Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. DATA SOURCES: MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. STUDY ELIGIBILITY CRITERIA: Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. METHODS: This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. RESULTS: A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26-6.32; I2=74%). Similar degrees of risk were reported for thresholds between 3.0 and 5.9 mm (relative risk, 5.08; 95% confidence interval, 2.26-11.41; I2=0%), 6.0 and 9.9 mm (relative risk, 4.34; 95% confidence interval, 1.68-11.23; I2=0%), 10.0 and 13.9 mm (relative risk, 4.11; 95% confidence interval, 1.55-10.87; I2=86%), and ≥14.0 mm (relative risk, 2.53; 95% confidence interval, 1.04-6.16; I2=78%) with no significant difference among subgroups (P=.885). Regarding diagnostic accuracy, the pooled sensitivity decreased from thresholds below 5.9 mm (relative risk, 0.81; 95% confidence interval, 0.49-0.85) to above 14.0 mm (relative risk, 0.28; 95% confidence interval, 0.18-0.40). Furthermore, the specificity increased from 0.70 (95% confidence interval, 0.61-0.78) for endometrial thickness between 3.0 and 5.9 mm to 0.86 (95% confidence interval, 0.71-0.94) when the endometrial thickness is ≥14.0 mm. For 3.0 to 5.9 mm and 10.0 to 13.9 mm thresholds, the highest diagnostic odds ratios of 10 (95% confidence interval, 3-41) and 11 (95% confidence interval, 2-49), with areas under the curve of 0.81 (95% confidence interval, 0.77-0.84) and 0.82 (95% confidence interval, 0.79-0.86), respectively, were retrieved. The summary point analysis revealed that the 3.0 to 5.9 mm cutoff point was placed higher in the summary receiver operator curve space than the other subgroups, indicating increased endometrial carcinoma or atypical endometrial hyperplasia diagnosis using these cutoffs. CONCLUSION: Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Efficacy of Hysteroscopy in Improving Fertility Outcomes in Women Undergoing Assisted Reproductive Technique: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Usefulness of hysteroscopy before assisted reproductive technique (ART) was considered debatable. However, over the last decade, several new trials have been added to available literature. We aimed to assess the impact of diagnostic and operative hysteroscopy on reproductive outcomes of infertile women with and without intrauterine abnormalities. MATERIALS AND METHODS: MEDLINE, Scopus, SciELO, Embase, Cochrane Library at CENTRAL, PROSPERO, CINAHL, grey literature, conference proceedings, and international controlled trials registries were searched without temporal, geographical, or language restrictions. Randomized controlled trials (RCTs) of infertile women comparing hysteroscopy versus no hysteroscopy prior to the first ART or after at least one failed attempt were included. RCTs of infertile women with intrauterine pathology comparing diagnostic versus operative hysteroscopy were included in separate analysis. Random-effect meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Grading of Recommendations, Assessment, Development and Evaluation and Cochrane criteria were used for quality of evidence and risk of bias assessment. Primary outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy (CPR) and pregnancy loss rate. RESULTS: Fifteen studies (5,038 women) were included. Compared to no hysteroscopy before first or after failed ART attempts, moderate-quality evidence showed that hysteroscopy increased the LBR (relative risk [RR] 1.24, 95% confidence interval [CI] 1.09-1.43, I2 = 21%), confirmed by subgroup analysis for women with failure after one or more ART cycles (RR 1.43, 95% CI: 1.19-1.72, I2 = 0%) but not before the first ART. Moderate-quality evidence showed that it increased the CPR (RR 1.36, 95% CI: 1.18-1.57; I2 = 51%), confirmed in subgroup analysis for both implantation failure (RR 1.40, 95% CI: 1.12-1.74, I2 = 52%) and before first ART (RR 1.32, 95% CI: 1.11-1.57, I2 = 42%). Low-quality data suggest that operative hysteroscopy increases CPR when used to treat intrauterine pathologies (RR 2.13, 95% CI: 1.56-2.92, I2 = 0%). CONCLUSIONS: Although moderate-quality evidence supports performing hysteroscopy before ART in women with history of implantation failure, hysteroscopic evaluation of uterine cavity should be considered a first-line technique in all infertile women undergoing ART. Additional high-quality RCTs are still needed, particularly to assess yield during couple's initial evaluation even before ART is considered.

Postsurgical barrier strategies to avoid the recurrence of intrauterine adhesion formation after hysteroscopic adhesiolysis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of mechanical strategies to avoid the recurrence of intrauterine adhesions, to evaluate the impact on subsequent fertility after hysteroscopic adhesiolysis and to rank the available antiadhesive options. DATA SOURCES: MEDLINE, Scopus, ClinicalTrials.gov, CINAHL, Scielo, EMBASE, PROSPERO, Cochrane Library, conference proceedings, and international controlled trials registries were searched without temporal, geographic, and language restrictions. STUDY ELIGIBILITY CRITERIA: Randomized trials that analyzed the recurrence, reproductive outcomes, or both in women undergoing hysteroscopic adhesiolysis followed by mechanical prevention of intrauterine adhesions were included. The exclusion criteria included the following: quasi-randomized trials and trials without randomization and studies including patients undergoing hysteroscopic surgery that was different from adhesiolysis. STUDY APPRAISAL AND SYNTHESIS METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension statement for network meta-analyses guidelines were followed. We performed a network meta-analysis based on the random effects model for mixed multiple treatment comparisons to rank the antiadhesive strategies by surface under the cumulative ranking curve area. Quality assessment was performed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was the recurrent presence of intrauterine adhesions. RESULTS: Eleven studies with data for 1596 women were identified as applicable. A copper intrauterine device together with an intrauterine balloon (surface under the cumulative ranking curve area=46.4%) or with cross-linked hyaluronic acid gel (surface under the cumulative ranking curve area=21.3%) seemed effective in preventing adhesions recurrence. Regarding the fecundity, hyaluronic acid gel demonstrated the highest pregnancy rates (surface under the cumulative ranking curve area=79.8%). The greatest degrees of change in the mean adhesions scores were found with the use of hyaluronic acid gel plus an intrauterine device (surface under the cumulative ranking curve area=38.9%). For postsurgical adhesion severity, hyaluronic acid gel plus intrauterine device (surface under the cumulative ranking curve area=49.9%) followed by intrauterine device alone (surface under the cumulative ranking curve area=30.8%) was ranked the highest. Dried amnion graft (surface under the cumulative ranking curve area=53.8%) and uterine balloon (surface under the cumulative ranking curve area=45%) showed the greatest menstrual pattern improvement. CONCLUSION: Cross-linked hyaluronic acid gel, with or without insertion of a copper intrauterine device, seems to be the most effective approach. However, the lack of a clear best therapy suggests the need for further studies to draw firm conclusions.

International Consensus Statement for Recommended Terminology Describing Hysteroscopic Procedures.

OBJECTIVE: To develop a consensus statement of recommended terminology to use for describing different aspects of hysteroscopic procedures that can be uniformly used in clinical practice and research. DESIGN: Open forum discussion followed by online video meetings. SETTING: International community of hysteroscopy experts PATIENTS: Not applicable. INTERVENTIONS: Series of online video meetings to complete a previously established agenda until a final agreement for standardized nomenclature was obtained. MEASUREMENT AND MAIN RESULTS: The adoption and implementation of a common terminology to standardize reporting of hysteroscopic procedures was proposed to cover five domains: pain management, healthcare setting, model of care, type of hysteroscopic procedure and the hysteroscopic approach to the uterine cavity. A final agreement was obtained after 3 online video meetings. CONCLUSION: Hysteroscopy is the gold standard technique for the evaluation and management of uterine disorders. A clear definition and understanding of the terminology used to describe hysteroscopic procedures is lacking. The production of this international consensus statement for terminology to describe hysteroscopic procedures, covering pain management, setting, model of care, type of procedure and hysteroscopic approach, has the potential to enable more effective communication for both clinical and research purposes with the ultimate aim of improving patient care and clinical outcomes.

See-and-treat in-office hysteroscopy versus operative hysteroscopy for the treatment of retained products of conception: A retrospective study.

AIM: To compare the efficacy and safety of in-office hysteroscopy with a see-and-treat approach with that of operative hysteroscopy for the treatment of retained products of conception (RPOC). METHODS: We retrospectively identified all consecutive patients who underwent hysteroscopic treatment of RPOC between 2015 and 2019. We excluded patients with RPOC larger than 2 cm at preoperative transvaginal ultrasounds. Between 2015 and 2017, all hysteroscopic removals of RPOC were performed by operative hysteroscopy. Between 2018 and 2019, all cases of RPOC less than 2 cm in size were hysteroscopically removed by the see-and-treat approach in the office setting. Sociodemographic, clinical, and procedure characteristics along with complications were retrieved from medical records. RESULTS: Between 2015 and 2019, 119 women underwent hysteroscopic removal of RPOC equal to or smaller than 2 cm: 53 patients by in-office hysteroscopy, and 66 by operative hysteroscopy. The two groups were similar in preoperative characteristics. Although the time required to complete the RPOC removal was similar, the total procedure and assistant time were significantly higher in the operative hysteroscopy group (p < 0.001). Moreover, operative hysteroscopy was associated with a higher proportion of cases complicated by excessive bleeding, cervical tear, or uterine perforation (p = 0.016). Failure to complete the procedure was similarly reported in the two groups (p = 0.58). CONCLUSIONS: In-office hysteroscopy with the see-and-treat approach for RPOC equal to or smaller than 2 cm appears as effective as operative hysteroscopy, but safer. In-office hysteroscopy may be considered the first choice for treating RPOC equal to or smaller than 2 cm.

MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Vasovagal Syncope during Office Hysteroscopy-A Frequently Overlooked Unpleasant Complication.

Due to technological advancements in miniaturization of instruments and improved optics, the number of office hysteroscopic procedures has increased over time. Office hysteroscopy is preferred due to avoidance of general anesthesia and decreased overall cost. Vasovagal syncope has been implied as the most common complication. Vasovagal syncope is associated with inappropriate reflex vasodilation and bradycardia in the setting of an acute malfunction between the autonomic nervous system and the cardiovascular system; however, there is no mortality associated with vasovagal syncope. A management strategy for acute vasovagal reflex during office hysteroscopy is proposed in order to manage this common complication.

Pain Management during Office Hysteroscopy: An Evidence-Based Approach.

Background and Objectives: Hysteroscopy is a reliable technique which is highly useful for the evaluation and management of intrauterine pathology. Recently, the widespread nature of in-office procedures without the need for anesthesia has been requesting validation of practical approach in order to reduce procedure-related pain. In this regard, we performed a comprehensive review of literature regarding pain management in office hysteroscopic procedures. Materials and Methods: MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), Global Health, Health Technology Assessment Database and Web of Science, other research registers (for example Clinical Trials database) were searched. We searched for all original articles regarding pain relief strategy during office hysteroscopy, without date restriction. Results have been collected and recommendations have been summarized according to the Appraisal of Guidelines for Research and Evaluation (AGREE) tool. Moreover, the strength of each recommendation was scored following the Grading of Recommendations Assessment (GRADE) system, in order to present the best available evidence. Results: Both pharmacological and non-pharmacological strategies for pain management are feasible and can be applied in office setting for hysteroscopic procedures. The selection of strategy should be modulated according to the characteristics of the patient and difficulty of the procedure. Conclusions: Accumulating evidence support the use of pharmacological and other pharmacological-free strategies for reducing pain during office hysteroscopy. Nevertheless, future research priorities should aim to identify the recommended approach (or combined approaches) according to the characteristics of the patient and difficulty of the procedure.

Quality of Life, Anxiety and Depression in Women Treated with Hysteroscopic Endometrial Resection or Ablation for Heavy Menstrual Bleeding: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Hysteroscopic endometrial resection (ER) or global endometrial ablation (GEA) are feasible methods to treat heavy menstrual bleeding (HMB). The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess patient's quality of life (QoL) in women treated with ER/GEA compared to hysterectomy. Materials and Methods: Electronic searches in MEDLINE Scopus, ClinicalTrials.gov, EMBASE, PROSPERO and Cochrane CENTRAL were conducted from their inception to July 2022. Inclusion criteria were RCTs of premenopausal women with HMB randomized to conservative surgical treatment (ER/GEA) or hysterectomy. The primary outcome was the evaluation of QoL using the SF-36 score. Results: Twelve RCTs (2773 women) were included in the analysis. Women treated with hysteroscopic ER/GEA showed significantly lower scores for the SF-36 general health perception (mean difference (MD) -8.56 [95% CI -11.75 to -5.36]; I2 = 0%), social function (MD -12.90 [95% CI -23.90 to -1.68]; I2 = 91%), emotional role limitation (MD -4.64 [95% CI -8.43 to -0.85]; I2 = 0%) and vitality (MD -8.01 [95% CI -14.73 to -1.30]; I2 = 74%) domains relative to hysterectomy. Anxiety, depression scores and complication rates were similar between treatments. Relative to uterine balloon therapy, amenorrhea was more common with EA/GER (relative risk 1.51 [95% CI 1.03 to 1.20] I2 = 28%), but posttreatment satisfaction was similar. Conclusions: Women's perception of QoL might be seen to be less improved after hysteroscopic ER/GEA rather than hysterectomy. However, such findings need to be confirmed by additional trials due to the high number of outdated studies and recent improvements in hysteroscopic instrumentation and techniques.

Office hysteroscopic metroplasty with diode laser for septate uterus: a multicenter cohort study.

OBJECTIVE: To investigate the effectiveness and safety of office hysteroscopic metroplasty by diode laser for the treatment of septate uteri. STUDY DESIGN: We performed a prospective cohort study including 41 nulliparous women diagnosed with septate uterus and a history of primary infertility or recurrent miscarriage. All patients underwent hysteroscopic metroplasty for the treatment of the uterine septum, which was performed in-office setting using a 4.3 mm continuous-flow hysteroscope and a 15-watt diode laser at 1470 nm. Surgical and reproductive outcomes after 2 years of follow-up are reported. RESULTS: The procedure was well tolerated by 93% of patients. No surgical complications were reported. Thirty women out of 38 (78.9%) became pregnant: 17 (56.7%) pregnancies were spontaneously conceived, and 13 (43.3%) were obtained with assisted reproductive techniques. Twenty-four (80%) of the 30 pregnant women had a live birth, with a cumulative live birth of 63.2% among the 38 women (95% CI: 45.9-78.2%). There were no cases of post-partum hemorrhage or uterine rupture among 14 (58.3%) women who had vaginal deliveries. CONCLUSION: Office hysteroscopic metroplasty for septate uterus using diode laser appears to be a feasible and safe alternative to other available techniques and has sufficient efficacy in terms of reproductive outcomes to be considered for further investigations.

Endometrial polyps: diagnosis and treatment options - a review of literature.

INTRODUCTION AND AIM: Endometrial polyps (EPs) are a common gynecologic condition, associated with abnormal uterine bleeding (AUB), infertility, and premalignant and malignant conditions. Technologies for diagnosis and treatment of EPs are constantly evolving. We aim to provide an updated review on diagnosis and management options for patients with EPs. MATERIAL AND METHODS: We conducted an electronic search in databases including MEDLINE, PubMed, Cochrane Central Register and others. We included 68 publications regarding EPs, their clinical burden, diagnostic modalities, treatment options and new technologies. RESULTS: Transvaginal ultrasound (TVS) is the common modality for EP detection and color doppler increases its diagnostic accuracy. Dilation and curettage (D&C) should be avoided for diagnosis and treatment of EPs. Hysteroscopy shows high diagnostic value in EPs and allows for both histological diagnosis and effective treatment. Office hysteroscopy and see and treat hysteroscopy without anesthesia is feasible and safe for EP diagnosis and treatment, gaining more trained surgeons globally. Effective and safe technological tools for EP resection include Laser, resectoscopes, morcellators, MyoSure, Truclear and scissors\graspers. CONCLUSIONS: EPs are safely and effectively diagnosed and treated with the hysteroscopic tools reviewed in this article. More research is needed to define the best treatment modality.

Innovations in hysteroscopic surgery: expanding the meaning of "in-office".

Surgical innovations in hysteroscopic surgery have radically changed the way of treating intrauterine pathologies, throughout the advent of the 'see-and-treat' philosophy, which transferred the advantages of inpatient surgery to the office setting. However, in-office operative hysteroscopy was mainly limited to minor pathology as a supplement to its diagnosis, whereas commonly larger abnormalities were left to be treated in the operating room. Nowadays, pre-surgical assessment of uterine pathology is based on modern ultrasound evaluation and the evolving role of in-office hysteroscopy as a well-planned treatment modality for larger lesions and more complex procedures. Office operative hysteroscopy has been accepted as a feasible, cost-effective, practical way to treat almost any intrauterine disease. Despite the growing role of other imaging tools in the proper evaluation of benign uterine diseases, especially extended beyond to direct hysteroscopic visualization, diagnostic hysteroscopy remains a valuable tool of direct endometrial sampling and may be used as the first line in the diagnosis of endometrial cancer and hyperplasia. Our aim is to describe the most recent innovations and future perspectives in the field of outpatient operative hysteroscopy: mini-resectoscopes, intrauterine morcellators, tissue retrieval systems, diode laser, new miniaturized mechanical instruments, endometrial ablation devices and portable and entry-level hysteroscopes.

Hysteroscopic endometrial biopsy: from indications to instrumentation and techniques. A call to action.

During the last twenty years, the diagnostic approach to endometrial pathology has radically evolved. For over a century, intrauterine blind biopsy techniques were considered the gold standard procedure for the histopathological diagnosis of intrauterine diseases. The advent of hysteroscopy, which made it possible to directly visualize the uterine cavity, and the subsequent miniaturization of the instruments allowing its use in the office setting without anesthesia are considered game-changers. To date, it is feasible to retrieve a targeted eye specimen of endometrial tissue with little or no discomfort for the patient in the office setting. To pursue this aim, several technological upgrades have improved the diagnostic accuracy of hysteroscopic endometrial biopsy. In this paper we provide an up-to-date review of the latest evidence regarding indications, instrumentations, and techniques for hysteroscopic endometrial biopsy, to help the operator in providing an adequate endometrial sampling for histopathological analysis.