An evaluation of sexual function and health-related quality of life following laparoscopic surgery in individuals living with endometriosis.

STUDY QUESTION: What is the relationship between sexual function, health-related quality of life (HRQoL), and laparoscopic surgery in individuals living with endometriosis? SUMMARY ANSWER: A higher number of laparoscopic surgeries is significantly associated with poorer HRQoL and greater levels of sexual dysfunction in individuals with endometriosis. WHAT IS KNOWN ALREADY: Prior research indicates that endometriosis is associated with lowered HRQoL and sexual function and that these outcomes are influenced by endometriosis-related symptom profiles, medical, and surgical management. A limited number of studies have examined changes in sexual function in individuals with endometriosis following laparoscopic surgery or following repeated surgeries. STUDY DESIGN, SIZE, DURATION: A cross-sectional community-based online survey was used to examine the relationships between sexual function, HRQoL, and laparoscopic surgery (n = 210). PARTICIPANTS/MATERIALS, SETTING, METHODS: Individuals with a self-reported diagnosis of endometriosis were recruited via online advertising through social media and gynaecology clinics. Endometriosis-specific data (e.g. diagnostic delay, symptom experience) was collected in addition to engagement with laparoscopic surgery, level of HRQoL (EuroQol-5 Dimension: EQ-5D-5L), and sexual function (Female Sexual Function Index: FSFI). Bivariate correlational analyses and hierarchical multiple regression were used to determine the associations between the variables of interest. MAIN RESULTS AND THE ROLE OF CHANCE: Individuals with endometriosis have substantially poorer HRQoL in comparison to Australian normative samples, with greater levels of endometriosis-related symptom burden, distress, and pain significantly associated with lower levels of HRQoL. The mean FSFI score was suggestive of clinically significant female sexual dysfunction, with the lowest level of function noted in the domain of sexual pain and the highest level of function noted in the sexual satisfaction domain. A greater number of laparoscopic surgeries was significantly associated with poorer overall HRQoL and greater levels of sexual dysfunction. LIMITATIONS, REASONS FOR CAUTION: The cross-sectional nature of the data precludes direct findings of causality and further longitudinal research is recommended. The information pertaining to engagement in laparoscopic surgery was self-report in nature and was not medically verified. WIDER IMPLICATIONS OF THE FINDINGS: The study's findings highlight the pervasive impact of endometriosis on all domains of living, emphasizing the need to extend treatment planning beyond that of physical pain management alone. Early referral for assessment and management of sexual wellbeing is recommended prior to, and post-surgical intervention, with a focus on maintaining post-surgical changes, potentially reducing the need for multiple surgeries. STUDY FUNDING, COMPETING INTEREST(S): The study was not associated with research funding. Author CN reports grant funding from the Australian Government and Medical Research Future Fund (MRFF) and was a previous employee of CSL Vifor (formerly Vifor Pharma Pty Ltd). TRIAL REGISTRATION NUMBER: N/A.

Guideline No. 449: Diagnosis and Impact of Endometriosis - A Canadian Guideline.

OBJECTIVE: To provide a contemporary approach to the understanding of the impact and methods for the diagnosis of endometriosis in Canada. TARGET POPULATION: Individuals, families, communities, health care providers, and health care administrators who are affected by, care for patients with, or manage delivery of services for endometriosis. OPTIONS: The diagnosis of endometriosis is facilitated by a detailed history, examination, and imaging tests with providers who are experienced in endometriosis care. Surgical evaluation with pathology confirms a diagnosis of endometriosis; however, it is not required for those whose diagnosis was confirmed with imaging. OUTCOMES: There is a need to address earlier recognition of endometriosis to facilitate timely access to care and support. Education directed at the public, affected individuals and families, health care providers, and health care administrators are essential to reduce delays in diagnosis and treatment. BENEFITS, HARMS, AND COSTS: Increased awareness and education about the impact and approach to diagnosis may support timely access to care for patients and families affected by endometriosis. Earlier and appropriate care may support a reduced health care system burden; however, improved clinical evaluation may require initial investments. EVIDENCE: Each section was reviewed with a unique search strategy representative of the evidence available in the literature related to the area of focus. The literature searches for each section of this guideline are listed in Appendix A and include information from published systematic reviews described in the text. VALIDATION METHODS: The recommendations were developed following two rounds of review by a national expert panel through an iterative 2-year consensus process. Further details on the process are shared in Appendix B. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix C (Table C1 for definitions and Table C2 for interpretations of strong and conditional recommendations). INTENDED AUDIENCE: This guideline is intended to support health care providers and policymakers involved in the care of those impacted by endometriosis and the systems required to support them. TWEETABLE ABSTRACT: Endometriosis impact and diagnosis updated guidelines for Canadian health care providers and policymakers. SUMMARY STATEMENTS: RECOMMENDATIONS.

Inter-observer reproducibility of the 2021 AAGL Endometriosis Classification.

BACKGROUND: Inter-observer agreement for the American Association of Gynecologic Laparoscopists (AAGL) 2021 Endometriosis Classification staging system has not been described. Its predecessor staging system, the revised American Society for Reproductive Medicine (rASRM), has historically demonstrated poor inter-observer agreement. AIMS: We aimed to determine the inter-observer agreement performance of the AAGL 2021 Endometriosis Classification staging system, and compare this with the rASRM staging system. MATERIALS AND METHODS: A database of 317 patients with coded surgical data was retrospectively analysed. Three independent observers allocated AAGL surgical stages (1-4), twice. Observers made their own interpretation of how to apply the tool in the first staging allocation. Consensus rules were then developed for a second staging allocation. RESULTS: First staging allocation: odds ratio (OR) (and 95% CI) for observer 1 to score higher than observer 2 was 8.08 (5.12-12.76). Observer 1 to score higher than observer 3 was 12.98 (7.99-21.11) and observer 2 to score higher than observer 3 was 1.61 (1.03-2.51). This represents poor agreement. Second staging allocation (after consensus): OR for observer 1 to score higher than observer 2 was 1.14 (0.64-2.03), observer 1 to score higher than observer 3 was 1.81 (0.99-3.28) and observer 2 to score higher than observer 3 was 1.59 (0.87-2.89). This represents good agreement. CONCLUSIONS: These findings suggest that in its current format the AAGL 2021 Endometriosis Classification staging system has poor inter-observer agreement, not superior to the rASRM staging system. However, performance improved when additional measures were taken to simplify and clarify areas of ambiguity in interpreting the staging system.

Current Practice Patterns, Challenges, and Need for Education in Performing and Reporting Advanced Pelvic US and MRI to Investigate Endometriosis: A Survey by the Canadian Association of Radiologists Endometriosis Working Group.

Purpose: The Canadian Association of Radiologists (CAR) Endometriosis Working Group developed a national survey to evaluate current practice patterns associated with imaging endometriosis using advanced pelvic ultrasound and MRI to inform forthcoming clinical practice guidelines for endometriosis imaging. Methods: The anonymous survey consisted of 36 questions and was distributed electronically to CAR members. The survey contained a mix of multiple choice, Likert scale and open-ended questions intended to collect information about training and certification, current practices and protocols associated with imaging endometriosis, opportunities for quality improvement and continuing professional development. Descriptive statistics were used to summarize the results. Results: Canadian radiologists were surveyed about their experience with imaging endometriosis. A total of 89 responses were obtained, mostly from Ontario and Quebec. Most respondents were community radiologists, and almost 33% were in their first five years of practice. Approximately 38% of respondents reported that they or their institution performed advanced pelvic ultrasound for endometriosis, with most having done so for less than 5 years, and most having received training during residency or fellowship. 70% of respondents stated they currently interpret pelvic endometriosis MRI, with most having 1-5 years of experience. Conclusion: Many radiologists in Canada do not perform dedicated imaging for endometriosis. This may be due to a lack of understanding of the benefits and limited access to training. However, dedicated imaging can improve patient outcomes and decrease repeated surgeries. The results highlight the importance of developing guidelines for these imaging techniques and promoting a multidisciplinary approach to endometriosis management.

The impact of diagnostic method on sense of control and powerlessness and social support in endometriosis patients-A retrospective cohort study.

INTRODUCTION: It is recognized that for individuals living with endometriosis, receiving a diagnosis is psychosocially beneficial, but little is known about whether this is influenced by the way in which the disease is diagnosed. The primary objective of this study was to determine the impact of the diagnostic test method (clinical, diagnostic imaging, or diagnostic laparoscopy) of endometriosis on the individual's sense of control over their disease and their perceived access to social supports. The secondary objectives were to identify the impact of the diagnostic method on perceived social support, and to explore if there was a difference in the diagnostic method utilization between countries. MATERIAL AND METHODS: This retrospective cohort study reports on data collected using the Endometriosis Health Profile-30 (EHP-30) section of a previously published larger survey conducted between May and July 2020. Women aged 18-55 years who had received a diagnosis of endometriosis were recruited by social media platforms. The two domains of interest on the EHP-30 were control and powerlessness and social support. Scores on these domains were analyzed with diagnosis method as the variable of interest. RESULTS: In all, 1634 valid survey responses were received. There was a small statistically significant difference found between control and powerlessness scores for patients that received a diagnosis via imaging (ultrasound/MRI; n = 120) vs clinical diagnosis (n = 121) (p = 0.049). However, this did not reach clinical significance when covariates were controlled for (p = 0.054). No other comparisons reached statistical significance. CONCLUSIONS: The diagnostic method of endometriosis does not appear to have a clinically significant impact on an individual's sense of control over their disease nor their access to social supports. However, further research into these domains to delineate the true impact of the diagnostic method is required.

External Validation of the "2021 AAGL Endometriosis Classification": A Retrospective Cohort Study.

STUDY OBJECTIVE: Externally validate the American Association of Gynecologic Laparoscopists (AAGL) staging system against surgical complexity and compare diagnostic accuracy with revised American Society for Reproductive Medicine (rASRM) stage, as was done in original publication. DESIGN: Retrospective, diagnostic accuracy study. SETTING: Multicenter (Sydney, Australia). PATIENTS: A total of 317 patients (January 2016-October 2021) were used in the final analysis. INTERVENTIONS: A database of patients with coded surgical data was analyzed. MEASUREMENTS AND MAIN RESULTS: Three independent observers assigned an AAGL surgical stage (1-4) as the index test and surgical complexity level (A-D) as the reference standard. Results from the most accurate of the 3 observers were used in the final analysis. The weighted kappa score for the overall performance of AAGL stage and rASRM to predict AAGL level was 0.48 and 0.48, respectively (no difference). This represents weaker agreement with AAGL level than was observed in the reference paper, which reported a weighted kappa of 0.62. Diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) for stage 1 to predict level A was 98.5%, 64.3%, 66.3%, and 98.3%; stage 2 to predict level B 31.2%, 90.5%, 27.0%, and 92.1 %; stage 3 to predict level C 12.3%, 94.1%, 59.3%, and 60.7%; stage 4 to predict level D 95.65%, 88.10%, 38.60%, and 99.62%. Area under the receiver operating characteristic curve for A vs B/C/D (cut point 9) was 0.87, A/B vs C/D (cut point 16) was 0.78, and A/B/C vs D (cut point 22) was 0.94. CONCLUSION: There was weak to moderate agreement between AAGL stage and AAGL surgical complexity level. Across all key indicators, the AAGL system did not perform as well in this external validation, nor did it outperform rASRM as it did in the reference paper. Results suggest the system is not generalizable.

Prevalence of Use and Perceived Effectiveness of Medical, Surgical, and Alternative Therapies for Endometriosis Pain in Canadians.

OBJECTIVES: To describe the use and perceived effectiveness of medical, surgical, and alternative therapies (e.g., diet, exercise, heat, cannabis, etc.) in managing endometriosis-associated pain in Canadians. METHODS: A cross-sectional online survey was distributed via The Endometriosis Network Canada (TENC) from February to March 2021. Canadians aged 18-50 years with diagnosed or suspected endometriosis were eligible to participate. RESULTS: A total of 434 survey responses were included, and 93.8% of respondents reported that they used at least 1 alternative therapy in the past 6 months for endometriosis-associated pain. Respondents used an array of medical (2.3/6 months), surgical (1.7/lifetime), and alternative therapies (6.9/6 months) to manage their pain, yet 61.9% of respondents did not feel it was adequately managed. The most common alternative therapies were heat, meditation/mindfulness/rest, and diet. CONCLUSION: Alternative therapies were commonly used by Canadians living with endometriosis to manage pain. Cannabis and heat were perceived as the most effective alternative therapies. Here, we gain a better understanding of alternative therapies that can provide an additional therapeutic avenue that clinicians and people living with endometriosis may wish to discuss and explore.

CAR Practice Statement on Advanced Pelvic Ultrasound for Endometriosis.

The Canadian Association of Radiologists (CAR) Endometriosis Working Group was tasked with providing guidance and benchmarks to ensure the quality of technique and interpretation for advanced imaging modalities associated with diagnosing endometriosis. This practice statement provides an overview of the state of the art of advanced pelvic ultrasound in the diagnosis and mapping of pelvic endometriosis. While acknowledging that advanced pelvic ultrasound in some practices falls within the scope of clinical colleagues rather than imaging departments, the statement seeks to guide radiologists interested in implementing these techniques into their practice for patients referred for evaluation and diagnosis of endometriosis. The statement covers indications, some components of the ultrasound assessment and technique, reporting, and recommendations for starting an ultrasound endometriosis evaluation program.

Comparison of #Enzian classification and revised American Society for Reproductive Medicine stages for the description of disease extent in women with deep endometriosis.

STUDY QUESTION: How is endometriosis extent described by the #Enzian classification compared to the revised American Society for Reproductive Medicine (rASRM) stages in women undergoing radical surgery for deep endometriosis (DE)? SUMMARY ANSWER: The prevalence and severity grade of endometriotic lesions and adhesions as well as the total number of #Enzian compartments affected by DE increase on average with increasing rASRM stage; however, DE lesions are also present in rASRM stages 1 and 2, leading to an underestimation of disease severity when using the rASRM classification. WHAT IS KNOWN ALREADY: Endometriotic lesions can be accurately described regarding their localization and severity by sonography as well as during surgery using the recently updated #Enzian classification for endometriosis. STUDY DESIGN, SIZE, DURATION: This was a prospective multicenter study including a total of 735 women between January 2020 and May 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Disease extent in women undergoing radical surgery for DE at tertiary referral centers for endometriosis was intraoperatively described using the #Enzian and the rASRM classification. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 735 women were included in the study. Out of 31 women with rASRM stage 1, which is defined as only minimal disease, 65% (i.e. 20 women) exhibited DE in #Enzian compartment B (uterosacral ligaments/parametria), 45% (14 women) exhibited DE in #Enzian compartment A (vagina/rectovaginal septum) and 26% (8 women) exhibited DE in #Enzian compartment C (rectum). On average, there was a progressive increase from rASRM stages 1-4 in the prevalence and severity grade of DE lesions (i.e. lesions in #Enzian compartments A, B, C, FB (urinary bladder), FU (ureters), FI (other intestinal locations), FO (other extragenital locations)), as well as of endometriotic lesions and adhesions in #Enzian compartments P (peritoneum), O (ovaries) and T (tubo-ovarian unit). In addition, the total number of #Enzian compartments affected by DE lesions on average progressively increased from rASRM stages 1-4, with a maximum of six affected compartments in rASRM stage 4 patients. LIMITATIONS, REASONS FOR CAUTION: Interobserver variability may represent a possible limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The #Enzian classification includes the evaluation of DE in addition to the assessment of endometriotic lesions and adhesions of the ovaries and tubes and may therefore provide a comprehensive description of disease localization and extent in women with DE. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. All authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

A consensus-based core feature set for surgical complexity at laparoscopic hysterectomy.

BACKGROUND: There are no current standardized and accepted methods to characterize the surgical complexity of a laparoscopic hysterectomy. This leads to challenges when trying to understand the relationship between the patient and the surgical features and outcomes. The development of core feature sets for laparoscopic hysterectomy studies would enable future trials to measure the similar meaningful variables that can contribute to surgical complexity and outcomes. OBJECTIVE: The purpose of this study was to develop a core feature set for the surgical complexity of a laparoscopic hysterectomy. STUDY DESIGN: This was an international Delphi consensus study. A comprehensive literature review was conducted to identify the features that were reported in studies on laparoscopic hysterectomy complexity. All the features were presented for evaluation and prioritization to key experts in 3 rounds of online surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core feature set. RESULTS: Experts represented North America, South America, Europe, Africa, Asia, and Oceania. Most of them had fellowship training in minimally invasive gynecologic surgery. Sixty-four potential features were entered into round 1. Experts reached a consensus on 7 features to be included in the core feature set. These features were grouped under the following domains: 1) patient features, 2) uterine features, and 3) nonuterine pelvic features. The patient features include obesity and other nonobesity comorbidities that alter or limit the ability of a surgeon to perform the basic or routine steps in a laparoscopic hysterectomy. The uterine features include the size and presence of fibroids. The nonuterine pelvic features include endometriosis, ovarian cysts, and adhesions (bladder-to-uterus, rectouterine pouch, and other adhesions). CONCLUSION: Using robust consensus science methods, an international consortium of experts has developed a core feature set that should be assessed and reported in all future studies that aim to assess the relationship between the patient features and surgical outcomes of laparoscopic hysterectomy.

An Ultrasound-based Prediction Model to Predict Ureterolysis during Laparoscopic Endometriosis Surgery.

STUDY OBJECTIVE: To develop a model, including clinical features and ultrasound findings, to predict the need for ureterolysis (i.e., dissection of the ureter) during laparoscopy for endometriosis. DESIGN: A retrospective observational study of patients who had undergone transvaginal ultrasound (TVS) according to the International Deep Endometriosis Analysis consensus and subsequent laparoscopy ± excision of endometriosis between January 2017 and February 2021 was conducted. SETTING: Sydney Medical School Nepean, University of Sydney, Nepean Hospital, and Blue Mountains Hospital, New South Wales, Australia. PATIENTS/PARTICIPANT: 177 patients. INTERVENTION: The demographic, clinical, TVS, and intraoperative data were extracted through electronic clinical records. MEASUREMENTS AND MAIN RESULTS: Multicategorical decision-tree and baseline models were built to choose the variables most correlated to the outcome under study. Receiver operating characteristic analysis was performed on the binary classification. Based on our results, we selected the variables performing with significant statistical differences (p <.05). During the study period, 177 consecutive patients were recruited and divided into 2 subgroups, ureterolysis (51.4%) and nonureterolysis (48.6%). Ureterolysis was noted in 87.5% of patients in which the left ovary was immobile (p <.001) and in 82.5% in which the right ovary was fixed (p <.001). For patients with right uterosacral ligament (USL) deep endometriosis (DE), ureterolysis was performed in 96.2% patients (p <.001) and 64.6% (p = .043) for left USL DE. Among patients with bowel DE, the proportion of patients undergoing ureterolysis was 95.5% (p <.001). The prognostic variables used in the final model to predict ureterolysis included dyschezia, absence of ovarian mobility, presence of right or left USL DE, and presence of bowel DE on TVS. According to the developed model, the baseline risk for performing ureterolysis is 20% in our sample. The overall model performance demonstrated an area under the receiver operating characteristic curve 0.82. CONCLUSION: Our study demonstrates that it is possible to predict the need for ureterolysis with clinical and sonographic data. Furthermore, patients presenting with a combination of the variables of our model (dyschezia, ovarian immobility, USL, and bowel DE lesions) have a high risk of ureterolysis. In contrast, patients without these features have a low risk (approximately 20%) of needing ureterolysis.

DIFFERENTIAL IMPACT OF PERIODONTAL TREATMENT STRATEGIES DURING PREGNANCY ON PERINATAL OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: This study aimed to evaluate the impact of different periodontal treatment strategies during pregnancy on perinatal outcomes. STUDY SELECTION: This systematic review and meta-analysis of clinical trials was conducted according to PRISMA guidelines to assess the effect of mouthwash in addition to scaling and root planning (SRPM) on pregnancy outcomes, including preterm birth, low birth weight, gestational age, and birth weight. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated using the random effect model. RESULTS: Twenty trials involving 5938 participants, including thirteen trials comparing scaling and root planning (SRP) and seven trials comparing SRPM with control groups. SRPM was associated with reduced risk of preterm birth (RR = 0.37; 95%CI = 0.16-0.84; P = .017; I2=93.26%; P < .001; number needed to treat (NNT): 3), low birth weight (RR = 0.54; 95%CI = 0.40-0.74; P < .0001; I2 = 0%; P = .46; NNT: 13), increased gestational age (MD = 0.78; 95%CI: 0.19-1.37; P = .009; I2 = 87.15%; P < .001), and birth weight (MD = 121.77; 95%CI = 3.19-240.34; P = .044; I2 = 80.68%; P < .001). There were no statistically significant differences in the analysis of SRP group, except for the increased birth weight (MD = 93.85; 95% CI = 3.27-184.42; P = .042; I2 = 84.11%; P < .001). CONCLUSION: Using mouthwash in addition to scaling and root planning (SRPM) for the treatment of periodontal disease during pregnancy significantly improves perinatal outcomes.

A critical appraisal of the circulating levels of differentially expressed microRNA in endometriosis†.

Endometriosis is a common gynecological condition characterized by estrogen dependence, chronic pelvic pain, infertility, and diagnostic delay of between 5.4 and 12 years. Despite extensive study, no biomarker, either alone or in combination with other markers, has proven superior to laparoscopy for the diagnosis of endometriosis. Recent studies report that circulating levels of differentially expressed microRNA (miRNA) in women with endometriosis compared with controls are potential diagnostic tools. However, the lack of replication and absence of validated differential expression in novel study populations have led some to question the diagnostic value of miRNA. To elucidate potential reasons for the lack of replication of study results and explore future directions to enhance replicability of circulating miRNA results, we carried out an electronic search of the miRNA literature published between 2000 and 2020. Eighteen studies were identified in which 63 different miRNAs were differentially expressed in the circulation of women with endometriosis compared with controls. However, the differential expressions of only 14 miRNAs were duplicated in one or more studies. While individual miRNAs lacked diagnostic value, miRNA panels yielded sensitivity and specificity equal to or better than laparoscopy in five studies. Important differences in study design, sample processing, and analytical methods were identified rendering direct comparisons across studies problematic and could account for the lack of reproducibility of study results. We conclude that while the results of miRNA studies to date are encouraging, refinements to study design and analytical methods should enhance the reliability of circulating miRNA for the diagnosis of endometriosis.

Exosomes and their cargo are important regulators of cell function in endometriosis.

Endometriosis is a chronic oestrogen-dependent gynaecological disorder characterized by non-menstrual pelvic pain, infertility and the extrauterine growth of endometrial-like glands and stroma. It has been noted that the eutopic endometrium of women with endometriosis is functionally distinct from that of women without endometriosis. Moreover, ectopic endometrial implants are functionally different from the eutopic endometrium of women with endometriosis. However, the mechanisms directing these differences are ill-defined. It is proposed here that small membrane-bound extracellular vesicles called exosomes are important vehicles in the protection and transport of signalling molecules central to the dysregulation of endometrial function in women with endometriosis. Therefore, a critical review of the literature linking exosomes and their cargo to the pathobiology of endometriosis was conducted. Circulating peritoneal fluid and endometrial cell exosomes contained long non-coding RNA, miRNA and proteins involved in histone modification, angiogenesis and immune modulation that differed significantly in women with endometriosis compared with controls. Moreover, experimental evidence supports a role for exosomes and their cargo in angiogenesis, neurogenesis, immune modulation and endometrial stromal cell invasion. It is therefore suggested that exosomes play an important role in the pathophysiology of endometriosis.

Surgical interventions for the management of chronic pelvic pain in women.

BACKGROUND: Chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping symptomatology, therefore the management of the condition is a formidable challenge for clinicians. The aetiology of CPP is heterogeneous and in many cases, no clear diagnosis can be reached. It is in this scenario that the label of chronic pelvic pain syndrome (CPPS) can be applied. We defined women with CPPS as having a minimum duration of pain of at least 6 months, including with a diagnosis of pelvic congestion syndrome, but excluding pain caused by a condition such as endometriosis. Many surgical interventions have been tried in isolation or in conjunction with non-surgical interventions in the management with variable results. Surgical interventions are invasive and carry operative risks. Surgical interventions must be evaluated for their effectiveness prior to their prevalent use in the management of women with CPPS. OBJECTIVES: To review the effectiveness and safety of surgical interventions in the management of women with CPPS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO, on 23 April 2021 for any randomised controlled trials (RCT) for surgical interventions in women with CPPS. We also searched the citation lists of relevant publications, two trial registries, relevant journals, abstracts, conference proceedings and several key grey literature sources. SELECTION CRITERIA: RCTs with women who had CPPS. The review authors were prepared to consider studies of any surgical intervention used for the management of CPPS. Outcome measures were pain rating scales, adverse events, psychological outcomes, quality of life (QoL) measures and requirement for analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies for inclusion and extracted data using the forms designed according to Cochrane guidelines. For each included trial, we collected information regarding the method of randomisation, allocation concealment, blinding, data reporting and analyses. We reported pooled results as mean difference (MDs) or odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. If similar outcomes were reported on different scales, we calculated the standardised mean difference (SMD). We applied GRADE criteria to judge the overall certainty of the evidence. MAIN RESULTS: Four studies met our inclusion criteria involving 216 women with CPP and no identifiable cause. Adhesiolysis compared to no surgery or diagnostic laparoscopy We are uncertain of the effect of adhesiolysis on pelvic pain scores postoperatively at three months (MD -7.3, 95% CI -29.9 to 15.3; 1 study, 43 participants; low-certainty evidence), six months (MD -14.3, 95% CI -35.9 to 7.3; 1 study, 43 participants; low-certainty evidence) and 12 months postsurgery (MD 0.00, 95% CI -4.60; 1 study, 43 participants; very low-certainty evidence). Adhesiolysis may improve both the emotional wellbeing (MD 24.90, 95% CI 7.92 to 41.88; 1 study, 43 participants; low-certainty evidence) and social support (MD 23.90, 95% CI -1.77 to 49.57; 1 study, 43 participants; low-certainty evidence) components of the Endometriosis Health Profile-30, and both the emotional component (MD 32.30, 95% CI 13.16 to 51.44; 1 study, 43 participants; low-certainty evidence) and the physical component of the 12-item Short Form (MD 22.90, 95% CI 10.97 to 34.83; 1 study, 43 participants; low-certainty evidence) when compared to diagnostic laparoscopy. We are uncertain of the safety of adhesiolysis compared to comparator groups due to low-certainty evidence and lack of structured adverse event reporting. No studies reported on psychological outcomes or requirements for analgesia. Laparoscopic uterosacral ligament ablation or resection compared to diagnostic laparoscopy/other treatment We are uncertain of the effect of laparoscopic uterosacral ligament/nerve ablation (LUNA) or resection compared to other treatments postoperatively at three months (OR 1.26, 95% CI 0.40 to 3.93; 1 study, 51 participants; low-certainty evidence) and six months (MD -2.10, 95% CI -4.38 to 0.18; 1 study, 74 participants; very low-certainty evidence). At 12 months post-surgery, we are uncertain of the effect of LUNA on the rate of successful treatment compared to diagnostic laparoscopy. One study of 56 participants found no difference in the effect of LUNA on non-cyclical pain (P = 0.854) or dyspareunia (P = 0.41); however, there was a difference favouring LUNA on dysmenorrhea (P = 0.045) and dyschezia (P = 0.05). We are also uncertain of the effect of LUNA compared to vaginal uterosacral ligament resection on pelvic pain at 12 months (MD 2.00, 95% CI 0.47 to 3.53; 1 study, 74 participants; very low-certainty evidence). We are uncertain of the safety of LUNA or resection compared to comparator groups due to the lack of structured adverse event reporting. Women undergoing LUNA may require more analgesia postoperatively than those undergoing other treatments (P < 0.001; 1 study, 74 participants). No studies reported psychological outcomes or QoL. AUTHORS' CONCLUSIONS: We are uncertain about the benefit of adhesiolysis or LUNA in management of pain in women with CPPS based on the current literature. There may be a QoL benefit to adhesiolysis in improving both emotional wellbeing and social support, as measured by the validated QoL tools. It was not possible to synthesis evidence on adverse events as these were only reported narratively in some studies, in which none were observed. With the inadequate objective assessment of adverse events, especially long-term adverse events, associated with adhesiolysis or LUNA for CPPS, there is currently little to support these interventions for CPPS.

A Multicenter International Temporal and External Validation Study of the Ultrasound-based Endometriosis Staging System.

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.

Diagnostic Accuracy of Transvaginal Ultrasound and Magnetic Resonance Imaging for Adenomyosis: Systematic Review and Meta-Analysis and Review of Sonographic Diagnostic Criteria.

We aim to first systematically review and perform a meta-analysis of the diagnostic accuracy of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) and, second, to evaluate the accuracy of various sonographic diagnostic criteria for adenomyosis. A search of PubMed and Embase yielded 32 eligible studies. In diagnosing adenomyosis, the diagnostic performance of TVUS was found to be high and comparable to the performance of MRI. Of the eight sonographic criteria, only five were assessable. The best individual criterion was echogenic subendometrial lines and buds. Limited data exist for the various sonographic criteria, and further studies are required to compare their performance.

Rationalizing the management of pregnancies of unknown location: Diagnostic accuracy of human chorionic gonadotropin ratio-based decision tree compared with the risk prediction model M4.

INTRODUCTION: The objective was to compare the diagnostic accuracy of the decision tree analysis prediction model P1, which incorporates the human chorionic gonadotropin (hCG) ratio (hCG 48 hours/hCG 0 hour), and risk prediction model M4 in the management of women with pregnancy of unknown location (PUL). MATERIAL AND METHODS: A retrospective diagnostic accuracy study was performed on PUL data collected between August 2011 and September 2018. Women with a PUL were prospectively managed according to the P1 prediction model, which utilizes the hCG ratio and, if necessary, a day (D) 7 hCG. We compared the performance of P1 with the M4 model, a logistic regression mathematical model using initial hCG and hCG ratio, to classify PULs as low risk (failed PUL [failed] or intrauterine pregnancy) or high risk (ectopic pregnancy or persistent PUL). The reference standard was defined as the final PUL outcome. RESULTS: Transvaginal ultrasound was done in 3847 consecutive women for early pregnancy complications, 437 (11.3%) of whom were classified as PUL. Final analysis comprised 413 cases with complete data. Final PUL clinical outcomes were: 247 (59.8%) failed PUL, 94 (22.7%) intrauterine pregnancy, 49 (11.8%) ectopic pregnancy and 23 (5.5%) persistent PUL. The sensitivity of P1 and M4 in predicting high-risk PUL were 81.9% (95% confidence interval [CI] 71.1-90.0) and 80.6% (95% CI 69.5-88.9), respectively. The specificities were 74.5% (95% CI 69.5-79.1) and 75.6% (95% CI 70.7-80.1), respectively. CONCLUSIONS: P1 and M4 performed similarly with respect to diagnostic accuracy in predicting PUL outcome. P1 needs to be externally validated.

Transvaginal Ultrasound Can Accurately Predict the American Society of Reproductive Medicine Stage of Endometriosis Assigned at Laparoscopy.

STUDY OBJECTIVE: To evaluate the diagnostic accuracy of transvaginal ultrasound in predicting a laparoscopic, surgically assigned, revised American Society of Reproductive Medicine (ASRM) endometriosis stage. DESIGN: A multicenter, retrospective, diagnostic accuracy study. SETTING: The patients visited 1 of 2 academic gynecologic ultrasound units and underwent laparoscopy led by 1 of 6 surgeons in metropolitan Sydney, Australia, between 2016 and 2018. PATIENTS: Patients with suspected endometriosis (n = 204). INTERVENTIONS: Ultrasound followed by laparoscopy. MEASUREMENTS AND MAIN RESULTS: Surgical cases were identified. The preoperative ultrasound report and surgical operative notes were each used to retrospectively assign an ASRM score and stage. The breakdown of surgical findings was as follows: ASRM 0 (i.e., no endometriosis), 24/204 (11.8%); ASRM 1, 110/204 (53.9%); ASRM 2, 22/204 (10.8%); ASRM 3, 16/204 (7.8%); ASRM 4, 32 204 (15.7%). The overall accuracy of ultrasound in predicting the surgical ASRM stage was as follows: ASRM 1, 53.4%; ASRM 2, 93.8%; ASRM 3, 89.7%; ASRM 4, 93.1%; grouped ASRM 0, 1, and 2, 94.6%; and grouped ASRM 3 and 4 of 94.6%. Ultrasound had better test performance in higher disease stages. When the ASRM stages were dichotomized, ultrasound had sensitivity and specificity of 94.9% and 93.8%, respectively, for ASRM 0, 1, and 2 and of 93.8% and 94.9%, respectively, for ASRM 3 and 4. CONCLUSION: Ultrasound has high accuracy in predicting the mild, moderate, and severe ASRM stages of endometriosis and can accurately differentiate between stages when ASRM stages are dichotomized (nil/minimal/mild vs moderate/severe). This can have major positive implications on patient triaging at centers of excellence in minimally invasive gynecology for advanced-stage endometriosis.

When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted. METHODS OF STUDY SELECTION: Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible. TABULATION, INTEGRATION, AND RESULTS: In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p <.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified. CONCLUSION: Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).