Prevalence of karyotype alterations in couples with recurrent pregnancy loss in a tertiary center in Brazil.

Objective: To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities. Methods: We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding. Results: Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations. Conclusion: The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

Polymorphisms in vitamin D receptor gene, but not vitamin D levels, are associated with polycystic ovary syndrome in Brazilian women.

This study aimed to investigate the association between vitamin D (VitD) levels, polymorphisms in VDR gene (ApaI, BsmI, FokI, and TaqI) and the polycystic ovary syndrome (PCOS) in a group of Brazilian women. A total of 100 patients with PCOS and 100 control women were included. The quantification of 25-hydroxyvitamin D (25(OH)D) was performed in high-performance liquid chromatography (HPLC). Polymorphisms on VDR gene were performed by PCR-RFLP. The BsmI AG genotype was more frequent in PCOS group, while the GG genotype was more frequent in the control group (p = .007). The frequency of the Taql CC genotype was higher in PCOS group, while the CT genotype was the most frequent in the control group (p = .021). Mean serum VitD levels were similar between the groups. However, there was a negative correlation between VitD levels and Ferriman-Gallwey score (p = .031, r = -.260) in the PCOS group. The TaqI and BsmI polymorphisms were associated with PCOS. Moreover, VitD levels are associated with the clinical hyperandrogenism. The data suggest the role of VitD in PCOS development and its complications.

Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta.

BACKGROUND/AIMS: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. METHODS: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6). Validation was performed using qPCR, immunohistochemistry and Western blot. MicroRNAs known to regulate P-glycoprotein (P-gp) were examined by qPCR. RESULTS: Up-regulation of ABCB9, ABCC2 and ABCF2 mRNA was detected in chorioamnionitis (p<0.05), whereas placental ABCB1 (P-gp; p=0.051) and ABCG2 (breast cancer resistance protein-BCRP) mRNA levels (p=0.055) approached near significant up-regulation. In most cases, the magnitude of the effect significantly correlated to the severity of inflammation. Upon validation, increased placental ABCB1 and ABCG2 mRNA levels (p<0.05) were observed. At the level of immunohistochemistry, while BCRP was increased (p<0.05), P-gp staining intensity was significantly decreased (p<0.05) in PTDC. miR-331-5p, involved in P-gp suppression, was upregulated in PTDC (p<0.01) and correlated to the grade of chorioamnionitis (p<0.01). CONCLUSIONS: Alterations in the expression of ABC transporters will likely lead to modified transport of clinically relevant compounds at the inflamed placenta. A better understanding of the potential role of these transporters in the events surrounding PTD may also enable new strategies to be developed for prevention and treatment of PTD.

Ferriman-Gallwey score correlates with obesity and insulin levels in polycystic ovary syndrome: an observational study / Correlação da escala de Ferriman-Gallwey com a obesidade e níveis de insulina na síndrome dos ovários policísticos: um estudo observacional

BACKGROUND: The Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy and one of the main causes of infertility in women. OBJECTIVES: This study aimed to evaluate the correlation between clinical hyperandrogenism assessed by modified Ferriman-Gallwey (F-G) score and metabolic parameters in Polycystic Ovary Syndrome women. METHODS: This observational study included fifty Polycystic Ovary Syndrome subjects. Detailed information about body mass index (BMI) and abdominal circumference (AC) were obtained from each subject. F-G score was applied to assess hirsutism through visual method. Serum levels of insulin, glucose and testosterone were measured. RESULTS: A positive correlation was observed between F-G score with body mass index, abdominal circumference and insulin. CONCLUSIONS: Obesity, mainly abdominal adipose tissue, and insulin levels correlate with hyperandrogenism in Polycystic Ovary Syndrome women, analyzed by F-G score. F-G score could be a marker to evaluate metabolic disorders in Polycystic Ovary Syndrome women.

JUSTIFICATIVA: A Síndrome dos Ovários Policísticos (SOP) é a endocrinopatia mais comum e uma das principais causas de infertilidade em mulheres. OBJETIVOS: O presente estudo teve como objetivo avaliar a correlação entre hiperandrogenismo clínico, avaliado pela escala de Ferriman-Gallwey (FG) modificada e parâmetros metabólicos em mulheres com a Síndrome dos Ovários Policísticos. MÉTODOS: Este estudo observacional incluiu cinquenta mulheres com Síndrome dos Ovários Policísticos. Informações detalhadas sobre o índice de massa corporal (IMC) e circunferência abdominal (CA) foram obtidas de cada participante. A escala FG foi aplicada para avaliar o hirsutismo através do método visual. Níveis séricos de insulina, glicose e testosterona foram também avaliados. RESULTADOS: Observou-se uma correlação positiva entre a escala FG e o índice de massa corporal, circunferência abdominal e insulina. CONCLUSÕES: A obesidade, principalmente o tecido adiposo abdominal, e os níveis de insulina se correlacionam com hiperandrogenismo em mulheres com Síndrome dos Ovários Policísticos, analisados por meio da escala FG. Desta forma, esta escala poderia ser um marcador para avaliar distúrbios metabólicos em mulheres com Síndrome dos Ovários Policísticos.

LAP (produto da acumulação lipídica) e síndrome metabólica em pacientes com síndrome dos ovários policísticos / LAP (lipid accumulation product) and metabolic syndrome in patients with polycystic ovary syndrome

INTRODUÇÃO: A síndrome dos ovários policísticos (SOP) é uma desordem endócrina comum que afeta 5 a 10% das mulheres em idade reprodutiva. A associação entre síndrome metabólica e alterações relacionadas à glicose e insulina é frequente em pacientes com SOP, eleva o risco cardiovascular dessas pacientes. O LAP é um índice de risco cardiovascular emergente que se baseia na combinação da circunferência abdominal (CA) e triglicérides (TGL) em jejum e reflete de forma simples a acumulação lipídica em adultos. OBJETIVOS: O presente estudo avaliou as possíveis correlações entre síndrome metabólica e o LAP nos parâmetros metabólicos e reprodutivos de pacientes com SOP. MATERIAIS E MÉTODOS: O estudo incluiu 299 pacientes portadoras de SOP, definida pelos critérios de Rotterdam, acompanhadas no Ambulatório de Hiperandrogenismo do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC‐UFMG). Foram avaliados: (1) dosagens séricas de triglicérides, testosterona total, glicemia de jejum e duas horas após sobrecarga de 75 gramas de dextrosol (GPD), TSH; (2) cálculo do LAP; (3) cálculo do índice de Ferriman; (4) avaliação do volume dos ovários; (5) medida da circunferência abdominal e (6) presença ou não de síndrome metabólica. RESULTADOS: A média do LAP foi 60,9 e a mediana 51,3. Pacientes com ou sem síndrome metabólica quando comparadas entre si não apresentaram diferenças quanto a volume ovariano, testosterona total, índice de Ferriman, glicemia de jejum e pós‐dextrosol. As mulheres com síndrome metabólica tiveram valores de TSH mais altos do que as mulheres sem síndrome metabólica. Já as mulheres no quartil superior do LAP tiveram TSH, índice de Ferriman e GPD maiores do que as mulheres nos quartis inferiores de LAP...

INTRODUCTION: Polycystic Ovary Syndrome (SOP) is a common endocrine disorder that affects 5-10% of women of reproductive age. The association between metabolic syndrome and changes related to glucose and insulin is frequent in patients with SOP, increasing the cardiovascular risk of these patients. The LAP is an emerging cardiovascular risk based on the combination of waist circumference (WC) and triglycerides (TGL) and fasting simply reflects the lipid accumulation in adults. OBJECTIVES: This study examined the possible correlation between metabolic syndrome or LAP and reproductive and metabolic parameters in patients with SOP. MATERIALS AND METHODS: The study included two hundred ninety-nine patients with SOP, defined by the Rotterdam criteria followed at HC-UFMG who had assessed their levels of triglycerides, total testosterone, fastingand two hours after 75 grams of overload dextrosol (GPD), TSH, LAP, Ferriman index, ovarian volume and abdominal circumference, and the presence or absence of metabolic syndrome. RESULTS: The mean LAP was 60.9 and the median 51.3. Patients with and without metabolic syndrome when compared to each others howed no differences in ovarian volume, total testosterone, Ferriman, fastingand post-dextrosol. Women with metabolic syndrome had higher TSH levels than women without metabolic syndrome. The women in the top quartile of the LAP had TSH, Ferriman and GPD higher than women in the lower quartiles of LAP...

O valor de um currículo / The value of a curriculum

O currículo conserva a identidade e a vocação da escola, mas também é reflexo do seu tempo e precisa mudar para acompanhar o que se passa no mundo.

A curriculum keeps the identity and vocation of a school, but it also reflects its time and needs to be changed in order to follow what happens worldwide.

Células-tronco: a resposta para os enigmas da patogênese da endometriose / Stem cells: the answer to the puzzles of the pathogenesis of endometriosis

A endometriose é uma doença crônica caracterizada pela presença de tecido endometrial ectópico. Esta doença frequentemente resulta em alta morbidade, incluindo dor pélvica crônica e infertilidade. A causa da endometriose é provavelmente multifatorial, sendo ainda objeto de muitos estudos. Fatores genéticos, ambientais e imunes estão possivelmente envolvidos na etiopatogenia desta doença, sendo especulada a associação com outros mecanismos. Nos últimos anos, alguns trabalhos têm demonstrado a presença de células-tronco/progenitoras no endométrio sadio; tais células possivelmente estão envolvidas na capacidade regenerativa desse tecido, assim como na patogênese de doenças ginecológicas proliferativas, como endometriose e carcinoma endometrial. Esta revisão avaliou as evidências disponíveis sobre a existência de células tronco/progenitoras endometriais e agrupou os resultados em uma hipótese de envolvimento dessas células na patogênese da endometriose. Foram selecionados os artigos mais relevantes sobre o tema. A identificação de células-tronco nos tecidos humanos e animais é presumida a partir da identificação de label retaining cells, células side population, marcadores de indiferenciação, potencial de clonogenicidade e diferenciação celular. A presença de supostas células-tronco no endométrio normal e ectópico foi demonstrada por alguns pesquisadores. Células endometriais no endométrio eutópico e em implantes endometrióticos, originadas a partir de células-tronco derivadas de medula óssea transplantada em humanos e de animais, também foram identificadas. Esses resultados sugerem que as células-tronco/progenitoras podem estar envolvidas na gênese da endometriose. No entanto, mais estudos são necessários para corroborar esta hipótese.

Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue. This disease often results in high degree of morbidity, including chronic pelvic pain and infertility. Probably, the cause of endometriosis is multifactorial and it has been the object of many studies. Genetic, environmental and immune factors are possibly involved in the pathogenesis of this disease, and it is speculated that there are other mechanisms associated. In recent years, some studies have shown the presence of adult stem cells in the healthy endometrium. These cells are possible involved in the regenerative capability of endometrium and in the pathogenesis of proliferative gynecological diseases, such as endometriosis and endometrial carcinoma. This review evaluated the available evidence on the existence of stem/progenitor cells in the endometrium and gathered the results in an hypothesis of involvement of these cells in the pathogenesis of endometriosis. The most relevant articles about this subject were selected. The identification of stem cells in animal and human tissues is presumed from the identification of label retaining cells, side population cells, undifferentiation markers, besides the potential of clonogenesis and cellular differentiation. The presence of putative stem cells in the normal and ectopic endometrium was demonstrated by some researches. Endometrial cells in eutopic endometrium and endometriotic implants, originated from bone marrow-derived stem cells transplanted into humans and animals, have also been identified. These results suggest that stem/progenitor cells may be involved in the genesis of endometriosis. However, more studies are necessary to this hypothesis

Aplicações das dosagens de inibinas em Ginecologia e Obstetrícia / Clinical usefulness of inhibin assays in Gynecology and Obstetrics

Na mulher, a principal fonte de inibina B são as células da granulosa de folículos em crescimento, enquanto a inibina A é secretada principalmente pelo corpo lúteo e pela placenta. Em mulheres inférteis submetidas a terapias de reprodução assistida, a inibina B se mostrou útil para predizer má resposta ovulatória, embora não tenha superado o desempenho de outros marcadores. No rastreamento pré-natal da síndrome de Down, a utilidade da inibina A foi repetidamente confirmada no segundo trimestre e começa a ser considerada também na bateria de testes do primeiro trimestre. Além das duas aplicações acima, a dosagem de inibina total pode contribuir para a identificação de casos de insuficiência ovariana autoimune. A inibina total também pode ser um marcador auxiliar no diagnóstico de tumores epiteliais do ovário, enquanto a dosagem de inibina B auxilia no diagnóstico de tumores de células da granulosa. O uso da inibina A pode se estender à avaliação de gestantes com ameaça de abortamento, com história de abortamento de repetição, com risco aumentado de pré-eclâmpsia, ou ainda nos primeiros dias de seguimento pós-esvaziamento de mola hidatiforme. Todas essas aplicações continuam em estudo, mas com possibilidade real de virem a ampliar o espectro diagnóstico das dosagens de inibinas em Ginecologia e Obstetrícia.

The main source of inhibin B in women is the growing follicle granulosa cells, while inhibin A is mainly produced by the corpus luteum and the placenta. In infertile women submitted to therapies of assisted reproduction, inhibin B has shown to be useful to predict a poor ovulatory response, though it has not yet overcome the performance of other markers. In the pre-natal screening of the Down syndrome, inhibin A has been repeatedly confirmed as useful in the second trimester and has also started to be considered in the first trimester test battery. Besides the two applications above, the dosage of total inhibin may contribute to the identification of cases of autoimmune ovarian insufficiency. Total inhibin may also be an auxiliary marker in the diagnosis of ovarian epithelial tumors, while the amount of inhibin B helps in the diagnosis of granulosa cells tumors. The use of inhibin A may be extended to the evaluation of pregnant women with risk of abortion, with a history of repeated abortion, with increased risk of pre-eclampsia, or even in the first days of follow-up of hydatiform mole post-emptying. All those applications are still under study, but with a real possibility of helping to extend the diagnostic spectrum of inhibin dosage in Gynecology and Obstetrics.

[Clinical usefulness of inhibin assays in gynecology and obstetrics]. / Aplicações das dosagens de inibinas em Ginecologia e Obstetrícia.

The main source of inhibin B in women is the growing follicle granulosa cells, while inhibin A is mainly produced by the corpus luteum and the placenta. In infertile women submitted to therapies of assisted reproduction, inhibin B has shown to be useful to predict a poor ovulatory response, though it has not yet overcome the performance of other markers. In the pre-natal screening of the Down syndrome, inhibin A has been repeatedly confirmed as useful in the second trimester and has also started to be considered in the first trimester test battery. Besides the two applications above, the dosage of total inhibin may contribute to the identification of cases of autoimmune ovarian insufficiency. Total inhibin may also be an auxiliary marker in the diagnosis of ovarian epithelial tumors, while the amount of inhibin B helps in the diagnosis of granulosa cells tumors. The use of inhibin A may be extended to the evaluation of pregnant women with risk of abortion, with a history of repeated abortion, with increased risk of pre-eclampsia, or even in the first days of follow-up of hydatiform mole post-emptying. All those applications are still under study, but with a real possibility of helping to extend the diagnostic spectrum of inhibin dosage in gynecology and obstetrics.

Reposiçäo hormonal no climatério: princípios terapêuticos embasados em evidências / Climateric hormonal replacement: therapy based on evidences

Esta revisäo tem por objetivo discutir, com base nas evidências clínicas e epidemiológicas disponíveis, as principais dúvidas que acompanham a terapia de reposiçäo hormonal no climatério (TRH). Embora a soluçäo de várias questöes controversas dependa de estudos ainda em andamento, pode-se concluir que: a TRH é eficaz no alívio dos sintomas climatéricos (Smith et al., 1975); as usuárias de TRH melhoram o perfil lipídico e podem ter menor incidência de doença coronariana, näo só por esse motivo, mas também por efeito direto dos estrogênios sobre as artérias (Ziel & Finkle, 1975); a TRH reduz a perda de massa óssea e previne a ocorrência de fraturas, mas esse benefício requer provavelmente um mínimo de 7 a 10 anos de tratamento contínuo (Whitehead, 1978); em mulheres saudáveis, a TRH näo altera a glicemia, a coagulaçäo nem a pressäo sangüínea, mas pacientes diabéticas, hipertensas ou com história de tromboembolismo requerem um seguimento mais rigoroso e, eventualmente, a administraçäo estrogênica por via näo oral (Voigt et al., 1991); a TRH aumenta sensivelmente o risco relativo de câncer de mama provavelmente a partir de 5-10 anos de uso e 55-59 anos de idade (Hulka, et al 1994); a TRH (estrogênio e progestogênio nas doses recomendadas) näo altera a incidência de câncer de endométrio (Hulka, 1994); a prescriçäo da TRH deve ser individualizada e contemplar os benefícios e riscos potenciais em funçäo da sintomatologia, idade, tempo de menopausa, história pessoal e familiar de cada paciente (Colditz, et al 1995).

Etiopatogenia do diabete melito gestacional / Etiopathogeny of gestational diabetes mellitus

Os fatores que concorrem para o chamado efeito metabólico diabetogênico da gravidez incluem modificaçöes da secreçäo hormonal e da açäo periférica dos hormônios no organismo materno, bem como a síntese e liberaçäo dos hormônios placentários. Ainda näo está claro se o diabete gestacional é causadopor uma secreçäo inadequada de insulina em resposta à ingestäo de carboidratos, por um aumento de resistência periférica à açäo da insulina, ou por ambos os fatores.