Preoperative Ultrasound Scoring of Endometriosis by AAGL 2021 Endometriosis Classification Is Concordant with Laparoscopic Surgical Findings and Distinguishes Early from Advanced Stages.

STUDY OBJECTIVE: To compare the accuracy of preoperative ultrasound (US) in predicting the laparoscopically defined 2021 American Association of Gynecologic Laparoscopists (AAGL) Endometriosis Staging. DESIGN: Retrospective multicenter study of patients treated at 3 specialized endometriosis centers. SETTING: Three specialized endometriosis surgical centers in São Paulo (Brazil), Barcelona (Spain), and Avellino (Italy) participated. PATIENTS: A total of 878 patients aged 15 to 45 years with no history of pelvic malignancy underwent laparoscopic (LPS) treatment for suspected endometriosis. INTERVENTIONS: Retrospective review of preoperative transvaginal and transabdominal US (index test) assessed for endometriosis at all sites used in the 2021 AAGL Endometriosis Classification and classified patients into AAGL-US stages 1 to 4. Results were compared with reference-standard LPS (AAGL-LPS) staging. MEASUREMENTS AND MAIN RESULTS: The AAGL-US and AAGL-LPS stage were concordant in 586 cases (66.7%) (weighted kappa [WK] 0.759; intraclass correlation = 0.906), with the highest agreement observed in patients with no endometriosis (n = 70, 75.3% concordance), AAGL-LPS stage 1 (104, 50.7%) and stage 4 disease (358, 88.2%). Endometriosis was most accurately diagnosed in the rectum/sigmoid colon (WK 0.862), bladder (WK 0.911), and ovaries (WK 0.835/0.795 for right/left, respectively) and least accurately diagnosed at superficial peritoneal (WK 0.442), tubal (WK 0.391/0.363 for right/left, respectively), and retrocervical/uterosacral ligament (WK 0.656) sites. CONCLUSION: Sonographic estimation of the 2021 AAGL Endometriosis Staging is greatest in AAGL-LPS stages 1 and 4 and among patients with no endometriosis. US best identifies endometriosis of the ovaries, bladder, and bowel but is more limited for the tubes and superficial peritoneum.

Systematic evaluation of endometriosis by transvaginal ultrasound can accurately replace diagnostic laparoscopy, mainly for deep and ovarian endometriosis.

STUDY QUESTION: What is the sensitivity and the specificity of preoperative transvaginal ultrasound with bowel preparation (TVUS-BP) compared to diagnostic laparoscopy (DL) for the identification of ovarian and deep sites of endometriosis? SUMMARY ANSWER: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP, whereas for vaginal and rectosigmoid endometriosis, DL had lower sensitivity and specificity than TVUS-BP. WHAT IS KNOWN ALREADY: TVUS-BP is a non-invasive examination with good accuracy for diagnosing ovarian and deep endometriosis. DL is expensive and can lead to surgical complications. STUDY DESIGN, SIZE, DURATION: This prospective study included a total of 120 consecutive patients who underwent surgery for suspected endometriosis with preoperative imaging (TVUS-BP), including a video of the laparoscopic procedure, between March 2017 and September 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two radiologists performed preoperative TVUS-BP using the same protocol for diagnosing endometriosis. Two surgeons, who were blinded to the results of the preoperative imaging and clinical data, reviewed the surgical videos from the entry of the abdominal cavity until the surgeon finalized a complete and systematic review prior to beginning any dissection (considered as a DL). A data sheet was used by surgeons and radiologists to record the sites and size of disease involvement, the American Society for Reproductive Medicine (ASRM) stage, and the Enzian score. The surgical visualization of endometriosis lesions that were confirmed by histological analysis was the gold standard. MAIN RESULTS AND THE ROLE OF CHANCE: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP. DL was not able to detect vaginal endometriosis (sensitivity and specificity 0%): this is compared to a sensitivity and specificity of 85.7% and 99.1%, respectively with the utilization of a preoperative TVUS-BP. In addition, DL was notably poor at detecting rectosigmoid endometriosis, with a sensitivity of 3.7-5.6%, and this compares to 96.3% sensitivity with utilization of a preoperative TVUS (P < 0.001). For the ASRM stage, TVUS-BP results were highly correlated with the degree of endometriosis and pouch of Douglas (POD) obliteration (weighted Kappa of 0.867 and 0.985, respectively). For the Enzian score, there was a substantial correlation between TVUSP-BP and DL for compartment A (weighted Kappa = 0.827), compartment B (weighted Kappa = 0.670), and compartment C (weighted kappa = 0.814). LIMITATIONS, REASONS FOR CAUTION: The number of participants included may be a limitation in this study and, as the evaluators were blinded to the physical exam, the DL accuracy could be underestimated. As biopsies of pelvic organs were obtained only if there was a suspicion of endometriosis, the gold standard was not always applicable. This aspect could underestimate the prevalence of lesions and overestimate the sensitivity and the specificity of both the TVUS-BP and the DL. WIDER IMPLICATIONS OF THE FINDINGS: Preoperative TVUS-BP was accurate in identifying all sites of ovarian and deep endometriosis that were evaluated. It had significantly higher sensitivity than DL in detecting rectosigmoid endometriosis and predicting intraoperative ASRM staging and the Enzian score. These results suggest that TVUS-BP can replace DL for the diagnosis and treatment planning for patients with ovarian and deep endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The authors declare no source of funding or conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

How to minimize bleeding in laparoscopic myomectomy.

PURPOSE OF REVIEW: Laparoscopic myomectomy is a common surgical procedure for symptomatic myomas. However, bleeding control during surgery may pose a challenge. Therefore, the aim of this study was to review recent evidence regarding interventions to control bleeding during laparoscopic myomectomy. RECENT FINDINGS: The use of vasopressin resulted in less blood loss compared to placebo. Barbed sutures reduced blood loss compared to conventional sutures. Intravenous infusion of tranexamic acid (TXA) in the intraoperative period of large myomectomies showed no significant difference compared to placebo. Uterine artery occlusion (UAO) and emergency uterine artery embolization were reported to be feasible and may reduce and treat bleeding before conversion to laparotomy. SUMMARY: Several methods can control bleeding during laparoscopic myomectomy. Vasopressin and barbed sutures resulted in decreased blood loss, and TXA did not have an impact on bleeding control. The use of UAO and emergency embolization techniques can contribute to the control of bleeding; however, further studies are needed to prove the efficacy of these and other agents.

AAGL 2021 Endometriosis Classification: An Anatomy-based Surgical Complexity Score.

STUDY OBJECTIVE: To develop a new endometriosis classification system for scoring intraoperative surgical complexity and to examine its correlation with patient-reported pain and infertility. DESIGN: Multicenter study of patients treated at 3 recognized endometriosis centers. SETTING: Three specialized endometriosis surgical centers in São Paulo, Brazil and Barcelona, Spain. PATIENTS: Patients aged 15 to 45 years with histologically proven endometriosis and no history of pelvic malignancy underwent laparoscopic treatment of endometriosis. INTERVENTIONS: Demographic data and clinical history, including dysmenorrhea, noncyclic pelvic pain, dyspareunia, dysuria and dyschezia, were prospectively recorded. All patients were staged surgically according to the new 2021 American Association of Gynecologic Laparoscopists (AAGL) and revised American Society of Reproductive Medicine (ASRM) classification systems. The staging for each system was compared against a 4-level surgical complexity scale defined by the most complex procedure performed. MEASUREMENTS AND MAIN RESULTS: A total of 1224 patients undergoing surgery met inclusion criteria. The AAGL score discriminated between 4 stages of surgical complexity with high reproducibility (κ = 0.621), whereas the ASRM score discriminated between the complexity stages with poor reproducibility (κ = 0.317). The AAGL staging system correlated with dysmenorrhea, dyspareunia, dyschezia, total pain score, and infertility comparably with the ASRM staging system. CONCLUSION: The AAGL 2021 Endometriosis Classification allows for identifying objective intraoperative findings that reliably discriminate surgical complexity levels better than the ASRM staging system. The AAGL severity stage correlates comparably with pain and infertility symptoms with the ASRM stage.

Laparoscopic Treatment of Ureteral Endometriosis: A Systematic Review.

OBJECTIVE: To review the literature for the preoperative clinical characteristics, surgical findings, and outcomes of patients who underwent laparoscopic surgical treatment of ureteral endometriosis (UE). DATA SOURCES: A systematic search was performed in the PubMed and Scopus databases. METHODS OF STUDY SELECTION: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies in English language that assessed UE treated surgically by laparoscopy published between 2008 and 2020 were selected. TABULATION, INTEGRATION, AND RESULTS: In an initial search, 1313 articles were identified, 193 in PubMed and 1120 in Scopus databases. A total of 1291 articles that did not meet eligibility criteria were excluded. The remaining 22 studies were included in the final qualitative analysis, with a total of 1337 patients. Data on preoperative patient's characteristics, preoperative imaging examinations, intraoperative findings, and postoperative complications were abstracted by 1 author. The descriptive nature of included studies prevented the performance of meta-analysis. Preoperative symptoms included dysmenorrhea (76.3%), pelvic pain (59.6%), dyspareunia (46.2%), lower urinary tract symptoms (21.3%), and ureteral obstructive symptoms (9.9%). Intraoperative findings showed that UE lesions were left-sided in 55% of the cases, right-sided in 28.9% of the cases, and bilateral in 8.7% of the cases. Ureterolysis alone or before another technique was performed in 69.1% of the cases, ureteral resection followed by ureteroureteral anastomosis in 6%, ureteroneocystostomy after ureteral resection in 21%, and nephrectomy in 0.45% of the patients. Double-J ureteral stent placement was reported in 33.3% of the cases. Concomitant resection of the bladder owing to endometriosis involvement was performed in 15.5% of the cases. The prevalence of ureteral injury was 3.1%. Postoperative complications included ureteral fistula (2.8%), ureteral stenosis (24.2%), persistence/recurrence of UE (3.8%), and reoperation for fistula and/or stricture treatment (3.9%). CONCLUSION: UE is associated with common endometriosis pain symptoms and a low rate of lower urinary tract symptoms. The standard surgical technique for UE treatment is not yet a consensus; however, the laparoscopic approach with previous ureterolysis, leaving ureteral resection only for refractory cases, seems to be a safe and effective treatment, with improvement of symptoms and few intraoperative and postoperative complications.

Comparison of Sensitivity and Specificity of Structured and Narrative Reports of Transvaginal Ultrasonogaphy for Adenomyosis.

STUDY OBJECTIVE: To compare the sensitivity and specificity of the transvaginal ultrasonography (TVUS) narrative report with those of the structured report for the diagnosis of adenomyosis. DESIGN: Retrospective study. SETTING: A tertiary teaching hospital. PATIENTS: One hundred ninety-two patients (45 with adenomyosis and 147 controls) who underwent hysterectomy between 2012 and 2016 and were aged 30 years to 55 years, with available preoperative TVUS images, were included. INTERVENTIONS: To compare preoperative TVUS with histologic analysis of the uterus after hysterectomy for the diagnostic of adenomyosis. MEASUREMENTS AND MAIN RESULTS: Data regarding the presence of the ultrasonographic characteristics previously described for the diagnosis of adenomyosis were obtained from the original TVUS report (narrative report) and the structured report from 2 blinded radiologists (R1 and R2). Histologic analysis is defined as the gold standard for the diagnosis of adenomyosis. The mean age (45.4 ± 5.3 years vs 44.9 ± 4.8 years; p = .496) and clinical symptoms were similar between the adenomyosis and control groups, except for dyspareunia, which was more frequently reported in the patients with adenomyosis (25.6% vs 9.4%; p = .006). Most of TVUS characteristics were more frequently observed in the structured reports than in the narrative reports. The structured report presented higher sensitivity (R1: 84.4%, R2: 69.1%; narrative report: 31.1%; p <.05) and lower specificity (R1: 28.0%, R2: 31.2%; narrative report: 90.5%; p <.05) for adenomyosis. The structured report presented higher sensitivity and lower specificity for most of sonographic characteristics evaluated. After logistic regression analysis, no sonographic characteristics presented with statistical significance for the diagnosis of adenomyosis on R1's structured report, while globular uterus (odds ratio [OR] 0.276; p = .006; 95% CI, 0.11-0.697) and poorly defined junctional zone (OR 3.6; p = .007; 95% CI, 1.4-9.2) were significantly associated with adenomyosis. In the narrative report, a myometrial cyst was associated with a higher risk of adenomyosis (odds ratio 9.486, p =.002; CI, 2.359-38.149). CONCLUSION: The narrative reports were more specific, whereas the structured reports were more sensitive for the diagnosis of adenomyosis. In addition, the sensitivity of most of sonographic feature of adenomyosis was higher and the specificity was lower in the structured report. Future prospective studies comparing both reports are needed to validate the current findings.

Is High-intensity Focused Ultrasound Effective for the Treatment of Adenomyosis? A Systematic Review and Meta-analysis.

STUDY OBJECTIVE: To systematically review the literature regarding the efficacy of high-intensity focused ultrasound (HIFU) in reducing adenomyotic lesions, patients' pain and bleeding symptoms, and the impact on patients' quality of life. DATA SOURCE: A search was performed through PubMed/MEDLINE and Cochrane databases. METHODS OF STUDY SELECTION: All available studies published in the English language in the last 10 years that evaluated the effects of HIFU for adenomyosis. TABULATION, INTEGRATION, AND RESULTS: A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A meta-analysis was performed on data from homogeneous studies. Pooled results from the meta-analysis showed that after HIFU treatment for adenomyosis, a large effect was observed in reducing the uterine volume at 12 months (standard mean difference [SMD] = 0.85), a significant reduction in dysmenorrhea at 3 months (SMD = 1.83) and 12 months (SMD = 2.37), and a significant improvement in quality of life at 6 months (SMD = 3.0) and 12 months (SMD = 2.75). Adverse reactions after HIFU were reported in 55.9% of patients. CONCLUSION: This review suggests a potential benefit for HIFU in the treatment of adenomyosis-related symptoms; however, findings of the meta-analysis were based on fewer, nonuniform studies, which did not equally account for each specific symptom/parameter across the board. Results showed there appears to be a potential of HIFU in the treatment of adenomyosis-related symptoms. To date, there are no comparative and randomized clinical trials comparing the HIFU technique with other conservative treatment options. As yet, there are insufficient data regarding fertility and pregnancy outcomes.

Postoperative Bowel Symptoms Improve over Time after Rectosigmoidectomy for Endometriosis.

STUDY OBJECTIVE: To evaluate bowel function (changes in stool caliber, sensation of incomplete evacuation, stooling frequency, and rectal bleeding) and urinary function (dysuria and retention) after segmental resection in patients with bowel endometriosis. DESIGN: Retrospective study. SETTING: Tertiary hospital. PATIENTS: A total of 413 (mean age = 33.6 ± 5.1 years) of reproductive aged women, with bowel endometriosis that underwent segmental bowel resection of the rectosigmoid from 2005 to 2018, without history of prior bowel surgery, without existing or history of malignancy. INTERVENTIONS: Laparoscopic segmental bowel resection performed by the same team and with the same technique. MEASUREMENTS AND MAIN RESULTS: Data collected from the patients' records included length of resected segment, distance of the lesion from the anal verge, and complications. Information on intestinal and urinary function was obtained from a questionnaire applied before the surgery and at 2, 6, and 12 months after the surgery. There was a significant increase in the incidence of stool thinning and rectal bleeding 2 months after surgical procedure; these symptoms decreased significantly over time. The incidence of urinary symptoms decreased significantly over time after surgery. The length of the bowel segment resected was not associated with the postoperative symptoms, but the rectosigmoid lesion was significantly closer to the anal verge in patients with rectal bleeding and urinary symptoms. There was no association between the length of intestinal segment resected and the frequency of stooling. At 6 months, patients who had a decreased frequency of stooling underwent a resection closer to the anal verge (9.7 cm) in comparison with the ones with unchanged or increase frequency of stooling (10.1 cm and 10.7 cm, respectively; p <.05). CONCLUSION: Patient complaints on bowel and urinary alterations after segmental resection were transient with significant improvement over time up to 12 months. Bowel and urinary symptoms were not associated with the size of the bowel segment resected, whereas rectal bleeding at 2 months after surgery was significantly associated with the distance from anal verge. Segmental resection was also associated with a great improvement in constipation at 12 months postoperative.

Transvaginal Ultrasound for the Diagnosis of Adenomyosis: Systematic Review and Meta-Analysis.

Adenomyosis is characterized by the presence of ectopic foci of endometrial glandular tissue and/or stroma within the myometrium. The diagnosis of adenomyosis is traditionally made through histologic evaluation of the postsurgical specimen. More recently, imaging with transvaginal ultrasound (TVUS) has been used for the preoperative diagnosis of adenomyosis. As yet, there is no consensus regarding the best imaging feature or combination thereof for the nonsurgical diagnosis of adenomyosis. This study systematically evaluated the literature in the last 10 years to determine the accuracy of 2-dimensional (2D) TVUS, different imaging features, enhancing methods such as 3-dimensional (3D) TVUS, elastography and color Doppler in the nonsurgical diagnosis of adenomyosis. A total of 8 studies were included. Pooled sensitivity and specificity for 2D TVUS for the diagnosis of adenomyosis for all combined imaging characteristics was 83.8% and 63.9%, respectively. Pooled sensitivity for 355 total patients with use of imaging feature of heterogeneous myometrium with 2D TVUS was highest (86.0%), and pooled specificity for 283 total patients with use of globular uterus was highest (78.1%). After including the "question mark" sign with other TVUS features, higher sensitivity and specificity, of 92% and 88%, respectively, were noted. For 3D TVUS, pooled sensitivity and specificity for all combined imaging characteristics was 88.9% and 56.0%, respectively. Poor definition of junctional zone showed the highest pooled sensitivity (86%) and the highest pooled specificity (56.0%) for the diagnosis of adenomyosis with 3D TVUS. There was no improvement in overall accuracy in 3D TVUS compared with 2D TVUS. Preliminary results of TVUS with color Doppler showed a high sensitivity and specificity for the differentiation between adenomyosis and myomas (95.6% and 93.4%, respectively). Also, TVUS elastography in 1 study showed an improvement in specificity (82.9%) compared with 2D TVUS (63.9%), albeit with comparable sensitivity. Larger studies are needed to advance our understanding of the different types of adenomyosis and their clinical impact.

Polymorphisms of mitochondrial DNA control region are associated to endometriosis.

PURPOSE: Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis. METHODS: Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence. RESULTS: The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups. CONCLUSION: mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.

Foxp3+CD39+CD73+ regulatory T-cells are decreased in the peripheral blood of women with deep infiltrating endometriosis.

Endometriosis's pathophysiology remains incompletely understood, with evidence pointing towards a dysregulated immune response. Regulatory T (Treg) cells, pivotal in maintaining self-tolerance, may facilitate the survival of ectopic endometrial cells within the abdominal cavity, thereby contributing to endometriosis development. This study aimed to assess the prevalence of CD39+CD73+ suppressor Treg cell subsets in the peripheral blood of endometriosis patients. This research focuses on the pivotal role of regulatory T-cells (Tregs), which are essential for maintaining immune tolerance and preventing autoimmune diseases. A case-control study was conducted, including 32 women diagnosed with endometriosis and 22 control subjects. The frequency of peripheral blood CD39+CD73+ suppressor Treg cells was quantified using flow cytometry. No significant differences were observed in the frequency of CD3+CD4+CD25High cells (Median [M]: 10.1; Interquartile Range [IQR]: 6.32‒18.3 vs. M: 9.72; IQR: 6.22-19.8) or CD3+CD4+CD25HighCD39+Foxp3+ cells (M: 31.1; IQR: 19.7-44.0 vs. M: 30.55; IQR: 18.5-45.5) between controls and patients. However, a significantly lower frequency of CD3+CD4+CD25HighCD39+CD73+ cells was observed in the endometriosis group compared to controls (M: 1.98; IQR: 0.0377-3.17 vs. M: 2.25; IQR: 0.50-4.08; p = 0.0483), suggesting a reduction in systemic immune tolerance among these patients. This finding highlights the potential role of CD39 and CD73 expression on Treg cells as biomarkers for assessing disease severity and progression. Furthermore, elucidating the mechanisms driving these alterations may unveil new therapeutic strategies to restore immune equilibrium and mitigate endometriosis symptoms.

Visual Analogue Scale Cut-off Point of Seven Represents Poor Quality of Life in Patients with Endometriosis.

Establishing objective criteria to assess endometriosis symptoms is crucial in defining therapeutic strategies. The visual analogue scale (VAS) is the most used system to enhance the accuracy and reduce the subjectivity of pain assessment, and symptoms of endometriosis are considered severe when the VAS score is ≥ 7 cm. Pain symptoms can significantly impact patients' quality of life, resulting in psychological and social distress. The aim of this study is to evaluate whether a VAS cut-off point of 7 cm for each pain symptom correlates with a diminished quality of life in women with endometriosis. This retrospective study included 1129 patients who underwent surgical treatment for endometriosis. Dysmenorrhea, acyclic pelvic pain, deep dyspareunia, dyschezia, and dysuria were assessed using a 0-10 cm VAS. The Short Form-36 (SF-36) questionnaire was employed to evaluate the quality of life 6 months prior to surgery. Dysmenorrhea was the most prevalent symptom reported in 93.6% of cases, with a mean VAS of 7.6 cm. The quality of life reported was reduced in most patients, with domain scores ranging from 49.4 to 80.1. The mean SF-36 scores in all domains were significantly lower in patients with severe pain (VAS score ≥ 7 cm) compared to those with mild to moderate pain (VAS < 7 cm). This trend was observed across all evaluated pain symptoms. Our research demonstrates that the prevalent VAS cut-off point for establishing severe pain symptoms in endometriosis (VAS ≥ 7 cm) accurately represents the negative impact of the disease on women's quality of life, as assessed via the SF-36 questionnaire.

Confocal Laser Endomicroscopy as a method for assessing endometriosis: A pilot study.

OBJECTIVES: To validate probe-based Confocal Laser Endomicroscopy (pCLE) as a method in assessing endometriosis during conventional and robot-assisted laparoscopy. STUDY DESIGN: Pilot study, including five women in Hospital Moriah, São Paulo, Brazil. During laparoscopic procedures, pCLE was used to assess endometriosis lesions, complemented by subsequent histological evaluations. 214 optical biopsies were performed. These assessments contributed to the development of a comparative atlas, which was used by surgeons to respond to a questionnaire to identify specific cellular structures related to endometriosis in selected confocal images. RESULTS: The patients had an average age of 35, exhibiting predominant symptoms like dysmenorrhea and dyspareunia. Despite varied familiarity with pCLE, surgeons demonstrated positive acceptance of the method, with 63.1% recommending its use for intraoperative diagnosis. The technique was particularly noted for its ability to provide real-time, detailed images aiding the identification of endometriosis and associated structures like adipocytes and vascularization, with average evaluation scores exceeding 8 of 10. CONCLUSIONS: This study underscores pCLE's potential as a transformative diagnostic tool in minimally invasive gynecological surgery. It highlights the feasibility and initial acceptance among surgeons, emphasizing the need for further improvements in device durability and cost-effectiveness. pCLE promises significant advancements in the diagnosis and management of endometriosis, suggesting a future direction for clinical applications and technological refinement.

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

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

Deep Endometriosis: the Involvement of Multiple Pelvic Compartments Is Associated with More Severe Pain Symptoms and Infertility.

Endometriosis can be classified into three phenotypes: superficial, ovarian, and deep. Deep endometriosis (DE) has been associated with more severe pain symptoms, although no large-scale studies have evaluated the association between pain intensity and infertility and the different compartments of the pelvis affected by superficial and DE. This retrospective study included 1116 women who underwent laparoscopy for endometriosis treatment at two referral centers between 2009 and 2019. For the evaluation of each symptom, patients were divided according to their visual analog scale score (< 7 and ≥ 7) and fertility status. On multiple logistic regression, severe dysmenorrhea and dyschezia were correlated with DE of the posterior compartment alone (odds ratio (OR) = 1.6, confidence interval (CI) 1.09-2.34, and p = 0.02 and OR = 2.09, CI 1.36-3.23, and p < 0.01, respectively) and in combination with other compartments. DE of the posterior and lateral compartments had the most consistent statistical power (OR = 3.55 for dysmenorrhea and OR = 4.4 for dyschezia). Infertility was associated with DE of the posterior compartment alone (OR = 1.6, CI 1.06-2.54, p = 0.04) and in combination with the anterior compartment (OR = 2.62, CI 1.29-5.29, p < 0.01), with the combination of posterior and anterior compartment having the highest OR value. Severe dyschezia and infertility were also correlated with the presence of multiple localizations of DE (p = 0.04 and p < 0.01). This study confirms the association between DE and severe pain symptoms as well as the influence of the number of DE compartments on the severity of symptoms and the chance of infertility.

Expression of ezrin protein and phosphorylated ezrin in pelvic endometriotic lesions.

OBJECTIVE: To evaluate the expression of Ezrin and Phosphorylated Ezrin (Phospho-Ezrin) in endometriosis lesions and its relation to the menstrual cycle phase, stage of endometriosis, histological classification, and clinical symptoms. MATERIAL AND METHODS: The authors conducted a retrospective study, with endometriotic lesions collected from women with endometriosis (n = 57) who underwent laparoscopy from 2017 to 2018. The expression of Ezrin and Phosphorylated Ezrin proteins was analyzed by immunohistochemistry. RESULTS: All the endometriotic lesions contained immunostaining for Ezrin in the glands. Phosphorylated Ezrin was expressed in the stroma of all endometriotic lesions. There was no difference in the Ezrin and Phosphorylated Ezrin's expression in the retrocervical, ovarian, superficial, and intestinal lesions in the same patient. Dysmenorrhea, dyspareunia, acyclic pain, infertility, and dysuria were similar in the three groups of Ezrin staining. There was an inversely proportional relationship between severe dyschezia and Ezrin's intensity, being 66.7% of Ezrin 1 (weak intensity), 36.7 Ezrin 2 (moderate intensity), and 10.0% of Ezrin 3 (p = 0.013). Regarding Phospho-Ezrin there wasn't a significant difference between all the analyzed variables. Histological classification and menstrual cycle phase had also no significant difference between Ezrin and Phospho-Ezrin immunostaining. CONCLUSION: Ezrin protein and Phospho-Ezrin can be considered important markers to elucidate the mechanisms related to migration and attachment of endometriotic lesions. It is still unclear if Ezrin and Phospho-Ezrin are a cause or consequence of endometriosis. Further studies comparing different types of lesions and eutopic endometrium are necessary to elucidate the role of these proteins in the pathogenesis of endometriosis.

The current role of robotic surgery in endometriosis management.

INTRODUCTION: Endometriosis is a chronic inflammatory disease that affects approximately 10%-15% of women of childbearing age. Laparoscopic surgery is the preferred surgical approach. Recently, robotic surgery has been used for benign gynecologic surgery, but its role in the treatment of endometriosis is still unknown. AREAS COVERED: We included studies that evaluated the outcomes of robotic surgery for endometriosis. Using the keywords 'endometriosis' and 'robotics', a comprehensive literature search on PubMed, Embase, and the Cochrane Library was performed in July 2021. EXPERT OPINION: Robotic surgery for endometriosis has similar outcomes as conventional laparoscopy, with no evidence of increased complication rates. Despite the non-inferiority of the surgical route, the associated costs of robotic surgery limit its availability. Rapid development of robot-assisted surgery necessitates long-term prospective randomized controlled trials. However, the limitations of robotic surgery should not be overlooked. If robotic surgery can facilitate the spread of minimally invasive surgery, it will be necessary to evaluate the cost, availability, complexity of the lesions, and most importantly, the results of patient satisfaction and values of value-based medicine.

The role of dendritic cells in endometriosis: A systematic review.

Endometriosis (EDT), a common estrogen-dependent inflammatory disorder, is characterized by endometrial-like tissue outside the uterus. While its pathogenesis is poorly understood, it is supposed that the immune system plays a role in its pathophysiology, and increased number of immune cells and changes in both cell-mediated and humoral immunity have been described. Dendritic cells (DCs) are antigen-presenting cells (APC) of the immune system that recognize, capture, and process complex antigens and present them to T cells, conferring them a unique ability as mediators between the innate and adaptive immune systems. This systematic review aims to enlighten possible disturbances (systemically and locally) of DCs in the development and progression of endometriosis. A search using the strategy: ("dendritic cells" AND "immunology" AND "endometriosis") in databases resulted in 490 citations; after applying inclusion and exclusion criteria, a total of 13 studies were assessed. The evaluated studies demonstrated that DCs are susceptible to pro-endometriotic changes which could inhibit immature DCs (imDCs) from their maturation and induce imDCs into a macrophage phenotype. In addition, the growth and vascularization of endometriosis requires the presence of endogenous DC, which infiltrate endometriotic lesions and enhance endothelial cell migration by secreting proangiogenic factors. Whereas DC maturation suppresses this response, imDC actively promote angiogenesis and growth, leading to a switch in their immunologic role from presenting antigens to support angiogenesis and EDT progression.