Influence of interleukin-8 polymorphism on endometriosis-related pelvic pain.

Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis' development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m2) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis' prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29-0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis' painful symptoms, preventing its complications, and allowing an individualized treatment.

DROSHA rs10719 and DICER1 rs3742330 polymorphisms in endometriosis and different diseases: Case-control and review studies.

OBJECTIVE: DROSHA and DICER1 enzymes participate in the main stages of microRNA synthesis. Polymorphisms can influence mRNAs stability and genes expression, and hence affect the binding of miRNAs. Thus, the present study evaluated the association of DROSHA and DICER1 polymorphisms in the development of endometriosis and other diseases. METHODS: A total of 240 endometriosis cases and 242 controls were genotyped for the DROSHA rs10719 G > A and DICER1 rs3742330 A > G polymorphisms using the TaqMan system. The association between polymorphisms and endometriosis was estimated by binary logistic regression. A literature review was also performed including all published articles (PubMed database) until December 2020, regarding the association of the studied polymorphisms and different diseases. RESULTS: DICER1 rs3742330GG was only found in endometriosis cases (2.1%) and deep infiltrative endometriosis (DIE) (2.5%). The DICER1 rs3742330GG genotype was significantly associated with endometriosis (P < 0.05), suggesting a tendency to present an increased risk for disease. DROSHA rs10719A and DICER1 rs3742330G allele frequencies varied among populations (6%-79% and 10.2%-55.1%, respectively). In the Brazilian population, the frequencies of these alleles were 42.3% and 7.3%, respectively. Both polymorphisms were risk factors for nonsyndromic orofacial clefts, tuberculosis, stroke ischemia and mortality after stroke, recurrent idiopathic pregnancy loss, and some types of cancer. Moreover, the DICER1 rs3742330 polymorphism was a protective factor for precancerous cervical lesions, different types of cancer and tuberculosis. CONCLUSIONS: The results suggest that only the DICER1 rs3742330 A > G polymorphism may be associated with susceptibility to endometriosis. The frequencies of both polymorphisms were significantly different among populations, and there were discrepancies in the risk associations with the development of diseases.

A dismenorreia e suas consequências em estudantes universitárias no Rio de Janeiro / Dysmenorrhea and its consequences in university students in Rio de Janeiro

Objetivo: Avaliar a prevalência da dismenorreia e suas consequências em uma população universitária. Métodos: Trata-se de um estudo descritivo, transversal, com 207 mulheres entre 18 e 46 anos de idade, universitárias. Os sujeitos da pesquisa responderam a um questionário desenvolvido para esse estudo. Resultados: A prevalência global de dismenorreia, entre as universitárias, foi de 84,1%; dessas, 58,6% classificaram a dor em intensidade leve a moderada e 41,4%, em intensa. O absenteísmo escolar e a dificuldade para se concentrar nos estudos durante o período menstrual foram significativamente influenciados pela dismenorreia intensa. Entre as estudantes, 60,9% deixaram de fazer atividades físicas ou de lazer e 41% tinham dificuldade para se concentrar e estudar devido à dismenorreia. Conclusão: A dismenorreia tem uma elevada prevalência na população universitária, contribuindo para um aumento do absenteísmo escolar e para um prejuízo social. A maioria utiliza a automedicação e poucas procuram atendimento médico eletivo com a finalidade de resolver esse problema.(AU)

Objective: Evaluate the prevalence of dysmenorrhea and its consequences in a university population. Methods: A cross-sectional descriptive study with 207 female university students between 18 and 46 years. Data collection was performed through a specific questionnaire developed for this study. Results: The overall prevalence of dysmenorrhea among university was 84.1%, of which 58.6% classified the pain intensity as mild to moderate and 41.4% as severe. School absenteeism and a difficulty to concentrate on studies during the menstrual period were significantly influenced by the presence of severe dysmenorrhea, with 60.9% of students interrupting some physical or leisure activity, and 41% reporting that they had difficulty concentrating and studying due to the dysmenorrhea. Conclusion: Dysmenorrhea has a high prevalence in the university population, contributing to a significant increase in school absenteeism and impairing social life. Most students use self-medication and few seek elective medical care to resolve this problem.(AU)

Epidemiological profile of women with endometriosis: a retrospective descriptive study / Perfil epidemiológico de mulheres com endometriose: um estudo descritivo retrospectivo

Abstract Objectives: to describe the epidemiological and clinical profile of women with endometriosis and to determine the association with the prognostic characteristics of the disease. Methods: retrospective descriptive study involving 237 women attended at two referral hospitals for endometriosis, between 2011 and 2017. Associations between groups were estimated using logistic regression models. Results: most women (65.4%) were of reproductive age (29-39 years), with a body mass index in the range of 18.5-24.9 kg/m2 and a high prevalence (23-81%) of symptoms of the disease, with 49.5% being infertile. The average time of diagnosis was 5 years. Ovarian endometrioma and/or deep infiltrative endometriosis (DIE) were the most frequent type of endometriosis (87%), and 59% of patients were in the III/IV stage of the disease. Approximately 87% of women with surgical diagnosis were aged over 30, married (70%) and had lower parity. Dyspareunia was negatively associated with superficial endometriosis. Infertility was positively associated with age (30-39 years) and DIE in the uterine tubes; dysmenorrhea with DIE in the uterosacral ligament; cyclic intestinal complaints with DIE in the rectosigmoid and intestine, and with DIE classification and III/IVstage. Conclusions: knowing the epidemiological and clinical profile of Brazilian women with endometriosis can help in diagnosis and treatment planning.

Resumo Objetivos: descrever o perfil epidemiológico e clínico de mulheres com endometriose e determinar a associação com as características prognósticas da doença. Métodos: estudo descritivo retrospectivo envolvendo 237 mulheres atendidas em dois hospitais de referência em endometriose, no período entre 2011 e 2017. As associações entre os grupos foram estimadas utilizando modelos de regressão logística. Resultados: a maioria das mulheres (65,4%) estava em idade reprodutiva (29-39 anos), com índice de massa corporal entre 18,5-24,9 kg/m2 e alta prevalência (23-81%) dos sintomas clínicos da doença, sendo que 49,5% eram inférteis. O tempo médio de diagnóstico foi de 5 anos. O endometrioma ovariano e/ou endometriose profunda infiltrativa (EPI) foram os tipos mais frequentes de endometriose (87%), sendo que 59% das pacientes estavam no estágio III/IVda doença. Aproximadamente 87% das mulheres com diagnóstico cirúrgico apresentavam idade acima dos 30 anos, eram casadas (70%) e apresentavam menor paridade. A dispareunia foi associada negativamente à endometriose superficial. A infertilidade foi associada positivamente com a idade (30-39 anos) e com a EPI nas tubas uterinas; a dismenorreia com a EPI no ligamento uterosacral; as queixas intestinais cíclicas com a EPI no retosigmóide e intestino, e com a classificação EPI e estágio III/IV. Conclusões: conhecer o perfil epidemiológico e clínico das mulheres brasileiras com endometriose pode auxiliar no diagnóstico e no planejamento do tratamento.

Role of cytochrome P450 2C19 polymorphisms and body mass index in endometriosis: A case-control study.

OBJECTIVE: To investigate the contribution of CYP2C19 polymorphisms and body mass index (BMI) in the development of endometriosis. STUDY DESIGN: This is a case-control study that includes 356 women (187 cases and 169 controls) recruited from two hospitals in the Brazilian public health system. The genotyping analyses of the CYP2C19*2 and CYP2C19*17 polymorphisms were performed using TaqMan allelic discrimination assays, and the association of the studied polymorphisms with endometriosis was evaluated by multivariate logistic regression. Pearson correlation coefficients were used to investigate the interaction between BMI and CYP2C19 polymorphisms. RESULTS: The variant allele frequencies of CYP2C19*2 were significantly different between cases and controls, and after adjusting for confounding factors, the CYP2C19*2 polymorphism was more frequent in women with endometriosis, considering all cases (CYP2C19*2: OR=1.83; 95% CI=1.17-2.85) and only deeply infiltrating endometriosis (DIE) cases (CYP2C19*2: OR=2.32; 95% CI=1.42-3.77). BMI was significantly lower in endometriosis patients (26.5±4.68) than in controls (27.8±5.65, P<0.02). Among obese women (BMI 30-40), the CYP2C19*2 polymorphism had a greater association with endometriosis (CYP2C19*2: OR=3.27; 95% CI=1.55-6.89). There was a positive correlation between CYP2C19*2 and BMI 30-40 (P=0.004). CONCLUSIONS: The findings of our study suggest that CYP2C19*2 is positively associated with endometriosis and that BMI may have a significant interaction with CYP2C19*2 and the risk of endometriosis.

Combined Effect of the PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis.

Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36.0 ± 7.3 versus 38.0 ± 8.5 respectively, p = 0.023), and they had a lower body mass index (26.3 ± 4.8 versus 27.9 ± 5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4 ± 4.9 versus 6.1 ± 4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2 ± 9.6 versus 27.5 ± 11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2 ± 6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR +331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09-2.72). Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

Objetivo Avaliar a magnitude de associação de polimorfismos nos genes PGR, CYP17A1 e CYP19A1 no desenvolvimento da endometriose. Métodos Este é um estudo retrospectivo do tipo caso-controle, envolvendo 161 mulheres com endometriose (casos) e 179 controles. Os polimorfismos foram genotipados pela reação em cadeia da polimerase em tempo real utilizando o sistema TaqMan. A associação dos polimorfismos estudados com a endometriose foi avaliada pela regressão logística multivariada. Resultados As pacientes com endometriose eram significativamente mais jovens do que os controles (36,0 ± 7,3 versus 38,0 ± 8,5, respectivamente, p = 0,023), apresentaram um índice de massa corporal menor (26,3 ± 4,8 versus 27,9 ± 5,7, respectivamente, p = 0,006), maior tempo médio de duração do fluxo menstrual (7,4 ± 4,9 versus 6,1 ± 4,4 dias, respectivamente, p = 0,03) e menor tempo médio do intervalo entre as menstruações (25,2 ± 9,6 versus 27,5 ± 11,1 dias, respectivamente, p = 0,05). Uma maior prevalência dos sintomas de dismenorreia, dispareunia, dor pélvica crônica, infertilidade, alterações intestinais e urinárias foi observada no grupo casos comparado ao grupo controle. O tempo médio entre o início dos sintomas e o diagnóstico definitivo de endometriose foi de 5,2 ± 6,9 anos. Comparando os dois grupos, não foram observadas diferenças significativas nas frequências alélicas e genotípicas dos polimorfismos PGR +331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A, e nem considerando os sintomas, a classificação e o estadiamento da endometriose. O genótipo combinado PGR +331TT/CYP17A1 -34AA/CYP19A11531AA está associado positivamente com a endometriose (razão de possibilidades [RP] = 1,72; intervalo de confiança de 95% [IC95%] = 1,09­2,72). Conclusões A análise combinada dos polimorfismos PGR-CYP17A1-CYP19A1 sugere uma interação gene-gene na susceptibilidade à endometriose. Estes resultados podem contribuir para a identificação de biomarcadores para o diagnóstico e/ou prognóstico da doença, assim como de possíveis alvos moleculares para um tratamento individualizado.

Combined Effect of the PGR + 331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis / Efeito combinado dos polimorfismos PGR + 331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A no risco de desenvolvimento da endometriose

Abstract Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36.0±7.3 versus 38.0±8.5 respectively, p = 0.023), and they had a lower body mass index (26.3±4.8 versus 27.9±5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4±4.9 versus 6.1±4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2±9.6 versus 27.5±11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2±6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR + 331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR + 331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09-2.72). Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

Resumo Objetivo Avaliar a magnitude de associação de polimorfismos nos genes PGR, CYP17A1 e CYP19A1 no desenvolvimento da endometriose. Métodos Este é um estudo retrospectivo do tipo caso-controle, envolvendo 161 mulheres com endometriose (casos) e 179 controles. Os polimorfismos foram genotipados pela reação em cadeia da polimerase em tempo real utilizando o sistema TaqMan. A associação dos polimorfismos estudados com a endometriose foi avaliada pela regressão logística multivariada. Resultados As pacientes com endometriose eram significativamente mais jovens do que os controles (36,0±7,3 versus 38,0±8,5, respectivamente, p = 0,023), apresentaram um índice de massa corporal menor (26,3±4,8 versus 27,9±5,7, respectivamente, p = 0,006), maior tempo médio de duração do fluxo menstrual (7,4±4,9 versus 6,1±4,4 dias, respectivamente, p = 0,03) e menor tempo médio do intervalo entre as menstruações (25,2±9,6 versus 27,5±11,1 dias, respectivamente, p = 0,05). Uma maior prevalência dos sintomas de dismenorreia, dispareunia, dor pélvica crônica, infertilidade, alterações intestinais e urinárias foi observada no grupo casos comparado ao grupo controle. O tempo médio entre o início dos sintomas e o diagnóstico definitivo de endometriose foi de 5,2±6,9 anos. Comparando os dois grupos, não foram observadas diferenças significativas nas frequências alélicas e genotípicas dos polimorfismos PGR + 331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A, e nem considerando os sintomas, a classificação e o estadiamento da endometriose. O genótipo combinado PGR + 331TT/CYP17A1 -34AA/CYP19A11531AA está associado positivamente com a endometriose (razão de possibilidades [RP] = 1,72; intervalo de confiança de 95% [IC95%] = 1,09-2,72). Conclusões A análise combinada dos polimorfismos PGR-CYP17A1-CYP19A1 sugere uma interação gene-gene na susceptibilidade à endometriose. Estes resultados podem contribuir para a identificação de biomarcadores para o diagnóstico e/ou prognóstico da doença, assim como de possíveis alvos moleculares para um tratamento individualizado.

Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study.

OBJECTIVE: Endometriosis is a multifactorial gynecological disease, whose pathogenesis is crucially dependent on angiogenesis, which is signaled via vascular endothelial growth factor (VEGF) and its receptor (VEGFR2). We hypothesize that single nucleotide polymorphisms (SNPs) in VEGF and VEGFR2 genes may influence the onset and/or the progression of endometriosis. The main aim of this study was to investigate the contribution of VEGF and VEGFR2 SNPs as risk factors for endometriosis, as well as their association with endometriosis symptoms. STUDY DESIGN: A case-control study was conducted, involving 293 endometriosis patients and 223 controls, who were submitted to laparoscopic or laparotomy surgery at hospitals from the Brazilian public health system. Genotyping of VEGF (-2578C>A, -460T>C, -1154G>A, +405G>C and +936C>T) and VEGFR2 (-604T>C, 1192C>T) SNPs was performed by TaqMan real-time polymerase chain reaction. The association between SNPs and endometriosis, deep infiltrating endometriosis (DIE) or endometriosis symptoms was estimated by odds ratios (OR) with their 95% confidence intervals (CI), which were calculated using multivariate logistic regression models. RESULTS: VEGF variant alleles -2578A and -1154A were associated with increased endometriosis risk (OR: 1.39, 95% CI: 1.04-1.87 and OR: 1.63, 95% CI: 1.12-2.37, respectively), whereas VEGF 405C and VEGFR2 1192T were associated with lower risk of endometriosis (OR: 0.66, 95% CI: 0.43-1.00 and OR: 0.58, 95% CI: 0.40-0.84, respectively). The combination of wild-type genotypes of both VEGF -2578C>A and -1154G>A with variant genotypes of both VEGF +405G>C and VEGFR2 1192C>T showed the best protective effect against the development of endometriosis, either considering all cases (OR: 0.33, 95% CI: 0.12-0.89) or only DIE (OR: 0.30, 95% CI: 0.10-0.87). The combination of variant genotypes of VEGF -2578C>A, -1154G>A, +405G>C and VEGFR2 1192C>T was also protective against DIE (OR: 0.67, 95% CI: 0.46-0.96). VEGFR2 1192C>T were associated with reduced cyclical urinary complaints (OR: 0.40, 95% CI: 0.18-0.88). CONCLUSIONS: Our results indicate that VEGF SNPs -2578C>A and -1154G>A increase endometriosis risk, whereas VEGF +405G>C and VEGFR2 1192C>T are protective against disease development, with VEGFR2 1192C>T also reducing cyclical urinary symptoms. The combined analysis of VEGF-VEGFR2 genotypes suggests a gene-gene interaction in endometriosis susceptibility.

Polymorphisms in VEGF and KDR genes in the development of endometriosis: a systematic review / Polimorfismos nos genes VEGF e KDR no desenvolvimento da endometriose: revisão sistemática

Abstract Objectives: to review studies that used case-control design to verify the association of polymorphisms in VEGF and KDR genes in the development of endometriosis. Methods: the systematic review selected articles published until September 1, 2015 from PubMed, MEDLINE, BVS, SciELO databases, considering the following key words: endometriosis and ("polymorphism" or "SNP" or "genetic polymorphism") and ("VEGF" OR "Vascular endothelial growth factor" or "VEGFR-2" or "Vascular endothelial growth factor-2" or "KDR" or "Kinase Insert Domain Receptor"). Results: 106 articles were identified, only 11 were eligible. Discrepant results were observed regarding polymorphisms in VEGF gene in the development of endometriosis, which can be explained by methodological differences, sample size, eligible control type, using the unadjusted risk estimates and the heterogeneity of the studied population. Only one study investigated polymorphisms in KDR gene in the development of endometriosis, however it was ineligible for this review. Conclusions: to avoid discrepancy in the results, we suggest that the ideal control group should be formed by fertile women and free of gynecological diseases. Multicentric studies with adequate design, involving different population besides the combined analysis on polymorphisms in VEGF and KDR genes are still necessary to contribute in the understanding of this disease, which are social, clinical and economical problems.

Resumo Objetivos: revisar os trabalhos que utilizaram o delineamento caso-controle para verificar a associação de polimorfismos nos genes VEGF e KDR no desenvolvimento da endometriose. Métodos: revisão sistemática que pesquisou nas bases de dados PubMed, MEDLINE, BVS, SciELO os artigos publicados até o dia 1 de setembro de 2015, considerando os descritores: endometriosis and ("polymorphism" or "SNP" or "geneticpolymorphism") and ("VEGF" or "Vascular endothelial growth factor" or "VEGFR-2" or "Vascular endothelial growth factor-2" or "KDR" or "Kinase Insert Domain Receptor"). Resultados: identificou-se 106 artigos, sendo 11 considerados elegíveis. Observou-se resultados discrepantes quanto aos polimorfismos no gene VEGF no desenvolvimento da endometriose, podendo ser explicados pelas diferenças metodológicas, pelo tamanho amostral, pelo tipo de controle elegível, pela utilização da estimativa de risco não ajustada e pela heterogeneidade das populações estudadas. Apenas um estudo investigou polimorfismos no gene KDR no desenvolvimento da endometriose, contudo não foi elegível nesta revisão. Conclusões: para evitar as discrepâncias dos resultados observados sugerimos que o grupo controle ideal deva ser formado por mulheres férteis e livres de doenças ginecológicas. Estudos multicêntricos com delineamento adequado, envolvendo diferentes populações, além da análise combinada de polimorfismos nos genes VEGF e KDR ainda são necessários para contribuir no entendimento desta doença que é um problema social, clínico e econômico.

Role of vascular endothelial growth factor polymorphisms (-2578C>A, -460 T>C, -1154G>A, +405G>C and +936C>T) in endometriosis: a case-control study with Brazilians.

BACKGROUND: Endometriosis is regarded as a complex and heterogeneous disease in which genetic and environmental factors contribute to the phenotype. The Vascular Endothelial Growth Factor (VEGF) plays important roles in the pathogenesis of endometriosis. The present study was aimed at investigating the contribution of VEGF polymorphisms as risk factors for the development of endometriosis. This is the first study to evaluate the combined influence of the five most common VEGF polymorphisms. METHODS: This study was conducted at two hospitals from the Brazilian public health system, and comprised 294 women submitted to laparoscopic or laparotomy surgery: 182 patients had a histologically confirmed diagnosis of endometriosis (cases), whereas 112 had no evidence of the disease (controls). The VEGF polymorphisms were determined by TaqMan real-time polymerase chain reaction. The odds ratio (OR) with their 95% confidence intervals (CI) were calculated using an unconditional logistic regression model. RESULTS: Endometriosis patients and controls did not differ regarding age distribution, whereas the body mass index was significantly lower in endometriosis patients, when compared with controls (23.1 ± 3.9 versus 27.3 ± 5.9, P < 0.001). The evaluation of gynecological symptoms, including dysmenorrhea, non-cyclic chronic pelvic pain, dyspareunia and infertility, indicates significantly higher prevalences among endometriosis cases. The variant allele -1154A was significantly associated with endometriosis, either considering all cases (OR: 1.90, 95% CI: 1.23-2.97), deep infiltrating endometriosis (DIE) (OR: 1.83, 95% CI: 1.16-2.90) or moderate and severe endometriosis (stages III-IV) (OR: 1.97, 95% CI: 1.21-3.19). No significant differences were found in allele or genotype distributions of the -2578C > A, -460 T > C, +405G > C and +936C > T polymorphisms between endometriosis cases and controls. A total of six haplotypes were inferred derived from four polymorphisms (-2578C > A, -460 T > C, -1154G > A and +405G > C). There was a protective association between CCGG haplotype and endometriosis, either considering all cases (OR: 0.36, 95% CI: 0.15-0.86), DIE (OR: 0.37 95% CI: 0.15 - 0.90) or stages III-IV (OR: 0.35 95% CI: 0.13 - 0.95). CONCLUSIONS: The present results indicate a positive association between VEGF -1154G > A and the risk of developing endometriosis, whereas the CCGG haplotype may be protective against the development of disease.

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model.

OBJECTIVE: To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis. DESIGN: Pharmacologic interventions in an experimental model of peritoneal endometriosis. SETTING: Research laboratory in the Federal University of Rio de Janeiro. ANIMAL(S): Twenty female Sprague-Dawley rats with experimentally induced endometriosis. INTERVENTION(S): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days. MAIN OUTCOME MEASURE(S): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed. RESULT(S): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2). CONCLUSION(S): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity.

Criopreservação de oócitos: pode ser considerada uma rotina na prática clínica?: uma revisão sistemática / Oocyte cryopreservation: can it be considered a routine in the clinical practice?: a systematic review

Considerando o grande interesse observado, os avanços nas técnicas para preservação da fertilidade feminina e levando em conta que a criopreservação de oócitos é uma atraente estratégia para preservação da fertilidade, foi realizada uma revisão sistemática para comparar a criopreservação de oócitos com outros métodos já estabelecidos para este intuito. Foram buscadas referências em dois bancos de dados (Medline e Lilacs), e identificados 869 estudos, mas nenhum deles conseguiu preencher os critérios de inclusão. Ainda há um longo caminho para este método ser incorporado à prática clínica.

Considering the great interest observed; the advancement of techniques to preserve female fertility and that oocyte cryopreservation is an attractive strategy to fertility preservation, this systematic review was conducted in order to compare the cryopreservation of oocytes with other already established methods. References were searched in two databases (Medline and Lilacs). A total of 869 studies were identified, however none of them could compare oocytes cryopreservation with other techniques to preserve female fertility. There is still a long way to go to integrate it into a routine clinical procedure.

Quando fazer ooforectomia profilática com base em evidências, não em suposições / When to do prophylactic oophorectomy based on scientific evidence, not beliefs

Considerando a importância da prevenção do câncer de ovário para a saúde pública e a falta de meios eficientes para o diagnóstico precoce dessa doença, esta revisão sistemática tem como objetivo avaliar o impacto da ooforectomia profilática sobre o risco de câncer de ovário. Buscamos referências bibliográficas que apresentassem associação entre a ooforectomia bilateral profilática e o câncer de ovário em pacientes sem risco aumentado para a doença em dois bancos de dados (Medline e Lilacs). Identificamos 302 artigos, mas apenas cinco foram incluídos. Somente foi encontrado um estudo em que os casos eram pacientes com ooforectomia bilateral, e o desfecho, câncer de ovário, fato que nos impediu de concluir, com base em evidências, o real papel da ooforectomia bilateral na diminuição do câncer de ovário

Considering the importance of the ovarian cancer prevention for the public health and the absence of effective techniques for the early detection of the disease, this systematic review aims at analyzing the impact of prophylactic oophorectomy on the risk of ovarian cancer. We have searched bibliographic references that studied the association between prophylactic bilateral oophorectomy and ovarian cancer in patients with average risk for this disease in two databases (Medline and Lilacs). We identified 302 articles, but only five of them were included. We only found one study in which there were patients with bilateral oophorectomy, and the outcome was ovarian cancer, what prevented us from concluding, based on evidences, the real role of bilateral oophorectomy in the reduction of ovarian cancer

Avaliação da concordância entre a ultrassonografia transvaginal e a ressonância magnética da pelve na endometriose profunda, com ênfase para o comprometimento intestinal / Evaluation of agreement between transvaginal ultrasonography and magnetic resonance imaging of the pelvis in deep endometriosis with emphasis on intestinal involvement

OBJETIVO: Comparar achados ultrassonográficos e de ressonância magnética na endometriose profunda,com ênfase para o comprometimento intestinal. MATERIAIS E MÉTODOS: Dezoito pacientes entre 23 e 49 anos de idade, com suspeita clínica e exame ginecológico sugestivo de endometriose profunda, foram submetidas a ultrassonografia e ressonância magnética para correlação dos achados. RESULTADOS: A ultrassonografia detectou 40 lesões e a ressonância magnética detectou 53 lesões na pelve. O estudo comparativo entre ultrassonografia e ressonância magnética na detecção das lesões não mostrou diferença estatística significativa (p > 0,19 e p > 0,14, respectivamente). Considerando-se a junção retossigmoide, a ressonânciamagnética detectou uma lesão (5,6%) e a ultrassonografia apontou quatro lesões (22,2%). Nas lesões retais, a ultrassonografia apontou oito lesões (44,4%) e a ressonância magnética, sete lesões (38,9%). CONCLUSÃO: A concordância entre a ressonância magnética e a ultrassonografia não foi boa na junção retossigmoide e no reto, sendo que a ultrassonografia detectou um número maior de lesões nessas localizações, mas identificou número menor de lesões na pelve. Na análise comparativa global entre os dois métodos na detecção das lesões não houve diferença estatística significativa. O baixo custo, a boa tolerabilidadee o fácil acesso tornam a ultrassonografia instrumento diagnóstico valioso na endometriose profunda.

OBJECTIVE: To compare sonographic and magnetic resonance imaging findings in deep endometriosis withemphasis on intestinal involvement. MATERIALS AND METHODS: Eighteen women aged between 23 and 49 years with clinical suspicion and gynecological signs suggestive of deep endometriosis were submitted to ultrasonography and magnetic resonance imaging for correlation between findings. RESULTS:Ultrasonography detected 40 lesions while magnetic resonance imaging detected 53 lesions in the pelvis. A comparative study has not shown any statistically significant intermethod difference in the detection of lesions(respectively p > 0.19 and p > 0.14). In the rectosigmoid junction, magnetic resonance imaging has detected one (5.6%) lesion, while ultrasonography has detected four lesions (22.2%). In the rectum, ultrasonography has detected eight lesions (44.4%), and magnetic resonance imaging has detected seven lesions (38.9%). CONCLUSION: The intermethod agreement has not been good for lesions in the rectosigmoid junction, considering that ultrasonography has detected a higher number of lesions in this region, but a lower number of lesions in the pelvis as compared with magnetic resonance imaging. The global comparative analysis has demonstrated no statistically significant intermethod difference in the detection of lesions. Low cost, good tolerability and high availability make ultrasonography a valuable diagnostic tool in cases of deep endometriosis.

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum.

OBJECTIVE: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium and in three different sites of endometriosis: the ovary, bladder, and rectum. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Thirty women with endometriosis (10 ovarian, 10 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). INTERVENTION(S): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. MAIN OUTCOME MEASURE(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. RESULT(S): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. CONCLUSION(S): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.