Selection of reference miRNAs for RT-qPCR assays in endometriosis menstrual blood-derived mesenchymal stem cells.

Choosing appropriate reference genes or internal controls to normalize RT-qPCR data is mandatory for the interexperimental reproducibility of gene expression data obtained by RT-qPCR in most studies, including those on endometriosis. Particularly for miRNAs, the choice for reference genes is challenging because of their physicochemical and biological characteristics. Moreover, the retrograde menstruation theory, mesenchymal stem cells in menstrual blood (MenSCs), and changes in post-transcriptional regulatory processes through miRNAs have gained prominence in the scientific community as important players in endometriosis. Therefore, we originally explored the stability of 10 miRNAs expressions as internal control candidates in conditions involving the two-dimensional culture of MenSCs from healthy women and patients with endometriosis. Here, we applied multiple algorithms (geNorm, NormFinder, Bestkeeper, and delta Ct) to screen reference genes and assessed the comprehensive stability classification of miRNAs using RefFinder. Pairwise variation calculated using geNorm identified three miRNAs as a sufficient number of reference genes for accurate normalization. MiR-191-5p, miR-24-3p, and miR-103a-3p were the best combination for suitable gene expression normalization. This study will benefit similar research, but is also attractive for regenerative medicine and clinics that use MenSCs, miRNA expression, and RT-qPCR.

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

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

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

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

Gynecological surgery and Covid-19: what is the impact and how should I manage it? / Cirurgia ginecológica e Covid-19: qual impacto e como devo conduzir?

Abstract It is estimated that around 28 million surgeries will be postponed or canceled worldwide as a result of this pandemic, causing a delay in the diagnosis and treatment of more than 2 million cancer cases. In Brazil, both the National Health Agency (ANS) and National Health Surveillance Agency (ANVISA) advised the postponement of elective and non-essential surgeries, causing a considerable impact on the number of surgical procedures that decreased by 33.4% in this period. However, some women need treatment for various gynecological diseases that cannot be postponed. The purpose of this article is to present recommendations on surgical treatment during the COVID-19 pandemic.

Resumo Estima-se que cerca de 28 milhões de cirurgias sejam postergadas ou canceladas nomundo em decorrência desta pandemia, causando atraso no diagnóstico e tratamento de mais de 2 milhões de casos oncológicos. No Brasil, tanto a ANS (Agencia Nacional de Saúde) comoa ANVISA (Agencia Nacional de Vigilância Sanitária) orientaram o adiamento das cirurgias eletivas e não essenciais, tendo um impacto considerável no número de procedimentos cirúrgicos comdiminuição de 33,4% neste período no Brasil.No entanto, algumasmulheres necessitam de tratamento para várias doenças ginecológicas, algumas das quais não podem ser adiadas. O objetivo deste artigo é apresentar recomendações sobre o tratamento cirúrgico durante a pandemia de COVID-19.

Analysis of body composition and pain intensity in women with chronic pelvic pain secondary to endometriosis / Análise da composição corporal e intensidade de dor em mulheres com dor pélvica crônica secundária a endometriose

Abstract Objective To determine the average body composition (percentage of body fat), the anthropometric markers, and the intensity of clinical pain in women with a clinical diagnosis of chronic pelvic pain (CPP) secondary to endometriosis. Methods A case-control study performed with 91 women, 46 of whom with CPP secondary to endometriosis and 45 of whom with CPP secondary to other causes. They underwent an evaluation of the anthropometric parameters by means of the body mass index (BMI), the perimeters (waist, abdomen, hip), and the percentage of body fat (%BF), which were assessed on a body composition monitor by bioimpedance; the intensity of the clinical pain was evaluated using the visual analog scale (VAS), and the symptoms of anxiety and depression, using the hospital's anxiety and depression scale (HAD). Results The groups did not differ in terms of mean age, BMI, %BF or regarding the available waist-to-hip ratio (WHR). The mean intensity of the clinical pain by the VAS was of 7.2 ± 2.06 in the group with CPP secondary to endometriosis, and of 5.93 ± 2.64 in the group with CPP secondary to other causes (p = 0.03), revealing significant differences between the groups. Conclusion We concluded that, despite the difference in the pain score assessed between the two groups, there was no difference regarding body composition and anthropometry.

Resumo Objetivo Determinar a composição corporal média (porcentagem de gordura corporal), os marcadores antropométricos, e a intensidade de dor clínica em mulheres com diagnóstico clínico de dor pélvica crônica (DPC) secundária a endometriose. Métodos Um estudo de caso-controle realizado com 91 mulheres, 46 das quais com DPC secundária a endometriose, e 45 das quais com DPC secundária a outras causas. As pacientes foram submetidas à avaliação dos parâmetros antropométricos por meio do índice de massa corporal (IMC), dos perímetros (cintura, abdômen, quadril), e do percentual de gordura corporal (%GC), que foram avaliados emmonitor de composição corporal por bioimpedância; a intensidade clínica da dor foi avaliada usando-se a escala visual analógica (EVA), e os sintomas de ansiedade e depressão, usando a escala de ansiedade e depressão do hospital (EADH). Resultados Os grupos não diferiram quanto à idade média, ao IMC, ao %GC, nem quanto à relação da cintura-quadril (RCQ) disponível. Amédia da intensidade clínica da dor pela EVA foi de 7,2 ± 2,06 no grupo com DPC secundária a endometriose, e de 5,93 ± 2,64 no grupo com DPC secundária a outras causas (p = 0,03), revelando diferenças significativas entre os grupos. Emrelação à EADH, ambos os grupos estavam acima da média de corte. Conclusão Concluímos que, apesar da diferença no escore de dor avaliado entre os dois grupos, não houve diferença com relação à composição corporal e à antropometria.

Thalidomide reduces cell proliferation in endometriosis experimentally induced in rats / A talidomida induz diminuição da proliferação celular em endometriose experimentalmente induzida em ratas

Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2mm2, a significantly higher value compared with Group II (49.4mm2, p = 0.023) and Group III (48.6mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1mg/kg/day and at the dose of 10 mg/kg/day.

Resumo Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamentemenor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesãomédia do Grupo I foi de 69,2mm2, valor significativamentemaior em relação ao Grupo II (49,4mm2, p = 0,023) e Grupo III (48,6mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1mg/kg/dia quanto na dose de 10 mg/kg/dia.

Increased expression levels of metalloprotease, tissue inhibitor of metalloprotease, metallothionein, and p63 in ectopic endometrium: an animal experimental study / Aumento nos níveis de expressão de metaloprotease, inibidor tecidual das metaloproteases, metalotioneina e p63 em endométrio ectópico: um estudo experimental animal

Abstract Objective To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. Methods Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. Results The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. Conclusion Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.

Resumo Objetivo Caracterizar o padrão de diferenciação celular, proliferação e invasão tecidual em endométrio eutópico e ectópico de coelhas com lesões de endometriose induzidas por um modelo experimental 4 e 8 semanas após o procedimento de implantação endometrial. Métodos Vinte e nove coelhas fêmeas Nova Zelândia foram submetidas a laparotomia para indução de endometriose através da ressecção de um dos cornos uterinos, isolamento do endométrio e fixação do tecido no peritônio pélvico. Dois grupos de animais (14 animais em um grupo e 15 animais no outro) foram sacrificados 4 e 8 semanas após a indução da endometriose. A lesão foi excisada junto com o corno uterino contralateral para determinação da presença de glândulas e de estroma endometrial. Reações de imunohistoquímica foram realizadas no tecido endometrial eutópico e ectópico para análise dos seguintes marcadores: metaloprotease (MMP9) e inibidor tecidual da metaloprotease 2 (TIMP-2), os quais estão envolvidos na capacidade de invasão do tecido endometrial; e metalotioneina (MT) e p63, os quais estão envolvidos na diferenciação e proliferação celular. Resultados A intensidade da imunomarcação para MMP9, TIMP-2, MT e p63 foi mais alta nos endométrios ectópicos do que nos endométrios eutópicos. Contudo, quando as lesões foram comparadas entre 4 e 8 semanas, nenhuma diferença foi observada, com exceção do marcador p63, o qual foi mais evidente depois de 8 semanas de evolução do tecido endometrial ectópico. Conclusão Lesões endometriais ectópicas parecem expressar maior poder de diferenciação celular e de invasão tecidual comparadas com endométrios eutópicos, demonstrando o potencial de invasão, de progressão e de apresentação heterogênea da endometriose.

Perineal Massage Improves the Dyspareunia Caused by Tenderness of the Pelvic Floor Muscles / Massagem perineal melhora a dispareunia causada por tensão dos músculos do assoalho pélvico

ABSTRACT Aim: To evaluate the long-term effectiveness of perineal Thiele massage in the treatment of women with dyspareunia caused by tenderness of the pelvic floor muscles. Methods: A total of 18 women with diagnoses of dyspareunia caused by tenderness of the pelvic floor muscles were included in the study. The women were divided in two groups: the dyspareunia (D) group - 8 women with dyspareunia caused by tenderness of the pelvic floor muscles; and the chronic pelvic pain group (CPP) group - 10 women with dyspareunia caused by tenderness of the pelvic floor muscles associated with CPP. Each patient filled out the Visual Analogue Scale (VAS), the McGill Pain Index, the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). After an evaluation, the women underwent transvaginal massage using the Thiele technique over a period of 5 minutes, once a week for 4 weeks. Results: All women had significant improvements in their dyspareunia according the VAS and the McGill Pain Index (p < 0,001), but the HADS scores did not show significant differences. Regarding sexual function, the D group showed improvements on all aspects of sexual function, while the CPP group showed differences only in the pain domain. Conclusion: Thiele massage is effective in the treatment of dyspareunia caused by tenderness of the pelvic floor muscles with a long-term pain relief.

RESUMO Objetivo: Avaliar a eficácia em longo prazo da massagem perineal de Thiele no tratamento de mulheres com dispareunia provocada pela tensão dos músculos do assoalho pélvico. Métodos: Foram incluídos no estudo dezoito mulheres com diagnóstico de dispareunia provocada pela tensão dos músculos do assoalho pélvico. As mulheres foram divididas em dois grupos: o grupo dispareunia (D) - 8 mulheres com dispareunia causada pela tensão dos músculos do assoalho pélvico; e o grupo de dor pélvica crônica (DPC): 10 mulheres com dispareunia causada pela tensão dos músculos do assoalho pélvico associados à DPC. Cada paciente preencheu Escala Visual Analógica (EVA), Índice de Dor de McGill, Índice de Função Sexual Feminino (IFSF) e Escala Hospitalar de Ansiedade e Depressão (EHAD). Após a avaliação, as mulheres foram submetidas a massagem transvaginal utilizando a técnica de Thiele ao longo de um período de 5 minutos, 1 vez por semana durante 4 semanas. Resultados: Todas as mulheres tiveram melhora significativa da dispareunia de acordo com a EVA e o Índice de Dor de McGill (p < 0,001), mas na pontuação do EHAD não mostraram diferenças significativas. Em relação à função sexual, o grupo D apresentou melhora de todos os aspectos da função sexual, enquanto o grupo DPC mostrou diferenças apenas no domínio dor. Conclusão: A massagem perineal de Thiele é eficaz no tratamento da dispareunia causada pela tensão dos músculos do assoalho pélvico, com alívio da dor a longo prazo.

Evaluation of embolization for periuterine varices involving chronic pelvic pain secondary to pelvic congestion syndrome

OBJECTIVES: To evaluate the clinical response and success rate after periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome and to report the safety of endovascular treatment and its rate of complications. METHODS: Retrospective cohort of patients undergoing endovascular treatment of pelvic congestion syndrome in our department from January 2012 to November 2015. Data were analyzed based on patient background, imaging findings, embolized veins, rate of complications, and clinical response as indicated by the visual analog pain scale. RESULTS: We performed periuterine varices embolization in 22 patients during the study, four of which required a second embolization. Seventeen patients reported a reduction in pelvic pain after the first embolization and three patients reported a reduction in pelvic pain after the second embolization. Minor complications were observed in our patients, such as postural hypotension, postoperative pain, and venous perforation during the procedure, without clinical repercussion. CONCLUSION: Periuterine varices embolization in patients with chronic pelvic pain secondary to pelvic congestion syndrome appears to be an effective and safe technique.

Cultural Adaptation of the Patient Satisfaction Questionnaire and Validation of Its Use in the Portuguese Language for Women with Chronic Pelvic Pain / Transculturação e validação do questionário de satisfação do paciente para a língua portuguesa para mulheres com dor pélvica crônica

Abstract Objectives to translate and adapt the Patient Satisfaction Questionnaire (PSQ) to Portuguese and to assess its psychometric properties based on internal consistency, test-retest, factor analysis and divergent and convergent construct validities. Methods The study involved 218 participants and was approved by the local Research Ethics Committee. All participants gave written informed consent and their anonymity was ensured. The instrument was translated and culturally adapted for use in the Portuguese language. The internal consistency and factorial analysis were assessed by patients and physicians. Convergent and divergent validities were also assessed specifically for the patient group, as well as test-retest reliability. The Portuguese versions of the Patient Health Questionnaire (PHQ-9) and State-Trait Anxiety Inventory (STAI) were used for the analysis of the convergent validity. In addition, we applied a questionnaire of clinical and demographic data for the analysis of the divergent validity. Results The adapted version of the PSQ showed good Cronbach’s α and test-retest values, and the results of the convergent construct validity between the PSQ and the PHQ-9 (r = 0.34; p = 0.02) and the STAI (r = 0.47; p = 0.001) were negative, significant and moderate correlations. Divergent validity showed significant correlations only with race and education. The Brazilian Portuguese versionof the PSQ proved to be a valid and reliable instrument, with psychometric properties suitable for the assessment of satisfaction among patients with chronic pelvic pain and their physicians in Brazil. The questionnairemay allow the homogenization of reports on this topic in the international literature.

Resumo Objetivo traduzir e adaptar o Patient Satisfaction Questionnaire (PSQ) para o Português e avaliar suas propriedades psicométricas com base na consistência interna, teste-reteste, análise fatorial e validades de construto divergente e convergente. Métodos O estudo incluiu 218 participantes e foi aprovado pelo Comitê de Ética em Pesquisa local. Todos os participantes assinaram o termo de consentimento livre e esclarecido, e o anonimato dos participantes foi assegurado. O instrumento foi traduzido e adaptado culturalmente para uso em Português. A consistência interna e análise fatorial foram avaliadas por pacientes e médicos. As validades convergente e divergente também foram avaliadas especificamente para o grupo de pacientes, bem como a confiabilidade teste-reteste. O Questionário de Saúde do Paciente (PHQ-9) e o Inventário de Ansiedade Traço-Estado (STAI) foram utilizados para a análise da validade convergente. Além disso, foi aplicado um questionário de dados clínicos e demográficos para análise da validade divergente. Resultados A versão adaptada do PSQ apresentou bons valores alfa de Cronbach e teste-reteste, e a validade de construto convergente entre o PSQ e o PHQ-9 (r = 0 ,34; p = 0,02) e o STAI (r = 0,47; p = 0,001) foram negativas, significativas e com correlação moderada. A validade divergente mostrou correlações significativas com raça e educação. Conclusão: a versão brasileira do PSQ provou ser um instrumento válido e confiável, com propriedades psicométricas adequadas para a avaliação da satisfação entre os pacientes com dor pélvica crônica e seus médicos no Brasil. O questionário pode permitir a homogeneização dos relatórios sobre este tema na literatura internacional.

Common Dysregulated Genes in Endometriosis and Malignancies / Genes comuns desregulados em endometriose e doenças malignas

Abstract Several authors have investigated the malignant transformation of endometriosis, which supports the hypothesis of the pre-neoplastic state of endometriotic lesions, but there are few data about the pathways and molecular events related to this phenomenon. This review provides current data about deregulated genes that may function as key factors in the malignant transition of endometriotic lesions. In order to do so, we first searched for studies that have screened differential gene expression between endometriotic tissues and normal endometrial tissue of women without endometriosis, and found only two articles with 139 deregulated genes. Further, using the PubMed database, we crossed the symbol of each gene with the terms related to malignancies, such as cancer and tumor, and obtained 9,619 articles, among which 444 were studies about gene expression associated with specific types of tumor. This revealed that more than 68% of the analyzed genes are also deregulated in cancer. We have also found genes functioning as tumor suppressors and an oncogene. In this study, we present a list of 95 informative genes in order to understand the genetic components that may be responsible for endometriosis' malignant transformation. However, future studies should be conducted to confirm these findings.

Resumo Vários autores têm estudado transformações malignas em endometriose que suportam a hipótese de um estado pré-neoplásico das lesões endometrióticas; contudo, existem poucos dados sobre as vias e eventos moleculares relacionados a este fenômeno. Esta revisão fornece dados atuais sobre genes desregulados que possam funcionar como fatores-chave para a transição maligna das lesões endometrióticas. Assim, inicialmente, estudos de expressão gênica diferencial em larga escala comparando tecido endometriótico e endométrio normal de mulheres sem endometriose foram procurados, e apenas dois artigos com 139 genes desregulados foram obtidos. Posteriormente, usando o banco de dados do PubMed, foram cruzados os símbolos de cada gene com termos relacionados à malignidade, como câncer e tumor, e 9.619 artigos foram obtidos, dos quais 444 eram estudos sobre expressão de genes associados a tipos específicos de tumor. Isto revela que mais de 68% dos genes analisados eram também desregulados em câncer. Também foram encontrados genes que funcionam como supressor tumoral e um oncogene. Este estudo apresenta uma lista de 95 genes informativos para compreender os componentes genéticos que possam ser responsáveis por transformações malignas na endometriose. Contudo, estudos futuros são necessários para confirmar estes achados.

Macroprolactinemia e hiperprolactinemia intermediária: manifestações clínicas e achados radiológicos / Macroprolactinemia and intermediate hyperprolactinemia: clinical manifestations and image

OBJETIVOS: Caracterizar as pacientes com valores indeterminados de hiperprolactinemia (teste de PEG para identificação de macroprolactinemias com recuperação entre 30 e 65 por cento) (PRLi) ou macroprolactinemia (PRLm), quanto às características clínicas, como intensidade e variação dos sintomas e presença ou não de tumores no sistema nervoso central. MÉTODOS: Estudo transversal, retrospectivo, de levantamento de prontuários, no qual foram incluídas 24 pacientes com diagnóstico de hiperprolactinemia (PRL>25 ng/dL), em idade reprodutiva, em seguimento em ambulatório de ginecologia endócrina. Foram incluídas 11 pacientes com PRLm e 13 com PRLi. Dos dois grupos (PRLm e PRLi), foram considerados para a análise registros dos dados relativos à idade, à paridade, ao índice de massa corporal, à presença de galactorreia, à infertilidade e ao tumor do sistema nervoso central. Os dados antropométricos foram expressos em média e desvio padrão e, para a comparação entre os grupos quanto à presença de tumor no sistema nervoso central, galactorreia e infertilidade, utilizou-se o teste t de Student. RESULTADOS: A galactorreia foi mais prevalente nas pacientes com PRLi (p=0,01). Setenta por cento das mulheres com PRLi apresentaram microprolactinoma de hipófise, enquanto que este achado foi evidente em 17 por cento das mulheres com PRLm (p=0,04). Dentre as pacientes com PRLm e PRLi, nove não foram investigadas com imagem do sistema nervoso central por apresentarem níveis pouco elevados de prolactina (cinco portadoras de PRLm e quatro de PRLi). Não houve diferença significativa quanto à ocorrência de infertilidade ou de ciclos menstruais irregulares. CONCLUSÕES: Mulheres com hiperprolactinemia intermediária apresentam mais sintomas de galactorreia e maior incidência de tumores do sistema nervoso central do que aquelas com macroprolactinemia.

PURPOSE: To characterize patients with indeterminate values of hyperprolactinemia (PEG test for the identification of macroprolactinemias with recovery between 30 and 65 percent) (PRLi) or macroprolactinemia (PRLm), in relation to clinical characteristics, such as the presence or absence of symptoms, as well as their intensity and variation, and the presence or absence of central nervous system tumors. METHODS: This is a cross-sectional retrospective survey of records of 24 patients with hyperprolactinemia, in reproductive ages, with prolactin >25 ng/dL. Eleven women with PRLm and 13 with PRLi were included. Records from the two groups were extracted for analysis: age, parity, body mass index, presence of galactorrhea, infertility, and central nervous system tumor. Anthropometrics data were expressed as mean and standard deviation. To compare groups regarding the presence of central nervous system tumor, galactorrhea, as well as infertility we used the Student's t-test. RESULTS: Galactorrhea was more prevalent in patients with PRLi (p=0.01). Seventy percent of women with PRLi presented pituitary tumor (microprolactinoma), whereas this finding was evident in 17 percent of the PRLm Group (p=0.04). Among the patients with and PRLm PRLi, nine were not investigated with the image of the central nervous system because they have low levels of prolactin (five carriers and four PRLm PRLi). There were no significant differences regarding the occurrence of infertility or irregular menstrual cycles between groups. DISCUSSION: Women with intermediate hyperprolactinemia present more galactorrhea symptoms as well as central nervous system tumors than women with macroprolactinemia.

Cryopreservation time does not decrease follicular viability in ovarian tissue frozen for fertility preservation

OBJECTIVE: To determine the effect of storage duration on cryopreserved ovarian tissue using fresh and frozenthawed samples. METHODS: Seventeen fertile patients underwent an ovarian biopsy during elective laparoscopic tubal ligation. The tissue sample was divided into three parts: one part was processed fresh (FG), and two were slowly frozen, cryopreserved for 30 (G30) or 180 days (G180), thawed and analyzed. Follicular density, follicular viability, and steroidogenic capacity were assessed. RESULTS: We observed no differences between the groups in follicular density, which was assessed in hematoxylin and eosin-stained tissue sections. A heterogeneous follicular distribution was observed in the parenchyma, with a mean density of 361.3±255.4, 454.9±676.3, and 296.8±269.0 follicles/mm3 for FG, G30 and G180, respectively (p = 0.46). Follicular viability was greater in FG (93.4 percent) when compared with the cryopreserved tissues (70.8 percent for G30 (p<0.001) and 78.4 percent for G180 (p<0.001)), with no difference in viability between the frozen samples (p>0.05). The steroidogenic capacity of the tissue was not significantly reduced following cryopreservation. CONCLUSION: The slow freezing procedures used for ovarian cryopreservation are capable of preserving follicular viability and maintaining the steroidogenic capacity of the tissue despite a roughly 30 percent decrease in follicular viability. Furthermore, short-term storage of ovarian tissue does not appear to compromise follicle integrity.

Uso dos marcadores endócrinosda reserva ovariana em reprodução assistida / Use of ovarian reserve endocrine markers in assisted reproduction

A avaliação da reserva folicular ovariana em reprodução assistida surge como uma tentativa de avaliar o potencial reprodutivo da mulher e nortear protocolos individualizados de estimulação, garantindo melhor aconselhamento aos casais e amenizando encargos emocionais e financeiros de um processo cujos resultados ainda se encontram a quém do desejado. Neste artigo, são abordados aspectos atuais do uso de marcadores endócrinos na propedêutica de casais subférteis.

Evaluation of ovarian follicular reserve in assisted reproduction programs appears as a strategy to assess woman’s reproductive potential andpermit to establish directions to delineate individualized stimulation protocols, providing adequate counseling to subfertile couples and diminishing emotional and financial duties in a process which is still far from desired results. In this article, recent aspects of ovarian reserve endocrine markers during subfertile couples’ evaluation are discussed.

Hysteroscopy as a standard procedure for assessing endometrial lesions among postmenopausal women

CONTEXT AND OBJECTIVES: Endometrial cancer is the most prevalent type of malignant neoplasia of the genital tract. The objective of this study was to calculate the sensitivity, specificity, accuracy and positive and negative predictive values for diagnostic hysteroscopy, in comparison with histopathological tests, for all lesions of the endometrial cavity. DESIGN AND SETTING: Retrospective descriptive study at the public tertiary-level university hospital of Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. METHODS: Diagnostic hysteroscopy was indicated in the following instances: endometrial thickness > 4 mm in asymptomatic patients; postmenopausal bleeding; and irregular endometrium or endometrium difficult to assess from ultrasound, with or without vaginal bleeding. Ultrasound evaluations were carried out no more than three months prior to hysteroscopy. RESULTS: There were 510 patients, with a mean age of 61.1 ± 2.0 years and mean time elapsed since the menopause of 12.7 ± 2.5 years. Endometrial biopsies were performed on 293 patients (57.5 percent). Histopathological analysis showed that 18 patients presented endometrial carcinoma or typical or atypical hyperplasia, and none of them presented endometrial thickness of less than 8 mm. No significant differences were found between the median thicknesses of the various benign lesions (p > 0.05). In our data, the sensitivity, specificity, accuracy and positive and negative predictive values for cancer or hyperplasia were 94.4 percent, 97.0 percent, 96.8 percent, 68 percent and 99.6 percent, respectively. CONCLUSIONS: Our results suggest that hysteroscopy is valuable as a diagnostic tool for malignant/hyperplastic and benign lesions, except for submucous myomas, for which the sensitivity was only 52.6 percent.

CONTEXTO E OBJETIVO: O câncer endometrial é o tipo mais prevalente de neoplasia maligna do trato genital. Os objetivos deste estudo foram: calcular a sensibilidade, especifi cidade e acurácia, bem como valor preditivo positivo e negativo das histeroscopias diagnósticas em comparação com a análise histopatológica de todas as lesões da cavidade endometrial. DESENHO E LOCAL: Estudo retrospectivo e descritivo no setor de endoscopia ginecológica do hospital universitário, terciário e público da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. MÉTODOS: A histeroscopia diagnóstica foi indicada nas seguintes situações: espessura endometrial > 4 mm em pacientes assintomáticas, sangramento na pós-menopausa, endométrio irregular ou endométrio de difícil avaliação pelo ultra-som, com ou sem sangramento vaginal. A avaliação ultra-sonográfi ca foi realizada não mais que três meses antes da histeroscopia. RESULTADOS: A idade média das pacientes foi 61,1 ± 2,0 anos, e a duração média do período pós-menopausa foi de 12,7 ± 2,5 anos. Das 510 pacientes, 293 (57,5 por cento) foram submetidas à biópsia endometrial, no estudo histopatológico, 18 pacientes apresentavam carcinoma endometrial, hiperplasia típica ou atípica e nenhuma delas apresentava espessura endometrial maior que 8 mm. Nenhuma diferença signifi cativa foi encontrada entre as espessuras medianas das várias lesões benignas (p > 0,05). A sensibilidade (94,4 por cento), especifi cidade (97 por cento), acurácia (96,8 por cento) e valores preditivos positivo e negativo (68 por cento e 99,6 por cento respectivamente) foram altos em nosso estudo. CONCLUSÃO: Nossos resultados sugerem que a histeroscopia diagnóstica apresenta boa validade como ferramenta diagnóstica para lesões malignas e hiperplasias, bem como para lesões benignas, com exceção dos leiomiomas submucosos, para o qual a sensibilidade foi de somente 52,6 por cento.