Pelvic pain symptoms and endometriosis characteristics in relation to oxidative stress among adolescents and adults with and without surgically-confirmed endometriosis.

Background: While the majority of reproductive-aged females will experience pelvic pain during their lives, biological mechanisms underlying pelvic pain are not well understood. We investigated associations between pelvic pain symptoms and oxidative stress among people with and without surgically-confirmed endometriosis. Methods: Using an enzyme-linked immunosorbent assay, we measured 8-Hydroxy-2'-deoxyguanosine (8-OHdG) in urine samples and corrected for creatinine levels in 434 surgically-confirmed endometriosis participants compared to 605 participants never diagnosed with endometriosis. At enrollment, participants reported details of their pelvic pain symptoms. Linear regression was used to compute geometric mean (GM) creatinine-corrected 8-OHdG levels with 95% confidence intervals (CI) among all participants and those with and without endometriosis separately, adjusting for potential confounders. Interactions by surgically-confirmed endometriosis status were tested by Wald statistics. Results: No trends in 8-OHdG were observed among those with or without endometriosis for severity or frequency of dysmenorrhea, acyclic pelvic pain, dyspareunia or pain with bowel movements. Among endometriosis participants, lower 8-OHdG levels were observed for participants with any white, blue/black, or brown lesions (GM=76.7 versus 82.9 ng/mg; p=0.10), which was primarily driven by lower levels of 8-OHdG for any blue/black lesions (GM=72.8 versus 81.6 ng/mg; p=0.05). Conclusion: While no associations were observed between 8-OHdG and pelvic pain symptoms, future research is needed to assess how other pathways of oxidative damage, e.g. through proteins or lipids, may affect endometriosis-associated symptoms. Additionally, further research is needed to understand differences in oxidative stress among endometriosis lesion sub-phenotypes.

Rare but Still There: A Scoping Review on Endometriosis-Associated Ovarian Cancer.

Endometriosis is a medical condition affecting at least up to 10% of women of reproductive age. This condition occurs when ectopic endometrial glands and stroma implant outside the uterus and there are several theories regarding the underlying origins of the disease. Endometriosis is one of the major causes of severe dysmenorrhoea, chronic pelvic pain and infertility. While endometriosis is generally a non-malignant condition, it rarely may transform into an invasive cancer, and increase the risk for epithelial ovarian cancer, notably endometrioid or clear cell ovarian cancer. Despite the increased risk, the mechanisms behind the development of endometriosis-associated ovarian cancer (EAOC) are not yet well understood. Recent investigations have delved into the intricate interplay between endometriosis and EAOC, exploring pathways involving oxidative stress, inflammation, hyperestrogenism, and the discovery of genetic mutations within endometriotic lesions that hint at a transition towards invasive carcinoma. Efforts have been made to identify intermediary lesions between endometriosis and EAOC, which may enable earlier detection of endometriosis at risk of malignant transformation or even prevention of the transformation altogether. However, given the rarity of this malignancy, there is still the risk of late or missed diagnosis, with the risk of inappropriate management being offered to the patient, and the higher risk of poor prognosis and increased morbidity and mortality. This scoping review aims to summarize existing data on EAOC, with a focus on endometrioid and clear cell histologic subtypes. It also provides insights into its identification, prognosis, and delineating management strategies, seeking to provide a holistic understanding of the complexities surrounding EAOC, facilitating further research and the development of more effective prevention and treatment approaches.

Prototype Salivary Assay for Quantification of Two Biomarkers for In Vitro Diagnosis of Endometriosis.

Endometriosis, a very common disease in women, is characterized by endometrial structures outside the uterine cavity. The lack of a reliable noninvasive diagnostic test and the often nonspecific symptoms of this pathology are responsible for the delay in definitive diagnosis of this disease. Recently, through a proteomics approach, our research group has identified two potential diagnostic markers for endometriosis in serum (Zn-alpha2-glycoprotein and complement C3 precursor). In this article, we describe the experimental conditions of a simple ELISA for rapid quantification of these two biomarkers in the saliva of patients with endometriosis. Finally, preliminary experiments on a small cohort of patients and controls have confirmed the potential diagnostic value of this assay.

Endometriosis-associated spontaneous major haemoperitoneum in pregnancy.

Spontaneous haemoperitoneum in pregnancy (SHiP) related to endometriosis is a rare and life-threatening complication. We report a case of a patient presenting to our department with major haemoperitoneum at 23+3 weeks of gestation due to a large rectovaginal endometriotic nodule. The patient required a midline laparotomy to evacuate 1 L of haemoperitoneum and achieve haemostasis. A large rectovaginal nodule was seen bleeding and was packed with haemostatic material and a large swab. After 24 hours, the swab was removed and haemostasis was confirmed. The patient was monitored very closely by a multidisciplinary team and the pregnancy was allowed to continue to try and achieve a better outcome for the baby and at 28 weeks of gestation, a girl was delivered in good condition via caesarean section.

Identification and validation of an endoplasmic-reticulum-stress-related gene signature as an effective diagnostic marker of endometriosis.

Background: Endometriosis is one of the most common benign gynecological diseases and is characterized by chronic pain and infertility. Endoplasmic reticulum (ER) stress is a cellular adaptive response that plays a pivotal role in many cellular processes, including malignant transformation. However, whether ER stress is involved in endometriosis remains largely unknown. Here, we aimed to explore the potential role of ER stress in endometriosis, as well as its diagnostic value. Methods: We retrieved data from the Gene Expression Omnibus (GEO) database. Data from the GSE7305 and GSE23339 datasets were integrated into a merged dataset as the training cohort. Differentially expressed ER stress-related genes (DEG-ERs) were identified by integrating ER stress-related gene profiles downloaded from the GeneCards database with differentially expressed genes (DEGs) in the training cohort. Next, an ER stress-related gene signature was identified using LASSO regression analysis. The receiver operating characteristic curve was used to evaluate the discriminatory ability of the constructed model, which was further validated in the GSE51981 and GSE105764 datasets. Online databases were used to explore the possible regulatory mechanisms of the genes in the signature. Meanwhile, the CIBERSORT algorithm and Pearson correlation test were applied to analyze the association between the gene signature and immune infiltration. Finally, expression levels of the signature genes were further detected in clinical specimens using qRT-PCR and validated in the Turku endometriosis database. Results: In total, 48 DEG-ERs were identified in the training cohort. Based on LASSO regression analysis, an eight-gene-based ER stress-related gene signature was constructed. This signature exhibited excellent diagnostic value in predicting endometriosis. Further analysis indicated that this signature was associated with a compromised ER stress state. In total, 12 miRNAs and 23 lncRNAs were identified that potentially regulate the expression of ESR1, PTGIS, HMOX1, and RSAD2. In addition, the ER stress-related gene signature indicated an immunosuppressive state in endometriosis. Finally, all eight genes showed consistent expression trends in both clinical samples and the Turku database compared with the training dataset. Conclusions: Our work not only provides new insights into the impact of ER stress in endometriosis but also provides a novel biomarker with high clinical value.

Neutrophil to lymphocytes ratio in deep infiltrating endometriosis as a new toll for clinical management.

Several mechanisms, including altered local and systemic immune system, apoptosis, and new angiogenesis, are responsible for the development and progression of endometriosis. Over the years many markers have been studied, like CA 125 and, recently, neutrophil-to-lymphocyte ratio (NLR). This tool is cost-effectiveness and non-invasiveness as a marker of systemic inflammatory diseases. The aim of this study is to assess the role of NLR in the real-life management of patients with endometriosis in order to evaluate the possible association between this value and symptoms. We performed a retrospective analysis of 199 premenopausal women affected by endometriosis, from January 2013 to December 2020, evaluating the characteristics of disease, the symptoms and the NLR. Analyzing the neutrophiles, the mean ± SD value was 6.1 ± 4.5 × 103/ul, while for lymphocytes mean ± SD value was 1.8 ± 0.7.NLR was categorized according to its median value (> 2.62 vs ≤ 2.62). The comparison between NLR values and CA 125, endometriosis stage, dysmenorrhea and presence of chronic pelvic pain, adjusting for previous therapy did not find a significant association. An interesting result, although not significant, was the association between NLR and chronic pelvic pain (OR = 1.9). In the sub-group of patients without previous therapy this association is even stronger (OR = 4.8, 95% CI 0.5-50.2, p = 0.190). The link between NLR and chronic pelvic pain can provide a further hint to the clinician even when taking symptoms into account to develop a particular therapeutic treatment related to the various expressions of NLR. Finally, NLR may enable the creation of customized follow-up protocols that divide patients into high- and low-risk categories for endometriosis recurrence.

The Antigen-Processing Pathway via Major Histocompatibility Complex I as a New Perspective in the Diagnosis and Treatment of Endometriosis.

Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson's theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.

[Endometriosis and pain]. / Endométriose et douleur.

Managing chronic pain in endometriosis requires multidisciplinary assessment and care. The aim is not complete disappearance of symptoms, but rehabilitation through medication, non-medication treatments and overall follow-up.

Inguinal endometriosis: a case series and review of the literature.

BACKGROUND: Inguinal endometriosis is one of the most common forms of endometriosis. The present study introduces 8 cases of inguinal endometriosis and discusses probable theories of inguinal endometriosis by reviewing the literature. CASE PRESENTATION: 8 Iranian cases of inguinal endometriosis with a mean age of 36 years were presented. Catamenial groin pain and swelling were the most common complications. Also, patients usually had accompanying symptoms such as pelvic pain and dysmenorrhea. One-half of patients had a history of previous abdominal surgery. Ultrasound was diagnostic in 4 patients (50%), and magnetic resonance imaging was used in two patients (25%). Among 6 patients who underwent hormonal therapy, 4 experienced an endometriosis size increase. Inguinal endometriosis was right-sided in 87.5% of patients, and among 4 patients who underwent surgery, 75% had proximal site involvement of the round ligament. CONCLUSION: According to the rarity of inguinal endometriosis, it is more likely to be a misdiagnosis with other inguinal disorders such as inguinal hernia. Inguinal endometriosis should be considered in patients who undergo inguinal herniorrhaphy, with suspected findings such as thickening of the hernia sac wall, bloody fluid inside the sac, or thickening of the extraperitoneal round ligament during the surgery.

[Understanding endometriosis]. / Mieux comprendre l'endométriose.

Endometriosis is a chronic disease defined by the presence of endometrial cells outside the uterus. Research is ongoing to better understand its etiologies, the anatomopathological forms it takes and the associated symptoms, which often have pain in common.

Actualización del abordaje de la endometriosis / Update in endometriosis work-up and treatment

El creciente compromiso con la salud ginecológica ha puesto de manifiesto la necesidad de actualizar el abordaje de la endometriosis, por lo que se ha querido llevar a cabo una revisión exhaustiva de la literatura científica con el fin de recopilar los últimos avances relevantes en su asistencia sanitaria. En este sentido, se llevó a cabo un congreso de ginecología el 30 de septiembre y 1 de octubre que convocó a diversos expertos para revisar aspectos clínicos, farmacológicos y vanguardistas. La revisión destaca los criterios directos, indirectos y soft markers que determinan la presencia de endometriosis durante la exploración, así como las pautas adecuadas para el diagnóstico mediante pruebas de imagen. Además, analiza la importancia de realizar un diagnóstico completo y detallado en pacientes que presenten síntomas de la enfermedad. Por otra parte, resalta los avances en el tratamiento de esta enfermedad, haciendo especial énfasis en los beneficios de la N-acetil cisteína. Finalmente, estudia el papel de la cirugía, destacando sus ventajas, pero señalando que la endometriosis no debe ser siempre asociada a la operación, ya que esta puede conllevar numerosas complicaciones.(AU)

The growing commitment to gynecological health has highlighted the need to update the approach to endometriosis. Therefore, a comprehensive review of the scientific literature has been carried out to gather the latest relevant advances in its healthcare. In this regard, a gynecology congress was held on September 30 and October 1, bringing together various experts to review clinical, pharmacological, and cutting-edge aspects. The review emphasizes the direct, indirect, and soft markers that determine the presence of endometriosis during examination, as well as the appropriate guidelines for diagnosis through imaging tests. Furthermore, it discusses the importance of conducting a complete and detailed diagnosis in patients exhibiting symptoms of the disease. Additionally, it highlights advancements in the treatment of this condition, with a particular emphasis on the benefits of N-acetyl cysteine. Finally, it explores the role of surgery, emphasizing its advantages but pointing out that endometriosis should not always be associated with surgery since it can entail numerous complications.(AU)

Actualización del tratamiento de fisioterapia en el abordaje de la endometriosis. Una revisión sistemática / Update on physiotherapy treatment in endometriosis: A systematic review

La endometriosis es una patología ginecológica crónica e inflamatoria caracterizada por la presencia de tejido endometrial fuera del útero. Entre las manifestaciones clínicas están el dolor pélvico crónico, la fatiga, la dismenorrea, la dispareunia, la infertilidad, la disuria y la disquecia. La fisioterapia puede formar parte del tratamiento sintomático de la endometriosis, es por ello, que con esta revisión se pretende analizar la bibliografía científica para evaluar el efecto de la fisioterapia en este padecimiento. Se realizó una búsqueda bibliográfica durante las dos primeras semanas del mes de diciembre de 2022 en las bases de datos PubMed, Medline, Scopus, Web of Science, Physiotherapy Evidence Database (PEDro), Cumulative Index to Nursing and Allied Health Literature (CINAHL) y Enfermería-Fisioterapia-Podología (ENFISPO). Se emplearon los descriptores «Endometriosis» «Physical Therapy Modalities», «Physiotherapy», «Physiotherapist», «Physical therapy» y «Physical rehabilitation». Los resultados se limitaron a estudios clínicos aleatorizados publicados en inglés o español. Se obtuvieron un total de 943 artículos, de los cuales seis fueron seleccionados tras aplicar los criterios de elegibilidad. Las investigaciones seleccionadas desarrollaron diferentes intervenciones de fisioterapia con técnicas tales como la electroterapia con estimulación nerviosa transcutánea (TENS) y láser pulsado de alta intensidad (HILT), el entrenamiento de relajación muscular progresiva, la actividad física aeróbica, la terapia manual y el ejercicio terapéutico a través del yoga. La fisioterapia parece aportar beneficios en cuanto a la reducción del dolor pélvico y mejora de la calidad de vida en mujeres con endometriosis.(AU)

Endometriosis is a chronic, inflammatory gynecological pathology characterized by the presence of endometrial tissue outside the uterus. Clinical manifestations include chronic pelvic pain, fatigue, dysmenorrhea, dyspareunia, infertility, dysuria and dyschezia. Physical therapy can be part of the symptomatic treatment of endometriosis; therefore, this review aims to analyze the scientific literature to evaluate the effect of physical therapy in endometriosis. A bibliographic search was carried out during the first two weeks of December 2022 in the databases PubMed, Medline, Scopus, Web of Science, PEDro, CINAHL and ENFISPO. The descriptors “Endometriosis” “Physical Therapy Modalities”, “Physiotherapy”, “Physiotherapist”, “Physical therapy” and “Physical rehabilitation” were used. Results were limited to randomized clinical studies published in English or Spanish. A total of 943 results were obtained, of which 6 were selected after applying the eligibility criteria. The selected studies develop different physiotherapy interventions with techniques such as electrotherapy with TENS and high intensity pulsed laser, progressive muscle relaxation training, aerobic training, manual therapy, and therapeutic exercise through yoga. Physiotherapy appears to provide benefits in terms of reducing pelvic pain and improving quality of life in women with endometriosis.(AU)

Psychometric evaluation of the endometriosis impact questionnaire (EIQ) in an Iranian population.

BACKGROUND: Endometriosis is a benign and chronic gynecological estrogen-dependent disease. Considering the prevalence and the importance of measuring the long-term effects of endometriosis in affected women's lives t the EIQ scale was designed and psychometrically analyzed in English in Australia, in three recall periods (last 12 months, 1 to 5 years ago and more than 5 years ago). It has never been used in Iran and its validity and reliability have not been assessed either. Therefore, the present study aimed to translate and investigate the psychometric properties of the EIQ. METHODS: In this study, 200 women were selected through random sampling in 2022. After forward and backward translation, the face validity, content validity, and construct validity of EIQ (through Corrected Item-Total Correlation) were examined. To assess the reliability of the scale, both internal consistency (Cronbach's alpha) and test-retest stability methods were employed. RESULTS: Impact Score with a score above 1.5 was approved. CVI and CVR values of the EIQ tool were 0.97 and 0.94, respectively. The Item to total Correlation confirmed the construct validity of all seven dimensions of the tool, more than the cut-off (0.3) except lifestyle. Cronbach's alpha coefficient and Intra Correlation Coefficient (ICC) were acceptable for all dimensions. CONCLUSION: The Persian version of EIQ is a valid and reliable scale. This tool is valid and reliable for investigating the long-term impact of endometriosis in Iranian society.

Identification of miR-30c-5p microRNA in Serum as a Candidate Biomarker to Diagnose Endometriosis.

The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.

[The historical aspects of development of concept of endometriosis: publications review].

The endometriosis is a chronic gynecological disease, etiology and pathogenesis of which are not fully clear to science. Its consequences are hardest burden for health care, society and every female patient and her family. The presented review tries to answer in historical aspect the question of interest to all scientists - why endometriosis, known to science for more than 300 years, still remains "disease of riddles and assumptions"? The search of publications was implemented in such databases as Web of Science, eLibrary, Scopus, PubMed/MEDLINE. The search was based on keywords "history", "endometriosis", "review", "myths", "authorship", "infertility", "reproductive dysfunction". The study covered full-text sources and publications reviews related to subject under study. The articles having no direct relation to the topic of endometriosis were excluded from the review. The review demonstrated that as before pathogenesis of endometriosis remains enigmatic and complex. The more and more evidences appear that endometriosis is part of syndrome of uterus reproductive dysfunction. Hence necessity in further research and experimental designs in this area. Perhaps in nearest future scientists nevertheless will find the clue to single etiopathogenetic mechanism of development of endometriosis which at a later date will be successfully applied by physicians in diagnostic and treatment of this disease.

An artificial intelligence approach for investigating multifactorial pain-related features of endometriosis.

Endometriosis is a debilitating, chronic disease that is estimated to affect 11% of reproductive-age women. Diagnosis of endometriosis is difficult with diagnostic delays of up to 12 years reported. These delays can negatively impact health and quality of life. Vague, nonspecific symptoms, like pain, with multiple differential diagnoses contribute to the difficulty of diagnosis. By investigating previously imprecise symptoms of pain, we sought to clarify distinct pain symptoms indicative of endometriosis, using an artificial intelligence-based approach. We used data from 473 women undergoing laparoscopy or laparotomy for a variety of surgical indications. Multiple anatomical pain locations were clustered based on the associations across samples to increase the power in the probability calculations. A Bayesian network was developed using pain-related features, subfertility, and diagnoses. Univariable and multivariable analyses were performed by querying the network for the relative risk of a postoperative diagnosis, given the presence of different symptoms. Performance and sensitivity analyses demonstrated the advantages of Bayesian network analysis over traditional statistical techniques. Clustering grouped the 155 anatomical sites of pain into 15 pain locations. After pruning, the final Bayesian network included 18 nodes. The presence of any pain-related feature increased the relative risk of endometriosis (p-value < 0.001). The constellation of chronic pelvic pain, subfertility, and dyspareunia resulted in the greatest increase in the relative risk of endometriosis. The performance and sensitivity analyses demonstrated that the Bayesian network could identify and analyze more significant associations with endometriosis than traditional statistical techniques. Pelvic pain, frequently associated with endometriosis, is a common and vague symptom. Our Bayesian network for the study of pain-related features of endometriosis revealed specific pain locations and pain types that potentially forecast the diagnosis of endometriosis.

Crimson clues: advancing endometriosis detection and management with novel blood biomarkers.

Endometriosis is an inflammatory condition affecting approximately 10% of the female-born population. Despite its prevalence, the lack of noninvasive biomarkers has contributed to an established global diagnostic delay. The intricate pathophysiology of this enigmatic disease may leave signatures in the blood, which, when detected, can be used as noninvasive biomarkers. This review provides an update on how investigators are utilizing the established disease pathways and innovative methodologies, including genome-wide association studies, next-generation sequencing, and machine learning, to unravel the clues left in the blood to develop blood biomarkers. Many blood biomarkers show promise in the discovery phase, but because of a lack of standardized and robust methodologies, they rarely progress to the development stages. However, we are now seeing biomarkers being validated with high diagnostic accuracy and improvements in standardization protocols, providing promise for the future of endometriosis blood biomarkers.