Progesterone and IL-1 receptors and VEGF gene polymorphisms in women with recurrent spontaneous abortions

Objetivo: avaliar se polimorfismos de genes que codificam a expressao do receptor de progesterona (PROGINS), do receptor de IL-1 (Pst I) e do fator de crescimento endotelial vascular (-634C/G e 936C/T) podem estar relacionados a ocorrencia de aborto espontaneo de repeticao. Pacientes e metodos: o estudo tem carater caso-controle. Para o grupo caso foram selecionadas pacientes com antecedente de pelo menos tres abortos espontaneos consecutivos (AER), sem etiologia definida. O grupo controle foi composto por mulheres com pelo menos duas gestacoes de termo sem intercorrencias e sem antecedentes de abortamento. Realizada coleta de sangue por puncao venosa periferica e extracao do DNA pelo metodo DTAB/CTAB. As genotipagens foram realizadas por reacao de polimerase em cadeia, seguida de diGestão por enzima de restricao, quando necessario. Resultados: 89 pacientes foram incluidas no grupo caso e 191 no grupo controle. As frequencias encontradas para o polimorfismo PROGINS foram de 72,3% T1/T1 e 27,7% T1/T2 no grupo com AER e 76,4% T1/T1, 22,3% T1/T2 e 1,3% T2/T2 no grupo controle. Nao houve diferencas entre os grupos, analisando-se as frequencias genotipicas (p=0,481) e alelicas (p=0,656). Para o polimorfismo Pst I: grupo com AER − 19,5% CC, 58,4% CT e 22,1% TT; grupo controle − 23,2% CC, 57,4% CT, 19,4% TT. Nao foram encontradas diferencas significantes considerando-se os modelos de heranca co-dominante (p=0,769), dominante (p=0,517) e alelos (p=0,512). Os genotipos encontrados para o polimorfismo -634C/G foram: 22,1% CC, 48,1% CG e 29,9% GG no grupo caso e 12,9% CC, 55,3% CG e 31,8% GG no grupo controle. Os valores encontrados para analises em modelos co-dominante, dominante e frequencias alelicas foram respectivamente de p=0,300; p=0,125 e p=0,317. Na analise do polimorfismo 936C/T, as frequencias do grupo com AER foram de 73,8% CC, 25,0% CT, 1,3% TT e no grupo controle, 78,3% CC, 20,9% CT, 0,8% TT, resultando valores de p=0,451 e p=0,446, respectivamente, para analise dos genotipos em modelo dominante e de alelos. Conclusoes: Nao foi observada associacao entre os polimorfismos de genes que codificam a expressao de receptores de progesterona (PROGINS), de receptor de IL- 1 (Pst I) e de VEGF (-634C/G e 936C/T) e a ocorrencia de aborto espontaneo de repeticaoBV UNIFESP: Teses e dissertaçõe

Evaluation of uterine cavity in patients with recurrent miscarriage

BV UNIFESP: Teses e dissertaçõe

Video laparoscopic intervention for an interstitial pregnancy after failure of clinical treatment

CONTEXT: Interstitial pregnancy is a rare form of ectopic pregnancy for which the best therapeutic course of action has yet to be determined. Surgical intervention entails a high risk of hemorrhage due to the great vascularization of the cornual region of the uterus. Case descriptions facilitate the analysis of results and aid clinicians in determining the most appropriate course of action in these situations. CASE REPORT: In a patient with an ultrasound diagnosis of interstitial pregnancy, clinical treatment using methotrexate was chosen. However, after one week, there was a marked decline in the serum level of the β subunit of chorionic gonadotropin hormone, although an ultrasound examination revealed embryonic cardiac activity. A second dose of the chemotherapy was administered. Embryonic cardiac activity persisted 48 hours later. Video laparoscopy was performed to achieve right-side cornual resection, which resulted in satisfactory resolution of the case

Intervenção videolaparoscópica na gestação intersticial após falha com o tratamento clínico

CONTEXT: Interstitial pregnancy is a rare form of ectopic pregnancy for which the best therapeutic course of action has yet to be determined. Surgical intervention entails a high risk of hemorrhage due to the great vascularization of the cornual region of the uterus. Case descriptions facilitate the analysis of results and aid clinicians in determining the most appropriate course of action in these situations. CASE REPORT: In a patient with an ultrasound diagnosis of interstitial pregnancy, clinical treatment using methotrexate was chosen. However, after one week, there was a marked decline in the serum level of the β subunit of chorionic gonadotropin hormone, although an ultrasound examination revealed embryonic cardiac activity. A second dose of the chemotherapy was administered. Embryonic cardiac activity persisted 48 hours later. Video laparoscopy was performed to achieve right-side cornual resection, which resulted in satisfactory resolution of the case

Polymorphisms in VEGF, progesterone receptor and IL-1 receptor genes in women with recurrent spontaneous abortion

Hormonal, inflammatory and vascular alterations during pregnancy are thought to be involved in pregnancy loss. the role of progesterone, the actions of which involve cytokines and vascular endothelial growth factor (VEGF), has been thoroughly studied. Genetic factors are involved in modulation of these molecules, and several genes have been associated with recurrent spontaneous abortion (RSA), as well other obstetric conditions. Here we investigate the relationship between RSA and gene polymorphisms of the progesterone receptor (PROGINS), interleukin-1 receptor 1 (PstI) and vascular endothelial growth factor (VEGF) (-634, 936). This case-controlled study comprised a total of 89 women with idiopathic RSA and a control group of 191 women with at least two successful pregnancies and no miscarriages. Genomic DNA was extracted from whole blood, and polymorphism genotyping was conducted by digesting PCR products with specific restriction endonucleases. No correlations were found in any of the investigated polymorphisms, even among dominant, co-dominant and additive inheritance models and alleles. Our results support the hypothesis that these specific gene polymorphisms are not the major determinant of pregnancy success. Although we did not find any correlations, the investigation of these and other polymorphisms remains a challenge in the evaluation of RSA. (C) 2010 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilFAPESP: 06/56312-7Web of Scienc

Thrombophilic Mutations and Polymorphisms, Alone or in Combination, and Recurrent Spontaneous Abortion

Generally, recurrent spontaneous abortions (RSAs) have no identifiable cause; yet, vascular alterations during pregnancy may be associated with pregnancy loss. Therefore, we evaluated the association between thrombophilic mutations and RSAs. This case-control study was conducted in 112 patients who had RSAs and 98 health control women. Genomic DNA was extracted from whole blood, and polymorphism genotyping was conducted using polymerase chain reaction. the following 6 genetic variants were analyzed: factor V Leiden, prothrombin mutation, methylenetetrahydrofolate reductase C677T and A1298C, plasminogen activator inhibitor type 1 (4G>5G), and factor XIII G103T (V34L). No correlations were found in any of the investigated polymorphisms. Moreover, 35.0% of cases and 25.5% of controls had at least 2 mutations in combination, and 4.8% of cases and 5.1% of controls had 3, but these combinations were not associated with additional risk. in conclusion, we found no association between the polymorphisms studied and the occurrence of RSAs.Universidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilColsan Assoc Beneficente Coleta Sangue, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Obstet, São Paulo, BrazilWeb of Scienc

Cervical cerclage placement decreases local levels of proinflammatory cytokines in patients with cervical insufficiency

BACKGROUND: Cervical insufficiency is characterized by premature, progressive dilation and shortening of the cervix during pregnancy. If left unattended, this can lead to the prolapse and rupture of the amniotic membrane, which usually results in midtrimester pregnancy loss or preterm birth. Previous studies have shown that proinflammatory cytokines such as interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha are up-regulated in normal parturition but are also associated with preterm birth. Studies evaluating such markers in patients with cervical insufficiency have evaluated only their diagnostic potential. Even fewer studies have studied them within the context of cerclage surgery. OBJECTIVES(S): The objective of the study was to evaluate the impact of local and systemic inflammatory markers on the pathogenesis of cervical insufficiency and the effect of cerclage surgery on the local immune microenvironment of women with cervical insufficiency. STUDY DESIGN: We recruited 28 pregnant women (12- 20 weeks' gestation) diagnosed with insufficiency and referred for cerclage surgery and 19 gestational age-matched normal pregnant women as controls. Serum and cervicovaginal fluid samples were collected before and after cerclage surgery and during a routine checkup for normal women and analyzed using a targeted 13-plex proinflammatory cytokine assay. RESULTS: Before surgery, patients with cervical insufficiency had higher levels of interleukin-1b, interleukin-6, interleukin-12, monocyte chemoattractant protein-1 and tumor necrosis factor alpha in cervicovaginal fluid compared to controls, but after surgery, these differences disappeared. No differences were found in serum of insufficiency versus control women. In patients with insufficiency, the levels of interleukin-1b, interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and interferon gamma in cervicovaginal fluid declined significantly after cerclage compared with before intervention, but these changes were not detected in serum. CONCLUSION: Compared with normal women, patients with cervical insufficiency have elevated levels of proinflammatory cytokines in cervicovaginal fluid but not in serum, suggesting a dysregulation of the local immune environment. Cerclage intervention led to a significant decline in these proinflammatory cytokines, suggesting that cerclage may help reduce local inflammation in cervical insufficiency.Canadian Institutes of Health ResearchMITACS GlobalinkQueens Univ, Dept Biomed & Mol Sci, Kingston, ON, CanadaUniv Fed Sao Paulo, Escola Paulista Med, Dept Obstet, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Obstet, Sao Paulo, BrazilWeb of Scienc

Why do we waste anti-D immunoglobulin in early miscarriage?

OBJECTIVE: evaluation of fetomaternal hemorrhage (FMH) in patients who would need Rh alloimmunization with anti-D immunoglobulin (300 mug) prophylaxis after early miscarriage. METHOD: we included in the study Rh (D) negative blood group patients with positive or unknown Rh (D) partners, who had had a miscarriage up to 12 weeks of gestation, and had been admitted to hospital for uterine curettage. After this procedure 5 ml of venous blood was collected from the patients and the rosette test was applied to screen which patients would need quantitative determination of fetal blood transferred to the maternal circulation, by the Kleihauer-Betke test (K-B). RESULTS: out of 26 patients evaluated the rosette test was positive in one , who showed an FMH of 1.5 ml in the K-B test. CONCLUSIONS: the dose of anti-D immunoglobulin used in cases of miscarriage up to 12 weeks of gestation should be substantially reduced. The availability of preparations of 50 mug is recommended, for a more inexpensive and rational treatment.OBJETIVO: avaliação da hemorragia feto-materna (HFM) nas pacientes que receberiam profilaxia da aloimunização Rh com emprego de imunoglobulina anti-D (300 mig), pós-aborto precoce. MÉTODO: foram admitidas no estudo pacientes do grupo sanguíneo Rh negativo, com parceiro Rh positivo ou ignorado, com quadro de aborto até 12 semanas de gestação internadas para curetagem uterina. Uma amostra de 5 ml de sangue venoso destas pacientes foi obtida após o procedimento, na qual realizamos o teste qualitativo de roseta para detectar quais casos necessitariam determinação quantitativa do volume de sangue fetal transferido para circulação materna, que foi então apurado pelo teste de Kleihauer-Betke (K-B). RESULTADOS: das 26 pacientes avaliadas, em uma o teste de roseta foi positivo, e o teste de K-B apontou HFM de 1,5 ml. CONCLUSÕES: a dose de imunoglobulina anti-D nos casos de abortamento até a 12ª semana de gestação deveria ser substancialmente reduzida, parecendo-nos oportuna a disponibilização no mercado nacional de apresentação com 50 mig, que representaria além da economia, maior racionalidade