. However, studies conducted in a recently developed baboon model indicate that collective cell migration may be implicated in the later events of invasion. This suggests that the invasiveness of this complex uterine disorder is not driven by a single mechanism of migration but by a time-dependent combination of two processes.

Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of reproductive age because of diagnostic imaging advancements. The new epidemiological scenario and the clinical evidence of pelvic pain, abnormal uterine bleeding and infertility are changing the classic perspective of adenomyosis as a premenopausal disease. In the last decade, the evaluation of multiple molecular mediators has improved our knowledge of pathogenic mechanisms of adenomyosis, supporting that this is an independent disease from endometriosis. Although they share common genetic mutations and epigenetic changes in sex steroid hormone receptors and similar inflammatory mediators, an increasing number of recent studies have shown pathogenic pathways specific for adenomyosis. A PubMed search up to October 2016 summarizes the key mediators of pain, abnormal uterine bleeding and infertility in adenomyosis, including sex steroid hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors and neuroangiogenic factors.

Gynecologic emergencies include various diseases that result from adnexal and uterine disorders. Adnexal disorders may be classified into the following three categories: (a) disorders that cause hemorrhage (hemorrhagic ovarian cysts and ectopic pregnancies); (b) disorders related to adnexal tumors (adnexal torsion and rupture of ovarian tumors); and (c) disorders related to pelvic inflammatory disease, such as tubo-ovarian abscesses. Unusual adnexal torsion, such as massive ovarian edema, isolated fallopian tube torsion, and paraovarian cyst torsion, has also been described. Uterine disorders in gynecologic emergencies may be classified into two categories: (a) acute fibroid complications, including red degeneration of a uterine leiomyoma, torsion of subserosal myomas, and torsion of the uterus; and (b) causes of acute uterine bleeding, including retained products of conception and uterine arteriovenous malformations. Some gynecologic diseases are self-limited, while others cause infertility or life-threatening infection or bleeding if left untreated. Therefore, prompt and accurate diagnosis is important for appropriate life-saving treatment and for the preservation of fertility. The imaging findings are important when evaluating acute gynecologic diseases because the symptoms and physical examination findings are often nonspecific and limited. Ultrasonography is the first-line imaging modality; however, when a definitive diagnosis cannot be established, computed tomography (CT) and magnetic resonance (MR) imaging may narrow the differential diagnosis. Appropriate management requires radiologists to be familiar with the CT and MR imaging features of gynecologic emergencies. With respect to rare conditions, radiologists should take into account the representative findings presented in this article to increase diagnostic accuracy. ©RSNA, 2017.

Introduction: Abnormal uterine bleeding is a common sign of a number of different uterine disorders ranging from dysfunctional (non organic) abnormalities or complications of pregnancy to organic lesions such as polyps, hyperplasia or carcinoma. Methods: This is a retrospective study conducted at Hospital of 2nd author during a period of 5 years (Jan 2008-Dec 2013). Histopathology records were retrieved and searched for cases of abnormal uterine bleeding. Relevant histopathological findings and clinical data were recorded and analyzed. The aim of the study was to determine the causes for abnormal uterine bleeding in women presenting to the hospital and to compare the histopathological findings at various age groups. Results: The age of patients ranged from 17 to 71 years with an average of 43 years. The most common cause of uterine bleeding was found to be proliferative phase endometrium; that were 649 cases (56.43%). Out of the pathological causes, the most common cause was found to be endometrial hyperplasia- 44 cases (3.82%). Endometrial carcinoma was found to be more common in the elderly postmenopausal women. A total of 6 cases (0.5%) of endometrial carcinoma were present. Conclusion: Endometrial hyperplasias and malignancies are common in increasing age group, especially in perimenopausal and postmenopausal women. So, a thorough work-up and diagnostic endometrial biopsy is therefore mandatory without delay in these patients to rule out malignancies.

Objective:Adenomyosis is a uterine disorder characterized by dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility. Pathogenesis indicates that endometrial cells invade and proliferate within myometrium, and inflammatory mediators participate to the intense painful symptoms. The aim of the present study was to investigate the messenger RNA (mRNA) and protein expression of inflammatory (interleukin 1β [IL-1β], corticotropin-releasing hormone [CRH], urocortin [Ucn]) and neurogenic (nerve growth factors [NGFs], synaptophysin [SYN], microtubule-associated protein 2 [MAP2]) factors in adenomyotic nodules.Materials and Methods:This prospective study enrolled 16 women, 8 women with nodular adenomyosis and 8 control women undergoing to hysterectomy. Specimens from adenomyotic nodules and eutopic endometrium were collected after surgery. Endometrial tissue was also obtained from the control group and also used for preparing primary culture of human endometrial stromal cells (HESCs). Messenger RNA e...

Asherman's syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury that adversely affects fertility and pregnancy. We have previously demonstrated that bone marrow-derived mesenchymal stem cells (BMDSCs) contribute to uterine repair after injury and that stem cells supplementation improves fertility. Here, we demonstrate that CXCL12 is the chemokine that mediates stem cell engraftment and functional improvement using a murine model of Asherman's syndrome. After uterine injury, we demonstrate that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4) antagonist, ADM3100, blocked stem cell recruitment. CXCL12 reduced, whereas ADM3100 increased fibrosis. CXCL12 treatment led to improved fertility and litter size, whereas ADM3100 treatment reduced fertility and litter size. ADM3100 prevented optimal spontaneous uterine repair mediated by endogenous CXCL12 production, reducing pregnancies after injury in the absence of supplemental CXCL12 administration; however, ADM3100 treatment could be partially rescued by CXCL12 augmentation. CXCL12 or other CXCR4 receptor agonists may be useful in the treatment of infertility or adverse pregnancy outcomes in Asherman's syndrome and other related uterine disorders.

Background: Hysterectomy is the most common operation performed by gynecologist, next to caesarean section. Currently, there are three main types of hysterectomy operations in practice for benign diseases-Abdominal hysterectomy (AH), vaginal hysterectomy (VH) and Laparoscopic hysterectomy (LH). Vaginal route for non-descentuterus is an acceptable method of hysterectomy. The objective of present study was to compare the operating time, intraoperative and postoperative complications between VH and TAH in non-descent uterus. Methods: The study was conducted in the Department of Obstetrics Gynaecology for a period of 18months at Darbhanga Medical College & Hospital, Laheriasarai, Bihar. Results: Over the study period 100 patients were taken, 50 patients underwent non-descent vaginal hysterectomy andlabelled as group A and 50 patients were under went total abdominal hysterectomy and labelled as group B. It wasseen that intraoperative complications and postoperative complications were less in group A patients and operating time is also less with group A patients when compared with group B patients. Conclusions: From the present study, it was concluded that NDVH is associated with less blood loss during surgery, quicker recovery, and early mobilization, less operative and less postoperative morbidity when compared to TAH. NDVH is a less invasive technique with shorter hospital stay and faster convalescence.

Dissertação de Mestrado Integrado em Medicina Veterinária O coelho de estimação tem-se tornado muito popular nos últimos anos. Das doenças mais diagnosticadas nesta espécie fazem parte as que afectam o aparelho reprodutor feminino, principalmente o útero. O adenocarcinoma uterino é uma doença muito frequente que afecta 50-80% das fêmeas com mais de 4 anos (Cintra et al. 2015). O presente estudo retrospectivo, com o objectivo de estudar a doença uterina na coelha, analisou os dados clínicos de 19 coelhas que haviam realizado Ovário-histerectomia (OVH) no Hospital Escolar Veterinário da Faculdade de Medicina Veterinária da Universidade de Lisboa (HEV-FMV-ULisboa) no período de Janeiro de 2017 a Julho de 2018. Foram registados dados relativos à idade, raça, motivo da OVH, sintomatologia apresentada, exames imagiológicos realizados e características macroscópicas e microscópicas dos úteros, de forma a perceber quais eram as doenças diagnosticadas mais frequentemente e a prevalência do adenocarcinoma relativamente a outras doenças. Cerca de 42% das fêmeas do presente estudo foram diagnosticadas com doença uterina e as alterações mais frequentes foram hematúria e palpação de massa no abdómen caudal durante o exame físico. A média de idades dos animais doentes foi de 4,1 anos sendo que todas as fêmeas com mais de 5 anos (21% da população) foram diagnosticadas com doença uterina. A doença mais frequente foi o adenocarcinoma (33,4%). As doenças uterinas de origem não tumoral diagnosticadas neste estudo foram os aneurismas venosos do endométrio e a hiperplasia quística do endométrio. A sintomatologia apresentada e os dados extraídos do exame físico revelaram-se inespecíficos. Os exames imagiológicos, nomeadamente a ultrassonografia, revelaram alterações ao nível do útero muito relevantes para o diagnóstico e a análise histopatológica revelou-se imprescindível para o diagnóstico definitivo das doenças. Totalizaram-se 12 relatórios histopatológicos analisados, sendo que 8 análises foram realizadas em úteros recolhidos durante o estágio curricular. Revelou-se importante a análise de úteros de coelhas de OVH electiva, uma vez que 2 úteros (16,7% do total das OVH electivas) sem alterações macroscópicas e de coelhas sem qualquer sintomatologia, apresentavam lesões compatíveis com doença uterina (um deles adenocarcinoma). A OVH é um procedimento cirúrgico simples, preventivo e curativo de doenças uterinas na coelha, portanto, deve ser recomendada precocemente pelos Médicos Veterinários. ABSTRACT - STUDY AND CHARACTERIZATION OF UTERINE DISORDERS IN FEMALE PET RABBITS - In recent years, rabbits have been growing in popularity as pets. Female reproductive problems, affecting the uterus are among the most often diagnosed disease in rabbits. Uterine adenocarcinoma is diagnosed in 50-80% of female rabbits over 4-years-old (Cintra et al. 2015). This retrospective study was set with the aim of studying uterine diseases in pet rabbits. Nineteen female rabbits, subjected to ovariohysterectomy (OVH) at the HEV-FMV-ULisboa, were studied between January 2017 and July 2018. Clinical records were reviewed and data on age, breed, cause of OVH, symptoms, diagnostic imaging and pathology recorded in order to study uterine diseases and adenocarcinoma prevalence. Forty two percent of female rabbits were diagnosed with a uterine disease. The most commonly presented signs were haematuria and a palpable mass in the caudal abdomen on physical examination. The mean age of animals diagnosed with uterine disease was 4.1 years and all females over 5-years-old (21% of population) were diagnosed with uterine disease. The most frequent disease was adenocarcinoma (33.4%). The non-neoplasic uterine disorders diagnosed within this study were endometrial venous aneurysms and endometrial hyperplasia. Physical examination findings were non-specific. The imaging exams were very relevant (mainly the abdominal ultrasound) to unveil major uterine changes. We also found the histopathologic analysis to be crucial to the final diagnosis. In total, 12 reports were analyzed and 8 of those uteri were collected during the internship. The uterine histopathology of females subject to elective surgical ovariohysterectomy was considered relevant, since two of the uteri (16.7% of elective OVH) without macroscopic changes showed changes compatible with uterine disease (including one case of adenocarcinoma). The OHV is a simple surgical procedure that can prevent and cure uterine diseases in pet rabbits and therefore should be recommended early by veterinarians. N/A

The innate and adaptive immune mechanisms are key components of regulation of reproductive physiological function and uterine disorders in equine uterus. The predominant immunological response in equine endometrium, characterized by an innate immune response, occurs under estrogens influence, in the follicular phase. Although, the increase in immune-related genes in equine endometrium during estrus has been suggested to play a role in uterine clearance after mating, immune cells and their product, i.e. cytokines play also mandatory role in the luteal development and maintenance, regression of equine corpus luteum, as well as in early pregnancy. Innate immune response is nonspecific and acts as the first line of defense against pathogens, foreign stimuli that include constituents of seminal fluid and local infections (endometritis). It has been recently established that a phagocytosis-independent mechanism to restrain bacteria, by means of neutrophil extracellular traps (NETs) formation, is involved in pathogenesis of in mare endometrial fibrosis (endometrosis). Moreover, persistent macrophages and mast cell activation could also have pro-fibrotic roles by secreting great amounts of pro-fibrotic factors and lead to fibrosis. This review will highlight the involvement of immune key components of the innate and adaptive immune system and their products in equine uterus and their contribution to reproductive physiological function and uterine disorders.

[EN]: Objective:To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. Design: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. Setting: Infertility research department affiliated with a university hospital. Patient(s): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II–IV endometriosis. Intervention(s): None. Main Outcome Measure(s): Genomewide gene expression and altered molecular functions in the endometrium of each uterine disorder. Result(s): Using robust analysis methods, we identified statistically significantly altered endometrial functions in all the uterine disorders. Cell cycle alterations were shared among all the pathologies investigated. Endometriosis was characterized by the down-regulation of ciliary processes. Among the endometriosis, ADC, and RIF samples, mitochondrial dysfunction and protein degradation were shared dysregulated processes. In addition, RPL had the most distinct functional profile, and 95% of affected functions were down-regulated. Conclusion(s): The most robust functions dysregulated in the endometrium of patients with uterine disorders across sample cohorts implicated an endometrial factor at the gene expression level. This shared endometrial factor affects endometrial receptivity processes., [ES]: Objetivo: Determinar las funciones moleculares de los genes que exhiben una expresión alterada en el endometrio de mujeres con trastornos uterinos que afectan la fertilidad. Diseño: Análisis retrospectivo integrando datos de casos y controles de múltiples cohortes con expresión del gen del endometrio en mujeres con trastornos uterinos. Lugar: Departamento de investigación de infertilidad afiliado a un hospital universitario. Paciente(s): Doscientas cuarenta mujeres, 121 de las cuales eran controles, 119 de las cuales tenían adenocarcinoma endometrial (ADC), fallo de implantación recurrente (RIF), pérdida recurrente del embarazo (RPL) o endometriosis en estadio II-IV. Intervención(es): Ninguna. Medida(s) principal(es) de resultado: Expresión génica del genoma completo y funciones moleculares alteradas en el endometrio de cada trastorno uterino. Resultado(s): Utilizando métodos de análisis robustos, identificamos funciones endometriales estadísticamente alteradas en todas las enfermedades uterinas. Las alteraciones del ciclo celular se compartieron entre todas las patologías investigadas. La endometriosis se caracterizó por la regulación a la baja de procesos ciliares. Entre las muestras de endometriosis, ADC y RIF, la disfunción mitocondrial y la degradación de proteínas fueron procesos desregulados en común. Además, RPL presentó el perfil funcional más distintivo y el 95% de las funciones afectadas estaban reguladas a la baja. Conclusión(es): Las funciones desreguladas más robustamente en el endometrio de pacientes con patologías uterinas en las cohortes implicó un factor endometrial a nivel de expresión génica. Este factor endometrial en común afecta los procesos de receptividad endometrial., The authors thank IVIRMA Global for their research support.

International audience; Leiomyoma, adenomyosis, and endometrial polyps are benign uterine disorders which seem to develop in the context of hormonal imbalances, due to steroid hormones, estrogen and progesterone, in association with various factors ranging from genetic factors to modifiable lifestyle factors. A growing body of evidence suggests that those hormones and their receptors are key modulators in the genesis and the growth of those pathologic entities. Further studies are required to understand their involvement in the pathogenesis of those lesions and their link to other factors such as extracellular matrix components, growth factors, chemokines, cytokines, and tissue repair mechanisms.

The objective of this study was to evaluate changes in sexual function after total laparoscopic hysterectomy (TLH) or transabdominal hysterectomy (TAH). This retrospective cohort study included patients with benign uterine tumors that were divided into TLH group and TAH group based on the hysterectomy technique used. Baseline, intraoperative, and postoperative characteristics were compared between groups. Postoperative sexual function was assessed using the Brief Index of Sexual Functioning for Women. The TLH and TAH groups contained 119 patients (age, 51.5±6.1 years) and 126 patients (age, 50.0±4.7 years), respectively. Baseline characteristics were comparable between groups, although uterine size was larger in the TAH group (P0.05). Both TLH and TAH had comparable negative effects on sexual function in women treated for benign uterine tumors in China, with a decreased frequency of sexual activity, reduced libido, orgasm dysfunction, and increased dyspareunia.

Introduction/Background Chronic metroendometritis is responsible for 75% of cases of uterine disorders in women of the reproductive age, such as adenomyosis, uterine fibroids or endometrial polyps. Infection is considered a promoter of polyposis and endometrial carcinoma (EC) in postmenopausal patients. Our purpose was to determine the influence of chronic infection on the formation of clinical and morphological variants of EC. Methodology Postoperative data on morphological and microbiological examination of EC tissues of 240 patients (mean age 64.5 years, 27% - reproductive age, 73% - peri- and menopausal patients) were studied. After removal of the preparation, the macroscopic state of tumors was evaluated intraoperatively together with the morphologist, and tumor tissues were collected for microbiological examination. The presence of bacterial or viral infections in EC tissues was detected by PCR and ELISA. Results EC tissues were morphologically studied with detailed characteristics of the tumor process. 87% - endometrioid EC, 13% - aggressive variants (papillary serous carcinoma and adenosquamous carcinoma). 62% of EC were infected with chlamydia, cytomegalovirus, herpes simplex viruses and HPV. Tumors in patients of reproductive age were infected in 92%. 54% of adenosquamous tumors were infected with HPV 18. Endometrioid tumors showed combined bacterial and viral infections in 83%, monoinfection (bacterial or viral) in 16%; combined viral infections were rare. Patients of reproductive age with monoinfections had the most favorable variants of G1-2 EC in 43% of cases. Older menopausal patients with tumors infected with viral agents demonstrated atrophic endometrium and aggressive G2-3 EC. Conclusion The presence of chonic infection in EC is directly associated with the morphological type and aggressiveness of tumors and the patient9s age. Disclosure Nothing to disclose.

The adaptation of the uterine environment into a favorable immunological and inflammatory milieu is a physiological process needed in normal pregnancy. A uterine hyperinflammatory state, whether idiopathic or secondary to hormonal or organic uterine disorders (polycystic ovary syndromes, endometriosis/adenomyosis and fibroids), negatively influences the interactions between decidua and trophoblast, early in gestation, and between chorion and decidua later in pregnancy. Abnormal activation of uterine inflammatory pathways not only contributes to the pathogenesis of the obstetric syndromes, i.e. recurrent pregnancy loss (RPL), pre-term delivery (PTD) and pre-eclampsia (PE), but also to correlates with severity. In this review, we summarize recent advances in the knowledge of uterine molecular mechanisms of inflammatory modulation in normal pregnancy and obstetric syndromes (RPL, PTD and PE). In particular, we focus on two regulators of uterine/placental inflammation: the NLRP3 inflammasome and the chemokines decoy receptor D6. We performed comprehensive review of the literature in PubMed and Google Scholar databases from 1994 to 2018. The available evidence suggests that: (i) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; (ii) there is a role for abnormal expression and function of D6 decoy receptor at the feto–maternal interface in cases of RPL and PTD and (iii) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets.

Background This study was performed to evaluate the clinical feasibility of a U-net for fully automatic uterine segmentation on MRI by using images of major uterine disorders. Methods This study included 122 female patients (14 with uterine endometrial cancer, 15 with uterine cervical cancer, and 55 with uterine leiomyoma). U-net architecture optimized for our research was used for automatic segmentation. Three-fold cross-validation was performed for validation. The results of manual segmentation of the uterus by a radiologist on T2-weighted sagittal images were used as the gold standard. Dice similarity coefficient (DSC) and mean absolute distance (MAD) were used for quantitative evaluation of the automatic segmentation. Visual evaluation using a 4-point scale was performed by two radiologists. DSC, MAD, and the score of the visual evaluation were compared between uteruses with and without uterine disorders. Results The mean DSC of our model for all patients was 0.82. The mean DSCs for patients with and without uterine disorders were 0.84 and 0.78, respectively (p = 0.19). The mean MADs for patients with and without uterine disorders were 18.5 and 21.4 [pixels], respectively (p = 0.39). The scores of the visual evaluation were not significantly different between uteruses with and without uterine disorders. Conclusions Fully automatic uterine segmentation with our modified U-net was clinically feasible. The performance of the segmentation of our model was not influenced by the presence of uterine disorders.

BACKGROUNDAdenomyosis 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 RATIONALEWe 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 METHODSPubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018.OUTCOMESThe 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 IMPLICATIONSThe 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.

Studies about prevalence of uterine pathologies in bitches are scarce. Although correlation between age and uterine disorders was documented, the most suitable age for a preventive sonographic screening has not been proposed yet. Present study aimed to estimate the eligible age for an ultrasonographic screening of uterine abnormalities in dogs. Data regarding ultrasound examination and clinical records of non-pregnant intact females were retrospectively analysed. The age of each bitch was expressed as age ratio (actual/maximum age expected for the respective breed). The cut-off age ratio was determined by a ROC curve for overall uterine abnormalities. Frequencies of different abnormalities below and over the cut-off derived from the ROC curve were calculated and statistically analysed by chi-Square and OR. Prevalence of three categories of ultrasonographic findings was as follows: cystic endometrial hyperplasia (CEH) 18%; uterine collections (UC) 10.5%; masses (M) 1.3%. By the cut-off age ratio (0.325), derived by ROC curve (AUC = 0.91; SP 84.23%; SE 79.2%; PPV 83.4%; NPV 80%), 228 cases were divided into two subgroups: bitches over (exposed group: n.83) and below cut-off (control group: n.145). All abnormalities resulted more frequent in exposed group: OR was 24.96 (p