Advanced Stages Of Endometriosis Research Articles

Robotic Surgery for Bladder Endometriosis: A Systematic Review and Approach.

Women with bladder endometriosis often present with more advanced stages of endometriosis. Robotic surgery has emerged as a promising approach to the management of bladder endometriosis. This systematic review aims to analyze the current literature on robotic surgery for bladder endometriosis and describe our systematic approach to surgical treatment. This review followed the PRISMA guidelines, which ensured a comprehensive and transparent approach to selecting and evaluating relevant studies. We conducted a thorough literature search to identify studies that investigated the use of robotic surgery for bladder endometriosis. Relevant databases were searched, and inclusion and exclusion criteria were applied to select eligible studies. Data extraction and analysis were performed to assess the outcomes and effectiveness of robotic surgery for the treatment of bladder endometriosis. We did not find any randomized clinical trials with the use of robotics in the treatment of bladder endometriosis. We found only two retrospective studies comparing robotic surgery with laparoscopy, and another retrospective study comparing robotic surgery, laparoscopy, and laparotomy in the treatment of bladder endometriosis. All the other 12 studies were solely case reports. Despite the lack of robust evidence in the literature, the studies demonstrated that robotic surgery is feasible and is associated with reduced postoperative pain, shorter hospital stays, and faster recovery. The utilization of robotic technology is a promising option for the surgical management of bladder endometriosis. We advocate a surgical systematic approach for the robotic treatment of bladder endometriosis. Robotic technology, with its 3D vision, instrumental degrees of freedom, and precision, particularly in suturing, may provide potential benefits over traditional laparoscopy.

P-339 Activities and changes in the number of natural killer cells in endometriosis: systematic review and meta-analysis

Abstract Study question What are the differences in peripheral, uterine, and peritoneal NK (uNK, pNK, pfNK) cell counts/percentages, and activities in women with endometriosis compared controls Summary answer The mean percentage level of uNK, pNK, and peritoneal NK (pfNK) cells has no significant difference in women with endometriosis compared controls What is known already NK cells play an important role in the pathogenesis of endometriosis Study design, size, duration This systematic review and meta-analysis included 36 experimental studies (case control and cross sectional). Narrative review is also conducted on the NK cell activity, cytokine expression, regulations and receptors. Participants/materials, setting, methods Women suffering with endometriosis confirmed with laparoscopy and/or pathology was the cases whereas, women having different pelvic pathology such as myoma, ovarian cyst, healthy woman and verified not having endometriosis with laparoscopy and/or pathology was considered as controls for this study. Databases (PubMed, Web of Science, Scopus, Google scholar, and EMBASE through OVID) were used to search for the available studies. RevMan 5.4 and STATA 14 were used to analyze the data. Main results and the role of chance The mean percentage level of uNK, pNK, and peritoneal NK (pfNK) cells has no significant difference (standard mean difference SMD 0.13, 95%CI -0.35, 0.62; P = 0.59, I2 74%; total 393 women, 6 studies), (SMD 0.27, 95%CI -0.07, 0.61; P = 0.12, I2 80%; total 825 women, 11 studies), and (SMD 0.31, 95%CI -0.68, 01.29; P = 0.59, I2 94%; total 404 women,7 studies) in endometriosis patients compared with controls respectively. The pooled NK (uNK, pNK, pfNK) cell cytotoxicity/activity level is significantly higher in controls compared with women with endometriosis (MD 5.43, 95%CI 2.29, 8.57; P < 0.007, I2 50%; total 323 women, 7 studies). The NK cytotoxicity/activity level in early stages of endometriosis has no significant difference compared with advanced stages of endometriosis (MD 2.29, 95%CI –1.98-6.57; P = 0.29, I2 87%; total 263 women, 7 studies). There are variations in studies conducted in NK cell activities in endometriosis: broadly categorized as NK cell cytotoxicity, cytokine expression and NK cell regulation and receptors (Inhibition and activation). The cytotoxic activity of NK cells decreased in women with endometriosis and correlated with the severity of the disease, however the cytokine expression and inhibitor receptors are equivocal across studies. Limitations, reasons for caution We unable to conduct sub-group analysis to investigate the cytotoxic activity of NK cell in women with endometriosis and its stages in different samples such as pNK, uNK, and pfNK due to the lack of studies for the analysis. Wider implications of the findings This study revealed that the activity of NK cells in women with endometriosis is significantly lower than controls.Though the mean difference of NK cell count and percentage has no significant difference, the cytotoxicity activity of NK cell is higher in controls compared with women with endometriosis Trial registration number CRD42022384060

True Prevalence of Diaphragmatic Endometriosis and Its Association with Severe Endometriosis: A Call for Awareness and Investigation

To identify characteristics indicating preoperatively the presence of diaphragmatic endometriosis (DE). Comparison of characteristics of patients with DE with characteristics of patients with abdominal endometriosis without diaphragmatic involvement, in a prospective cohort study. Tertiary referral center; endometriosis center. 1372 patients with histologically proven endometriosis. Surgery performed laparoscopically under general anesthesia. All patients with suspected endometriosis underwent a complete bilateral inspection of the diaphragm. Demographic and clinical pathologic characteristics were evaluated using basic descriptive statistics (comparison of the groups using the chi-square test and the Mann-Whitney t-test). A logistic regression analysis was performed to evaluate the relationship (hazard ratio) between symptoms and the presence of DE. DE was diagnosed in 4.7% of the patients (65/1372). There was no significant difference between the two groups (patients with abdominal endometriosis with or without DE) with regard to typical endometriosis pain (dysmenorrhea, dyschezia, dysuria, and/or dyspareunia). However, in the DE group, diaphragmatic pain was present significantly more often pre-operatively (27.7% vs 1.8% p<.001). Four DE patients (6.1 %) were asymptomatic (with infertility the indication for surgery). In the DE group, 78.4 % had advanced stages of endometriosis (rAFS III° or IV°); the left lower pelvis was affected in more patients (73.8%). In cases of ovarian endometriosis, patients with DE showed a significantly higher prevalence of left ovaries involvement (left 63% vs right 35.7%, p<.001). Patients with DE had a significantly higher rate of infertility (49.2% vs 28.7%, p<.05). Patients with shoulder pain, infertility, and/or endometriosis in the left pelvis have a significant higher risk of DE and therefore need specific preoperative counseling and if indicated surgical treatment.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Epidemiology of Endometriosis in Tamil Nadu, India

Endometriosis is an enigmatic disease of women of the reproductive age group. Pain and infertility are the main symptoms. This paper attempts to study the incidence of endometriosis among infertility patients undergoing laparoscopy. Following parameters such as age, SE status, body mass index (BMI), type of infertility, parity, symptoms, family history, menstrual history, medical history, ultrasound (USG) findings, stages of endometriosis, associated findings, and laparoscopy findings were analyzed. Incidence of endometriosis was higher between 26 and 35 years and at all ages stage 3 and stage 4 endometriosis were higher than stage 1 and stage 2. Endometriosis is more common in higher socio-economic class and in women with lower BMI and primary infertility. Among all the symptoms of endometriosis, dysmenorrhea is the most common and most important pointer towards the diagnosis of endometriosis. There is also higher incidence of family history among endometriosis patients. Menstrual cycles are invariably regular. Diagnosis of endometriosis is mainly through USG and rarely magnetic resonance imaging is performed to confirm the presence of endometriosis. In early stages of endometriosis, USG may not show any positive findings. USG can pick up endometriomas, deep infiltrative endometriosis, adenomyosis, and associated findings such as polycystic ovary syndrome, fibroids, and Mullerian anomalies. Laparoscopy is the gold standard in the diagnosis and treatment of endometriosis. Staging is done based on laparoscopy and simultaneously treatment is also carried out. Stage 1 and 2 patients underwent cauterization of the lesions. Advanced stages of endometriosis underwent cystectomy, adhesiolysis, and excision of the deep lesions and ultimately the pelvic anatomy is regained. Women were planned for further fertility treatment based on the staging of the disease.

Effectiveness of ultra-long protocol on in vitro fertilization/intracytoplasmic sperm injection-embryo transfer outcome in infertile women with endometriosis: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the effectiveness of ultra-long protocol on reproductive and controlled ovarian hyperstimulation outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in infertile women with endometriosis versus long protocol. We retrieved articles without language restrictions in the Elsevier ScienceDirect, Embase, Medline, PubMed, Web of Science, China National Knowledge Infrastructure, Wan Fang Data Knowledge Service Platform and China Science and Technology Journal Database from inception to August 2020. RCTs including the comparison of reproductive outcome of infertile patients with endometriosis who underwent ultra-long protocol and long protocol were selected. Data extraction was conducted using RevMan 5.3. A total of nine RCTs in compliance with the standard literature were included. This meta-analysis suggested that ultra-long protocol with a 3-month downregulation could increase clinical pregnancy rate of infertile women with endometriosis (RR=1.31, 95% CI:1.11 ~ 1.55, P = 0.002) versus long protocol. However, subgroup analysis found the different protocol provided no significant difference in improving clinical outcomes in patients with different disease stage of endometriosis. The ultra-long protocol could improve the clinical pregnancy rate of infertile women with endometriosis compared with long protocol with a 3-month downregulation. And ultra-long protocol could be effective to increase the ongoing pregnancy rate compared to long-protocol. But, the efficacy of ultra-long protocol is not different between early and advanced stage of endometriosis.

IL-2 and IL-27 synergistically promote growth and invasion of endometriotic stromal cells by maintaining the balance of IFN-γ and IL-10 in endometriosis.

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-β led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.

Alterations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis.

BackgroundEndometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of this study was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells (Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endome- triosis with a control group.Materials and MethodsIn this case control study, PB and PF samples were collected from women aged 24-40 years who underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and com- pared between three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control (no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups.ResultsNo statistically significant difference was found between the study groups regarding the numbers of Th1, Th2 and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells compared to the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2 cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase (P=0.035). The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046). However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (P values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PB in the advanced stages of endometriosis (P= 0.013).ConclusionThere were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis, which could be related to the severity of this disease.

Recurrence of Endometriosis After Laparoscopic Hysterectomy

Video Objective Endometriosis is known to have a remarkably negative effect on the Quality of Life (QOL) of the women. Surgery is considered when medical therapy is unsuccessful or in the setting of infertility. A high recurrence rate is reported in advanced stages of endometriosis. Thus, Complete excision and prevention of recurrence is particularly important. Following hysterectomy, pelvic pain and vaginal bleeding are a rare but real occurrence. We evaluated the recurrence of pain and bleeding in patients following hysterectomy and infertility sparing procedures. Design Retrospective cohort. Setting Kurashiki medical center, private hospital, in Japan. Interventions We evaluated postoperative recurrence of endometriosis from January, 2004 to December, 2018 in patients who underwent laparoscopic excision of endometriosis, with or without postoperative hormone therapy. Main Results In our facility, endometriosis recurred in 20 cases (3.85%) out of 519 total laparoscopic hysterectomy (TLH) with ovarian sparing procedures. 17 of the 20 cases were not treated with hormone therapy postoperatively. No recurrence was found in 288 patients who underwent TLH plus bilateral salpingo-oophorectomy. In fertility sparing cases, 7.5%(152/2012 cases) had recurrence after surgery. Recurrence rate decreased to 4.9%(85/1750 cases) after January, 2008 compared with 24.7%(67/271) before December, 2007.For fertility sparing endometriosis excision surgery, postoperative recurrence without hormone therapy was found in six (1case in rectum, 5 cases in ovaries) out of fifteen cases. With postoperative hormone treatment using dienogest, a “fourth-generation” progestin, recurrence was found in only one case out of fifteen hormone therapy groups. Median recurrent period was 6 months. Surprisingly, 11 out of 22 fertility sparing cases were diagnosed as endometrioma with 1 month postoperative MRI. Conclusion Approval of dienogest in 2008 may have contributed to the dramatic improvement in preventing recurrence of endometriosis. Hysterectomy significantly decreases patient symptoms and recurrence rate. Ovarian conservation conferred a higher rate of recurrence of symptoms of endometriosis.

The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression.

Endometriosis is a frequent and chronic illness in young women which could be defined by the existence of endometrial stroma and glands outside of the normal site of the lining of the uterus. It has painful symptoms. The advanced stage of endometriosis may lead to gynecological malignancies, such as ovarian cancer, and other complications, including infertility. However, its exact physiopathology is not well known. Recent studies have shown the possible roles of inflammation along with oxidative stress. Additionally,angiogenesis and apoptosis dysregulation contribute to endometriosis pathophysiology. Therapeutic strategies and continuing attempts, to conquer endometriosis should be done regarding molecular signaling pathways. Thus, the present review summarizes current studies and focuses on molecular mechanisms.

Could surgical management improve the IVF outcomes in infertile women with endometrioma?: a review.

Endometriosis is a chronic inflammatory condition that affects fertility and could be toxic to the ovary. Endometrioma per se and surgical interventions for endometrioma significantly reduce the ovarian reserve. Therefore, to prepare for surgical intervention for endometrioma, the high-risk group with decreased ovarian reserve must be considered. There is no evidence to support the use of surgical intervention before in vitro fertilization (IVF) to improve the reproductive outcomes of subsequent IVF in infertile women with advanced-stage endometriosis or endometrioma. As surgical treatment has few benefits, IVF could be recommended immediately for aiding conception in these women. However, the reproductive prognosis of IVF may be worse in the more advanced stages of endometriosis. When dysmenorrhea is severe or when cancer is suspected, surgery prior to IVF may be necessary and justified. When the size of the endometrioma is very large, surgery could be required prior to IVF to facilitate access to follicles during oocyte retrieval or to improve the ovarian response to controlled ovarian stimulation. Prolonged pituitary downregulation in women with surgically diagnosed endometriosis may be helpful to increase the clinical pregnancy rate in subsequent IVF cycles. The purpose of this paper was to review the efficiency and clinical application of the surgical intervention and IVF for infertile women with advanced-stage endometriosis or endometrioma.

Down-regulation of long non-coding RNA MALAT1 inhibits granulosa cell proliferation in endometriosis by up-regulating P21 via activation of the ERK/MAPK pathway.

Is there a specific mechanism underlying the association between lung adenocarcinoma transcript 1 (MALAT1) and endometriosis-related infertility? The down-regulation of MALAT1 in endometriosis granulosa cells (GCs) may have an adverse effect on the growth and development of oocytes by inhibiting GC proliferation, due to cell cycle-dependent mechanisms that enhance P21 expression through activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. The association between endometriosis and infertility is well supported throughout the literature, and endometriosis per se and its surgical treatment have an adverse effect on the ovarian reserve and on oocyte development. MALAT1, one of the most extensively expressed and evolutionarily conserved transcripts, has been implicated to play a role in human development and many diseases. However, little is known about the role of MALAT1 long non-coding RNA (lncRNA) in endometriosis and its associated infertility. We measured MALAT1 lncRNA expression levels in GCs from 52 endometriosis patients and 52 controls. Also, MALAT1 was knocked down in a human GC tumor-derived cell line, KGN, to investigate the role of MALAT1 and its molecular mechanism in cell proliferation. GCs were collected from women with or without endometriosis undergoing IVF or ICSI treatment. All endometriosis patients were diagnosed by laparoscopy or laparotomy, and control patients were limited to male factor or tubal disease and had a normal ovarian reserve. Quantitative real-time PCR (qRT-PCR) was used to measure the differential expression levels of MALAT1 lncRNA between endometriosis patients and controls. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic values of MALAT1 in endometriosis. In the KGN cell line, MALAT1 was knocked down with locked nucleic acid GapmeRs. Cell counting kit-8 assays, ethynyl-2-deoxyuridine assays and flow cytometry were used to study the role of MALAT1 in cell proliferation and cell-cycle progression, and western blotting was performed to detect the potential underlying mechanism. We first found that MALAT1 lncRNA was significantly down-regulated in endometriosis GCs and was associated with the antral follicle count (R = 0.376, P < 0.001 versus control). In addition, MALAT1 lncRNA levels were significantly lower in the GCs of infertile women with advanced stages of endometriosis (P = 0.01 versus control). The ROC curves illustrated strong separation between all the endometriosis patients and the control group (AUC: 0.705; 95% CI: 0.606-0.804; P < 0.001), Stage I-II and control group (AUC: 0.651; 95% CI: 0.536-0.767; P = 0.016), and Stage III-IV and control group (AUC: 0.827; 95% CI: 0.718-0.936; P < 0.001). MALAT1 lncRNA was primarily localized in the nuclei of GCs. We found a negative correlation between MALAT1 lncRNA and P21 mRNA in the GCs from patients (R = -0.628; P < 0.001). MALAT1 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression. In addition, MALAT1 knockdown induced an increase in both the mRNA and protein levels of P21, and of P53, phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated c-Jun N-terminal protein kinase (p-JNK) protein levels, as well as causing a decrease in cyclin dependent kinase 2 (CDK2), cyclin D1 and p-P38 MAPK protein levels. Furthermore, inhibition of the ERK/MAPK pathway with U0126, the up-regulation of p-ERK1/2, P21 and P53, and the down-regulation of CDK2 and cyclin D1 by the knockdown of MALAT1 were all attenuated by MALAT1 knockdown. Therefore, MALAT1 may regulate GC proliferation through P21/P53-dependent control of the cell cycle, and the ERK/MAPK pathway participates in this process. None. The hormonal treatment used in IVF and surgical removal of endometriotic lesions may have altered MALAT1 expression in GCs. The ovarian granulosa-like tumor cell line, KGN, was used for further functional and mechanistic studies due to the difficulties in obtaining human GCs in sizable amounts and maintaining primary cultures. Our finding represents the first example of an lncRNA-based mechanism in endometriosis GCs. Women with endometriosis show altered MALAT1 expression levels in GCs that may impair fertility by regulating the function of GCs. Therefore, analysis of MALAT1 and its molecular mechanisms of action provide new insights into the pathogenesis of endometriosis and its associated infertility. This work was supported by the National Natural Science Foundation of China (grant number: 81671524) and the National key research and development program of China (grant number: 2017YFC1001100). The authors declare there is no conflict of interest.

Vascular endothelial growth factor genetic polymorphisms at +405C/G and -460 C/T and the association with advanced stages of endometriosis

Purpose of investigation: Endometriosis is a common gynecologic disease, with a genetic component, a series of studies involving different vascular endothelial growth factor (VEGF) genetic variants in endometriosis pathogenesis. In this study, the authors aimed to describe the presence of VEGF genetic polymorphisms in relationship with endometriosis, to evaluate their relationship with VEGF serum levels, and to investigate its impact on endometriosis susceptibility. Materials and Methods: The authors studied the frequency of alleles, genotypes, and haplotypes of VEGF +405 C/G and -460 C/T genetic polymorphisms in patients with endometriosis, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: This study did not find any significant relationship between the presence of mutant allele and endometriosis. Regarding VEGF serum levels and the presence of a different allele, there was also no statistically significant difference. Conclusion: This research shows that VEGF +405 C/G and -460 C/T genetic polymorphisms are not associated with advanced endometriosis, and VEGF serum levels did not correlate significantly in relationship with the presence of a different allele and/or genotypes, thus suggesting no involvement for this polymorphism in the pathogenesis of endometriosis.

Correlation between serum and peritoneal fluid glutathione S-transferases T1 concentration with different stages of endometriosis

Abstract Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Ectopic endometrial cell proliferation and chronic inflammation in endometriosis were shown to be associated with oxidative stress (OS) induction. OS is a condition in which reactive oxygen species (ROS) overproduction and antioxidant deficiency cause a shift in oxidant/antioxidant balance. Glutathione S-transferases (GSTs) comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The aim of this project was to study the concentrations of GSTT1 in the serum and peritoneal fluid (PF) of patients with different stages of endometriosis. Frothy two PF and serum from normal and 152 from different stages of patients with endometriosis (stage I: n = 30, stage II: n = 39, stage III: n = 43 and stage IV: n = 40) were included in this study. The level of GSTT1 in the serum was determined by enzyme linked immunosorbent assay (ELISA). The results showed the presence of GSTT1 in all serum and peritoneal fluid samples, while, starting from stages I to IV endometriosis, a significant decrease in GSTT1 concentration was seen as compared to controls. It is concluded that levels of GSTT1 is negatively correlated with advanced stages of endometriosis. It is also suggested that the detection of serum and/or peritoneal fluid GSTT1 concentration may be valuable in the classifying of endometriosis.

CCDC22 gene polymorphism is associated with advanced stages of endometriosis in a sample of Brazilian women

Based on the assumption that genetic factors are involved in the etiology of endometriosis, this study aimed to investigate the possibility of rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), and rs2294021 (CCDC22 gene) polymorphisms being associated with the occurrence of this disease in a sample of Brazilian women. We conducted a case-control study with 100 women with histological confirmation of endometriosis (endometriosis group) and 100 women submitted to laparoscopy for benign disorders, in whichthe absence of endometriosis was confirmed (control group). All samples were genotyped by real-time PCR technique for rs498679, rs1799964, rs3024496, and rs2294021 polymorphisms. No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs498679 (TLR4 gene), rs1799964 (TNF-α gene), rs3024496 (IL-10 gene), neither when comparing endometriosis subgroups (I-II versus III-IV). On the other hand, significant difference between stages I-II and III-IV of the disease was found in genotypic and allelic frequencies for the rs2294021 (CCDC22 gene) SNP (p=0.048 and p=0.017, respectively). Our results suggest that the rs2294021 (CCDC22 gene) polymorphism could be associated with increased susceptibility to endometriosis in Brazilian women when the allele C is present. In order to clarify this result, further studies should be conducted on a larger population.

Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options.

Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosis have lower success rates with IVF.

Detecting Endometriosis in Adolescents

Endometriosis is characterized by the presence of endometrial glands and stroma external to the uterus. Up to 17% of postmenarcheal females and nearly 40% of adolescents with chronic pelvic pain are found to have endometriosis. While endometriosis traditionally was thought to be a disease of adulthood, two-thirds of adult women with endometriosis report symptoms beginning before 20 years of age. While endometriosis in adults often presents with cyclic pelvic pain, dysmenorrhea, dyspareunia, infertility, and ovarian lesions, such predictive signs and symptoms are rare in the adolescent. Endometriosis in adolescents is no exception and is certainly a common subject for debate in the relevant circles. These controversies relate to its prevalence, natural course and treatment. Diagnostic delay represents a major problem for endometriosis patients including adult women and adolescent girls. Symptomatic endometriosis should be detected at an early stage, if required also during adolescence, as a longer delay before surgical diagnosis is associated with more advanced stages of endometriosis and with a higher likelihood of fertility problems. Therefore, understanding the origins and progression of adolescent endometriosis is needed to screen all female adolescents and to identify female adolescents at risk to develop endometriosis. Here, I present 1) origins and prevalence of adolescent endometriosis, 2) pathophysiology and risk factors of adolescent endometriosis, and 3) clinical course, diagnosis and treatment of adolescent endometriosis.

IMMUNOLOGICAL ASPECTS OF ENDOMETRIAL DISEASE

Background: Immunological processes involving peritoneal macrophages could play a critical role in pathophysiology of external genital endometriosis. Aim: To assess levels of MCP-1, RANTES, and C-reactive protein and to identify their correlations with endometriosis. Materials and methods: Seventy two patients were evaluated: 26 healthy controls and 46 with endometriosis. Patients were divided into groups as follows: 17 with superficial endometriosis, 18 with endometriomas and 11 with deep infiltrative endometriosis. All patients underwent a laparoscopy during the proliferative phase of the cycle; levels of peritoneal and serum MCP-1, RANTES and C-reactive protein were measured using standard ELISA assays. Results: There were positive correlations between serum MCP-1 (p = 0.03) and C-reactive protein(p = 0.045) and severity of endometriosis, that could indicate malfunctioning of peritoneal macrophages in advanced stages of endometriosis. Conclusion: MCP-1 and C-reactive protein levels in peripheral blood can be used as markers of endometriosis activity.

The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis.

Aim of the studyAim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis.Material and methodsIL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored.ResultsInterleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ2 = 0.496, and χ2 = 0.928, OR = 1.3636, CI: 0.725-2.564).ConclusionsThe results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism.

A Multivariate Analysis of Correlation between Severity and Duration of Symptoms, Patient Profile and Stage of Endometriosis

Background: Endometriosis is an important cause of infertility and chronic pelvic pain. Our study aims to understand the cause and effect relationship of endometriosis with these two clinical presentations. Objectives: 1) To study the correlation between stage of endometriosis with pain and infertility; 2) To evaluate role of transvaginal ultrasound for diagnosis of endometriosis using laparoscopic diagnosis as gold standard. Methodology: Total of 89 women presenting with infertility and or pain and with laparoscopic findings of endometriosis were included in the study. The results were analysed by logistic regression. Results: The mean age of women was 29.67 years. Seventy three percent of patients had moderate to severe disease while 31.46% of patients with endometriosis were infertile. Symptom of pain could be categorised as dysmenorrhea (71.47%), dyspareunia (41.5%) and dyschezia (15.7%). There was no association of endometriosis stage with the pain type, duration of symptoms. Transvaginal ultrasound seems a reliable test for diagnosis of ovarian endometriosis and advanced stage disease. 87.5% of patients with ovarian endometrioma had advanced disease (higher than Stage II rAFS). Conclusion: No correlation was found between the stage of endometriosis and severity of symptoms. Presence of endometrioma on USG was associated with advanced stage of endometriosis.