FEMaLe: The use of machine learning for early diagnosis of endometriosis based on patient self-reported data-Study protocol of a multicenter trial.

INTRODUCTION: Endometriosis is a chronic disease that affects up to 190 million women and those assigned female at birth and remains unresolved mainly in terms of etiology and optimal therapy. It is defined by the presence of endometrium-like tissue outside the uterine cavity and is commonly associated with chronic pelvic pain, infertility, and decreased quality of life. Despite the availability of various screening methods (e.g., biomarkers, genomic analysis, imaging techniques) intended to replace the need for invasive surgery, the time to diagnosis remains in the range of 4 to 11 years. AIMS: This study aims to create a large prospective data bank using the Lucy mobile health application (Lucy app) and analyze patient profiles and structured clinical data. In addition, we will investigate the association of removed or restricted dietary components with quality of life, pain, and central pain sensitization. METHODS: A baseline and a longitudinal questionnaire in the Lucy app collects real-world, self-reported information on symptoms of endometriosis, socio-demographics, mental and physical health, economic factors, nutritional, and other lifestyle factors. 5,000 women with confirmed endometriosis and 5,000 women without diagnosed endometriosis in a control group will be enrolled and followed up for one year. With this information, any connections between recorded symptoms and endometriosis will be analyzed using machine learning. CONCLUSIONS: We aim to develop a phenotypic description of women with endometriosis by linking the collected data with existing registry-based information on endometriosis diagnosis, healthcare utilization, and big data approach. This may help to achieve earlier detection of endometriosis with pelvic pain and significantly reduce the current diagnostic delay. Additionally, we may identify dietary components that worsen the quality of life and pain in women with endometriosis, upon which we can create real-world data-based nutritional recommendations.

Postoperative reproductive outcomes in patients with endometriosis-associated infertility: A single-centre retrospective study.

OBJECTIVES: Endometriosis is a chronic inflammatory disease known to contribute to infertility. Laparoscopic excision of endometriotic lesions represents a standard treatment modality for symptomatic women. Our study aims to assess the potential benefits of laparoscopic excision of endometriosis in patients experiencing infertility associated with the condition, as well as to define the clinical factors that may impact the cumulative pregnancy rate. DESIGN: In this retrospective analysis, a total of 102 patients with endometriosis-related infertility were enrolled. MATERIALS, SETTING, METHODS: All participants underwent reproductive surgery and were then categorized into two groups: those who conceived were assigned to Group A, while those who did not were assigned to Group B. The correlation between clinical factors and pregnancy rate was assessed using the log rank test, and both univariate and multivariate analyses were conducted utilizing the Cox regression model. Results The median age of the patients was 33.5 years, with a median follow-up duration of 70 months. Throughout the study period, 71 patients (69.6%) conceived (Group A), while the remaining 31 patients (30.4%) did not conceive (Group B), irrespective of the use of Assisted-Reproduction Technologies. The Cox regression model revealed that factors such as the duration of infertility, presence of deep infiltrating endometriosis, bowel endometriosis, rASRM stages, pelvic adhesions, and recurrent disease negatively impacted postoperative conception rates. Conversely, complete excision and coagulation of endometriotic lesions, as well as ablation of ovarian endometriomas, emerged as independent positive predictive factors for postoperative clinical pregnancy. LIMITATIONS: The retrospective design of the study, as well as a small number of patients. CONCLUSIONS: Complete excision of endometriosis during reproductive surgery may yield a positive effect and optimize the likelihood of pregnancy in patients with endometriosis-related infertility.

Hormonal Therapies before in vitro fertilization in women with endometriosis: The Minotaur's Labyrinth and the Ariadne's Thread.

Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as a mean of improving the assisted reproduction technologies (ART) success rates in endometriosis patients. GnRH agonists, dienogest, medroxyprogesterone acetate, and aromatase inhibitors are the most studied medications. Conflicting results and a high risk of bias exist in almost all of the conducted studies in the field. However, current evidence suggests that pre-cycle treatment with GnRH agonists may be beneficial for patients with stage III/IV endometriosis. Dienogest and medroxyprogesterone acetate-based progestin-primed ovarian stimulation protocol was shown to be comparable to the prolonged GnRH agonists protocol. Finally, aromatase inhibitors seem to be of limited benefit to the assisted reproductive outcomes of endometriosis patients. Although it is challenging to draw any clinical conclusions, pre-cycle hormonal treatments seem to be best indicated in endometriosis patients who had previously failed ART treatment.

MRI-Based Radiomics as a Promising Noninvasive Diagnostic Technique for Adenomyosis.

Background: MRI diagnostics are important for adenomyosis, especially in cases with inconclusive ultrasound. This study assessed the potential of MRI-based radiomics as a novel tool for differentiating between uteri with and without adenomyosis. Methods: This retrospective proof-of-principle single-center study included nine patients with and six patients without adenomyosis. All patients had preoperative T2w MR images and histological findings served as the reference standard. The uterus of each patient was segmented in 3D using dedicated software, and 884 radiomics features were extracted. After dimension reduction and feature selection, the diagnostic yield of individual and combined features implemented in the machine learning models were assessed by means of receiver operating characteristics analyses. Results: Eleven relevant radiomics features were identified. The diagnostic performance of individual features in differentiating adenomyosis from the control group was high, with areas under the curve (AUCs) ranging from 0.78 to 0.98. The performance of ML models incorporating several features was excellent, with AUC scores of 1 and an area under the precision-recall curve of 0.4. Conclusions: The set of radiomics features derived from routine T2w MRI enabled accurate differentiation of uteri with adenomyosis. Radiomics could enhance diagnosis and furthermore serve as an imaging biomarker to aid in personalizing therapies and monitoring treatment responses.

Robotic surgery for deep-infiltrating endometriosis: is it time to take a step forward?

Endometriosis is a chronic debilitating disease that affects nearly 10% of women of the reproductive age. Although the treatment modalities of endometriosis are numerous, surgical excision of the endometriotic implants and nodules remains the sole cytoreductive approach. Laparoscopic excision of endometriosis was proven to be beneficial in improving the postoperative pain and fertility. Moreover, it was also proved to be safe and efficient in treating the visceral localization of deep endometriosis, such as urinary and colorectal endometriosis. More recently, robotic-assisted surgery gained attention in the field of endometriosis surgery. Although the robotic technology provides a 3D vision of the surgical field and 7-degree of freedom motion, the safety, efficacy, and cost-effectiveness of this approach are yet to be determined. With this paper, we aim to review the available evidence regarding the role of robotic surgery in the management of endometriosis along with the current practices in the field.

Colorectal endometriosis. A proposal of complementary classification and surgical management in stages.

OBJECTIVE: To organize the experience and international knowledge in the surgical management and staging of colorectal endometriosis, with a management proposal in stages. METHOD: An extensive non-systematic review of the literature was carried to organize the disease in stages (limited, intermediate and advanced) according to a scoring system, which considers the characteristics of the endometrioma, the personal history and surgical findings. We tested the proposed staging in a retrospective group of patients. RESULTS: From January 2017 to April 2023, we collected 19 patients with a confirmed diagnosis of colorectal endometriosis, treated laparoscopically, by the same group of surgeons, in whom we found a strong correlation between the stage of the disease and the presence of complications that required reinterventions. CONCLUSIONS: We suggest a sequence of colorectal surgical management in stages according to the staging of the disease and we hope that this work will be followed by joint efforts to test it prospectively in order to compare results between hospital centers and make planned decisions.

OBJETIVO: Organizar la experiencia y el conocimiento internacional en el manejo quirúrgico y la estadificación de la endometriosis colorrectal, con una propuesta de manejo por etapas. MÉTODO: Se realizó una revisión amplia no sistemática de la literatura para organizar la enfermedad en etapas (limitada, intermedia y avanzada) de acuerdo con un sistema de puntuación que considera las características del endometrioma, los antecedentes personales y los hallazgos en la cirugía. La estatificación propuesta se probó en un grupo retrospectivo de pacientes. RESULTADOS: De enero de 2017 a abril de 2023 recopilamos 19 pacientes con diagnóstico confirmado de endometriosis colorrectal, tratadas por vía laparoscópica, por el mismo grupo de cirujanos, en las que encontramos una fuerte correlación entre el estadio de la enfermedad y la presencia de complicaciones que requirieron reintervenciones. CONCLUSIONES: Sugerimos una secuencia de manejo quirúrgico colorrectal en etapas de acuerdo con la estadificación de la enfermedad y esperamos que el presente trabajo sea seguido de esfuerzos compartidos por probarla de manera prospectiva para poder comparar resultados entre centros hospitalarios y tomar decisiones planificadas.

Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: now and the future.

INTRODUCTION: This Expert Opinion covers recent updates in the use of Inositol in polycystic ovary syndrome (PCOS) and type II diabetes and gives support to researchers and clinicians. AREAS COVERED: This article discusses the role of Myo-Inositol (MI) and D-Chiro-Inositol (DCI) in physiological function, the use of MI in PCOS, the risks of using DCI in reproductive conditions, the 40:1 combination of MI/DCI in PCOS. Furthermore, we discuss the issues of insulin resistance and how α-lactalbumin may increase the intestinal bioavailability of MI. The paper then transitions to talk about the use of inositols in diabetes, including type II diabetes, Gestational Diabetes Mellitus (GDM), and double diabetes. Literature searches were performed with the use of PubMed, Google Scholar, and Web of Science between July and October 2023. EXPERT OPINION: Inositol therapy has grown in the clinical field of PCOS, with it demonstrating an efficacy like that of metformin. The use of α-lactalbumin has further supported the use of MI, as issues with intestinal bioavailability have been largely overcome. In contrast, the effect of inositol treatment on the different PCOS phenotypes remains an outstanding question. The use of inositols in type II diabetes requires further study despite promising analogous data from GDM.

Hormonal Contraception and the Risk of Breast Cancer in Women of Reproductive Age: A Meta-Analysis.

This study aims to summarize evidence from observational studies about the lifetime use of HC and the risk of BC in women of reproductive age. The PubMed, Cochrane, and EMBASE databases were searched for observational studies published from 2015 to February 2022. Meta-analyses were performed using adjusted odds ratios and relative risks with a random-effects model using the I2 statistic to quantify the heterogeneity among studies. Of the 724 studies identified, 650 were screened for title/abstract selection, 60 were selected for full-text revision, and 22 were included in the meta-analysis. Of these, 19 were case-control studies and 3 were cohort studies. The results of the meta-analysis indicate a significantly higher risk of developing BC in ever users of HC (pooled OR = 1.33; 95% CI = 1.19 to 1.49). This effect is larger in the subgroups of case-control studies (pooled OR = 1.44, 95% CI = 1.21 to 1.70) and in the subgroup of studies that strictly define menopausal status (pooled OR = 1.48; 95% CI, 1.10 to 2.00). Although our meta-analysis of observational studies (cohort and case-control) suggests a significantly increased overall risk of BC in users or ever-users of modern hormonal contraceptives, the high heterogeneity among studies (>70%) related to differences in study design, measurement of variables, confounders, among other factors, as well as publication biases should be considered when interpreting our results.

Diaphragmatic Endometriosis-A Single-Center Retrospective Analysis of the Patients' Demographics, Symptomatology, and Long-Term Treatment Outcomes.

Diaphragmatic endometriosis is rare and forms 0.67-4.7% of all endometriosis cases. Evidence regarding its optimal management is lacking. In this study, we retrospectively analyzed the patient characteristics and long-term treatment outcomes of diaphragmatic endometriosis patients. Over a 4-year period, 23 patients were diagnosed with diaphragmatic endometriosis. The majority of patients had coexisting deep pelvic endometriosis. Cyclic upper abdominal pain was reported by 60.9% of patients, while cyclic chest and shoulder pain were reported by 43.5% and 34.8% of patients, respectively. Most patients were treated with laparoscopic lesion ablation, while 21.1% were treated with minimally invasive excision. The mean follow-up time was 23.7 months. Long-lasting resolution of the chest, abdominal, and shoulder pain occurred in 50%, 35.7%, and 25% of patients, respectively. Nonetheless, 78.9% of patients reported major improvement in their symptoms postoperatively. Significantly higher rates of postoperative shoulder, abdominal, and chest pain were observed in patients who received postoperative hormonal therapy compared with those who did not. All patients treated expectantly remained stable. Therefore, we recommend treating diaphragmatic endometriosis only in symptomatic patients. The risk of incomplete surgery should be minimized by a multidisciplinary diagnostic and therapeutic approach with a careful assessment of the diaphragm and the thoracic cavity.

A Large Ovarian Endometrioma Occupying the Abdominal Cavity in a Postmenopausal Patient: A Case Report.

Endometriosis is defined by the presence of endometrial-like glands and/or stroma outside the uterus. The prevalence of endometriosis in postmenopausal women is reported to be 2.55%, which is much lower than that in reproductive-aged women. Ovarian endometriomas are the most common form of endometriosis. However, these form only 4.3% of ovarian masses in patients in the sixth decade of life. In this manuscript, we report the case of a 60-year-old patient who was referred to our department with an external diagnosis of an abdominal mass. The patient was in good general condition and asymptomatic. A computed tomography scan revealed the presence of a cystic mass originating from the right adnexa and measuring 26 cm. No signs of malignancy were observed. Due to the cyst's size, a midline laparotomy and a bilateral salpingo-oophorectomy were performed successfully. A postoperative histopathologic examination confirmed the diagnosis of an ovarian endometrioma with no signs of hyperplasia or atypia. Cases of postmenopausal large ovarian endometriomas are few. However, due to the risk of malignant transformation, an oophorectomy could be considered the treatment of choice, even in asymptomatic patients.

Modified Oxford technique of colpopexy for the treatment of uterine and vaginal vault prolapse: a retrospective pilot cohort study.

Introduction: Pelvic organ prolapse is a common health issue that affects 30.8% of women. Laparoscopic sacrocolpopexy and colpopectopexy are two of the most common procedures to restore the pelvic anatomy. Mesh application on the other hand carries an increased complications risk over the short and long terms. The aim of this study is to provide a basis for meshless sacrocolpopexy and colpopectopexy. Methods: This study is a retrospective cohort pilot study that analyzed the data of patients with a pelvic organ prolapse according to the pelvic organ prolapse quantification system and underwent the modified technique for sacrocolpopexy and colpopectopexy. Descriptive statistics were used to express the different variables. Results: A total of 36 patients met the inclusion criteria and provided consent for the participation in this study. The majority of patients were postmenopausal. 22 out of 36 patients received a previous prolapse surgery. All patients presented with reducible vaginal lump. Dyspareunia and sexual dysfunction were the most commonly reported symptoms. The intraoperative complications rate was 0%. Only one patient had a postoperative persistent urinary retention that was managed medically. Discussion: Sacrocolpopexy and colpopectopexy seems to be a safe alternative to the mesh-based pelvic surgeries with a very low rate of intraoperative complications and favorable follow up outcomes.

The Future of Minimal-Access Myoma Surgery with In-Bag Contained Morcellation.

Contained electromechanical morcellation has emerged as a safety approach for laparoscopic myomatous tissue retrieval. This retrospective single-center analysis evaluated the bag deployment practicability and safety of electromechanical in-bag morcellation when used for big surgical benign specimens. The main age of patients was 39.3 years (range 21 to 71); 804 myomectomies, 242 supracervical hysterectomies, 73 total hysterectomies, and 1 retroperitoneal tumor extirpation were performed. A total of 78.7% of specimens weighed more than 250 g (n = 881) and 9% more than 1000 g. The largest specimens, weighing 2933 g, 3183 g, and 4780 g, required two bags for complete morcellation. Neither difficulties nor complications related to bag manipulation were recorded. Small bag puncture was detected in two cases, but peritoneal washing cytology was free of debris. One retroperitoneal angioleiomyomatosis and three malignancies were detected in histology (leiomyosarcoma = 2; sarcoma = 1); therefore, patients underwent radical surgery. All patients were disease-free at 3 years follow-up, but one patient presented multiple abdominal metastases of the leiomyosarcoma in the third year; she refused subsequent surgery and was lost from follow-up. This large series demonstrates that laparoscopic bag morcellation is a safe and comfortable method to remove large and giant uterine tumors. Bag manipulation takes only a few minutes, and perforations rarely occur and are easy to detect intraoperatively. This technique did not result in the spread of debris during myoma surgery, potentially avoiding the additional risk of parasitic fibroma or peritoneal sarcoma.

Advanced cervical stump cancer after laparoscopic subtotal hysterectomy: a case report of imaging, laparoscopic staging and treatment approach.

BACKGROUND: Advanced cancer of the cervical stump, occurring years after a laparoscopic supracervical hysterectomy (LASH), is a rare but serious clinical condition. Many patients who undergo a LASH are unaware of this possible complication. Upon diagnosis of advanced cervical stump cancer, a holistic approach including imaging, laparoscopic surgery and multimodal oncological therapy is required. CASE PRESENTATION: A 58-year-old patient presented to our department with the suspicion of advanced cervical stump cancer eight years after LASH. She reported pelvic pain, irregular vaginal bleedings and irregular discharge. Gynaecological examination revealed a locally advanced tumor of the uterine cervix with suspicion of infiltration of the left parametria and bladder. After thorough diagnostic imaging and laparoscopic staging, the tumor stage was determined as FIGO IIIB and the patient was treated with combined radiochemotherapy. The patient presented with tumor recurrence 5 months after the completion of therapy and she is currently being treated with multichemotherapy and immunotherapy regimens as palliative treatment. CONCLUSION: Patients should be made aware about the risk of cervical stump carcinoma after LASH and the necessity for regular screening. Cervical cancer after LASH is often diagnosed at advanced stages and the treatment requires an interdisciplinary approach.

Treatment after endometrioma recurrence: a narrative review.

INTRODUCTION: Ovarian endometrioma is a common subtype of endometriosis with a prevalence between 17 and 44%. The reported average recurrence of endometrioma after surgical management is 21.5% after 2 years and 40-50% after 5 years. The aim of this narrative review was to summarize the existing literature focusing on treatment options after endometrioma recurrence in order to provide an evidence-based approach for the clinical practice. EVIDENCE ACQUISITION: Three electronic databases (MEDLINE, EMBASE and Cochrane) were searched until September 2022 for eligible studies. EVIDENCE SYNTHESIS: The available studies showed that repeated surgery has a negative impact on ovarian function, without improving the fertility outcomes. Transvaginal aspiration as an alternative option for surgery has a high rate of recurrence, which varies from 8.20 to 43.5% depending on the technique used and on the study population. Pregnancy related outcomes were similar between transvaginal aspiration groups and no intervention groups in patients with endometrioma recurrence. Regarding medical treatments, only four studies were found, showing that progestins reduce the pain and the diameter of the ovarian cyst. CONCLUSIONS: Recurrent endometrioma is a challenging condition which could be encountered during the care of women with endometriosis. The decision about the treatment-strategy has to be individualized considering family planning status, age, ovarian reserve and transvaginal ultrasound findings. Well-designed randomized clinical trials are needed to export safer conclusions about the most appropriate treatment in each specific condition after endometrioma recurrence.

Evaluation of complications, conversion rate, malignancy rate, and, surgeon's experience in laparoscopic assisted supracervical hysterectomy (LASH) of 1274 large uteri: A retrospective study.

INTRODUCTION: Hysterectomy now belongs to standard gynecological procedures. Moreover, a shift towards laparoscopic techniques is ever more apparent as they provide many advantages such as less traumatization and shorter convalescence. Large uteri are still mentioned as contraindications for laparoscopic hysterectomy even though those patients might benefit from the lower morbidity associated with minimal invasive techniques. In this study, the largest reported so far, we analyzed intraoperative and postoperative complications as well as the surgeon's experience of laparoscopic assisted supracervical hysterectomy (LASH) in patients with a uterus weight over 500 g. MATERIAL AND METHODS: The present retrospective study, between June 27, 1998 and August 31, 2019, evaluates 1274 patients with a uterus weight over 500 g who were treated with LASH for benign uterine diseases at the Clinic for Minimal Invasive Surgery (Berlin, Germany). All surgeries were performed by one of four in-house surgeons with experience in LASH: they had performed at least 500 LASH procedures before the study. Patients receiving surgical treatment for malignant tumors were not included in the study. Major and minor intraoperative and postoperative complications were recorded and evaluated. Additionally, medical files were evaluated for demographic data, American Society of Anesthesiologists score (I-IV), name of the surgeon, duration and indication for surgery, history of previous gynecological procedures and concomitant surgical interventions, weight of removed uterine tissue, duration of postoperative hospitalization in patients with complications, intraoperative conversion from laparoscopy to laparotomy, and malignancy rate. RESULTS: The mean age was 47.0 ± 7.3 years and mean body mass index was 25.6 ± 7.1 kg/m2 . Average parity was 1.04 ± 1.57. Average uterus weight was 761.8 ± 317.9 g (500-4065 g). The mean duration of surgery was 96.9 ± 49.5 min; 54% of all patients were treated without concomitant intervention, conversion rate was 2.12%. The malignancy rate was 0.4% and the complication rate was 6.81% with 1.36% intraoperative complications and 5.45% postoperative complications. CONCLUSIONS: The overall low complication and malignancy rates observed in this study allow us to present LASH as a safe and efficient alternative laparoscopic approach to remove uteri of any size in the hands of experienced surgeons.

To Laparoscopically Preserve Fertility in Intraabdominal Giant Myoma with Application of Contained In-Bag Morcellation: Mission Impossible?

A technical video was produced to demonstrate in step-by-step fashion a multiple contained myomectomy of a 20 × 30 cm giant myoma and seven additional fibroids found in the same patient, which required two different types of specimen retrieval bags for the electronic power morcellation. This complete surgical procedure included leiomyomata enucleation, contained in-bag electronic power morcellation, uterine reconstruction and the application of an adhesion prophylactic medical product.

Prevalence of adenomyosis in women undergoing hysterectomy for abnormal uterine bleeding, pelvic pain or uterine prolapse - A retrospective cohort study.

Background: Adenomyosis can cause symptoms like dysmenorrhea, dyspareunia, pelvic pain and bleeding disorders and is related to subfertility and obstetrical complications. The disease is probably underestimated and underdiagnosed because of difficulties in reliable clinical examination and imaging results. The age-related prevalence of adenomyosis still remains unclear. In this retrospective analysis we describe the rate of adenomyosis in two independent cohorts of patients undergoing hysterectomy for benign diseases (2011-2013 and 2015-2018) and its correlation to presurgical symptoms respectively indications for hysterectomy. Materials and methods: All surgeries have been performed in the same department of minimally invasive gynecological surgery by a total of two experienced surgeons following a surgical internal standard for the indication bleeding disorder, dysmenorrhea. We analyzed the overall rate of patients with adenomyosis in both cohorts and related the histological presence of adenomyosis to presurgical symptoms. We also analyzed a subgroup of postmenopausal patients with uterine prolapse. Results: In 307 patients we detected 42.0% of cases with histologically proven adenomyosis. In the group of patients with bleeding disorders and dysmenorrhea as indication for surgery we found the highest rate of adenomyosis (59.3%, cohort 1). 81,1% patients with adenomyosis (cohort 1) reported symptoms. In the subgroup of 42 postmenopausal patients, we found 23.8% of cases with adenomyosis. Conclusion: Our data shows that a positive anamnesis regarding the symptoms bleeding disorders and dysmenorrhea is suspicious for adenomyosis. In hysterectomy specimen adenomyosis can be found in more than 40%. The role of adenomyosis-related symptoms requires further investigation, especially in adolescent and postmenopausal patients.

Laparoscopic Fluorescence Guided Detection of Uterine Niche-The Next Step in Surgical Diagnosis and Treatment.

(1) Background: Uterine niche is a frequent condition in patients with a history of cesarean section. Although the relation to uterotomy seems to be clear, the exact pathogenesis is not fully understood. Uterine niche can easily be diagnosed by transvaginal ultrasound. It can be related to symptoms like dysmenorrhea, bleeding disorders, dysuria and dyspareunia. Uterine niche can be the cause of scar pregnancy, a rare form of ectopic pregnancy which can be related to severe complications; (2) Methods: We present a series of nine cases with different uterine niche related findings and discuss the diagnostic and therapeutic options reviewing the current literature and introduce a novel intrauterine ICG use for laparoscopic niche detection in one case; (3) Results: Most of uterine niche related symptoms and complications can be treated by a minimally invasive approach. Laparoscopic fluorescence guided niche detection is feasible; (4) Conclusions: Hysteroscopic and laparoscopic techniques allow the treatment of uterine niche related symptoms and complications. Intrauterine ICG application during fluorescence guided laparoscopy may allow easy niche detection.