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Study Question: Are there neurobiological changes induced by endometriosis?, Summary Answer: Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis., What Is Known Already: Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied by comorbid mental disorders. Only one study with a number of limitations has investigated changes in gray matter volumes and functional connectivity in a small group of patients with endometriosis., Study Design, Size, Duration: This prospective study recruited 53 women undergoing a laparoscopy due to suspicion of symptomatic endometriosis and 25 healthy, pain-free women. Clinical and psychological characteristics, thermal pain perception, and voxel- and surface-based morphology were assessed in all study participants. Thereafter, the patients underwent a laparoscopy, where endometriosis was either histologically confirmed and removed, or ruled out. Correspondingly, patients were assigned into the group with endometriosis (n = 27) or with endometriosis-independent CPP (n = 26) and compared to the pain-free controls., Participants/materials, Setting, Methods: The study groups were generally representative for the population of women with endometriosis. Sociodemographic, medical, clinical, and psychological characteristics were collected using various questionnaires and a structured clinical interview. Thermal pain perception and voxel- and surface-based morphometry were assessed using thermode and MRI, respectively., Main Results and the Role of Chance: Despite comparable pain intensity and burden of mental disorders, both patient groups demonstrated distinct neurobiological patterns. Women with endometriosis exhibited increased gray matter volume (GMV) in the left cerebellum, lingual gyrus and calcarine gyrus, compared to those with endometriosis-independent CPP. Patients with CPP had decreased GMV in the right cerebellum as compared to controls. Dysmenorrhoea severity correlated positively with GMV in the left inferior parietal lobule, whereas depressive symptoms were associated with decreased GMV in the right superior medial gyrus across patient groups. Dyspareunia correlated negatively with cortical thickness in the left inferior temporal gyrus and left middle temporal gyrus., Limitations, Reasons for Caution: The study groups differed in a few baseline-characteristics, including educational levels, smoking and BMI. While measuring pain perception thresholds, we did not attempt to mimic CPP by placement of the thermode on the abdominal wall., Wider Implications of the Findings: Changes in gray matter volume associated with endometriosis differ from those observed in women with endometriosis-independent CPP. Our results underline an involvement of the cerebellum in pain perception and the pathogenesis of pain associated with endometriosis., Study Funding/competing Interest(s): This work was funded by the START Program of the Faculty of Medicine, RWTH Aachen, Germany, and supported by the International Research Training Group (IRTG 2150) of the German Research Foundation (DFG)-269953372/GRK2150, Germany. S.T. was supported by postdoctoral fellowship of the Faculty of Medicine, RWTH Aachen, Germany. There are no conflicts of interest., Trial Registration Number: DRKS00021236., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits. Mechanosensitivity of vagina-innervating primary afferents was examined using an ex vivo single-unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin-1 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitization of spinal circuitry in endometriosis. These results demonstrate endometriosis-induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain relief treatments for this debilitating disorder., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers' presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: The World Endometriosis Research Foundation established the Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) to create standardized documentation tools (with common data elements) to facilitate the comparison and combination of data across different research sites and studies. In 2014, 4 data research standards were published: clinician-reported surgical data, patient-reported clinical data, and fluid and tissue biospecimen collection. Our current objective is to create an EPHect standard for the clinician-reported physical examination (EPHect-PE) for research studies., Design: An international consortium involving 26 clinical and academic experts and patient partners from 11 countries representing 25 institutions and organizations. Two virtual workshops, followed by the development of the physical examination standards underwent multiple rounds of iterations and revisions., Subjects: N/A MAIN OUTCOME MEASURE(S): N/A RESULT(S): The EPHect-PE tool provides standardized assessment of physical examination characteristics and pain phenotyping. Data elements involve examination of back and pelvic girdle; abdomen including allodynia and trigger points; vulva including provoked vestibulodynia; pelvic floor muscle tone and tenderness; tenderness on unidigital pelvic examination; presence of pelvic nodularity; uterine size and mobility; presence of adnexal masses; presence of incisional masses; speculum examination; tenderness and allodynia at an extra-pelvic site (e.g., forearm); and recording of anthropometrics., Conclusion(s): The EPHect-PE standards will facilitate the standardized documentation of the physical examination, including the assessment and documentation of examination phenotyping of endometriosis-associated pelvic pain., Competing Interests: Declaration of Interests T.L. has nothing to disclose. C.A. reports consultancy fees from AbbVie and Pfizer. S.A.-S reports consultancy fees from Myovant-Pfizer, Organon, and Bayer. P.S. has received royalties from UpToDate for a section about acute pelvic pain and from Frontiers in Reproductive Health as Specialty Editor for Gynecology, and participated in an AbbVie advisory board and is part of a team that received botulinum toxin and funds for monitoring a clinical trial that were provided by Allergan, Inc. through a Clinical Trials Agreement with the National Institutes of Health (NIH). K.V. has received research funding from Bayer AG and honoraria for consultancy from Bayer AG, Eli Lilly, AbbVie, and Reckitts. G.D.A. reports consultancy fees from Organon, Labcorp, and Cooper, and is the CEO of and has equity in ARC Fertility. L.A.-N. has nothing to disclose. D.B. is the owner of EPP Coaching and Consulting and has received travel expenses and speaking fees from Myovant and Guerbet. F.J., J.L and L.R., have nothing to disclose. J.S. is part of a team that received botulinum toxin and funds for monitoring a clinical trial that was provided by Allergan, Inc. through a Clinical Trials Agreement with the NIH. A.T. has nothing to disclose. L.H. is remunerated by WERF as the EPHect-PE project manager. S.A.M. reports consultancy and grant funding from AbbVie for population-based research unrelated to this project and from Frontiers in Reproductive Health as Field Chief Editor. P.J.Y. has nothing to disclose. The WERF EPHect Working Group (not listed in the author list): E.A. has nothing to disclose. J.C. is the IPPS vice-president and a consultant for SoLa Therapy, AbbVie, and Myovant; E.C. is an employee of Endometriosis UK; H.C.G has nothing to disclose. A.W.H.’s institution (University of Edinburgh) has received payment for consultancy and grant funding from Roche Diagnostics to assist in the early development of a possible blood diagnostic biomarker for endometriosis, consultancy fees from Gesynta and Joii, and grant funding from the UKRI, NIHR, CSO, and Wellbeing of Women for endometriosis research. A.W.H. has received payment for a lecture from Theramex, is president-elect of the World Endometriosis Society, co-editor in chief of Reproduction and Fertility, was a member of the NICE and ESHRE Endometriosis Guideline Groups, and is a trustee and medical advisor to Endometriosis UK; A.J. has nothing to disclose. G.L. is an employee of the US Veterans Health Administration, reports research funding from the NIH and Department of Defence, and has served as a consultant for Myovant, AbbVie, and Pelvic Sola Therapy. D.C.M. and O.C.N. have nothing to disclose. F.F.T. has royalties from Wolters Kluwer, has consulted for Bayer and Tremeau Pharmaceuticals, and received research support from Dot Laboratories., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: Cystoscopy has been routinely performed in patients suspected to be suffering from bladder pain syndrome/interstitial cystitis (BPS/IC) across the globe. The methodology reported by various guidelines appears to have differences in the techniques and hence there is a need for a review of all those techniques in order to arrive at a consensus. The aim was to review the literature describing the prevalent techniques of cystoscopy for patients of BPS/IC and try to evolve a consensus., Methods: The group the Global Interstitial Cystitis, Bladder Pain Society (GIBS) has worked collectively to systematically review the literature using the key words, "Cystoscopy in Hunner's lesions, bladder pain syndrome, painful bladder syndrome and interstitial cystitis" in the PubMed, COCHRANE, and SCOPUS databases. A total of 3,857 abstracts were studied and 96 articles referring to some part of technique of cystoscopy were short-listed for review as full-length articles. Finally, six articles with a description of a technique of cystoscopy were included for final tabulation and comparison. The group went on to arrive at a consensus for a stepwise technique of diagnostic and therapeutic cystoscopy in cases of BPS/IC. This technique has been compared with the previously described techniques and may serve to be a useful practical guide for treating physicians., Conclusion: It is important to have a uniform standardized technique for performing a diagnostic and therapeutic cystoscopy in patients with BPS/IC. Consensus on one such a technique has been arrived at and described in the present article., (© 2023. The International Urogynecological Association.)

Clinical/methodical Issue: Groin pain in athletes can have various causes. Radiologically, osteitis pubis and clefts with affection of the interpubic disc as well as muscle and tendon tears near the pubic bone can be clearly identified., Standard Radiological Methods: Magnetic resonance imaging (MRI) is the imaging modality of choice, as well as single-leg stand imaging (flamingo view radiographs), and where appropriate symphysography., Methodical Innovations: Optimized MRI sequence protocol with oblique (axial oblique) slices parallel to the linea arcuata of the iliac bone is recommended. High-resolution MRI sequences and symphysography can detect superior and secondary cleft formation. Instabilities of the pubic symphysis can be diagnosed using flamingo view radiographs., Performance: The MRI findings of osteitis pubis and clinical symptoms correlate. The presence of parasymphyseal bone marrow edema is the earliest morphological sign of acute osteitis pubis on MR imaging. Edema in the periosteal tissue and isolated muscle lesions next to the symphysis are generally associated with more severe clinical symptoms., Achievements and Practical Recommendations: Close communication between radiologists and the referring physicians is indispensable when planning an adequate imaging protocol, and precise knowledge of the clinical symptoms in the case of clinical suspicion of osteitis pubis allows for a reliable diagnosis and provides important prognostic information., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Importance: Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms., Objective: To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition., Design, Setting, and Participants: A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022., Main Outcomes and Measures: Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche., Results: In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis., Conclusions and Relevance: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.

In Brief: Traditionally viewed as enigmatic and elusive, adenomyosis is a fairly common gynecological disease but is under-recognized and under-researched. This review summarizes the latest development on the pathogenesis and pathophysiology of adenomyosis, which have important implications for imaging diagnosis of the disease and for the development of non-hormonal therapeutics., Abstract: Traditionally considered as an enigmatic disease, adenomyosis is a uterine disease that affects many women of reproductive age and is a contributing factor for pelvic pain, heavy menstrual bleeding (HMB), and subfertility. In this review, the new development in the pathogenesis and pathophysiology of adenomyosis has been summarized, along with their clinical implications. After reviewing the progress in our understanding of the pathogenesis and describing the prevailing theories, in conjunction with their deficiencies, a new hypothesis, called endometrial-myometrial interface disruption (EMID), which is backed by extensive epidemiologic data and demonstrated by a mouse model, is reviewed, along with recent data implicating the role of Schwann cells in the EMI area in the genesis of adenomyosis. Additionally, the natural history of adenomyotic lesions is elaborated and underscores that, in essence, adenomyotic lesions are fundamentally wounds undergoing repeated tissue injury and repair (ReTIAR), which progress to fibrosis through epithelial-mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation, and smooth muscle metaplasia. Increasing lesional fibrosis propagates into the neighboring EMI and endometrium. The increased endometrial fibrosis, with ensuing greater tissue stiffness, results in attenuated prostaglandin E2, hypoxia signaling and glycolysis, impairing endometrial repair and causing HMB. Compared with adenomyosis-associated HMB, the mechanisms underlying adenomyosis-associated pain are less understood but presumably involve increased uterine contractility, hyperinnervation, increased lesional production of pain mediators, and central sensitization. Viewed through the prism of ReTIAR, a new imaging technique can be used to diagnose adenomyosis more accurately and informatively and possibly help to choose the best treatment modality.

Background: Microbiota play essential roles in the pathogenesis of prostatitis and depression. However, the changes in prostate microbiota have not yet been explored in rats with prostatitis/depression. This study aimed to investigate the changes of prostate microbiota in rats with prostatitis/depression., Methods: Rats with experimental autoimmune prostatitis (EAP) complicated with depression were constructed through injection of rat prostate antigen with immunoadjuvants followed by application of chronic unpredictable mild stress (CUMS). The rats were subjected to inflammatory factor detection and behavioral testing to confirm the establishment of the model. Subsequently, the prostate microbiota was assayed in the rats and compared by 16S rRNA gene sequencing., Results: A rat model of EAP complicated with depression was established and confirmed by increases in IL-1β, IL-6, and TNF-α as well as the occurrence of depressive-like behaviors. EAP/CUMS significantly altered the richness, evenness, and composition of prostate microbiota. Forty-six taxonomic biomarkers for prostate microbiota were enriched in rats with EAP/depression and exhibited statistically significant and biologically consistent differences. Metabolomics profiling revealed that EAP/depression was associated with reductive acetyl coenzyme A pathway, L-lysine fermentation to acetate and butanoate, protein N-glycosylation and purine nucleobases degradation I, which is regulated by DCE29, Nocardioes, Helicobacter and Dorea ., Conclusion: Findings from the study demonstrate the existence of abnormal prostate microbiota in EAP complicated with depression and may be helpful in the treatment of comorbid diseases of prostatitis and depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xu, Wang and Wu.)

CD44 partcipates in multiple inflammatory reactions. Here, we aimed to investigate the role of CD44 and the ligand, hyaluronan (HA), on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) pathogenesis. We found that CD44 was universally expressed in CD4 + lymphocytes in the peripheral blood of CP/CPPS patients. After silencing CD44 expression or delivering 4-methylumbelliferone (4-MU), the pain severity and prostatic inflammation were significantly relieved. In vitro assay found that HA/CD44 was able to regulate T helper 1 (Th1) cells differentiation, the deficiency of which diminished experimental autoimmune prostatitis (EAP) susceptibility. Bioinformatic analysis suggested that after HA or 4-MU treatment, mTOR signaling was significantly altered, and these results were confirmed by subsequent Western blotting assay. Besides, mass spectrometry and co-immunoprecipitation assays found that CD44 was able to interact with Annexin A1 (ANX A1), and this kind of interaction stabilized ANX A1 protein and maintained the activation of Akt/mTOR pathway. Meanwhile, HA-treatment-enhanced prostatic inflammation, Th1 cell differentiation, and Akt/mTOR pathway activation were reversed after silencing the expression of ANX A1 using shANX A1-lentivirus. The present study systematically investigates the functional role of HA/CD44 in CP/CPPS and identifies novel mechanisms for HA/CD44 promoting Th1 cell differentiation. Targeting the HA/CD44/ANX A1/Akt/mTOR signaling represents novel potential therapeutic strategies for patients with CP/CPPS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Meng, Li, Li, Liu, Jin, Zhang, Hao, Chen, Zhang and Liang.)

Endometriosis is a gynaecological disease defined by the growth of endometrium-like tissue outside the uterus. The disease is present in approximately 5-10% of women of reproductive age and causes pelvic pain and infertility. The pathophysiology is not completely understood, but retrograde menstruation and deficiency in natural killer (NK) cells that clear endometriotic cells in the peritoneal cavity play an important role. Nowadays, hormonal therapy and surgery to remove endometriosis lesions are used as treatment. However, these therapies do not work for all patients, and hormonal therapy prevents patients from getting pregnant. Therefore, new treatment strategies should be developed. Since the cytotoxicity of NK cells is decreased in endometriosis, we performed a literature search into the possibility of NK cell therapy. Available treatment options include the inhibition of receptor-ligand interaction for KIR2DL1, NKG2A, LILRB1/2, and PD-1/PD-L1; inhibition of TGF-β; stimulation of NK cells with IL-2; and mycobacterial treatment with BCG. In preclinical work, these therapies show promising results but unfortunately have side effects, which have not specifically been studied in endometriosis patients. Before NK cell treatment can be used in the clinic, more research is needed.

Objective: To determine the UPOINT-positive domain numbers and evaluate the significance of the sexual dysfunction domain in patients with chronic prostatitis or chronic pelvic pain (CP/CPPS) in Japan., Methods: A total of 58 patients with CP/CPPS with moderate or greater symptoms were included. Symptom severity was determined by > 14 on the chronic prostatitis symptom index (CPSI). The main outcome was to confirm the number and distribution of the positive UPOINT domains in this group. As secondary outcomes, the correlation between positive domain numbers and CPSI scores was evaluated. We also examined whether the sexual dysfunction subdomain, as determined by the five-item international index of erectile function, could improve the correlation with symptom severity., Results: The mean age was 48.6 ± 15.4 years, CPSI score 24.3 ± 6.1, and positive UPOINT domain number 2.4 ± 0.9. The distribution of each positive domain was 67.2% for urinary, 15.5% for psychosocial, 75.8% for organ-specific, 3.4% for infection, 5.1% for neurological/systemic conditions, and 75.8% for tenderness. Although the mean CPSI total scores tended to increase with an increasing number of positive UPOINT domains, a significant correlation was not observed (r = 0.134, p = 0.312). The sexual dysfunction domain was positive in 62.0% of the cases, but the correlation could not be improved., Conclusions: Urinary, organ specific, and tenderness domains were mainly observed in patients with CP/CPPS. When patients with moderate or grater CPSI scores are clinically evaluated, clinicians should recognize that the UPOINT-positive domain and CPSI score are clinically and pathologically different concepts. (250 words)., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS., Competing Interests: None

Interstitial cystitis (IC) is a chronic inflammatory disease characterized by bladder pain and increased urinary frequency. Although the C57BL/6J (B6) and FVB/NJ (FVB) mouse strains are commonly used as animal models for studies involving the urinary system, few reports have compared their lower urinary tract anatomy, despite the importance of such data. Our study aimed to characterize bladder function changes in FVB and B6 mouse strains with lipopolysaccharide (LPS)-induced IC, to understand mouse model-based bladder research. The bladder function parameters were measured by cystometrogram. Histological assay was examined by hematoxylin and eosin stain, Masson's trichrome stain, and immunofluorescence staining. Results indicated that the two strains in the control group exhibited different bladder structures and functions, with significant anatomical differences, including a larger bladder size in the FVB than in the B6 strain. Furthermore, cystometry tests revealed differences in bladder function pressure. LPS-treated B6 mice presented significant changes in peak pressure, with decreased intercontraction intervals; these results were similar to symptoms of IC in humans. Each strain displayed distinct characteristics, emphasizing the care required in choosing the appropriate strain for bladder-model studies. The results suggested that the B6 mouse strain is more suitable for IC models.

This study aimed to evaluate the efficacy and adverse effects of dienogest for the treatment of endometriomas. Dienogest (2 mg/day) was administered to patients with endometrioma continuously through the 6-month study period. The patients were prospectively examined on the efficacy and side effects at baseline, at third months, and sixth months of the treatment. Twenty-four out of 30 patients were able to complete the study. The mean volume of the endometrioma decreased significantly from 112.63 ± 161.31 cm³ at baseline to 65.47 ± 95.69 cm³ at a 6-month follow-up (-41%) ( p  = .005). The VAS score for pelvic pain decreased significantly from 7.50 to 3.00 ( p  < .001) at the sixth months of treatment. The most common side effects were menstrual irregularities. Laboratory parameters did not change during the study. Dienogest considered being effective for 6 months of use in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile.Impact statement What is already known on this subject? Laparoscopic excisional surgery for endometrioma is currently the most valid approach in the treatment of endometriomas. However, there are concerns about ovarian reserve damage during surgery. What do the results of this study add? Dienogest considered being effective in decreasing the size of endometrioma, reducing endometriosis-associated pain with a favourable safety and tolerability profile. Long-term use of dienogest in younger patients with endometriomas who are yet to give birth may reduce the possibility of surgery by reducing the size of the endometriomas and may preserve ovarian reserve. What are the implications of these findings for clinical practice and/or further research? Dienogest may reduce the incidence of infectious complications such as pelvic abscess after oocyte retrieval and the surgical procedures in infertile patients with endometrioma.

Purpose: Our objective was to evaluate the associations with interstitial cystitis during pregnancy using a United States inpatient database., Materials and Methods: We conducted a retrospective cohort study utilizing the Nationwide Inpatient Sample database from the Healthcare Cost and Utilization Project. ICD-9 code number 595.1 was used to extract cases of chronic interstitial cystitis and these pregnancies were compared to pregnancies without chronic interstitial cystitis, using the Chi-squared test to evaluate nominal variables. A multivariate logistic regression model was subsequently used to adjust for statistically significant confounders (p value <0.05)., Results: There were 9,095,995 deliveries during the study period; 793 pregnant women were found to have chronic interstitial cystitis. When controlling for confounding effects in terms of pregnancy outcomes, the diagnosed group had a greater risk of developing pregnancy-induced hypertension (adjusted OR 1.57, 95% CI 1.21-2.05), preeclampsia (adjusted OR 2.06, 95% CI 1.47-2.87), preterm delivery (adjusted OR 1.63, 95% CI 1.23-2.17), preterm premature rupture of membranes (adjusted OR 2.18, 95% CI 1.25-3.79), chorioamnionitis (adjusted OR 2.05, 95% CI 1.24-3.37), delivery via cesarean section (adjusted OR 1.57, 95% CI 1.32-1.88), maternal infection (adjusted OR 2.19, 95% CI 1.40-3.43), and deep venous thromboembolism (adjusted OR 10.56, 95% CI 3.37-33.09)., Conclusions: Interstitial cystitis diagnosis is associated with an increased risk of preeclampsia, preterm birth, and other adverse pregnancy outcomes in this database study. Prospective studies are required to confirm the findings of the correlation between interstitial cystitis and adverse pregnancy outcomes.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is not only a chronic urinary bladder pain syndrome but is also associated with multifactorial etiology. Our study aimed to test the hypothesis that IC/BPS is associated with subsequent increased risks of outpatient visits and hospitalizations. Using nationwide database, the diagnoses were based on the International Classification Codes (ICD-9-CM) (595.1) of at least three outpatient services during 2002-2008, (n = 27,990) and cystoscopic finding Hunner type and/or glomerulation with pre-audit criteria. All recruited cases monitored for subsequent outpatient visits and hospitalizations for 2 years, including all-cause and specialty-specific departments, were classified according to medical specialty and age group (<40, 40-60, ≥60 years of age). IC/BPS patients have more overall outpatient department (OPD) visits and an overall adjusted incidence rate ratio (IRR) of 1.64. As for specialty, IRRs were higher in psychiatry (2.75), Chinese medicine (2.01), and emergency medicine (2.00), besides urology and gynecology. The IRRs decreased as age advanced (2.01, 1.71, and 1.44, respectively), except for gynecology (2.42, 2.52, and 2.81). A similar phenomenon happens in hospitalization with IRR of 1.69. Due to claim data characteristics, whether ulcer type IC/BPS findings can be deductive to non-ulcer type remains inclusive. Current results indicate the impacts of healthcare burden in broad spectrum about IC/PBS patients. IC/BPS has been suggested to be associated with lower threshold of healthcare visits and some coexisting disease and is comprised of systemic dysregulation, and is beyond the scope of local bladder-urethra disease. Adequate recognition of associated or comorbid factors and possible recommendation or referral for IC/BPS patients can help provide better healthcare quality., Competing Interests: The authors have declared that no competing interests exist.

Deep infiltrating endometriosis frequently affects the rectosigmoid region. It clinically presents as a chronic painful condition affecting women in their reproductive time. Here, we present a case of a 28-yr-old female patient who had a history of dysmenorrhea, dyspareunia, chronic abdominal and pelvic pain, and constipation secondary to rectal wall endometriosis. Microscopic examination of the resected rectal segment showed endometriosis with vascular and lymph node involvement. Vascular involvement is an uncommon histologic finding that may raise concern for potential malignancy. The aim of this report is to alert pathologists and physicians about this infrequent pitfall that can be mistaken for a neoplastic process and to discuss the underlying pathophysiology of vascular involvement by endometrial tissue in otherwise benign conditions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Background: Currently, there is no efficacious treatment method for chronic prostatitis type IIIb/chronic pelvic pain syndrome (CP/CPPS). Aim of the study was to investigate and compare the efficacy and safety of low-intensity shockwave therapy (LiST) vs. sham treatment in CP/CPPS patients., Methods: Patients with CP/CPPS diagnosis were randomized in this prospective, sham-controlled, double-blind study either to the active groups (Group B, C) who received 5000 shockwaves per session with energy flux density 0.1 mJ/mm 2 or to the sham group (Group A) who received 5000 shockwaves from a visually identical sham probe. All groups underwent six sessions (once/week). LiST effects on pain, micturition, quality of life (QoL), and erectile function were evaluated at 4, 12, and 24 weeks after treatment. The parameters were investigated using validated questionnaires. Uroflowmetry and post void residual calculation were performed at baseline and at 4- and 12-week FU visit. Prostate mpMRI and PSA measurement were performed at baseline and 12-week FU visit., Results: Overall, 45 men were randomized to the active (n = 30) and sham groups (n = 15). Regarding impact of LiST in National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain, and QoL subdomains scores a clear and persistent in all FU timepoints improvement was found compared to sham treatment. NIH-CPSI urinary subdomain, International Prostate Symptom Score [IPSS], PSA, and mpMRI-PIRADS scores did not differ between the two groups. The mean difference between the LiST and sham group in the change of the NIH-CPSI pain-domain score (Q1-4) from baseline to 12 weeks after final treatment which was 3.3 (95% CI, 1.8, 4.7). Perineal LiST was easy and safe to perform without anesthesia or any side-effects., Conclusions: LiST seems to be a safe and effective treatment option for CP/CPPS, considerably improving pain and quality of life. Lack of any side-effects, and the potential for repetition make LiST a promising treatment choice for CP/CPPS patients.

Background: As one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated., Methods: The PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg's funnel plot, Egger's regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings., Results: A total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1β, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable., Conclusions: Immune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: We sought to assess hernia characteristics and classification through comprehensive review of the literature involving broad ligament herniation., Methods: A literature search via MEDLINE and Embase databases was conducted to identify and select broad ligament herniation studies published between January 1, 2000 and September 30, 2020. Extracted data included previous surgical history, previous obstetric history, diagnostic imaging, herniated organ, hernia classification, and repair performed. The reported data has been compared to a unique case of broad ligament herniation that presented to our institution., Results: A total of 44 articles with 49 cases were identified for the study. Eighteen (36.7%) patients had a history of previous abdominal surgery while 29 (59.2%) had a history of previous childbirth. Type I (51.0%) and Type II (18.4%) defects were most commonly reported with most patients reporting only one defect (85.7%) using the Cilley classification. Twenty-nine patients underwent primary laparoscopic repair of the defect while 19 patients underwent exploratory laparotomy., Conclusions: The analysis of previously reported cases adds to the limited literature on broad ligament hernias and highlights the surgical management of this uncommon pathology. It also highlights the need for a broad differential diagnosis when female patients present with pelvic pain or symptoms of small bowel obstruction. The broad ligament should be fully inspected when mesenteric defects are suspected as multiple defects can be present as evidenced by the attached case study., Competing Interests: Conflict of interests: none., (© 2021 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain. Extracorporeal shock wave therapy (ESWT) has been used to treat patients with CP/CPPS, but the parameters used by ESWT are not uniformly determined. Herein, this study aims to assess the effects of ESWT with different energy flux densities on pelvic pain in CP/CPPS rats and to explore the mechanisms. A rat model of CP/CPPS was induced by intraprostatic injection of 1% carrageenan. ESWT with different energy flux densities (0.09, 0.20, 0.30, 0.40 mJ/mm 2 ) was applied in the pelvic region of CP/CPPS rats once a week for 4 weeks. The results showed that compared with the other energy flux densities (0.09, 0.30, and 0.40 mJ/mm 2 ), ESWT with 0.20 mJ/mm 2 exhibited a more powerful effect in alleviating pelvic pain and prostate damage. The therapeutic effect is associated with the reduction of the number of total and degranulated mast cells. Collectively, ESWT with 0.20 mJ/mm 2 achieved the optimal therapeutic effect in alleviating pelvic pain in CP/CPPS rats.

To evaluate the characteristics of the spinopelvic parameters on radiography in patients with sacroiliac joint pain (SIJP). Two hundred fifty patients were included and divided into the SIJP group (those diagnosed with SIJP based on physical findings and response to analgesic periarticular injections; n = 53) and the non-SIJP group (those with low back pain [LBP] because of other reasons; n = 197). We compared their demographic characteristics and spinopelvic parameters using radiography. All differences found in the patients' demographic characteristics and spinopelvic parameters were analyzed. More female participants experienced SIJP than male participants (P = 0.0179). Univariate analyses revealed significant differences in pelvic incidence (PI) (P = 0.0122), sacral slope (SS) (P = 0.0034), and lumbar lordosis (LL) (P = 0.0078) between the groups. The detection powers for PI, SS, and LL were 0.71, 0.84, and 0.66, respectively. Logistic regression analyses, after adjustment for age and sex, revealed significant differences in PI (P = 0.0308) and SS (P = 0.0153) between the groups, with odds ratios of 1.03 and 1.05, respectively. More female participants experienced SIJP than male participants. Higher PI and SS values were related to SIJP among LBP patients.

Study Objective: Endometriosis fertility index (EFI) is a robust tool to predict the pregnancy rate in patients with endometriosis who are attempting non-in vitro fertilization conception. However, EFI calculation requires laparoscopy. Newly established imaging techniques such as sliding sign, which is used to diagnose pouch of Douglas obliteration, could provide a promising alternative. The objective of this study was to investigate the practicality of using ultrasound data to predict a low EFI (score ≤6)., Design: Observational study from a prospective registry (Endometriosis Pelvic Pain Interdisciplinary Cohort, clinicaltrials.gov #NCT02911090). Analyzed data were captured from December 2013 to June 2017., Setting: Tertiary referral center at British Columbia Women's Hospital., Patients: We analyzed data for 2583 participants from the Endometriosis Pelvic Pain Interdisciplinary Cohort. In this cross-sectional study, we included 86 women aged <40 years., Interventions: Dynamic ultrasonography for the sliding sign testing and EFI calculation during laparoscopic surgery., Measurements and Main Results: Logistic regression was used to obtain receiver operating characteristic area under the curve (AUC) for the prediction models. Significance was p <.05. Patients with a negative sliding sign were older and had severe endometriosis and longer duration of infertility. Patients with a negative sliding sign had significantly lower total EFI scores and lower surgical factors scores than patients with a positive sliding sign. Logistic regression showed that a negative sliding sign and EFI historic factors score can predict an EFI score ≤6 (sensitivity = 87.9%, specificity = 81.1%, AUC = 0.93 [95% confidence interval, 0.88-0.98]). Adding the diagnosis of endometrioma to the previous prediction model resulted in AUC = 0.95 (95% confidence interval, 0.90-0.995), sensitivity = 84.8%, and specificity = 92.5%., Conclusion: The sliding sign could be a potential alternative to the EFI surgical factors, and it could be used in combination with EFI historic factors and the diagnosis of endometrioma to predict an EFI score ≤6 for patients who are not scheduled for immediate surgery., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to compare the clinical effects of uterine artery embolization (UAE) with those of high-intensity focused ultrasound (HIFU) ablation for the treatment of symptomatic uterine myomas., Data Sources: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrials.gov for studies from January 2000 to August 2020. Related articles and relevant references of the included studies were also searched., Methods of Study Selection: Two researchers independently performed the data selection. We included comparative studies that compared the clinical outcomes of UAE with those of HIFU ablation in women with myomas., Tabulation, Integration, and Results: We assessed the study quality using the Cochrane Handbook for Systematic Reviews of Interventions for evaluating the risk of bias. Two independent researchers performed the article selection according to the screening criteria and rated the quality of evidence for each article. We calculated pooled mean difference with 95% confidence interval (CI) for continuous data and relative risk (RR) with 95% CI for dichotomous data. The systematic review registration number is CRD42020199630 on the International Prospective Register of Systematic Reviews. A total of 7 articles (5 trials), involving 4592 women with symptomatic uterine myomas, were included in the meta-analysis. Compared with the HIFU ablation group, the decrease in "uterine fibroid symptom" scores as well as the increase in quality-of-life scores at the time of follow-up were higher in the UAE group, with overall mean difference 19.54 (95% CI, 15.21-23.87; p <.001) and 15.72 (95% CI, 8.30-23.13; p <.001), respectively. The women in the UAE group had a significantly lower reintervention rate (RR 0.25; 95% CI, 0.15-0.42; p <.001). The women undergoing UAE had a significantly lower pregnancy rate than those undergoing HIFU ablation (RR 0.06; 95% CI, 0.01-0.45; p = .006). The difference in the incidence of adverse events between the 2 groups was not statistically significant (p = .53)., Conclusion: Compared with HIFU ablation, UAE provided more significant alleviation of symptoms and improvement in quality of life, lower postoperative reintervention rate, and lower pregnancy rate for women with uterine myomas. However, we cannot conclude that HIFU ablation is more favorable for desired pregnancy than UAE because of the confounding factors., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7 - 28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

Objective: The objective of this video is to demonstrate different clinical presentations of peritoneal defects (peritoneal retraction pockets) and their anatomic relationships with the pelvic innervation, justifying the occurrence of some neurologic symptoms in association with these diseases., Design: Surgical demonstration of complete excision of different types of peritoneal retraction pockets and a comparison with a laparoscopic retroperitoneal cadaveric dissection of the pelvic innervation., Setting: Private hospital in Curitiba, Paraná, Brazil., Interventions: A pelvic peritoneal pocket is a retraction defect in the surface of the peritoneum of variable size and shapes [1]. The origin of defects in the pelvic peritoneum is still unknown [2]. It has been postulated that it is the result of peritoneal irritation or invasion by endometriosis, with resultant scarring and retraction of the peritoneum [3,4]. It has also been suggested that a retraction pocket may be a cause of endometriosis, where the disease presumably settles in a previously altered peritoneal surface [5]. These defects are shown in many studies to be associated with pelvic pain, dyspareunia, and secondary dysmenorrhea [1-4]. Some studies have shown that the excision of these peritoneal defect improves pain symptoms and quality of life [5]. It is important to recognize peritoneal pockets as a potential manifestation of endometriosis because in some cases, the only evidence of endometriosis may be the presence of these peritoneal defects [6]. In this video, we demonstrate different types of peritoneal pockets and their close relationship with pelvic anatomic structures. Case 1 is a 29-year-old woman, gravida 0, with severe dysmenorrhea and catamenial bowel symptoms (bowel distension and diarrhea/constipation) that were unresponsive to medical treatment. Imaging studies were reported as normal, and a laparoscopy showed a posterior cul-de-sac peritoneal pocket infiltrating the pararectal fossa, with extension to the lateral border of the rectum. Case 2 is a cadaveric dissection of a posterior cul-de-sac peritoneal pocket infiltrating the pararectal fossa, with extension to the pelvic sidewall. After dissection of the obturator fossa, we can observe that the pocket is close to the sacrospinous ligament, pudendal nerve, and some sacral roots. Case 3 is a 31-year-old woman, gravida 1, para 1, with severe dysmenorrhea that was unresponsive to medical treatment and catamenial bowel symptoms (catamenial bowel distention and diarrhea). Imaging studies were reported as normal and a laparoscopy showed left uterosacral peritoneal pocket infiltrating the pararectal fossa in close proximity to the rectal wall. Case 4 is a cadaveric dissection of the ovarian fossa and the obturator fossa showing the proximity between these structures. Case 5 is a 35-year-old woman, gravida 0, with severe dysmenorrhea that was unresponsive to medical treatment, referring difficulty, and pain when walking only during menstruation. A neurologic physical examination revealed weakness in thigh adduction, and the magnetic resonance imaging showed no signs of endometriosis. During laparoscopy, we found a peritoneal pocket infiltrating the ovarian fossa, with involvement in the area between the umbilical ligament and the uterine artery. This type of pocket can easily reach the obturator nerve. Because the obturator nerve and its branches supply the muscle and skin of the medial thigh [7,8], patients may present with thigh adduction weakness or difficulty ambulating [9,10]. Case 6 is a cadaveric dissection of the sacrospinous ligament and the pudendal nerve from a medial approach, between the umbilical artery and the iliac vessels. Case 7 is a 34-year-old woman, gravida 1, para 1, with severe dysmenorrhea and catamenial bowel symptoms as well as deep dyspareunia. The transvaginal ultrasound showed focal adenomyosis and a 2-cm nodule, 9-cm apart from the anal verge, affecting 30% of the bowel circumference. In the laparoscopy, we found a posterior cul-de-sac retraction pocket associated with a large deep endometriosis nodule affecting the vagina and the rectum. In all cases, endometriosis was confirmed by histopathology, and in a 6-month follow-up, all patients showed improvement of bowel, pain, and neurologic symptoms., Conclusion: Peritoneal pockets can have different clinical presentations. Depending on the topography and deepness of infiltration, they can be the cause of some neurologic symptoms associated with endometriosis pain. With this video, we try to encourage surgeons to totally excise these lesions and raise awareness about the adjacent key anatomic structures that can be affected., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: The aim of this study was to validate temporally and externally the ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis., Design: A multicenter, international, retrospective, diagnostic accuracy study was carried out between January 2016 and April 2018 on women with suspected pelvic endometriosis., Setting: Four different centers with advanced ultrasound and laparoscopic services were recruited (1 for temporal validation and 3 for external validation)., Patients: Women with pelvic pain and suspected endometriosis., Interventions: All women underwent a systematic transvaginal ultrasound and were staged according to the UBESS system, followed by classification of laparoscopic level of complexity according to the Royal College of Obstetricians and Gynaecologists (RCOG) levels 1 to 3., Measurements and Main Results: UBESS I, II, and III were then correlated with RCOG levels 1, 2, and 3, respectively. A comparison between temporal and external sites (skipping "A") and between each site was performed in terms of the diagnostic accuracy of UBESS to predict RCOG laparoscopic skill level. A total of 317 consecutive women who underwent laparoscopy with suspected endometriosis were included. Complete transvaginal ultrasound and laparoscopic surgical outcomes were available for 293/317 (92.4%). At the temporal site, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of UBESS I to predict RCOG level 1 were 80.0%,73.8%, 94.9%, 97.2%, 60.2%, 14.5%, and 0.3%, respectively; of UBESS II to predict RCOG level 2 were 81.0%, 70.6%, 82.0%, 26.7%, 96.8%, 3.9%, and 0.3%, respectively; of UBESS III to predict RCOG level 3 were 91.0%, 85.7%, 92.4%, 75.0%, 96.1%, 11.3%, and 0.2%, respectively. At the external sites, the results of UBESS I to predict RCOG level 1 were 90.3%, 92.0%, 88.4%, 90.2%, 90.5%, 7.9%, and 0.1% respectively; UBESS II to predict RCOG level 2 were 89.2%, 100.0%, 88.5%, 37.5%, 100.0%, 8.7%, and 0.0%, respectively; and UBESS III to predict RCOG level 3 were 86.0%, 67.6%, 98.2%, 96.2%, 82.1%, 37.8%, and 0.3%, respectively. When patients requiring ureterolysis (i.e., RCOG level 3) in the absence of bowel endometriosis were excluded (n = 54), the sensitivity of UBESS III to correctly classify RCOG level 3 increased from 85.7% to 96.7% at the temporal site (n = 42) and from 67.6% to 96.0% at the external sites (n = 12) (p <.005)., Conclusion: The results from this external validation study suggest that UBESS in its current form is not generalizable unless there is either or both bowel deep endometriosis and cul-de-sac obliteration present. The major limitation appears to be the misclassification of women who require surgical ureterolysis in the absence of bowel endometriosis., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

The female genital tract system is rarely affected by neurofibromatosis type 1 (NF1). Plexiform neurofibromas are congenital lesions that occur in patients with NF1. The vulva is the most frequent genital location but vaginal, cervical, uterine, and ovarian neurofibromas have rarely been reported. We describe a case of plexiform neurofibromas involving the uterine cervix in a patient with known NF1 that presented with chronic pelvic pain and heavy menstrual bleeding.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified from Isodon eriocalyx var. laxiflora, was previously reported to have antitumor effects via multiple immune-related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms., Methods: The EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay tests. We then explored anti-inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF-κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model., Results: Histological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P < .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose-dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF-κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF-κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF-κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF-κB pathway during EriB treatment., Conclusions: The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS., (© 2020 Wiley Periodicals LLC.)

Objectives: To describe the clinical and ultrasound characteristics of adnexal torsion., Methods: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ., Results: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion., Conclusion: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Study Objective: To evaluate the diagnosis of appendiceal endometriosis (AppE) in coincidental appendectomy specimens using standard versus modified histopathologic analysis., Design: Prospective analysis of 300 consecutive patients undergoing coincidental appendectomy at the time of a primary gynecologic procedure., Setting: Academic tertiary referral hospital in the northeastern United States., Patients: Women aged 22 to 52 years undergoing gynecologic surgery for the management of endometriosis or chronic pelvic pain between 2013 and 2015., Interventions: Each appendix specimen underwent standard pathologic analysis with 4 sections performed. Modified pathologic analysis, consisting of standard analysis plus serial sectioning and complete evaluation of the appendix and mesoappendix, was then performed. The first pathologist reviewed all the slides to render a diagnosis. The slides of the subjects with abnormal pathology were rereviewed. On rereview, the diagnosis was confirmed, and the data on which protocol, standard or modified, achieved the diagnosis was rendered. The pathologist performing the second review was blinded to whether the slides from the standard or modified histopathology protocol achieved the original diagnosis. This allowed each specimen to serve as its own control., Measurements and Main Results: The primary outcome is the detection of AppE. The standard analysis identified endometriosis in 7.7% (n = 23) of appendiceal specimens, whereas the modified analysis identified endometriosis in 10.0% (n = 30; odds ratio 1.3; confidence interval, 1.1-1.7; p = .01). When all pathology findings were combined, the standard analysis identified abnormal pathology in 9.3% (n = 28) of the specimens, whereas the modified analysis identified abnormal pathology in 12.3% (n = 37; odds ratio 1.4; confidence interval, 1.1-1.7; p <.01). Other abnormal appendiceal pathology identified in this study included polyps, neuroendocrine tumors, and acute appendicitis. The average number of slides required for the standard analysis was 1.4 compared with 4.9 slides for the modified analysis. At this institution, the average increase in the cost of slide production for the modified protocol was $12.07., Conclusion: Modified pathologic analysis resulted in a significantly higher rate of diagnosis of endometriosis and abnormal pathology in coincidental appendectomy performed during a primary gynecologic procedure for endometriosis and/or chronic pelvic pain. The use of a standard pathologic protocol likely contributes to underdiagnosis of AppE. The implementation of a modified histopathologic protocol should be considered for improving diagnosis rates of appendiceal pathology in coincidental appendectomy specimens., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable problem of the urogenital system. The aetiopathogenesis and effective treatments for CP/CPPS are needed to be untangled. Pirfenidone is a molecule that exhibits anti-inflammatory, antifibrotic, and antioxidative stress capacities in a variety of animal experiments and clinical trials. This study was aimed to investigate the therapeutic effect of pirfenidone on CP/CPPS and to identify the mechanism responsible for it., Methods: A CP/CPPS model was induced in rats by intraprostatic injection of complete Freund's adjuvant (CFA). Blood and prostatic tissues were harvested for assessment after the administration of pirfenidone or vehicle for 4 weeks., Results: The findings revealed that pirfenidone significantly ameliorated chronic pelvic pain and inhibited prostatic inflammation and fibrosis. Further study found that pirfenidone suppressed the expression of proinflammatory mediators, including tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, IL-8. Pirfenidone exhibited a potent antioxidant capacity through improving the activities of glutathione, catalase, total superoxide dismutase, and reducing the production of malondialdehyde. Furthermore, pirfenidone also facilitated the polarization of M2 macrophages and suppressed the activation of the nuclear factor-κB (NF-κB) signaling pathway., Conclusions: Pirfenidone can exert a beneficial effect against CFA-induced CP/CPPS by anti-inflammatory, antioxidative, antifibrotic properties, and the function is mediated at least partly through the M2 polarization of macrophages and the inhibition of NF-κB signaling pathway. These findings suggest that pirfenidone holds promise as a potential therapeutic for the treatment of CP/CPPS., (© 2020 Wiley Periodicals LLC.)

Purpose: The aim of our study is to evaluate the spectrum of MRI findings in transplanted Multiple Myeloma (MM) patients with hip/pelvic pain and to correlate these findings with standard prognostic clinical outcomes., Methods: A retrospective interpretation of the MRI findings of 54 MM patients with hip/pelvic pain were done according to MY-RADS guidelines. MRI findings included: type of bone marrow involvement and incidental findings (osteonecrosis and fractures). Inter- and intra-reader agreement were calculated using Cohen's kappa test. Survival and relapse rates, type of transplantation and days of hospitalization were correlated with MRI findings., Results: 1/52 patient presented normal bone marrow pattern, 10/52 focal pattern, 26/52 diffuse pattern and 15/52 mixed. No cases of micronodular was reported. Among the incidental findings, n = 6 osteonecrosis and n = 5 pathological fractures were found, with average length of stay higher. The intra- and inter-reader agreement assessing MY-RADS, were good (k value between 0.61-0.8). Focal pattern was most represented in patients with osteonecrosis and the worst survival rate. Diffuse pattern was most represented in relapses. No statistically significant correlations were found between bone marrow infiltration patterns and the type of transplantation., Conclusion: MRI can recognize different infiltration patterns and complications in transplanted MM patients with hip/pelvic pain, correlating with clinical parameters., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Studies have been published on the efficacy of Dienogest in the management of pain symptoms in endometriosis. Nonetheless, few data are available on the reducing effect on endometrioma's size. The aim of the study was to evaluate if Dienogest could determine significant changes in size, as well as in symptoms. In this prospective observational study, patients were enrolled with pain symptoms and at least one endometrioma diagnosed via TV-US. The volume of the endometrioma and pain symptoms was measured according to the LxDxWx0.5233 formula and VAS, respectively. Dienogest 2 mg was administered daily. Follow-up visits were scheduled after 6 and 12 months of treatment to assess changes in patients' symptoms and endometrioma's volume. Seventy patients were enrolled, 63 patients completed a 6-month treatment. The reduction of the mean volume after 6 months was 66.71%. Fifty-eight patients completed the 12 month-treatment. The reduction of the mean volume after 12 months was 76.19%. Dysmenorrhea showed a 74.05% reduction after 6 months and a 96.55% reduction after 12 months. Patients reported a reduction in dyspareunia and chronic pelvic pain of 42.71% and 48.91% after 6 months and 51.93% and 59.96% after 12 months, respectively. Dienogest leads to a statistically significant reduction of endometrioma's volume and pain symptoms.

Study Objective: Beside the pain, there are 2 further problems in the management of endometriosis: the high recurrence rate (10% per year) and the high rate of impaired fertility. The objective of this study was to investigate the pathogenesis of these 2 factors., Design: This is a retrospective cohort study, and the aim is to evaluate the complete excision of endometriotic lesions, including the posterior compartment of the peritoneum, with regard to postoperative outcome, focusing on relieving pain, increasing fertility rate, and decreasing recurrence rate., Setting: Charité-University Clinic, Department of Gynaecology, Endometriosis research Centre., Patients: Fifty-four patients were enrolled in this study, with severe deep infiltrating endometriosis (scored by ENZIAN) and superficial endometriosis, as well as endometriomas (revised American Society for Reproductive Medicine [rASRM] I = 3; II = 15; III = 10; and IV = 26)., Interventions: Posterior compartment peritonectomy (visible endometriotic lesions and inflamed altered peritoneum) was performed in all patients as part of a complex surgery: complete excision of endometriosis., Measurements and Main Results: Postoperative outcomes were evaluated, based on the postoperative follow-up (up to 5 years) of 54 investigated patients. In 36 women (66%) preoperative complaints were eliminated. Furthermore, of 28 women seeking improved fertility, pregnancy was reported in 13 cases (46%). In 7 (54%) cases pregnancy occurred spontaneously, and in the remainder with assisted fertilization. In addition, long-term follow-up demonstrated a recurrence rate in 1.8% of patients., Conclusion: Overall, the number of complaints was significantly reduced. Only in the case of reproductive-aged women with ongoing postoperative complaints was it important to preserve the uterus. Although this pilot study on systematic posterior peritonectomy showed improvement in recurrence and fertility rate, the main question remains: will this surgical technique achieve better results and outcomes in the future? This has to be addressed in a prospective randomized study., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To assess the relationship between age, location of the disease, and surgical procedures performed in patients undergoing surgical management of endometriosis., Design: Retrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database., Setting: University tertiary referral center., Patients: Women who underwent surgical management of symptomatic endometriosis between April 2009 and April 2014., Interventions: Patients were allocated to 6 groups according to their age at the time of surgery: ≤20, 21 to 25, 26 to 30, 31 to 35, 36 to 40 and >40 years. Patient characteristics, prior history, location of endometriotic lesions, stage of disease, intraoperative findings, and surgical procedures were retrieved from a prospectively recorded database., Measurements and Main Results: Patient characteristics, symptoms, location of endometriosis, and type of surgery performed were compared between groups. In total, 1560 procedures were performed. Of these, more than one-half were carried out in women between the age of 26 to 35 years and the majority were performed in women aged between 26 and 30 years. Only 2% of procedures were performed in women under the age of 20 years. The mean stage of the disease at the time of surgical diagnosis was stage II for women younger than 20 years, stage III for those in the age group of 21 to 25 years, and stage IV for those older than 26 years. The rate of diagnosis of deep colorectal nodules increased progressively from 20 to 26 years and remained stable thereafter., Conclusion: Our data confirm that endometriosis is a disease that probably progresses from adolescence until the adult period when symptoms (pain or infertility) become debilitating and require surgery. Our data suggest that policies relating to the prevention and early diagnosis of endometriosis should focus on women younger than 25 years., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: Genitourinary atrophy is a menopausal pathological change determined by the definitive drop of ovarian hormones' production that can impact heavily on the health status of women, with important direct and indirect social costs. Unfortunately, available treatments are only symptomatic, and they are not able to reverse the atrophy and other related symptoms. Regenerative medicine, with single local injection of autologous micro-fractured fat tissue, could represent a viable new solution for these patients as it not only helps to relieve symptoms, but it also counteracts the mechanisms that lead to the menopausal genitourinary atrophy. The objective of this paper is to evaluate the long-term effectiveness of micro-fractured fat vulvar injection for genito-urinary atrophy in patients, affected by severe genitourinary atrophy (at least 4 symptoms lasting for at least 4 years)., Patients and Methods: We present a case series of 35 patients followed for 36 months to evaluate the effectiveness and safety of a single subcutaneous vulvar injection of autologous micro-fragmented fat tissue (MFAT)., Results: We have not observed any adverse effects in any patients. All symptoms, and especially pelvic pain and dyspareunia, improved in almost half of patients within 3 months. Ninety-nine percent of patients recovered completely from all symptoms after 9-12 months, reporting no relapse of the symptoms up to the third year of follow up., Conclusions: Our case series is the first case series, evaluating the long-term (3 years) safety and effectiveness of micro-fragmented adipose tissue graft for urogenital atrophy.

Objective: To further understand the current status of diagnosis and treatment of endometriosis in China, the implementation of guideline in different levels of hospitals, and the need for continuing education in endometriosis among primary doctors. Methods: The survey was conducted in the form of convenience sampling questionnaire among the Wechat public platform. The doctors were free to participate in the investigation without any reward. All questions answered were assessed as valid questionnaire. The datas were collected on the questionnaire network platform and analyzed by SPSS 19.0. Results: Totally 1 494 valid questionnaires were collected in this survey. 60.17% (899/1 494) of them were from tertiary hospital, and 32.60% (487/1 494) were from grade two hospital. Only the hospitals where 9.97% (149/1 494) participants based opened the specialist clinic for endometriosis. 70.35% (1 051/1 494) of participants said they had read the second edition of guideline for the diagnosis and treatment of endometriosis which published in 2015. The American Society for Reproductive Medicine (ASRM) staging system was adopted in the clinical practices of only 25.03% (374/1 494) participants. And 18.74% (280/1 494) participants used the endometriosis fertility index (EFI) scoring during the laparoscopic surgery for endometriosis with infertility. 45.18% (675/1 494) of participants said they had not attended any academic conference on endometriosis in the past six months. 64.46% (963/1 494) of the participants believed their diagnosis and treatment in practice should be improved and standardized. 87.15% (1 302/1 494) of the participants expressed the hope that more conferences or workshops on endometriosis would be held. Conclusions: At presents, the diagnosis and treatment of endometriosis in China has been greatly improved, but the implementation of guidelines and the new concept is still a long-term job. The specialist clinic are held only in a few hospitals. It's the expectation and voice of primary doctors to the association to organize the more academic congresses on endometriosis.

Competing Interests: The authors have no conflicts of interest to declare.

Objectives. We recently suggested that increased intramural pressure may often explain pain and/or bleeding. Hysterectomies for bleeding tend to have outward bulges and endometrial vascular ectasia, while hysterectomies for pain tend to have deflection of pressure inward by subserosal ridges, which promote inner myometrial elastosis (IME). Study design. We analyzed causes of increased intramural pressure in 58 hysterectomies for pain and/or bleeding, excluding clinically fibroid uteri and prolapsed uteri. Postfixation photographs were used to avoid missing grossly obvious myometrial hyperplasia (MMH). Results. The most common cause of increased intramural pressure was grossly obvious MMH in 40/58 cases (69%). Other causes included clinically occult myomas (3 cases), adenomyosis (6 cases), and multifactorial causes (7 cases). Hysterectomies for bleeding weighed more than hysterectomies for pain ( P = .035). Hysterectomies for pain had more IME than hysterectomies for bleeding ( P = .029). Conclusions. When subserosal ridges deflect pressure inward, bulky MMH may cause pelvic pain and IME, but when they do not, bulkier MMH in heavier uteri may lead to both outward bulges and abnormal bleeding from endometrial vascular ectasia.

Cowper's syringoceles are uncommon, usually described in children and most commonly limited to the ducts. We describe more complex variants in an adult population affecting with varying degrees of severity, the glands themselves, and the complications they may lead to. One hundred consecutive urethrograms of patients with unreconstructed strictures were reviewed. Twenty-six patients (mean age: 41.1 years) with Cowper's syringoceles who were managed between 2009 and 2016 were subsequently evaluated. Presentation, radiological appearance, treatment (when indicated), and outcomes were assessed. Of 100 urethrograms in patients with strictures, 33.0% demonstrated filling of Cowper's ducts or glands, occurring predominantly in patients with bulbar strictures. Only 1 of 26 patients with non-bulbar strictures had a visible duct/gland. Of 26 symptomatic patients, 15 presented with poor flow. In four patients, a grossly dilated Cowper's duct obstructed the urethra. In the remaining 11 patients, a bulbar stricture caused the symptoms and the syringocele was identified incidentally. Eight patients presented with perineal pain. In six of them, fluoroscopy and magnetic resonance imaging (MRI) revealed complex multicystic lesions within the bulbourethral glands. Four patients developed perineoscrotal abscesses. In the 11 patients with strictures, the syringocele was no longer visible after urethroplasty. In three of four patients with urethral obstruction secondary to a dilated Cowper's duct, this resolved after transperineal excision (n = 2) and endoscopic deroofing (n = 1). Five of six patients with complex syringoceles involving Cowper's glands were excised surgically with symptomatic relief in all. In conclusion, Cowper's syringocele in adults is more common than previously thought and may cause lower urinary tract symptoms or be associated with serious complications which usually require surgical treatment., Competing Interests: None

Objective: Current estimates of endometriosis prevalence and incidence are highly variable, leading to uncertainty regarding true endometriosis frequency or validity of quantified changes over time. We present a comprehensive review of the prevalence, incidence, and stage of endometriosis worldwide as reported over the past 30 years., Data Sources: We conducted a systematic search of observational studies using the PubMed, Web of Science, EMBASE, and CINAHL databases to identify research papers published in English between January 1989 and June 2019. Search terminologies were limited to titles containing endometriosis and prevalence or incidence, or epidemiology, or frequency, or occurrence, or statistics., Methods of Study Selection: Two independent reviewers screened abstracts for study eligibility, and data from included studies were abstracted., Tabulation, Integration, and Results: Overall, 69 studies describing the prevalence and/or incidence of endometriosis met the inclusion criteria. Among these, 26 studies involved general population samples, 17 of which were from regional/national hospitals or insurance claims systems. The other 43 studies were conducted in single clinic or hospital settings. Prevalence estimates for endometriosis widely varied from 0.2% to 71.4% depending on the population sampled. The prevalence reported in general population studies ranged from 0.7% to 8.6%, whereas that reported in single clinic- or hospital-based studies ranged from 0.2% to 71.4%. When defined by indications for diagnosis, endometriosis prevalence ranged from 15.4% to 71.4% among women with chronic pelvic pain, 9.0% to 68.0% among women presenting with infertility, and 3.7% to 43.3% among women undergoing tubal sterilization. A meta-regression was conducted with year as the predictor of prevalence. No trend across time was observed among "general population in country/region" studies (β = 0.04, p = .12) or among "single hospital or clinic" studies (β = -0.02, p = .34); however, a decrease over time was observed among general population studies abstracted from health systems or insurance systems (β = -0.10, p = .005)., Conclusion: As with all human studies, population sampling and study design matter. Heterogeneity of inclusion and diagnostic criteria and selection bias overwhelmingly account for variability in endometriosis prevalence estimated across the literature. Thus, it is difficult to conclude if the lack of observed change in frequency and distribution of endometriosis over the past 30 years is valid., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ~176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy., (Copyright © 2020 Hogg, Horne and Greaves.)

Objective: The aim of the study was to expand the understanding of pathogenesis of adenomyosis-associated pelvic pain., Material and Methods: We studied 30 (n = 30) biopsy samples obtained after hysterectomy in women with diffuse adenomyosis of grade II-III, accompanied by severe pain syndrome, who did not receive hormonal therapy. The morphologic comparison group comprised 30 (n = 30) biopsy samples obtained from women with adenomyosis, without pain syndrome, operated on for abnormal uterine bleeding, who also did not receive hormone therapy., Results: The total density of immunological OTR labeling in the adenomyotic lesion foci was 73.7 ± 1.8%, and in the morphological control group it was 35.2 ± 1.4% (p <0.05), which indicates a significant effect of oxytocin as a ureterotonic peptide. Processes of local neurogenesis and growth of nerve fibers was established due to an increase in the expression of the nervous system growth factor NGF in the myometrium stroma, in comparison with biopsy samples of morphological control., Conclusion: Pelvic pain pathogenesis in women with diffuse adenomyosis compared with the painless form of the disease is an increase in the activity of ureterotonic factors of OTR oxytocin. Compared to the painless form of adenomyosis, the myometrial innervation apparatus of patients with pelvic pain is characterized by a significantly higher expression of nerve growth factor.

Aim: Endometriosis is one of the most common gynecological diseases diagnosed in almost 70% of patients with chronic pelvic pain (CPP). However, a quarter of women with pelvic pain is diagnosed with external genital endometriosis (EGE) during laparoscopy. A special group is represented by patients with PP that did not stop after the removal of endometrial foci. The mechanisms of the pathogenesis of the formation of pain syndrome are not completely explored yet. According to several authors, a significant role in the pathogenesis of pelvic pain recurrence after surgical treatment of EGE is played by active neuroangiogenesis, both in ectopic and eutopic endometrium. The aim of the study was to expand the understanding of the pathogenesis of pelvic pain that did not stop (recurrence) after surgical treatment of external genital endometriosis., Material and Methods: The study involved 2 stages. At the first stage (algological), data from B&B, NRS and VRS algological questionnaires, which were completed by patients with recurrent PP after surgical treatment of EGE, were analyzed ( n  = 130, aged 18-45 years old, average age 32.5 ± 7.6 years). All women were operated on for EGE no later than 3-6 months after assessing the patients by the algological questionnaires; they did not receive drug therapy after surgical treatment and sought medical attention for recurrent pelvic pain. Materials for the study of the endometrium were obtained by the pipelle biopsymethod. The control group was formed from a number of women with EGE without PP, who applied for surgical treatment of infertility ( n  = 30)., Results: The results of the study have shown that the basis of pathogenesis of pelvic pain recurrence in patients who did not receive medical therapy after surgical treatment of EGE is the activation of neuro-angiogenesis processes and reduction of apoptosis. The results show a statistically significant 1.6 times increasing expression of NGF in eutopic endometrium (57.9 ± 2.5 vs 35.3 ± 2.1% of patients with the silent form of the gene and its receptor NTRK1 1.8 times (2.78 ± 0.25 versus 1.56 ± 0.21.e. respectively). Conclusion: The pathogenesis of pelvic pain in patients who did not receive medical therapy after surgical treatment of endometriosis compared to no pain form of the disease is the activation of the processes of neurogenesis in the eutopic endometrium.

Pelvic pain is a common symptom of endometriosis. Our understanding of its etiology remains incomplete and medical management is limited by poor translation from preclinical models to clinical trials. In this review, we briefly consider the evidence, or lack thereof, that different subtypes of lesion, extra-uterine bleeding, and neuropathic pathways add to the complex and heterogeneous pain experience of women with the condition. We summarize the studies in rodent models of endometriosis that have used behavioral endpoints (evoked and non-evoked) to explore mechanisms of endometriosis-associated pain. Lesion innervation, activation of nerves by pronociceptive molecules released by immune cells, and a role for estrogen in modulating hyperalgesia are key endometriosis-associated pain mechanisms replicated in preclinical rodent models. The presence of ectopic (full thickness uterus or endometrial) tissue may be associated with changes in the spinal cord and brain, which appear to model changes reported in patients. While preclinical models using rats and mice have yielded insights that appear relevant to mechanisms responsible for the development of endometriosis-associated pain, they are limited in scope. Specifically, most studies are based on models that only resulted in the formation of superficial lesions and use induced (evoked) behavioral 'pain' tests. We suggest that translation for patient benefit will be improved by new approaches including models of ovarian and deep infiltrating disease and measurement of spontaneous pain behaviors. Future studies must also capitalize on new advances in the wider field of pain medicine to identify more effective treatments for endometriosis-associated pain.

Objective: Genital endometriosis (GE) is a widespread gynecological disease which requires its further pathogenesis investigation and search for new effective treatments. The known data of oxytocin receptor presence in endometrioid heterotopy smooth muscle cells give some grounds to assume oxytocin participation in the pathogenesis of endometriosis. The present study objective was to evaluate oxytocin level in peripheral blood (PB) in patients with endometriosis associated pain syndrome and to estimate the efficacy of oxytocin receptor inhibitors (IOXTR) administration based on animal endometriosis model., Materials and Methods: The basic group comprised 61 patients with endometriosis associated pain syndrome, while 21 patients formed the control group. VAS, MPQ, and BBS objective tests were applied for pain syndrome evaluation. Oxytocin level in PB was measured by immunoenzyme method. After confirmation of endometriosis experimental model formation in rats and further randomization, a daily IOXTR intra-abdominal injection was performed in a dose of 0.35 mg/kg/24 h in the basic group ( n  = 12) or saline solution administration in the control ( n  = 12). On the final stage, endometrioid heterotopy size measuring was performed along with histological examination., Results: Oxytocin level in PB was authentically higher in patients with GE compared to the control: 51.45 (35.54-62.76) pg/mL and 27.64 (23.23-34.12) pg/mL, respectively ( p <.001). Positive correlation between oxytocin PB level and pain syndrome expression was established in patients with GE: VAS ( r  = 0.76; p <.001), MPQ ( r  = 0.52; p <.001), and BBS ( r  = 0.57; p <.001). Based on the experimental disease model authentical decrease of endometrioid heterotopy average area was observed after IOXTR therapy compared to the control (7.3 ± 1.8 mm 2 and 22.2 ± 1.2 mm 2 , respectively, p <.05)., Conclusions: The obtained results confirm the oxytocin role in the pathogenesis of endometrioid associated pain syndrome. The high efficacy of IOXTR administration based on animal model of surgically induced endometriosis allows viewing this method as a perspective therapy.