Follitropin delta combined with menotropin in patients at risk for poor ovarian response during in vitro fertilization cycles: a prospective controlled clinical study.

BACKGROUND: The maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 µg (180 IU), according to the algorithm developed by the manufacturer, and based on patient's ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL. METHODS: This study involved a prospective intervention group of 44 women who received 12 µg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 µg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome. RESULTS: Women who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001). CONCLUSIONS: In women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 µg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely. TRIAL REGISTRATION: U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm ).

Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles.

OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Higher Oxidative Stress in Endometriotic Lesions Upregulates Senescence-Associated p16ink4a and ß-Galactosidase in Stromal Cells.

Endometriosis affects a significant proportion of women worldwide; however, no definitive cure for this disease has been discovered to date. Oxidative stress promotes endometriotic lesion maintenance in the peritoneal cavity in women. Furthermore, there is evidence of the mitogen-activated protein kinase (MAPK) signaling pathway and senescence involvement in the physiopathogenesis of endometriosis. Reactive oxygen species (ROS) cause oxidative damage and are expected to trigger senescence in the endometrium while also causing alterations in MAPK signaling. However, the role of ROS in the senescence-associated phenotype in endometriosis remains unknown. In this context, this study attempted to delineate the pathways linking ROS to senescence in endometrial and endometriotic lesions of healthy individuals and those with endometriosis. Our results indicate a higher presence of ROS in endometriotic lesions, and the upregulation of MAPK. Furthermore, we show that endometriotic lesions in stromal cells stimulated with hydrogen peroxide develop more senescence traits than eutopic and non-endometriosis endometrium. Overall, endometriotic cells respond differently to extracellular distress. Our contribution to further research in this field contributed to the roadmap of endometriosis' search for alternative treatments.

Cervical Cancer-Related Knowledge, Attitudes, Practices and Self-Screening Acceptance Among Patients, Employees, and Social Media Followers of Major Brazilian Hospital.

BACKGROUND: Brazil has a high burden of cervical cancer, even though it is preventable, traceable and treatable. Hence, this study evaluated levels of knowledge, attitudes and practices (KAP) related to cervical cancer screening and diagnosis and acceptance of self-screening techniques among women aged 24 and greater. METHODS: A cross-sectional KAP survey was administered to n = 4206 women and spanned questions relating to cervical cancer, HPV, speculum, Pap test and colposcopy. Questionnaire was disseminated through a major hospital's social media platforms, intranet and gynecologic-oncology clinics. Logistic regressions evaluated associations between sociodemographic characteristics and knowledge, attitudes, and preventative behaviors against cervical cancer. Participants indicated willingness to try DNA-HPV self-sampling and cervix self-visualization (self-colposcopy). FINDINGS: Participants were mostly white individuals (70.5%) with higher education and from social classes A and B. They demonstrated superior levels of KAP than described in the literature, with over 57.8% having answered 80+% of questions correctly. KAP scores were predicted by social class, educational attainment, race, history of premalignant cervical lesions and geographic location. About 80% and 63% would be willing to try DNA-HPV self-sampling and cervix self-visualization, respectively. Interest in self-screening was associated with adequate attitude (OR = 1.85) and inadequate practice (OR = .83). INTERPRETATION: Adequate KAP are fundamental for the successful implementation of a self-screening program. Participants were interested in methods that provide them with greater autonomy, control and practicality. Self-screening could address barriers for under-screened women such as shame, discomfort, distance from clinics and competing commitments, enabling Brazil to reach the WHO's cervical cancer elimination goals. It could also decrease excess medical intervention in over-screened populations by promoting shared decision-making.

Graft-versus-host disease in the female genital tract: a prospective cohort study.

BACKGROUND: Graft-versus-host disease (GVHD) is the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD in the female genital tract can cause sinusorrhagia, dyspareunia, synechia, and even complete vagina occlusion. PURPOSE: This prospective study aimed to evaluate the clinical characteristics and effects of preventive and prompt treatment for genital GVHD in females undergoing HSCT (n = 40). RESULTS: Genital GVHD was diagnosed in 11 of 40 patients (27.5%), and the most common complaint was vaginal dryness (54.6%). The majority of patients (63.6%) presented mild genital GVHD (clinical score 1), with interlabial fissures and lichen-like lesions, while a minority of patients (9.1%) presented advanced genital GVHD (clinical score 3) with the fusion of the small and large lips. The median time of onset of genital GVHD signs was 10 months after HSCT, concomitant with GVHD in the skin and oral cavity. Personalized and topical therapy was effective in most cases (81.8%), and no patient required surgical intervention. CONCLUSION: We confirmed that female genital GVHD affects approximately one-third of females undergoing HSCT, highlighting the importance of periodic gynecological monitoring for early detection and treatment to improve care for these females.

Altered p16Ink4a, IL-1ß, and Lamin b1 Protein Expression Suggest Cellular Senescence in Deep Endometriotic Lesions.

Endometriosis causes immunological and cellular alterations. Endometriosis lesions have lower levels of lamin b1 than the endometrium. Moreover, high levels of pro-inflammatory markers are observed in the peritoneal fluid, follicular fluid, and serum in endometriosis lesions. Thus, we hypothesized that the accumulation of senescent cells in endometriosis tissues would facilitate endometriosis maintenance in an inflammatory microenvironment. To study senescent cell markers and the senescence-associated secretory phenotype (SASP) in endometriosis lesions, we conducted a cross-sectional study with 27 patients undergoing video laparoscopy for endometriosis resection and 19 patients without endometriosis. Endometriosis lesions were collected from patients with endometriosis, while eutopic endometrium was collected from patients both with and without endometriosis. Tissues were evaluated for senescence markers (p16Ink4a, lamin b1, and IL-1ß) and interleukin concentrations. The expression of p16Ink4a increased in lesions compared to that in eutopic endometrium from endometriosis patients in the secretory phase. In the proliferative phase, lesions exhibited lower lamin b1 expression but higher IL-4 expression than the eutopic endometrium. Further, IL-1ß levels were higher in the lesions than in the eutopic endometrium in both the secretory and proliferative phases. We believe that our findings may provide targets for better therapeutic interventions to alleviate the symptoms of endometriosis.

A systematic review of toll-like receptors in endometriosis.

INTRODUCTION: The pathogen-associated molecular patterns and the danger-associated molecular patterns are possibly responsible for the activation of the inflammatory process in endometriosis through the activation of toll-like receptors (TLRs). OBJECTIVE: The aim of this systematic review was to critically analyze the findings of published articles on TLRs in endometriosis. METHODS: The keywords used were "endometriosis" and "toll-like" and the search was performed in Pubmed, Scielo and Lilacs databases. This study followed the PRISMA guidelines and the risk of bias of articles was conducted by Newcastle-Ottawa scale (NOS). RESULTS: Overall, the studies analyzed in this review point toward an increased expression of TLRs two, four and nine in women with endometriosis. Among all TLRs, TLR4 was the most cited receptor. CONCLUSION: Despite the evidence demonstrating elevated TLR levels in endometriosis, the relationship with the disease is still unclear and needs to be clarified in further studies about innate immune response.

Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

Endometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are related to its multifactorial nature, a condition that hinders the recreation of its pathology and the identification of clinically relevant metrics to assess drug efficacy. In this review, we report and comment endometriosis models and how they have led to new therapies. We envision a roadmap for endometriosis research, integrating Artificial Intelligence, three-dimensional cultures and organ-on-chip models as ways to achieve better understanding of physiopathological features and better tailored effective treatments.

The Effect of Rutin and Extracts of Uncaria guianensis (Aubl.) J. F. Gmeland on Primary Endometriotic Cells: A 2D and 3D Study.

There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two- and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.

Interleukin in endometriosis-associated infertility-pelvic pain: systematic review and meta-analysis.

The objective is to study the significance of altered interleukin levels in endometriosis-related infertility or pelvic pain. The present systematic review and meta-analysis includes a discussion on the roles of interleukin in the physiopathology of endometriosis-associated infertility and/or pelvic pain. We included all studies in which interleukins in peritoneal fluid, follicular fluid or serum from patients were measured and that correlated the findings with either peritoneal or deep endometriosis-associated infertility or pelvic pain. For the meta-analysis, we selected studies on the following cytokines: interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8). Endometriosis is a chronic inflammatory disease. Inflammatory processes clearly participate in the etiology of endometriosis. Cytokines are mediators of inflammation, and increase in their concentration in plasma or other body fluids signals the presence and extent of tissue lesions. A number of studies have reported on the association between higher cytokine levels and progression or maintenance of endometriosis and coexisting infertility or pelvic pain. The results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility. Such association was not found for endometriosis-associated pain. In spite of accumulated evidence on the association of pro-inflammatory cytokines and endometriosis, it still is not clear if and how these mediators participate in the physiopathology of endometriosis-associated infertility or pelvic pain, in part due to poor quality of the evidence established in the vast majority of interleukins and challenges in endometriosis research reproducibility. In summary, the results of the analyses support that an association exists between elevated serum IL-6 and/or IL-8 concentrations and the occurrence of endometriosis-associated infertility.

Interleukin-15 and Interleukin-7 are the Major Cytokines to Maintain Endometriosis.

OBJECTIVE: The objective of this study was to evaluate cytokines related to natural killer and T-regulatory cells in endometriotic lesions, peritoneal fluid (PF) and the peripheral blood (PB) of patients with deep infiltrative endometriosis. STUDY DESIGN: A case-control study was conducted in a tertiary referral hospital. Sixty-four consecutive patients after laparoscopy were divided into 2 groups: with endometriosis (Group A - n = 32) and without endometriosis (Group B - n = 32). MAIN OUTCOME MEASURES: Interleukin (IL)-2, IL-4, IL-7, IL-10, IL-12, IL-15, transforming growth factor ß1, and IFNγ concentration was measured using a LuminexTM multiplex suspension bead array. Tissues from endometriotic lesions of patients with endometriosis and from eutopic endometrium were evaluated, as well as PF and PB of all patients. RESULTS: Compared to the other analyzed groups, IL-15 concentration was significantly higher in the ectopic endometrium and IL-7 in the eutopic endometrium of the endometriosis group (p < 0.05). Compared to endometriosis group, IFNγ, IL-7, and IL-15 were observed to be significantly higher in the PF of the control group, and IL-10 was lower in the control group (p < 0.05). In PB, compared to endometriosis group, IL-4, IL-10, IL-12, IL-15, and IFNγ concentrations were significantly higher in the control group (p < 0.05). CONCLUSIONS: Our hypothesis is that deep endometriosis is a disease out of control. This disease's nature is of progression and invasion of adjacent structures, and proof of this disease state is the disorganized secretion of cytokine regulation and inflammation, which seem to be among the factors responsible for the maintenance of the disease.

Validation of Laser Capture Microdissection Protocol in Endometriosis Studies.

Background and Objectives: The presence of endometrial-like tissue outside the uterine cavity is a key feature of endometriosis. Although endometriotic lesions appear to be histologically quite similar to the eutopic endometrium, detailed studies comparing both tissues are required because their inner and surrounding cellular arrangement is distinct. Thus, comparison between tissues might require methods, such as laser capture microdissection (LCM), that allow for precise selection of an area and its specific cell populations. However, it is known that the efficient use of LCM depends on the type of studied tissue and on the choice of an adequate protocol. Recent studies have reported the use of LCM in endometriosis studies. The main objective of the present study is to establish a standardized protocol to obtain good-quality microdissected material from eutopic or ectopic endometrium. Materials and Methods: The main methodological steps involved in the processing of the lesion samples for LCM were standardized to yield material of good quality to be further used in molecular techniques. Results: We obtained satisfactory results regarding the yields and integrity of RNA and protein obtained from LCM-processed endometriosis tissues. Conclusion: LCM can provide more precise analysis of endometriosis biopsies, provided that key steps of the methodology are followed.

Polymorphisms of mitochondrial DNA control region are associated to endometriosis.

PURPOSE: Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis. METHODS: Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence. RESULTS: The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups. CONCLUSION: mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.

Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis?

PROPOSE: Endometriosis is a benign disease characterized by implantation and the growth of endometrial tissue outside the uterine cavity and it shares similarities with cancer. Lamin B1, p16 and p21 play a role on cell cycle regulation, development, cell repair and its activities are related to cancers. Considering the similarities between endometriosis and cancer, the aim of the present cross-sectional study is to detect p16, p21 and Lamin B1 in the ectopic endometrium of patients with endometriosis (n = 8) with eutopic (n = 8) and control endometrium (n = 8) and relate them to the maintenance and development of endometriosis. METHODS: Biopsies were obtained from both eutopic and ectopic, from deep infiltrating lesions, endometrium frozen and used for immunofluorescent (p16) or immunohistochemistry procedures (p16, p21, lamin B1). RESULTS: Detected higher lamin B1 in the eutopic endometrium when compared with ectopic endometrium, with no differences between endometriosis tissue with control endometrium. Similar presence of p16 in all groups of patients and no p21 detection was observed. CONCLUSION: We observed reduced detection of lamin B1 in the ectopic endometrium raising the possibility that the presence of senescent cells might be contributing to the maintenance and progression of endometriosis by apoptosis resistance and peritoneal stress inherent of the disease.

Acute genital ulcers: keep Lipschütz ulcer in mind.

AIM: Lipschütz ulcers (LU) were first described as rare vulvar ulcerations that affect adolescents without previous history of sexual contact. However, more LU patients have been identified in acute genital ulcers (AGU) services in Europe. PURPOSE: To review cases of AGU and analyze the occurrence of LU in the Ob/Gyn Emergency Department of a Brazilian private hospital, using the currently used diagnostic criteria. METHODS: All female patients who sought our service with AGU complaints from January 2009 to July 2015 were selected and had their medical records reviewed, considering the clinical data and some diagnostic criteria, that included: < 20 years old, first AGU episode, sudden onset, absence of sexual contact 3 months before onset and the absence of immunodeficiency. RESULTS: 273 patients eligible for analysis were identified according to the criteria and 12 (4.39%) of them were identified with the possible diagnosis of LU. By applying less restrictive criteria that allowed the inclusion of patients of any age and sexual status, 98 were identified (35.89%). CONCLUSIONS: Despite being described as a rare pathology, ours and previous results indicate a considerable number of AGU cases, suggesting that LU should be better known and considered for differential diagnosis.

mRNA levels of low-density lipoprotein receptors are overexpressed in the foci of deep bowel endometriosis.

STUDY QUESTION: Is mRNA expression of LDL receptors altered in deep bowel endometriotic foci? SUMMARY ANSWER: mRNA expression of LDL receptors is up-regulated in deep bowel endometriotic foci of patients with endometriosis. WHAT IS KNOWN ALREADY: Several studies have demonstrated the overexpression of low-density lipoprotein receptors in various tumour cell lines and endometriosis has similar aspects to cancer, mainly concerning the pathogenesis of both diseases. This is the first study we know of to investigate lipoprotein receptors expression in deep endometriosis with bowel involvement. STUDY DESIGN, SIZE, DURATION: During 2014-2015, an exploratory case-control study was conducted with 39 patients, including 20 women with a histological diagnosis of deep endometriosis compromising the bowel and 19 women without endometriosis who underwent laparoscopic tubal ligation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were collected on the day of surgery for lipid profile analysis, and samples of endometrial tissue and of bowel endometriotic lesions were also collected. The tissue samples were sent for histopathological analysis and for LDL-R and LRP-1 gene expression screening using quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with deep endometriosis had lower LDL-cholesterol than patients without the disease (119 ± 23 versus 156 ± 35; P = 0.001). Gene expression analysis of LDL receptors revealed that LDL-R was more highly expressed in endometriotic lesions when compared to the endometrium of the same patient but not more than in the endometrium of women without endometriosis (0.027 ± 0.022 versus 0.012 ± 0.009 versus 0.019 ± 0.01, respectively; P < 0.001). LRP-1 was more highly expressed in endometriotic lesions, both when compared with the endometrium of the same patient and when compared with the endometrium of patients without the disease (0.307 ± 0.207 versus 0.089 ± 0.076 and versus 0.126 ± 0.072, respectively; P < 0.001). The study also showed that LDL-R gene expression in the endometrium of women with endometriosis was higher during the secretory phase of the menstrual cycle (P = 0.001). LRP-1 gene expression was increased during the secretory phase in the endometrium of women without the disease (P = 0.008). LIMITATIONS, REASONS FOR CAUTION: In the endometriotic lesions, the presence of fibrosis is substantial, restricting access to the stromal and glandular components of the lesion. Despite that, we found that LDL receptor mRNA was overexpressed. Future studies may perform laser microdissection to isolate the area of interest in the target tissue, excluding fibrosis contamination. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the feasibility of LDL-R targeted therapy in the treatment of deep endometriosis. STUDY FUNDING/COMPETING INTERESTS: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2011/17245-0). The authors have no conflicts of interest to declare.

Endometriosis doubles the risk of sexual dysfunction: a cross-sectional study in a large amount of patients.

INTRODUCTION: Endometriosis affects several aspects of a woman's life, including sexual function, but which specific aspects of sexual function remains unclear. METHODS: A cross-sectional study was performed involving 1001 women divided into two groups, according to the presence or absence of endometriosis. We assessed sexual function, anxiety and depression of patients and correlated these findings with symptoms, locations and types of endometriosis and the affected domains of sexual function. Eighteen completed the forms incorrectly, 294 women (29.9%) were excluded due to severe anxiety and depression. One hundred and six patients had symptoms that could have any relation to endometriosis, so they were also excluded. The final cohort was composed of 254 patients with endometriosis and 329 patients without the disease. Sexual function score was assessed using the female sexual quotient (FSQ); Beck inventories were used to assess anxiety and depression. RESULTS: Patients with endometriosis were affected in all phases of sexual response: desire, sexual arousal, genital-pelvic pain/ penetration and orgasm/ sexual satisfaction. In the overall assessment, 43.3% of patients with endometriosis had sexual dysfunction, while the population without endometriosis sexual dysfunction occurred in 17.6% of women. CONCLUSIONS: Patients with endometriosis have more than twice sexual dysfunctions as compared to women without the disease.

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

PURPOSE: 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. METHODS: 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 which the absence of endometriosis was confirmed (control group). All samples were genotyped by real-time PCR technique for rs498679, rs1799964, rs3024496, and rs2294021 polymorphisms. RESULTS: 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). CONCLUSION: 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.

Polymorphisms of ICAM-1 and IL-6 genes related to endometriosis in a sample of Brazilian women.

PURPOSE: This study investigated the possibility of K469E (rs5498) and G241R (rs1799969) polymorphisms, in ICAM-1 gene, and G634C (rs1800796), in IL-6 gene, being associated with the occurrence of endometriosis in a sample of Brazilian women. METHODS: We genotyped 200 women (100 in control group and 100 in endometriosis group) by PCR-RFLP technique for G634C, K469E, and G241R polymorphisms. RESULTS: No significant difference was observed in genotypic frequency between control and endometriosis groups for G634C and K469E polymorphisms (p = 0.61 and p = 0.22, respectively). In addition, no significant difference between stages I-II and III-IV of the disease was found for both SNPs (p = 0.63 and p = 0.24, respectively). All individuals were wild homozygotes for G241R polymorphism. CONCLUSION: This study suggests that polymorphisms K469E, G241R, and G634C are not associated with increased susceptibility to endometriosis in Brazilian women.