As trombofilias na perda gestacional de repetição: uma revisão de prevalência e condutas / Thrombophilias in recurrent pregnancy loss: a review of prevalence and conduct

Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.

Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.

Atualidades em perda gestacional de repetição: definição, diagnóstico e propedêutica / Current guidelines for recurrent pregnancy loss: definition, diagnostic tests and investigation

Classicamente, a perda gestacional de repetição (PGR) é a ocorrência de três ou mais perdas consecutivas antes de 20 semanas de gestação. Entretanto, as diretrizes para definição, propedêutica e tratamento são controversas. As causas de PGR podem ser multifatoriais e incluem alterações anatômicas do útero, distúrbios endócrinos, alterações imunológicas, infecções, alterações genéticas, obesidade materna, entre outras. Entretanto, na maioria dos casos, a causa de PGR é desconhecida. Os protocolos para o diagnóstico de PGR variam muito e são direcionados à pesquisa de possíveis fatores causais. Neste artigo foi realizada uma revisão e comparação das últimas diretrizes para diagnóstico e propedêutica das causas de PGR da Sociedade Europeia de Reprodução Humana e Embriologia (ESHRE), da Sociedade Americana de Medicina Reprodutiva (ASRM) e do Royal College of Obstetricians and Gynaecologists (RCOG).(AU)

Recurrent pregnancy loss (RPL) is traditionally defined by the occurrence of three or more consecutive losses before 20 weeks of gestation. The guidelines for definition, investigations and treatments are controversial. The causes of RPL can be multifactorial and includes structural uterine anomalies, endocrine alterations, immunological dysfunction, infections, genetic anomalies, maternal obesity, among others. However, in most cases the cause of RPL is unknown. The diagnosis protocols of RPL vary widely and causal factors are the major goal. In this article, we review and compare the latest RPL diagnosis and investigations guidelines, including the European Society for Human Reproduction and Embryology (ESHRE), American Society for Reproductive Medicine (ASRM) and the UK Royal College of Obstetricians and Gynaecologists (RCOG).(AU)

Anticoagulação e prevenção de morbidade obstétrica em trombofilias hereditárias: mito ou verdade? / Anticoagulation and prevention of obstetric morbidity in hereditary thrombophilia: myth or truth?

Tem sido observado, corriqueiramente, o uso indiscriminado de anticoagulantes durante a gravidez com a finalidade de evitar perdas gestacionais. A eficácia do uso de anticoagulantes na prevenção de perdas, precoces e tardias, tem sido questionada, levando-se em consideração os impactos econômicos, sociais e psicológicos gerados nas famílias a partir da indicação da utilização dessa terapia. Dada a relevância do tema, realizou-se uma revisão da literatura nos bancos de dados PubMed, Cochrane Library e Medline com a finalidade de avaliar evidências científicas do uso e da eficácia de anticoagulação na gravidez. Na literatura revisada, não foi possível sustentar a hipótese de que a anticoagulação é capaz de intervir ativamente no sucesso do curso da gravidez. Conclui-se, portanto, que mais estudos devem ser realizados a fim de determinar intervenções eficazes ao casal, preservar a saúde do concepto e minimizar o impacto econômico, social e psicológico da utilização de anticoagulantes durante a gravidez.(AU)

In medical practice, the anticoagulants indiscriminate use during pregnancy has been commonly observed to prevent future pregnancy losses. The effectiveness of using anticoagulants in preventing losses, early and late, has been questioned taking into account the economic, social and psychological impacts generated on families from the indication of the use of such drugs. Given the relevance of the topic, a literature review was carried out in the PubMed, Cochrane Library and Medline databases in order to assess scientific evidence on the anticoagulation efficacy use in pregnancy. It was not possible to support the hypothesis that anticoagulation is able to actively intervene in the success of the course of pregnancy. It is concluded, therefore, that more studies should be carried out in order to determine effective interventions for the couple, preserve the health of the fetus and minimize the economic, social and psychological impact of the anticoagulants use during pregnancy.(AU)

Models for releasing the lupus anticoagulant test / Modelos de liberação do teste anticoagulante lúpico

ABSTRACT Introduction: Thrombophilia is a thrombosis susceptibility of genetic, acquired or mixed nature. Among acquired causes, the antiphospholipid syndrome (APS) stands out as an autoimmune disease characterized by antiphospholipid antibodies, thrombotic events or recurrent gestational loss. Laboratory diagnosis is based on the detection of lupus anticoagulant (LAC), anti-β2-glycoprotein 1 and anticardiolipin; however the determination of LAC still demands uniformity. The last guideline published by the Clinical and Laboratory Standards Institute (CLSI) prioritizes the screening and confirmatory steps, to the detriment of the mixing phase. Objectives: To compare the forms of releasing the LAC and to adopt an investigation protocol in agreement with the international guidelines. Methods: Thirty-six samples with prolonged results in the screening step by the dilute Russell viper venom time (dRVVT) or activated partial thromboplastin time (APTT) were subjected to the mixing steps (1:1) and to the confirmatory steps with high concentrations of phospholipids. Results: For APTT, values whose indexes of circulating anticoagulant (ICA) were greater than 15% were considered positive. For dRVVT, the ratio between screening and confirmation was also used. Of the 36 tested samples, 14 showed correction in the mixing step, but only one resulted negative. Conclusion: ICA aided in identifying the weak antibodies that were probably diluted in the mixing step. There is no gold standard test for the diagnosis of APS, and LAC detection still requires standardization of technique and interpretation.

RESUMO Introdução: Trombofilia é a suscetibilidade à trombose, de natureza genética, adquirida ou mista. Entre as causas adquiridas, destaca-se a síndrome do anticorpo antifosfolípide (SAF) - doença autoimune caracterizada por anticorpos antifosfolípides, eventos trombóticos ou perda gestacional recorrente. O diagnóstico laboratorial baseia-se na detecção do anticoagulante lúpico (ACL), do anti-β2-glicoproteína 1 e da anticardiolipina; entretanto a execução do ACL ainda demanda uniformização. A última diretriz publicada pelo Clinical and Laboratory Standards Institute (CLSI) prioriza as etapas de triagem e confirmatória, em detrimento da mistura. Objetivos: Comparar as formas de liberação do ACL e adotar um protocolo de investigação em anuência às normas internacionais. Métodos: Trinta e seis amostras com resultados prolongados na etapa de triagem pelo ensaio do tempo do veneno da víbora de Russel (dRVVT) ou tempo de tromboplastina parcial ativada (TTPA) foram submetidas às etapas de mistura (1:1) e confirmatórias com altas concentrações de fosfolipídios. Resultados: Para o TTPA, foram considerados positivos os valores cujo cálculo do índice de circulação de anticoagulante (ICA) resultasse superior a 15%. Para o dRVVT, utilizou-se também o valor da razão entre triagem e confirmatória. Das amostras testadas, 14 revelaram correção na etapa da mistura, mas somente uma resultou em pesquisa negativa. Conclusão: O cálculo do ICA auxiliou na identificação dos anticorpos fracos que possivelmente sofreram diluição na etapa da mistura. Não há um exame padrão-ouro para o diagnóstico da SAF, e a pesquisa do ACL ainda demanda uniformização da técnica e da interpretação.

Study on the Relationship Between Estrogen Receptor β Gene Polymorphism and Unexplained Recurrent Spontaneous Abortion / 实用妇产科杂志

Objective:To study the relationship between polymorphism of estrogen receptor β gene(ESR2)and unexplained recurrent spontaneous abortion(URSA).Methods:A total of 85 women with recurrent spontaneous abortion were recruited in our hospital from August 2010 to May 2015.A total of 85 healthy ethnically matched women with two or more successful pregnancies and live births and no history of complicated pregnancies were recruited as the control group.5 ml elbow vein blood was extracted in the menstrual cycle of 2-3 days,and serum levels of follicle stimulating hormone(FSH),luteinizing hormone(LH),and estradiol(E2) were measured and compared between two groups,the rs1256049,rs4986938 and rs1256030 polymorphisms of ESR2 gene were detected and the correlation between ESR2 gene locus polymorphism and URSA was analyzed.Results:There was no significant difference in FSH and E2 level between the two groups (P ＞ 0.05).The level of LH in the study group was significantly higher than that in the control group (P ＜ 0.05).There were no significant differences in the rs1256049 locus,rs4986938 locus and rs1256030 locus between the two groups.The level of FSH,LH and E 2 in rs1256049 locus,rs4986938 locus,rs1256030 locus of all genotypes of females were not statistically significant (P ＞ 0.05).There was a negative correlation between the polymorphism of rs1256049 locus and the rs4986938 locus among all subjects,and rs4986938 locus were positively correlated with rs1256030 polymorphism.There was a positive correlation between the rs4986938 locus and rs1256030 locus polymorphism (r =0.38,P =0.00) in the control group,and there was a negative correlation between the rs1256049 locus and the polymorphism of the rs4986938 locus in the study group (r =-0.17,P =0.02).Conclusions:There is no significant relationship between ESR2 polymorphism and URSA.There is a certain correlation between the three mutation sites of ESR2 gene,and this correlation is different between the two groups,but whether there is a link between URSA and this difference still needs further study.

Professor LU Qibin's Clinical Experience in the Diagnosis and Treatment of Recurrent Spontaneous Abortion / 浙江中医药大学学报

[Objective]In this paper, valuable experience would be shared and the culture of Chinese medicine will be inherited through introducing the clinical experience of Professor LU Qibin in the diagnosis and treatment of RSA. [Methods]From the point of cause and pathology as well as therapeutic method of the disease, the author discussed the special treatment of Professor LU Qibin. At the same time, the author focuses on introducing the dialectics and characteristics of professor LU Qibin's treatment of complicated recurrent spontaneous abortion. In order to elaborate clearly, some clinical cases were reported. [Results]Professor LU Qibin has summarized that spleen-kidney deficiency is the foundation of recurrent spontaneous abortion. In consequence, invigorating the spleen and kidney is the basic treatment. For the complicated recurrent spontaneous abortion, Professor LU Qibin has many assistant methods on the basis of invigorating spleen and kidney. Such as clearing heat and activating blood, warming and invigorating the spleen and kidney and so on. Furthermore, Professor LU Qibin insists the treatment of traditional Chinese medicine coordinate with western medical therapies. In the reported cases, patients were successfully cured. [Conclusion]Professor LU Qibin is experienced and the clinical curative effect is remarkable. Hence, the clinical experience of Professor LU Qibin in the diagnosis and treatment of recurrent spontaneous abortion was worth of learning and wide application.

Etiological evaluation of repeated biochemical pregnancy in infertile couples who have undergone in vitro fertilization

OBJECTIVE: This study aims to investigate whether there are any notable etiologies for repeated biochemical pregnancy (RBP) and, if so, to compare those etiologies associated with repeated spontaneous abortion in infertile couples who have undergone in vitro fertilization (IVF). METHODS: Forty-four infertile couples who underwent IVF and experienced RBP were included in this study. RBP was defined as more than 2 early pregnancy losses that occurred before the detection of a gestational sac, with ectopic pregnancies specifically excluded by serial serum beta human chorionic gonadotropin evaluation. Forty-three infertile couples who underwent IVF and experienced recurrent spontaneous abortion (RSA) were included as a control group. Karyotype analysis, anatomic evaluation of uterus, endocrine and immunological evaluation were performed. In addition, the number of pregnant women confirmed by 12 weeks' gestation was compared between groups. RESULTS: Immunological factors (RSA: 20.9% vs. RBP: 29.5%, P=0.361), diminished ovarian reserve (RSA: 10.9% vs. RBP: 17%, P=0.552), and parental chromosomal abnormalities (RSA: 18.6% vs. RBP: 9.1%, P=0.218) were not different between groups. Additionally, the incidence of uterine factors (RSA: 11.6% vs. RBP: 4.6%, P=0.206), unknown cause (RSA: 48.8% vs. RBP: 54.5%, P=0.161), and the pregnancy outcome identified until 12 weeks' gestation (RSA: 46.5% vs. RBP: 38.6%, P=0.520) did not differ between groups. CONCLUSION: In the present study, the causes of RBP after IVF were similar to those of RSA. Accordingly, we suggest that efforts should be made to define the etiology of RBP, particularly for infertile couples, and that possible management strategies should be offered.

Depression in Women with Recurrent Miscarriages - an Exploratory Study / Depressão em mulheres com perdas gestacionais recorrentes - um estudo investigativo

ABSTRACT Objective: To assess depression, domestic violence and the use of substances in women with recurrent miscarriages. Methods: The Abuse Assessment Screen (AAS), the Edinburgh Postnatal Depression Scale (EPDS) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were used to assess violence, depression and the use of substances among women with recurrent miscarriages. The population corresponded to patients receiv-ing prenatal care from June to August 2014. Multiple logistic regression was used to assess the multivariable relationship between depression and sociodemographic, psychosocial and medical characteristics (p < 0,10). Results: The prevalence of depression was of 41.3% (95% confidence interval [CI] 1/4 28.3-55.7%). One third of the pregnant women (32.6%) reported emotional or physical violence, and 13% were classified as abusing or addicted to tobacco according to ASSIST. History of psychiatric diseases was associated with depression (p 1/4 0.005). Violence during life demonstrated a modest association (p 1/4 0.073) with depression, as well as the number of miscarriages (p 1/4 0.071). Conclusion: Depression is a frequent disease among pregnant women with recurrent miscarriages. The results of this investigation suggest that a systematic assessment of depression and its associated conditions, such as domestic violence and the use of substances, should be part of the prenatal follow-up visits for women with recurrent miscarriages.

RESUMO Objetivo: Avaliar a presença de depressão, violência doméstica e uso de substâncias em gestantes com história de perdas gestacionais de repetição. Métodos: Foram utilizados os instrumentos: Edinburgh Postnatal Depression Scale (EPDS), Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Abuse Assessment Screen (AAS), além de um questionário com dados sociodemográficos e clínicos elaborado pelos investigadores. As variáveis que apresentaram associação com depressão na análise bivariada (p < 0,10), tais como número de abortos e violência durante a vida, entraram no modelo de regressão logística. Resultados: Foram entrevistadas 46 pacientes, sendo encontrada uma prevalência de depressão de 41,3% (intervalo de confiança [IC] de 95% 1/4 28,3-55,7%). Com relação à violência contra a mulher, um terço das gestantes (32,6%) foi vítima de violência emocional ou física pelo seu parceiro ou por alguém próximo a elas. O abuso e/ou dependência de tabaco estava presente em 13% das gestantes, segundo o ASSIST. Na análise bivariada, observou-se uma associação significativa entre histórico de doença psiquiátrica e depressão em mulheres com abortamento de repetição (p 1/4 0,005). Observamos também uma tendência de associação entre depressão, número de abortos (p 1/4 0,071) e histórico de violência durante a vida (p 1/4 0,073) . Conclusão: Depressão é uma doença frequente entre as gestantes com abortamento de repetição. A sobreposição entre depressão, violência doméstica e uso de substâncias aponta para a necessidade do rastreio sistemático dessas condições no pré-natal de gestantes com perdas gestacionais de repetição.

Clinical Observation of Habitual Abortion Patients Treated by Yishen Tianjing Zhuyun Prescription Together with Active Lymphocyte Immunotherapy / 广州中医药大学学报

Objective To investigate the therapeutic effect of Yishen Tianjing Zhuyun Prescription(a Chinese herbal recipe consisting of Xianqi Yizhen Capsules and Xianzi Yizhen Capsules, having the actions of strengthening kidney-essence and promoting gestation) together with active lymphocyte immunotherapy for habitual abortion (HA)patients. Methods A total of 139 HA outpatients with negative blocking antibodies(BA)were randomly divided into treatment group(70 cases) and control group(69 cases). The control group was treated only with active lymphocyte immunotherapy, while the treatment group was treated with Yishen Tianjing Zhuyun Prescription and active lymphocyte immunotherapy . Results (1) After treatment, the BA-positive rate was 82.86% in the treatment group and was 60.87% in control group, and there existed significant difference between the two groups (P < 0.05 ). (2) The total anti-abortion effective rate was 87.14% in the treatment group and was 66.67% in control group, the difference being significant between the two groups(P<0.05 ). Conclusion Yishen Tianjing Zhuyun Prescription combined with active lymphocyte immunotherapy is more effective than active lymphocyte immunotherapy alone for the treatment of HA patients with negative BA.

Aborto Recurrente de Etiología Autoinmune / Autoimmune Recurrent Abortion

El curso normal del embarazo implica una serie de cambios inmunológicos que permiten el desarrollo armónico fetal. En mujeres con pérdida recurrente de la gestación, diversas etiologías se han relacionado como desencadenantes de dichas pérdidas; jugando el factor autoinmune un papel cada vez más importante. En el presente artículo, a partir de una búsqueda sistemática de información, se exponen en detalle los aspectos inmunológicos del embarazo normal, así como las alteraciones que a este nivel se presentan en mujeres con aborto recurrente. Además, se realiza una orientación diagnóstica y se exponen las diversas opciones terapéuticas utilizadas, haciendo énfasis en la necesidad de establecer protocolos estandarizados para el manejo de esta entidad.

Normal development of the pregnancy involves a number of immunological changes that allow harmonic fetal development. In women with recurrent pregnancy loss several etiologies have been implicated as triggers of such losses; autoimmune factor is nowadays playing an increasingly more important roll. In this article, based on a systematic search of information, are exposed in details the immunological aspects of normal pregnancy, as well as the immune alterations that occur in women with recurrent abortion. In addition, a diagnostic guidance is made and the various therapeutic options used are pointed out, emphasizing the need to establish standardized protocols for the management of this entity.

Predictors of miscarriage: a matched case-control study / 한국역학회지

OBJECTIVES: The risk factors for miscarriage vary across communities and countries. This study was conducted to investigate the predictors of miscarriage in the west of Iran. METHODS: This matched case-control study was conducted in Hamadan Province from April 2013 to March 2014. Cases were selected from women who had a recent spontaneous abortion and controls were selected from women who had a recent live birth. Two controls were selected for every case and matched for date of pregnancy and area of residence. Multivariate conditional logistic regression analysis was performed and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Five hundred fifty cases were compared with 1,091 controls. The OR of miscarriage was 1.58 (95% CI=1.30-1.92) for every five-year increase in age, 0.20 (95% CI=0.14-0.28) for every live birth, and 3.43 (95% CI=2.03-5.79) for a history of previous spontaneous abortion. Compared to nulliparous women, primiparous or multiparous women had an OR of 17.85 (95% CI=6.65-47.91) for miscarriage. There was a strong association between miscarriage and abnormal amniotic status (OR, 2.46; 95% CI, 0.46-13.09) and also abnormal placenta status (OR, 10.44; 95% CI, 0.95-114.92); however, these associations were not statistically significant. No significant associations were observed between miscarriage and body mass index, previous history of stillbirth, low birth weight, congenital anomaly, ectopic pregnancy, impaired thyroid function, or high blood pressure. CONCLUSIONS: Our study suggests that miscarriage is a multifactorial outcome associated with several modifiable and non-modifiable risk factors that may vary among different communities.

Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases

OBJECTIVE: The purpose of this study was to determine the frequency and distribution of cytogenetically abnormal miscarriages in couples with spontaneous abortions (SA) or recurrent miscarriages (RM). METHODS: Karyotyping of specimens from 164 abortuses with SA and 86 abortuses with RM was successfully performed according to the standard cytogenetic methods using G-banding technique. RESULTS: Among the total 164 cases of SA group, 81 (49.4%) were euploid and the rest (83, 50.6%) showed chromosomal abnormalities. In RM(> or =2) and RM(> or =3) group, 31 (36.0%)/27 (34.6%) cases were euploid and 55 (64.0%)/51(65.4%) cases were abnormal, respectively. A statistically significant difference was found in the rate of cytogenetic abnormality between SA and RM groups (P or =35 years) had a higher rate of chromosome anomalies compared with women younger than age 35 (normal:abnormal = 32.4%:67.6% for > or =35 years and 53.8%:46.2% for or =35 years and 43.3%:56.7%/40.0%:60.0% for or =2) and RM(> or =3), respectively; P<0.05). In SA group, an increase of normal karyotypes was noted with increased gestational age (<10 week, 38.0%; 10-15 week, 53.5%; 16-20 week, 65.7%). In RM group, most of cases were in <10 week and the frequency of trisomies with chromosomes 1 to 10 were increased compared with that of SA. CONCLUSION: There was a statistically significant difference in the frequency and distribution of chromosomal abnormalities between SA and RM groups. Our results will provide useful information for diagnosis and genetic counseling of patients with SA or RM.

Aborto recurrente de etiología aloinmune / Alloimmune recurrent spontaneous abortion

Los mecanismos que subyacen la reproducción humana son muy complejos, por lo que cualquier pérdida gestacional implica el tener que considerar diversas etiologías, más aun si se trata de pérdidas gestacionales recurrentes dentro de las que la inmunidad juega un papel especialmente importante. Desde hace varias décadas, el factor aloinmune ha sido reconocido como un desencadenante frecuente de la interrupción del embarazo, haciéndose de esta forma relevante su estudio en mujeres con aborto recurrente. En el presente artículo, a partir de una búsqueda sistemática de información, se revisan con detalle los aspectos relacionados con la fisiopatología, el diagnóstico y el tratamiento del aborto recurrente de etiología aloinmune, buscando con esto sensibilizar al profesional de la salud sobre su consideración ante una mujer con pérdida recurrente de la gestación.

The mechanisms underlying the human reproduction are very complex, so any pregnancy loss implies the need of considering various etiologies, even more if those pregnancy losses are recurrent within which the immunity plays an important role. Since decades, the alloimmune factor has been recognized as a frequent trigger of the pregnancy interruption, thus becoming relevant its study in women with recurrent miscarriage. In the present article, through a systematic search of information, details concerning to the physiopathology, diagnosis and treatment of the recurrent miscarriage of alloimmune etiology are reviewed, looking to sensitize the health professional about its consideration when evaluating a woman with recurrent pregnancy loss.

Uso de la heparina de bajo peso molecular y aspirina en una paciente con síndrome antifosfolípido y pérdida gestacional recurrente / Use of low molecular weight heparin and aspirin in a patient with antiphospholipidsyndrome and recurrent pregnancy loss

Introducción: La pérdida gestacional recurrente (PGR) es una patología frecuente, que causa gran impacto en las parejas conllevando frustración, ansiedad, depresión, gastos excesivos y hasta rupturas de la relación de pareja. Su etiología es multicausal y frecuentemente no se logra determinar . Se presenta el caso de una paciente con PGR quien luego de seis pérdidas gestacionales, en el séptimo embarazo se detectaron anticuerpos antifosfolípidos altos, recibiendo tratamiento de tromboprofilaxis doble hasta la semana 32, obteniéndose un producto pretérmino vivo y sano que evolucionó satisfactoriamente. Se discuten dificultades para la precisión diagnóstica y las modalidades de tratamiento descritos. [Salazar HA, Lancheros EA, Becerra CH. Uso de heparina de bajo peso molecular y aspirina en una paciente con síndrome antifosfolípido y pér-dida gestacional recurrente. MedUNAB 201 1;14(3):188-192].

Recurrent pregnancy lost (RPL) is a common condition that causes great impact on partners leading frustration, anxiety , depression, excessive spending and even breaks in the relationship. Its etiology is multifactorial and often can not be determined. This paper describes a case of a patient who after six RPL losses, in the seventh pregnancy is detected high positive antiphospholipid antibodies. She receive thromboprophylaxis twice a week until 32 weeks of gestational age, produced an healthy preterm newborn with a good prognosis. We discuss difficulties in the diagnostic accuracy and treatment modalities described. [Salazar HA, Lancheros EA, Becerra CH. Use of low molecular weight heparin and aspirin in a patient with antiphospholipidsyndrome and recurrent pregnancy loss. MedUNAB 2011;14(3):188-192].

The role of methylenetetrahydrofolate reductase C677T polymorphism on the peripheral blood natural killer cell proportion in women with unexplained recurrent miscarriages / 대한생식의학회지

OBJECTIVE: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. METHODS: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. RESULTS: No differences were found between the two groups' mean plasma homocysteine levels (7.6+/-1.5 micromol/L vs. 7.1+/-2.1 micromol/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant (7.7+/-1.1 micromol/L) had higher homocysteine levels than those with the CC and CT variants (7.4+/-1.9 micromol/L and 7.4+/-1.2 micromol/L) and those with the CT variant (19.2+/-8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7+/-6.6% and 17.9+/-7. 0%), but the results of both comparisons were statistically insignificant. CONCLUSION: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.

Hidrops fetal como manifestación ecográfica de una enfermedad familiar: incontinentia pigmenti (síndrome de bloch-sulzberger) / Hydrops fetalis as a echographic manifestations of a familial disease: incontinentia pigmenti (bloch-sulzberger syndrome)

Diagnóstico de un caso de enfermedad familiar a partir de un hidrops fetal. Gestante con 2 abortos previos ocurridos al inicio del segundo trimestre, ambos fetos masculinos. Se detecta en la semana 12 un higroma quístico en el contexto de un hidrops fetal. Estudio serológico (TORCH y parvovirus B12), con resultado negativo y biopsia corial con cariotipo 46 XY. La anamnesis y exploración detallada hacen sospechar una enfermedad ligada al cromosoma X, dado que la paciente y una hermana están afectas de una genodermatosis desde la infancia: Incontinentia Pigmenti.

We revealed a family disease by a fetal anomaly. The patient had a history of two early miscarriages of male fetuses. In the present pregnancy hydrops fetalis was demonstrated by routine ultrasound sean at 12 weeks. Serological tests were negative and chorionic villous sampling revealed normal karyotype, 46XY. We suspected a X-linked disease. Detailed family history leaded to the demonstration that the patient and a sister were affected of a rare genodermatosis: Incontinentia Pigmenti.

Casais com abortamento espontâneo recorrente: participação das translocações cromossômicas / Couples with recurrent miscarriages: contributions of chromosome translocations

Objetivo: A etiologia do abortamento recorrente (AR) é multifatorial e, em cerca de 50% dos casos, não éesclarecida. Dentre os diferentes fatores associados (anatômico, genético, imunológico, endócrino, ambiental), as causas cromossômicas têm um papel relevante. Portanto, este estudo teve como objetivo investigar citogeneticamente a ocorrência de anomalias cromossômicas em casais com pelo menos dois abortamentos espontâneos no primeiro trimestre de gestação. Método: Foram avaliados os cariótipos de 24 casais, encaminhados ao Laboratório de Citogenética e Biologia Molecular, IBILCE-UNESP, Campus de São José doRio Preto, SP, devido história de pelo menos dois abortamentos espontâneos em primeiro trimestre de gestação.Os cariótipos foram estabelecidos a partir de cultura de linfócitos de sangue periférico e bandeamentos G eC. Resultados: Estes casais relataram um total de 49 abortos, com uma média de 2 abortos/casal, principalmenteentre as 6-8 semanas de gestação. A análise cromossômica identificou um indivíduo com aumento da constrição secundária do braço longo do cromossomo 9 (46,XX,9qh+), considerado uma variante cromossômica normal e a ocorrência de translocações balanceadas em quatro casais (17%): 46,XY,t(8;13)(q22;q22);46,XY,t(4;5)(q25;q33); 46,XX,t(11;14)(p10;q10) e 46,XY,t(10;13)(p10;q10). Estas translocações ocorreram mais freqüentemente no cônjuge do sexo masculino, e com freqüência média acima da relatada na literatura (5% a10%). Conclusão: Os resultados são importantes, pois reforçam a contribuição das translocações na etiologia dos AR e auxiliam quanto ao risco e ao aconselhamento genético dos casais nas gestações futuras.

Objective: The etiology of the recurrent abortion (RA) is multifactorial. Approximately 50% of the cases arenot well identified. Among the different associated factors (anatomical, genetic, immunological, endocrine, environmental), the chromosomal causes play an important role. Therefore, the objective of this study was to investigate cytogenetically the occurrence of chromosomal abnormalities in couples who presented at least two spontaneous abortions in the first trimester of gestation. Method: The karyotypes of 24 couples wereevaluated, after lymphocytes culture of peripheral blood and G and C banding analysis. These couples were referred to the Cytogenetic and Molecular Biology Laboratory, IBILCE-UNESP, São José do Rio Preto, SP, forchromo some analysis, after two or more miscarriages in the first trimester of gestation. Results: These couples reported a total of 49 abortions, and the mean number of miscarriages per couple was two, mainly between the 6-8 weeks of gestation. The chromosomal analysis identified an individual with increased secondary constriction of the long arm of chromosome 9 (46, XX, 9qh+), which is considered a normal chromosomal variant, and the occurrence of balanced translocations in four couples (17%):46,XY,t(8;13)(q22;q22); 46,XY,t(4;5)(q25;q33); 46,XX,t(11;14)(p10;q10) and 46,XY,t(10;13)(p10;q10). These translocations were more frequent in the male gender, and with a mean higher frequency than the ones reported in the literature (5%-10%). Conclusions: These results are important to reinforce the contribution ofthe translocations in RA etiology, and to advise towards the risk and genetic counseling for couples infurther gestations.

Evaluación de cinco polimorfismos de genes trombofílicos en parejas con aborto habitual / Assessment of five thrombophilic genetic polymorphisms among couples with habitual abortion

Se han propuesto factores genéticos trombofílicos asociados con anormalidades obstétricas que implican la terminación temprana del embarazo. El propósito del estudio fue investigar la posible asociación de polimorfismos génicos trombofílicos con el aborto habitual (AH). Se analizaron muestras de dos grupos de personas que participaron voluntariamente en el estudio. El primero (n>100) consistió en mujeres atendidas en el Centro Médico de Occidente del Instituto Mexicano del Seguro Social y a sus parejas, por el antecedente reproductivo de por lo menos tres abortos idiopáticos (n>100). El grupo de referencia (n>200) lo formaron adultos sanos de ambos sexos residentes de Jalisco. El ADN se extrajo de una muestra de sangre periférica y se tipificaron, mediante PCR–RFLP o –SSP, los polimorfismos FII G20210A, FV G1691A, MTHFR C677T, ECA I/D y TNF G–308A. Las proporciones genotípicas en el grupo de referencia fueron similares a las predichas por la ley de Hardy–Weinberg y las comparaciones intergrupales alélicas, genotípicas y fenotípicas no mostraron diferencias significativas para ninguno de los polimorfismos estudiados. Estos resultados sugieren que los polimorfismos de los genes trombofílicos no representan un factor de riesgo para AH en nuestro medio.

An association between thrombophilic genes and obstetric conditions with early pregnancy termination has been previously proposed. In the present study we attempted to evaluate the possible association between thrombophilic genetic polymorphisms and habitual abortion (HA). Samples from two groups of volunteers were analyzed. The experimental group (n>100) was conformed by women attending the Centro Medico de Occidente, IMSS and their male couples, with a reproductive history ofat least three miscarriages. The reference group (n > 200) was composed by male and female healthy adults living in the state of Jalisco, Mexico. DNA was extracted from peripheral blood, and polymorphisms FII G20210A , FVG1691A, MTHFR C677T, ECA IID y TNF G-308A were typed by PCR-RFLP or -SSP. Genotype proportions in the reference group were in agreement with the HardyWeinberg expectations. Allele, genotype, and phenotype proportion inter-group comparisons did not show statistically significant differences. The present results could not demonstrate that thrombophilic polymorphisms constitute risk factors for HA in Jalisco.

Clinical Characteristics of Habitual Abortion According to the Etiological Classification / 대한산부인과학회지

OBJECTIVE: To determine the frequency of factors associated with habitual abortion in 198 Korean couples. METHODS: A total of 198 cases at the department of Obstetrics and Gynecology, Asan Medical Center, Korea from July 1989 to December 2001 that were diagnosed as habitual abortions were included in this study. The cases were divided into 2 main groups; a primary habitual abortion group and a secondary habitual abortion group. They were classified according to etiology. RESULTS: The number of primary habitual abortion cases was 157 (79.3%) and that of secondary habitual abortion cases was 41 (20.7%). The mean age and number of previous abortions were not different between the two groups. The etiologic factors of the primary habitual abortions were anatomical (31.8%, 42/132), immunologic (24.2%, 32/132), unexplained (23.5%, 31/132), endocrinologic (15.2%, 20/132), genetic (12.9%, 17/132), and infection (1.5%, 2/132). The factors of the secondary habitual abortions were immunologic (36.8%, 14/38), unexplained (28.9%, 11/38), anatomical (21.1%, 8/38) and endocrinologic (13.2%, 5/38). The successful pregnancy rate following secondary habitual abortion was 42.0% (17/38), significantly higher than that following primary habitual abortion which was 34.8% (50/132) (p-value<0.05). CONCLUSION: The differences in etiologic factors between primary and secondary habitual abortions are statistically significant. The prognosis of a later successful pregnancy was significantly better in cases of secondary habitual abortion.

Contribution of Thymidylate Synthase Enhancer Region (TSER) Polymorphism to Total Plasma Homocysteine Levels in Korean Patients with Recurrent Spontaneous Abortion / 대한불임학회지

OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) mutation are commonly associated with hyperhomocysteinemia, and through their defects in homocysteine metabolism, they have been implicated as a risk factor for recurrent spontaneous abortion. Recent report describe that 28-bp tandem repeat polymorphism in thymidylate synthase enhancer region (TSER) that influence enzyme activity would affect plasma homocysteine level. We have investigated the relationship between TSER genotype and plasma homocysteine level in 54 patients with recurrent spontaneous abortion. METHODS: Plasma homocysteine level was measured by fluorescent polarizing immunoassay. MTHFR mutation (C677T and A1298C) was identified by PCR-restriction fragment length polymorphism assay and TSER mutation was analyzed by PCR method. The data were analyzed using the program SAS 8.2 for Windows. RESULTS: Total homocysteine level was significantly higher in MTHFR 677TT genotype (9.80+/-3.87 mumol/L) than MTHFR 677CC genotype (8.14+/-1.74 mumol/L) in Korean patients with unexplained recurrent spontaneous abortion (p=0.0143). However, the plasma homocysteine level was not significantly different in the MTHFR 1298AA (8.42+/-2.65 mumol/L) and 1298CC (6.09+/-0.32 mumol/L; p=0.2058) and, TSER 2R2R (8.61+/-1.68 mumol/L) and 3R3R (8.05+/-2.81 mumol/L; p=0.9319) mutant genotypes, respectively. In this study, we found the combination effects of TSER and MTHFR C677T genotypes. Plasma homocysteine levels were the highest (11.47+/-4.66 mumol/L) in individuals with TSER 3R3R (8.05+/-2.81 mumol/L) and MTHFR 677TT (9.80+/-3.87 mumol/L) genotypes. Individuals with a combination of both TSER 2R2R/2R3R and MTHFR 677CC/CT genotypes (7.69+/-1.77 mumol/L) had lower plasma homocysteine levels than TSER 2R2R (8.61+/-1.68 mumol/L) and MTHR 677CC (8.14+/-1.74 mumol/L) genotypes, respectively. The effect of MTHFR polymorphism in the homocysteine metabolism appears to be stronger than that of TSER polymorphism. CONCLUSION: Although statistically not significant, we found the elevated level of plasma homocysteine in combined genotypes with TSER and MTHFR (C677T and A1298C) in Korean patients with unexplained habitual abortion. In this study, we reported the possibility that TSER polymorphism is a genetic determinant of plasma homocysteine levels in the Korean patients as well as MTHFR C677T polymorphism. A large prospective study is needed to verify our findings.