Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists.

Objective: Fertility preservation is a priority in oncology for female cancer patients. However, there is a lack of communication between infertility specialists and oncologists. This study aimed to evaluate infertility specialists' perceptions and experiences regarding fertility preservation. Methods: Conduct an online survey to profile infertility specialists. Participants were infertility affiliated with the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO). The specialists received an online survey, which response rate were 30.9%, most of whom were in southern and southeastern. The survey consisted on 14 questions about the infertility specialists' location, techniques in clinical practice, treatment successful rate, patients idea, etc. Results: The average experience in human reproduction were 15.5 ± 10.2 years (mean ± standard deviation, range 1-40). Among reproductive-aged female cancer patients recommended for fertility preservation, 60.3 ± 28.8% (range 10-100%) underwent preservation procedures. Main barriers were cost (41%), oncologists' knowledge or acceptance (35%) and accessibility (9%). Most infertility specialists (58%) considered 40 years the limit for fertility preservation. Leukemia, lymphoma, breast and ovarian cancers were prioritized for fertility preservation, while lung, thyroid, gastric, and brain cancers were less relevant. Conclusion: This is the first Brazilian study about infertility specialists' perceptions on oncology patients access to fertility preservation. These patients primarily receive treatment in the public health system, while infertility specialists mainly work in the private healthcare. This healthcare mode is currently fragmented, but integrating these experts is enhancing patient access to fertility preservation. Studies on this topic are still warranted.

Reconhecimento e diagnóstico dos sintomas cutâneos do hiperandrogenismo em mulheres: proposta do Grupo Appropriate Care for Women with Androgen Excess (AWARE)) / Recognition and diagnosis of hyperandrogenic skin symptoms in women: proposal of the Appropriate Care for Women with Androgen Excess group (AWARE))

O hiperandrogenismo representa um problema de saúde pública complexo. Essa condição pode acome- ter 1/5 das mulheres na idade reprodutiva e apresenta um impacto negativo importante na qualidade de vida. As mulheres com hiperandrogenismo podem apresentar uma combinação de diferentes sintomas e repercussões clínicas. Os sintomas cutüneos incluem a seborreia, acne, hirsutismo e aIopecia. Trata-se de uma condição desafiadora tanto para as mulheres afetadas quanto para os profissionais de saúde. A nomenclatura atribuída ao hiperandrogenismo é confusa e faltam ainda recomendações diagnósticas e terapêuticas padronizadas. O grupo Appropriate Care for Women with Androgen Excede (AWARE) foi criado com proposta de aborda os aspectos confusos e inconclusivos do hiperandrogenismo. Foram elaborados protocolos simplificados referentes ao diagnóstico e tratamento do hiperandrogenismo visando contribuir de forma mais eficaz com os médicos em seus diferentes cenários de atuação. O roteiro para o reconhecimento e abordagem dos sintomas cutâneos do hiperandrogenismo em mulheres compreende perguntas chaves e ações específicas, sinalizando para a indicação de métodos propedêuticos adicionais.(AU)

Hyperandrogenism is a complex public health problem. This condition can affect 1/5 of women in repro- ductive age and has a significant negative impact on quality of life. Women with hyperandrogenism may exhibit a combination of different symptoms and clinical repercussions. Cutaneous symptoms include seborrhea, acne, hirsutism, and alopecia. It is a challenging condition for both affected women and health professionals.The nomenclature attributed to hyperandrogenism is confusing, and standard diagnostic and therapeutic recommendations are lacking. The Appropriate Care for Women with Androgen Excess (AWARE) group was created to address the confusing and inconclusive aspects of hyperandrogenism. Simplified protocols have been developed for the diagnosis and treatment of hyperandrogenism, aiming to contribute more effectively to physicians in their different settings.The roadmap for recognizing and approaching the cutaneous symptoms of hyperandrogenism in women comprises key questions and specific actions, signaling for indication of additional propaedeutic methods.(AU)

Immunohistochemical WWOX expression and association with angiogenesis, p53 expression, cell proliferation and clinicopathological parameters in cervical cancer / Avaliação da expressão do gene WWOX por avaliação imunohistoquímica, sua associação com marcador de angiogênese, expressão do p53, proliferação celular e parâmetros clinicopatológicos no câncer de colo uterino

Abstract Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type BC1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in thebenign cervix (p = 0.019). TheWWOXexpressionwas inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association betweentheWWOXexpression with the p53 expression (p = 0.464)or the Ki-67expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

Resumo Objetivo O presente estudo avaliou a expressão do WWOX, sua associação com características clinicopatológicas e com a expressão do p53, ki-67 (proliferação celular) e CD31 (angiogênese) em pacientes com carcinoma invasivo de células escamosas do colo uterino, ou simplesmente câncer do colo uterino (CCE). Métodos Foram avaliadas prospectivamente pacientes com CCE no estágio IB (n = 20) e mulheres com mioma uterino, no grupo controle (n = 20). As pacientes com CCE foram submetidas à histerectomia radical e à linfadenectomia pélvica do tipo B-C1. As mulheres no grupo-controle foram submetidas à histerectomia vaginal. As amostras de tecido foramcoradas comhematoxilina e eosina para avaliação histológica e a expressão das proteínas foi detectada por imuno-histoquímico. Resultados A expressão do WWOX foi significativamente menor no tumor quando comparada com sua expressão no colo do útero benigno (p = 0,019). A expressão tumoral de CD31 foi inversamente associada à expressão de WWOX (p = 0,018). Sua expressão não foi associada à expressão tumoral de p53 e Ki-67 em pacientes com CCE (p = 0,464 e p = 0,360, respectivamente). Não houve associação entre a expressão de WWOX e o tamanho do tumor (p = 0,156), grau de diferenciação (p = 0,914), presença de invasão vascular linfática (p = 0,155), comprometimento do paramétrio (p = 0,421) ou metástase dos linfonodos pélvicos (p = 0,310) em pacientes com CCE. Conclusão Os resultados sugeriram que o WWOX pode estar envolvido na carcinogênese do CICECU e esse marcador foi associado à angiogênese tumoral.

Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer.

OBJECTIVE: The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. METHODS: Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. RESULTS: The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. CONCLUSION: The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

OBJETIVO: O presente estudo avaliou a expressão do WWOX, sua associação com características clinicopatológicas e com a expressão do p53, ki-67 (proliferação celular) e CD31 (angiogênese) em pacientes com carcinoma invasivo de células escamosas do colo uterino, ou simplesmente câncer do colo uterino (CCE). MéTODOS: Foram avaliadas prospectivamente pacientes com CCE no estágio IB (n = 20) e mulheres com mioma uterino, no grupo controle (n = 20). As pacientes com CCE foram submetidas à histerectomia radical e à linfadenectomia pélvica do tipo B-C1. As mulheres no grupo-controle foram submetidas à histerectomia vaginal. As amostras de tecido foram coradas com hematoxilina e eosina para avaliação histológica e a expressão das proteínas foi detectada por imuno-histoquímico. RESULTADOS: A expressão do WWOX foi significativamente menor no tumor quando comparada com sua expressão no colo do útero benigno (p = 0,019). A expressão tumoral de CD31 foi inversamente associada à expressão de WWOX (p = 0,018). Sua expressão não foi associada à expressão tumoral de p53 e Ki-67 em pacientes com CCE (p = 0,464 e p = 0,360, respectivamente). Não houve associação entre a expressão de WWOX e o tamanho do tumor (p = 0,156), grau de diferenciação (p = 0,914), presença de invasão vascular linfática (p = 0,155), comprometimento do paramétrio (p = 0,421) ou metástase dos linfonodos pélvicos (p = 0,310) em pacientes com CCE. CONCLUSãO: Os resultados sugeriram que o WWOX pode estar envolvido na carcinogênese do CICECU e esse marcador foi associado à angiogênese tumoral.

Non-hormonal and hormonal intrauterine contraception: survey of patients' perceptions in four Latin American countries.

OBJECTIVES: This study sought to understand women's perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America. METHODS: We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS). RESULTS: The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p < 0.001), mood swings (14.1% vs. 38.7%; p < 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p < 0.001), pelvic infections (42.1% vs. 15.7%; p < 0.001) and ectopic pregnancy (43.5% vs 23.5%; p < 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p < 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388). CONCLUSIONS: Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions.

Fertility-preservation in endometrial cancer: is it safe? Review of the literature.

Almost 5% of women with endometrial cancer are under age 40, and they often have well-differentiated endometrioid estrogen-dependent tumors. Cancer survival rates have improved over the last decades so strategies to avoid or reduce the reproductive damage caused by oncologic treatment are needed. We reviewed the published literature to find evidence to answer the following questions: How should we manage women in reproductive age with endometrial cancer? How safe is fertility preservation in endometrial cancer? Can pregnancy influence endometrial cancer recurrence? What are the fertility sparing options available? Progestins may be prescribed after careful evaluation and counseling. Suitable patients should be selected using imaging methods and endometrial sampling since surgical staging will not be performed. Conservative treatment should only be offered to patients with grade 1 well-differentiated tumors, absence of lymph vascular space invasion, no evidence of myometrial invasion, metastatic disease or suspicious adnexal masses, and expression of progesterone receptors in the endometrium. The presence of co-existing ovarian metastatic of synchronous cancer should be investigated and ruled out before the decision to preserve the ovaries. The availability of Assisted Reproductive Technology (ART) has made it possible for women with endometrial cancer to give birth to a child without compromising their prognoses. Gamete, embryo or ovarian tissue cryopreservation techniques can be employed, although the latter remains experimental. Unfortunately, fertility preservation is rarely considered. Current recommendations for conservative management are based on the overall favorable prognosis of grade 1 minimally invasive tumors. Selected patients with endometrial cancer may be candidates to a safe fertility-preserving management.

Tratamento do sangramento uterino anormal: uma análise sob a perspectiva dos custos no Sistema Único de Saúde e da medicina suplementar / Treatment of abnormal uterine bleeding: an analysis from the perspective of costs in the public health system and supplementary medicine

Objetivos: Comparar os custos diretos e indiretos do sistema intra‐uterino de liberação de levonorgestrel (SIU‐LNG), ablação endometrial com balão térmico (AEBT) e histerectomia no tratamento de mulheres com sangramento uterino anormal (SUA). Métodos: Foram avaliadas retrospectivamente 88 pacientes tratadas para SUA pelo SIU‐LNG (n = 30), AEBT (n = 28) e histerectomia (n = 30). Foram considerados todos os procedimentos, consultas e exames envolvidos no tratamento das pacientes por um período de 5 anos, assim como os custos resultantes das falhas dos tratamentos utilizados. Foram estimados os custos pelo Sistema Único de Saúde (SUS) e sistema de saúde suplementar. As diferenças entre os grupos foram avaliadas pelo teste do t de Student ou ANOVA. Resultados:O custo do tratamento do SUA com AEBT foi significante mais elevado em comparação ao SIU‐LNG e histerectomia após um e cinco anos de seguimento, tanto no SUS quanto na medicina suplementar (p < 0,001). No SUS, o tratamento com o SIU‐LNG foi de 38,2% dos custos da histerectomia no primeiro ano (R$ 769,61 vs. R$ 2.012,21, p < 0,001) e de 45,2% após cinco anos (R$ 927,83 vs. R$ 2.052,21, p < 0,001). Na saúde suplementar essa diferença foi ainda mais expressiva. Nesse contexto, o custo do SIU‐LNG foi de 29,1% dos custos da histerectomia no primeiro ano (R$ 1.551,92 vs. R$5.324,74, p < 0,001) e de 37,4% após cinco anos (R$ 2.069,35 vs. R$ 5.538,74, p < 0,001). Conclusões: O uso do SIU‐LNG resulta em custos diretos e indiretos menores do que a AEBT e histerectomia no tratamento do SUA. A custo‐efetividade do SIU‐LNG aliado à reversibilidade e por ser um procedimento ambulatorial reforçam o seu papel no tratamento de mulheres com SUA tanto na perspectiva do SUS quanto na saúde suplementar.

Objectives: To compare direct and indirect costs of the levonorgestrel‐releasing intrauterine system (LNG‐IUS), thermal balloon endometrial ablation (TBEA) and hysterectomy in the treatment of women with abnormal uterine bleeding (AUB). Methods: 88 patients treated for AUB by LNG‐IUS (n = 30), TBEA (n = 28) and hysterectomy (n = 30) were retrospectively evaluated. All procedures, medical appointments and tests involved in the treatment of patients were considered for a period of five years, as well as all costs arising from failures of the treatments used. The costs for the Unified Health System (SUS) and the private health care system were estimated. Differences between groups were evaluated by the test t of Student or ANOVA. Results: The cost of the treatment of AUB with TBEA was significantly higher versus LNG‐IUS and hysterectomy after a five‐year follow‐up in both SUS and private health care system (p <0.001). In SUS, the treatment with the LNG‐IUS represented 38.2% of the hysterectomy cost in the first year (R$ 769.61 vs. R$ 2,012.21, p <0.001) and 45.2% after five years (R$ 927.83 vs. R$ 2,052.21, p <0.001). As for the private health care system, this difference was even more significant. In this context, the cost of LNG‐IUS represented 29.1% of the hysterectomy cost in the first year (R$ 1,551.92 vs. R$ 5,324.74, p <0.001) and 37.4% after five years (R$ 2,069.35 vs. R$ 5,538.74, p <0.001). Conclusions: The use of LNG‐IUS results in lower direct and indirect costs versus TBEA and hysterectomy in the treatment of women with AUB. The cost‐effectiveness of LNG‐IUS, together with the reversibility and also by this being an outpatient procedure, highlights its role in the treatment of women with AUB, both in SUS perspective as in private health care system's.

Assessment of chemokine serum levels in epithelial ovarian cancer patients.

AIMS AND BACKGROUND: The study was undertaken to investigate CCL2/MCP-1, CCL3/ MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 women with epithelial ovarian cancer. METHODS AND STUDY DESIGN: Sixteen patients diagnosed with epithelial ovarian cancer and 18 healthy women with no evidence of malign neoplasia (control group) aged from 23 to 89 years (mean ± SEM, 58.7 ± 2.3) were included. The epithelial ovarian cancer patients underwent laparotomy and debulking surgery. Chemokines serum levels were measured by cytometric bead array. Statistical analysis was performed using Mann-Whitney and Kendall's tau. P <0.05 was considered statistically significant for all analyses. RESULTS: The tumor staging (FIGO) was classified into: I in 4 cases (25%), III in 5 cases (31.3%) and stage IV in 7 cases (43.8%). Sera chemokine dosages of CCL2/MCP-1 and CCL4/MIP-1ß were lower in epithelial ovarian cancer patients than in the control group (P = 0.021 and P = 0.030, respectively). No significant difference between groups was observed in the levels of CCL3/MIP-1α, CCL5/RANTES and CXCL8/IL-8. No association between the chemokines analyzed and tumor stage was found. The serum level of CCL4/MIP-1ß was correlated with CA-125. CONCLUSIONS: The study of serum levels of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1ß, which suggests that the two chemokines may play an important role in the pathophysiology of ovarian cancer.

Preservação da fertilidade em mulheres com câncer: atualização e perspectivas / Fertility preservation in women with cancer: update and perspectives

Com o aumento do diagnóstico de câncer em mulheres jovens e os avanços no seu tratamento, muitas pacientes que poderão ter sua fertilidade comprometida com a quimioterapia têm manifestado desejo de engravidar futuramente. O congelamento de embriões, após fertilização in vitro, para preservar a fertilidade está bem estabelecido. A criopreservação de oócitos por vitrificação evoluiu bastante nos últimos anos, deixando de ser experimental. Até 2009 nasceram mais de 900 crianças a partir de oócitos criopreservados, sem aumento do risco de anomalias congênitas. O uso de análogos do GnRH para a supressão ovariana durante a quimioterapia na tentativa de prevenir a falência ovariana prematura apresenta resultados incertos. Outras técnicas ainda são consideradas experimentais, como a criopreservação e posterior autotransplante de tecido ovariano. Já foram relatados 24 nascimentos com o seu uso, persistindo, entretanto, dúvidas que motivam o seu estudo. A maturação de folículos ovarianos in vitro é alternativa promissora para preservação da fertilidade nessas pacientes e tem apresentado resultados positivos em roedores, macacos e humanos. Muita cautela deve ser tomada com o uso de técnicas experimentais, especialmente quando oferecidas para pacientes diante de fragilidade emocional. Por isso, é importante transmitir corretamente informações sobre chances de gravidez com tratamentos existentes e as limitações das técnicas experimentais...

With the increased number of cancer diagnoses among young women and the advances in treatment, many patients who may have had their fertility compromised by chemotherapy express desire to become pregnant in the future. Freezing embryos for later IVF so as to preserve fertility is a well established process. Oocyte cryopreservation by vitrification has evolved greatly in recent years and is no longer considered experimental. By 2009 more than 900 children were born from cryopreserved oocytes, without increased risk of congenital anomalies. The preventive use of GnRH analogues for ovarian suppression during chemotherapy to avoid premature ovarian failure has uncertain outcomes. Other techniques such as cryopreservation of ovarian tissue for later autograft are still considered experimental. Although use has already been reported in 24 births, doubts still persist and motivate further study. In vitro maturation of ovarian follicles is a promising alternative for preserving patient fertility and has shown positive results in rodents, monkeys, andhumans. Caution should be used with experimental techniques, especially when offered to emotionally fragile patients. Therefore it is important to thoroughly convey information on the chances of pregnancy with existing treatments and the limitations of experimental techniques...

Propedêutica básica da infertilidade conjugal / Basic propedeutics of conjugal infertility

A infertilidade é um problema que afeta cerca de 10%-20% da população, com incidência variável em todo o mundo. A avaliação do casal infértil é geralmente indicada depois de um ano, tempo em que a maioria dos casais normais teria sido bem sucedida na tentativa de concepção. Algumas investigações são controversas, e, na presença de múltiplos métodos, o custo, a segurança e a conveniência deveriam ajudar a decidir o mais apropriado.

Infertility is a problem affecting approximately 10%-20% of the population with variable incidences across the world. Evaluation of a couple is generally indicated after one year, by which time most normal couples attemptiong conception would have been successful. Some of the investigations are controversial and in the presence of multiple methods of investigating one aspect, the cost, safety, convenience and evidence-base should help in deciding on the appropriate method.

Immune response evaluation through determination of type 1, type 2, and type 17 patterns in patients with epithelial ovarian cancer.

Innate and adaptive immune cells secrete different cytokines, which participate through distinct mechanisms in cell-mediated immunity and humoral immune responses. The aim of this study was to evaluate the immune response through analysis of type 1 (Th1), Th2, and Th17 cells in patients with epithelial ovarian cancer (EOC). Our study included 44 patients with EOC (study group) and 32 gynecological patients with no ovarian disease (control group). Fragments of ovarian tissue and blood samples were collected in both groups and aliquots of intracystic fluid and peritoneal fluid were recovered from the EOC patient group. Interleukin (IL)-2/IL-4/IL-6/IL-10/IL-17/tumor necrosis factor (TNF)-α/interferon (IFN)-γ levels were measured by cytometric bead array. Statistical analysis included chi-squared, Student t, Mann-Whitney, Kruskal-Wallis tests, and Cox regression model. Patients with EOC were associated with higher levels of TNF-α/IL-4/IL-6/IL-10 compared to the control group. Both IL-10 and TNF-α concentrations were higher in patients with stage III/IV EOC and also associated with higher levels of cancer antigen 125. Higher Th1-mediated immune response was observed when the cytoreduction was considered optimal. However, patients with EOC with unsatisfactory cytoreductive surgery and undifferentiated tumors were associated with higher concentrations of Th2 cytokines in the 4 sites studied. Higher IL-6/IL-10 and lower IFN-γ concentrations were also associated with a lower overall survival rate in patients with EOC. The EOC group presented a predominantly Th2 response and an immunosuppressant standard and had association between IL-6/IL-10/IFN-γ and prognosis.

Evaluation of N-acetilglucosaminidase and myeloperoxidase activity in patients with endometriosis-related infertility undergoing intracytoplasmic sperm injection.

AIM: Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI). MATERIAL AND METHODS: This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval. RESULTS: There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (τ = 0.256, P = 0.025; and τ = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016). CONCLUSION: Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.

Inflammatory response patterns in ICSI patients: a comparative study between chronic anovulating and normally ovulating women.

The aim of this study was to evaluate inflammatory response in chronic anovulating infertility women undergoing intracytoplasmic sperm injection. Thirteen infertile women with chronic anovulation and 23 normally ovulating women were prospectively evaluated. N-acetylglucosaminidase (NAG), myeloperoxidase (MPO), monocyte chemoattractant protein 1 (MCP-1), and C-reactive protein (CRP) concentrations were evaluated in serum and follicular fluid. Women with chronic anovulation presented higher NAG and MPO activity in follicular fluid when compared with normally ovulating women. Serum MPO activity was higher in the control group compared to the chronic anovulation group. Both serum and follicular fluid CRP concentrations were higher in women with chronic anovulation in comparison with the control group. Higher MCP-1 follicular fluid concentrations and serum levels of CRP were associated with the occurrence of ovarian hyperstimulation syndrome. Patients with chronic anovulation exhibited significantly higher follicle macrophage/neutrophil activation as well as unspecific inflammatory response by comparison with normally ovulating women.

Analysis of systemic inflammatory response in the carcinogenic process of uterine cervical neoplasia.

The inflammatory response is an active process in cervical cancer and may act in the progression and/or regression of the lesion. At the site of inflammation, macrophages and neutrophils are present as well as cytokines such as TNF-α and IFN-γ. This study aims to evaluate the inflammatory response levels in women with cervical intraepithelial lesions (CIN) and with squamous cell carcinoma (SCC) of the cervix. Serum samples obtained from women without evidence of disease (n=30), with CIN (n=30) and with SCC of the cervix (n=30) were analyzed for the activities of N-acetylglucosaminidase (NAG) and myeloperoxidase (MPO) by enzymatic assay and the serum levels of TNF-α and IFN-γ by ELISA assay. The activities of NAG and MPO and the level of TNF-α were higher in women with CIN compared to the women with SCC. The levels of IFN-γ were lower in the group of women with CIN compared to the group with SCC. There was not a significant association between the degree of the CIN and the staging of the SCC of the cervix and the degree of inflammation as assessed by the levels of inflammatory markers. The inflammatory response was inversely correlated with the progression of the carcinogenic process. In the three groups, the control group, women with CIN and women with invasive SCC, there was no association between the degree of preinvasive lesions and staging of the SCC of the cervix.

Expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen.

This study was undertaken to investigate the expression of p53, Ki-67, and CD31 proteins in endometrial polyps of postmenopausal women treated with tamoxifen (TAM). Postmenopausal women with endometrial polyps treated with TAM (n = 20), postmenopausal women with endometrial polyps without hormone use (n = 20), postmenopausal women with atrophic endometrium (n = 20), and postmenopausal women with endometrial adenocarcinoma (n = 20) were prospectively investigated. Tissue samples were immunohistochemically evaluated by monoclonal antibodies for p53, Ki-67, and CD31. The data were analyzed using the Student t test, analysis of variance, and χ2 to evaluate significant differences between the groups. The level of significance was set at P < 0.05. There was no difference in the expression of p53 between the groups (P = 0.067). The expression of Ki-67 was higher in the polyp samples from TAM-treated women compared with those from the women using no hormone (P = 0.0047) and those from the women with atrophic endometrium (P = 0.008). Samples from the women with endometrial cancer was associated with higher Ki-67 expression compared with the polyp samples from TAM-treated women (P = 0.004). The expression of CD31 was higher in the polyp samples of TAM-treated women compared with that of the samples from the women with atrophic endometrium (P < 0.001) and similar to the polyp samples from the women using no hormone (P = 0.319) and to the samples from the women with endometrial cancer (P = 0.418). The use of TAM in postmenopausal women might be associated with increased cellular proliferation in endometrial polyps without interfering angiogenesis or inactivation of tumor suppressor proteins.

Avaliação da resposta inflamatória no soro e líquido folicular em pacientes com anovulação crônica submetidas a hiperestimulação ovariana controlada / Evaluation of inflammatory response in serun follicular fluid in patients with chronic anovulation submitted to controlled ovarian hyperstimulation

A anovulação crônica é o distúrbio ovariano mais frequente associado com quadros de infertilidade. Mecanismos inflamatórios apresentam um importante envolvimento na determinação da anovulação crônica. Esse estudo foi realizado para avaliar a resposta inflamatória no líquido folicular e soro de pacientes com infertilidade causada por anovulação crônica comparadas a pacientes ovulatórias e com ciclos regulares, submetidas à injeção intracitoplasmática de espermatozóides (ICSI). Métodos: Treze pacientes com anovulação crônica (casos) e 23 mulheres ovulatórias e com ciclos regulares (grupo controle) foram estudadas prospectivamente. As dosagens de N-acetilglucosaminidase (NAG), Miloperoxidase (MPO), proteína quimioatrativa de monócitos-1 (MCP-1) e proteína C reativa (PCR) foram avaliadas no soro e líquido folicular obtidos no período da coleta dos oócitos. Resultados: A media de idade das pacientes variou de 20 a 37 anos (28,9 mais ou menos 0,6 anos). O valor médio do índice de massa corporal (IMC) foi 21,7 mais ou menos 0,4 kg/cm2 (17,6 to 28,0 Kg/cm2)). Não houve diferenças entre os grupos com relação à média de idade, IMC e dosagens de hormônio folículo estimulante (FSH). As pacientes com anovulação crônica apresentaram níveis maiores de hormônio luteinizante (LH), contagem de folículos antrais e volume ovariano. Nas pacientes com anovulação crônica foram observadas atividades elevadas de NAG (p igual 0,025) e MPO (p igual 0,030) no líquido folicular quando comparadas a mulheres ovulatórias, submetidas a ICSI. Os níveis de MCP-1 no líquido folicular foram maiores que no soro em todas as pacientes. O PCR no fluido folicular (p igual 0,025) e soro (p igual 0,024) estavam mais elevados nas pacientes com anovulação crônica que no grupo controle. A ocorrência de síndrome do hiperestímulo ovariano (SHO) foi associada com níveis elevados de MCP-1 no líquido folicular (p igual 0,038) e PCR no soro (p igual 0,016)...