Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

Downregulation of DROSHA: Could It Affect miRNA Biogenesis in Endometriotic Menstrual Blood Mesenchymal Stem Cells?

Menstrual blood mesenchymal stem cells (MenSCs) have gained prominence in the endometriosis scientific community, given their multifunctional roles in regenerative medicine as a noninvasive source for future clinical applications. In addition, changes in post-transcriptional regulation via miRNAs have been explored in endometriotic MenSCs with a role in modulating proliferation, angiogenesis, differentiation, stemness, self-renewal, and the mesenchymal-epithelial transition process. In this sense, homeostasis of the miRNA biosynthesis pathway is essential for several cellular processes and is related to the self-renewal and differentiation of progenitor cells. However, no studies have investigated the miRNA biogenesis pathway in endometriotic MenSCs. In this study, we profiled the expression of eight central genes for the miRNA biosynthesis pathway under experimental conditions involving a two-dimensional culture of MenSCs obtained from healthy women (n = 10) and women with endometriosis (n = 10) using RT-qPCR and reported a two-fold decrease in DROSHA expression in the disease. In addition, miR-128-3p, miR-27a-3p, miR-27b-3p, miR-181a-5p, miR-181b-5p, miR-452-3p, miR-216a-5p, miR-216b-5p, and miR-93-5p, which have been associated with endometriosis, were identified through in silico analyses as negative regulators of DROSHA. Because DROSHA is essential for miRNA maturation, our findings may justify the identification of different profiles of miRNAs with DROSHA-dependent biogenesis in endometriosis.

Altered Differential Expression of Genes and microRNAs Related to Adhesion and Apoptosis Pathways in Patients with Different Phenotypes of Endometriosis.

We aim to investigate the expression of genes (MAPK1 and CAPN2) and microRNAs (miR-30a-5p, miR-7-5p, miR-143-3p, and miR-93-5p) involved in adhesion and apoptosis pathways in superficial peritoneal endometriosis (SE), deep infiltrating endometriosis (DE), and ovarian endometrioma (OE), and to evaluate whether these lesions share the same pathophysiological mechanisms. We used samples of SE (n = 10), DE (n = 10), and OE (n = 10), and endometrial biopsies of these respective patients affected with endometriosis under treatment at a tertiary University Hospital. Endometrial biopsies collected in the tubal ligation procedure from women without endometriosis comprised the control group (n = 10). Quantitative real-time polymerase chain reaction was performed. The expression of MAPK1 (p < 0.0001), miR-93-5p (p = 0.0168), and miR-7-5p (p = 0.0006) was significantly lower in the SE group than in the DE and OE groups. The expression of miR-30a (p = 0.0018) and miR-93 (p = 0.0052) was significantly upregulated in the eutopic endometrium of women with endometriosis compared to the controls. MiR-143 (p = 0.0225) expression also showed a statistical difference between the eutopic endometrium of women with endometriosis and the control group. In summary, SE showed lower pro-survival gene expression and miRNAs involved in this pathway, indicating that this phenotype has a different pathophysiological mechanism compared to DE and OE.

Prevalence of chronic pelvic pain and primary dysmenorrhea in women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain (CPP) and primary dysmenorrhoea are debilitating conditions that can impair the quality of life of affected women. These conditions are frequently neglected, delaying proper diagnosis and healthcare provision. This study aimed to estimate the prevalence of CPP and primary dysmenorrhoea in Ecuador and identify potential variables associated with their occurrence. METHODS: We conducted a cross-sectional survey in an urban neighbourhood of Quito, the capital of Ecuador. A total of 2397 participants of 14-49 years of age were included. The data were collected through questionnaires administered by trained interviewers.The crude and adjusted prevalence ratios were calculated using a log-binomial regression model. The correlation between pain intensity catastrophising of symptoms were statistically analysed. RESULTS: The prevalence of CPP and primary dysmenorrhoea was 9.8% and 8.9%, respectively. Irritative urinary symptoms, primary dysmenorrhoea, and underlying mental disorders were associated with CPP, while smoking, irritable bowel syndrome, sleep disturbance, dyspareunia, and mental disorders were associated with primary dysmenorrhoea. CONCLUSIONS: The prevalence of CPP and primary dysmenorrhoea in Ecuador was similar to that in other Latin American countries. Primary dysmenorrhoea is a risk factor of CPP, and less than a quarter of women are undergoing treatment for the condition. Our findings reinforce the importance of healthcare interventions in anticipating the diagnosis of these conditions in women of reproductive age.

Therapeutic ultrasound versus injection of local anesthetic in the treatment of women with chronic pelvic pain secondary to abdominal myofascial syndrome: a randomized clinical trial.

BACKGROUND: Chronic pelvic pain (CPP) is defined as recurrent or continuous pain in the lower abdomen or pelvis, either non-menstrual or noncyclical, lasting for at least 6 months. There is strong evidence that up to 85% of patients with CPP have serious dysfunctions of the musculoskeletal system, including abdominal myofascial pain syndrome (AMPS). AMPS is characterized by intense and deep abdominal pain, originating from hyperirritable trigger points, usually located within a musculoskeletal band or its lining fascia. In the literature, there are few studies that address AMPS. OBJECTIVES: To evaluate and compare the efficacy of therapeutic ultrasound (TUS) and injection of local anesthetic (IA) to improve pain in women with abdominal myofascial syndrome secondary to CPP. STUDY DESIGN: Randomized controlled clinical trial. SETTING: Tertiary University Hospital. MATERIALS AND METHODS: A randomized clinical trial was conducted, patients were allocated to two types of treatment: group TUS (n = 18), and group IA (n = 20). The instruments used for evaluation and reassessment were the Visual Analog Scale, Numerical Categorical Scale, McGill Pain Questionnaire, and SF-36 quality of life assessment questionnaire. They were evaluated before starting treatment, 1 week after the end of treatment, and at 1, 3, and 6 months. RESULTS: TUS and IA were effective in reducing clinical pain and improving quality of life through the variables analyzed among study participants. There was no significant difference between groups. LIMITATIONS: absence of blinding; exclusion of women with comorbidities and other causes of CPP, the absence of a placebo group, the difference between the number of sessions used for each technique, and the COVID-19. CONCLUSION: Treatment with TUS and IA were effective in reducing clinical pain and improving quality of life in women with AMPS secondary to CPP. TRAIL REGISTRATION: We declare that this clinical trial has been registered under the number [(ReBEC) no. RBR-39czsv] on 07/18/2018 in the Brazilian Registry of Clinical Trials.

Current usage of qualitative research in female pelvic pain: a systematic review.

PURPOSE: Qualitative research has received growing attention in the multidisciplinary investigation of patients' perceptions about chronic diseases. The purpose of this systematic review was to characterize the usage of qualitative research in women with chronic pelvic pain (CPP). METHODS: We performed a structured search in Web of Science, Pubmed, and EMBASE platforms until June 2019. The search combined the keywords: "pelvic pain", "endometriosis", "dyspareunia", "dysmenorrhea", "vaginismus", "focus groups", "qualitative research", "hermeneutics", "grounded theory", and "women". Qualitative studies on female CPP were included and the main findings combined using thematic synthesis. RESULTS: We found 1211 citations, of which 52 were included in this review. The majority of included studies were based on phenomenological design. The main method for data collection was semi-structured interviews. Endometriosis was the theme of 23 studies, chronic pelvic pain of eight, dysmenorrhea of eight, dyspareunia of four, interstitial cystitis of two, vaginismus of two, vulvodynia of two, and pelvic inflammatory disease of one study. We found a wide variety of contributions. Among them, the impact of the disease on women's lives was the commonest. CONCLUSION: Qualitative research has the potential to reveal and explain several aspects of CPP in women. The medical community may better accept knowledge gained from these studies if the methods are described more transparently in published articles.

Peritoneal fluid of women with endometriosis reduces SOD1 in bovine oocytes in vitro maturation.

Studies have demonstrated oxidative stress in peritoneal fluid (PF) from women with endometriosis and the importance of enzymatic antioxidant machinery to avoid oocyte oxidative damage. Considering that PF constantly surrounds the ovaries and has direct contact with the oocyte at ovulation, we wonder if PF from women with endometriosis may affect antioxidant enzyme gene expression. Thus, the present study aims to evaluate the PF impact from infertile women with minimal and mild endometriosis and from fertile control women without endometriosis on SOD1, CAT, GSR gene's expression in experimental bovine oocytes matured in vitro. Samples of PF were obtained from women who underwent videolaparoscopy-7 infertile with EI/II and 7 fertile without endometriosis. Immature bovine oocytes underwent in vitro maturation in the absence of PF and in the presence of three concentrations (1, 5 and 10%) of PF from fertile and from infertile women with EI/II. After 22 to 24 h of IVM, oocytes were denuded and stored for analysis of SOD1, CAT and GSR by real-time polymerase chain reaction. Oocyte SOD1 expression was significantly lower in the 10% endometriosis group (0.67 ± 0.32) when compared with no-peritoneal fluid (1.05 ± 0.24, p < 0.008) and 10% control groups (1.06 ± 0.22, p < 0.006). These findings raise the possibility of a deleterious influence of PF from women with EI/II on the oocyte, not only after ovulation but also during the maturation process, which could contribute to worsening oocyte quality, being one of the mechanisms related to infertility in patients with endometriosis.

Treatment of bladder pain syndrome and interstitial cystitis: a systematic review.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness. METHODS: A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale. RESULTS: Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire. CONCLUSION: Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.

Validation and cultural translation for Brazilian Portuguese version of the Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Floor Distress Inventory (PFDI-20).

INTRODUCTION AND HYPOTHESIS: Pelvic floor disorders [urinary (UI) and/or fecal C (FI) incontinence, pelvic organ prolapse (POP)] may have a significant impact in womens' quality of life (QoL). The Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Floor Distress Inventory (PFDI-20) help assess these disorders; however, we do not have them culturally translated in the Brazilian Portuguese language. METHODS: A cross-sectional study was performed of 185 women with pelvic floor disorders (PFD group) and 65 healthy patients (control group). A translated, pilot-tested, Brazilian Portuguese version were given to these women. Internal consistency, construct validity, and floor/ceiling effect were assessed. Test-retest was performed in 79 patients after 4 weeks, and responsiveness was assessed in 42 patients after surgical treatment. RESULTS: Internal consistency (Cronbach's alpha) was adequate between PFD and control groups on the PFDI-20 (0.816-0.844) and PFIQ-7 (0.823-0.846). Test-retest reliability was also adequate [intraclass correlation coefficient (ICC) 0.803-0.843]. Subscales [Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7) and Colorectal-Anal Impact Questionnaire (CRAIQ-7) from the PFIQ-7 demonstrated floor effect (42.70, 60, and 18.38 %, respectively) in the PFD group, with no influence at total score. No ceiling effect was observed. Construct validity was adequate at all correlations between clinical symptoms and subscales in both questionnaires in both groups. Responsiveness was demonstrated by a statistically significant reduction in scale/subscale scores from PFDI-20 and PFIQ-7 after surgical treatment. CONCLUSION: The PFDI-20 and PFIQ-7 presented adequate cultural translation and are reliable and valid in the Brazilian Portuguese language.

Reduction of Pain Sensitivity is Associated with the Response to Treatment in Women with Chronic Pelvic Pain.

OBJECTIVE: The objective of this study was to evaluate whether pain thresholds to electrical stimulation of the skin change in the response to treatment in women with chronic pelvic pain (CPP). METHODS: Fifty-eight women with persistent pelvic pain for at least 6 months, from a tertiary care setting, were included in this study. All women were evaluated before the therapeutic intervention and at 6 months of multidisciplinary treatment. To estimate the pain threshold, we used transcutaneous electrical nerve stimulation on the anterior surface of the nondominant arm. The intensity of clinical pain was estimated by a visual analog scale and by the McGill questionnaire. RESULTS: The mean of pain threshold increased from 14.2 to 17.4 after 6 months of treatment (P < 0.0001). The effect sizes of the increase of electrical pain threshold were 0.86 (95% CI, 0.38 to 1.34) in the group with pain reduction and 0.53 (95% CI, -0.08 to 1.15) in the group without pain reduction. CONCLUSION: The sensitivity to experimental pain was reduced after 6 months of multidisciplinary treatment for CPP. Our data provided additional evidence of central sensitization in women with CPP.

Identification of a rare copy number polymorphic gain at 3q12.2 with candidate genes for familial endometriosis.

Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaß pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaß pathway in predisposition to endometriosis.

Uterine administration of C-X-C motif chemokine ligand 12 increases the pregnancy rates in mice with induced endometriosis.

OBJECTIVE: To study the effect of intrauterine injection of C-X-C motif chemokine ligand 12 (CXCL12), also known as a stem cell chemoattractant (stromal cell-derived factor 1), on fertility and endometrial receptivity in mice with endometriosis. DESIGN: Laboratory study. SETTING: Academic Medical Center. ANIMAL(S): Fifty-six mice underwent chemotherapy and bone marrow transplantation. Thirty-six of these mice underwent either surgery to induce endometriosis (n = 20) or sham surgery (n = 16). INTERVENTION(S): Injection of CXCL12 as a potential therapeutic agent to improve fertility in endometriosis. MAIN OUTCOME MEASURE(S): Pregnancy rate, bone marrow-derived cell (BMDC) recruitment and endometrial receptivity markers. RESULT(S): The mice with or without endometriosis received a single uterine injection of either CXCL12 or placebo. Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. Mice were euthanized after delivery, and implantation markers homeobox A11, alpha-v beta-3 integrin, and progesterone receptor were analyzed by immunohistochemistry, whereas green fluorescent protein positive BMDC recruitment was quantified by immunohistochemistry and immunofluorescence. The sham surgery groups without endometriosis had the highest cumulative pregnancy rate (100%) regardless of CXCL12 treatment. The endometriosis group treated with placebo had the lowest pregnancy rate. An increased pregnancy rate was noted in the endometriosis group after treatment with CXCL12. There was also an increase in BMDC recruitment and endometrial expression of progesterone receptor and alpha-v beta-3 integrin in the endometriosis group that received CXCL12 compared with that in the endometriosis group that received placebo. CONCLUSION(S): Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. These results suggest that CXCL12 has a potential role as a therapeutic agent in women with infertility related to endometriosis and potentially other endometrial receptivity defects.

Current Challenges in the Management of Chronic Pelvic Pain in Women: From Bench to Bedside.

Chronic pelvic pain (CPP) affects a significant proportion of women worldwide And has a negative impact on several aspects of these women's lives including mental health, work, relationships and sexual function, among others. This set of factors ultimately reflects negatively on quality Of life. The physiopathology of CPP is complex and remains to be fully clarified; however, recent advances have increased understanding of the mechanisms involved in chronic pain in general, and more specifically, CPP. Nonetheless, even when a detailed clinical history is obtained, meticulous physical examination is performed and imaging resources are appropriately used, the organic cause of the pain may still fail to be identified in a substantial number of women with CPP. Management of CPP may therefore be challenging. This narrative review was aimed at adding to the available literature on the subject, presenting and discussing the principal characteristics of CPP in women. The paper highlights gaps in the literature while providing the most up-to-date evidence associated with the physiopathology and classification of pain, its diagnosis and treatment. In addition, current challenges in the management of women with CPP are discussed.

Overexpression of miR-200b-3p in Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Women.

The key relationship between Sampson's theory and the presence of mesenchymal stem cells in the menstrual flow (MenSCs), as well as the changes in post-transcriptional regulatory processes as actors in the etiopathogenesis of endometriosis, are poorly understood. No study to date has investigated the imbalance of miRNAs in MenSCs related to the disease. Thus, through literature and in silico analyses, we selected four predicted miRNAs as regulators of EGR1, SNAI1, NR4A1, NR4A2, ID1, LAMC3, and FOSB involved in pathways of apoptosis, angiogenesis, response to steroid hormones, migration, differentiation, and cell proliferation. These genes are frequently overexpressed in the endometriosis condition in our group studies. They were the trigger for the miRNAs search. Therefore, a case-control study was conducted with MenSCs of women with and without endometriosis (ten samples per group). Crossing information obtained from the STRING, PubMed, miRPathDB, miRWalk, and DIANA TOOLS databases, we chose to explore the expression of miR-21-5p, miR-100-5p, miR-143-3p, and miR-200b-3p by RT-qPCR. We found an upregulation of the miR-200b-3p in endometriosis MenSCs (P = 0.0207), with a 7.93-fold change (ratio of geometric means) compared to control. Overexpression of miR-200b has been associated with increased cell proliferation, stemness, and accentuated mesenchymal-epithelial transition process in eutopic endometrium of endometriosis. We believe that dysregulated miR-200b-3p may establish primary changes in the MenSCs, thus favoring tissue implantation at the ectopic site.

Eutopic endometrium from women with endometriosis and chlamydial endometritis share immunological cell types and DNA repair imbalance: A transcriptome meta-analytical perspective.

The aim of this study was to identify the key similarities between the eutopic endometrium of women with endometriosis and chlamydia-induced endometritis taking into account tissue microenvironment heterogeneity, transcript gene profile, and enriched pathways. A meta-analysis of whole transcriptome microarrays was performed using publicly available data, including samples containing both glandular and stromal endometrial components. Control samples were obtained from women without any reported pathological condition. Only samples obtained during the proliferative menstrual phase were included. Cellular tissue heterogeneity was predicted using a method that integrates gene set enrichment and deconvolution approaches. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Differentially expressed genes were identified using an adjusted p-value < 0.05 and fold change = 1.5. The protein-protein interaction network was built using the STRING database and interaction score over 400. The Molecular Signatures Database was used to analyse the functional enrichment analysis. Both conditions showed similarities in cell types in the microenvironment, particularly CD4+ and CD8+ Tem cells, NKT cells, Th2 cells, basophils, and eosinophils. With regards to the regulation of cellular senescence and DNA integrity/damage checkpoint, which are commonly enriched pathways, 21 genes were down-regulated and directly related to DNA repair. Compared to the endometriosis samples, some chlamydial endometritis samples presented a lack of enriched immune pathways. Our results suggest that both conditions show similar distributions of microenvironment cell types, the downregulation of genes involved in DNA repair and cell cycle control, and pathways involved in immune response evasion.

Importance of pelvic muscle tenderness evaluation in women with chronic pelvic pain.

OBJECTIVE: To determine the prevalence of pelvic muscle tenderness in women with chronic pelvic pain (CPP) and to assess the importance of evaluating muscle tenderness in such women. DESIGN: Observational study of 48 healthy female volunteers and 108 women with CPP, who were clinically evaluated for pelvic muscle tenderness by two researchers blinded to all clinical data. RESULTS: The frequency of clinically detected pelvic muscle tenderness was significantly higher in women with CPP than in healthy volunteers (58.3% vs 4.2%, P < 0.001). Among women with CPP, those with pelvic muscle tenderness had higher Beck Depression Index scores (22 [6-42] vs 13 [3-39], P = 0.02) and higher rates of dyspareunia (63.5% [40/63] vs 28.9% [13/45], P < 0.004) and constipation (46.0% [29/63] vs 26.7% [12/45], P = 0.05) than those without pelvic muscle tenderness. CONCLUSION: Tenderness of pelvic muscles was highly prevalent among women with CPP and was associated with higher BDI scores and higher rates of dyspareunia and constipation. Determination of pelvic muscle tenderness may help in identifying women who require more intense treatment for CPP.

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu.

Eutopic endometrium appears to be crucial for endometriosis development. Despite of the evident importance, data regarding the cellular microenvironment remain unclear. Our objective was to explore the tissue microenvironment heterogeneity, transcripts, and pathways that are enriched in all phases of the menstrual cycle by analysing publicly deposited data derived from whole transcriptome microarrays of eutopic endometria of women with and without endometriosis. A meta-analysis of the transcriptome microarrays was performed using raw data available from a public database. Eligibility criteria included eutopic endometrium samples from women with endometriosis and healthy controls without any pathological condition reported the presence of an adequately reported normal menstrual phase, and samples containing both glandular and stromal components. Raw data were processed using a robust multiarray average method to provide background correction, normalisation, and summarisation. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Cellular tissue heterogeneity was inferred using the xCell package. Differentially expressed genes were identified based on a 5% adjusted p value and a 2.0-fold change. Pathways were identified by functional enrichment based on the Molecular Signatures Database, a p value of < 5%, and an FDR q value of ≤ 25%. Genes that were more frequently found in pathways were identified using leading edge analysis. In a manner independent of cycle phase, the subpopulations of activated dendritic cells, CD4 T effector memory phenotype cells, eosinophils, macrophages M1, and natural killer T cells (NKT) were all higher in stage I-II endometriosis compared to those in healthy controls. The subpopulations of M2 macrophages and natural killer T cells were elevated in eutopic endometriums from women with stage III-IV endometriosis, and smooth muscle cells were always more prevalent in healthy eutopic endometriums. Among the differently expressed genes, FOS, FOSB, JUNB, and EGR1 were the most frequently mapped within the interaction networks, and this was independent of stage and cycle phase. The enriched pathways were directly related to immune surveillance, stem cell self-renewal, and epithelial mesenchymal transition. PI3K AKT mTOR, TGF signalling, and interferon alpha/gamma responses were enriched exclusively in stage III-IV endometriosis. The cellular microenvironments and immune cell profiles were different between eutopic endometriums from women with stage I-II and stage III-IV endometriosis, and these differences were independent of the hormonal milieu. Specifically, a pro-inflammatory profile was predominant in stage I-II endometriosis, and M1-M2 polarization into eutopic endometrium may be crucial for the progression of the disease. The higher prevalence of NKT cells in eutopic endometriums from women with endometriosis that was independent of cycle phase or staging suggested a sustained stress and/or damage to these eutopic endometriums. Based on this, the results of this meta-analysis are important for identifying challenges and opportunities for future research.

Laparoscopic bowel resection of deep infiltrating endometriosis. Comparative outcomes of a public teaching hospital and a referral private hospital.

PURPOSE: To compare the operative outcomes of laparoscopic surgical treatment for bowel endometriosis in a public teaching hospital versus in a private referral hospital. METHODS: The indications for surgery, type and time of operation, length of hospital stay, need for a temporary stoma, rate of conversion to open surgery, and postoperative complications were evaluated. RESULTS: One hundred eighty-one patients were included (150 patients, 82.9%, in a private hospital). In the private hospital, there were more patients with infertility [56% vs. 29%; P=0.01] as an indication for surgery) and segmental resection was more common in the private hospital (48% vs. 29%, p=0.05). The average operative time (211.9±83.4 minutes vs. 128 ± 55 minutes, p<0.001) as well as the length of hospital stay (3.97±1.7 days vs. 1.56±0.85 days, p<0.001) was higher in the public hospital; the rate of conversion to open surgery was significantly lower in the private hospital (2% vs. 32.3%, p<0.001). Operations performed at the public hospital were associated with higher rates of postoperative complications (Clavien-Dindo II and II) (38.7% x 11.3%, p=0.021; OR 3.2, CI 95% 1.2-8.0). CONCLUSION: Laparoscopic surgery in private centers was associated with reductions in major complications, surgical times, lengths of stay and rates of conversion to open surgery compared to that in public teaching hospitals.