Low-molecular-weight heparin in the prevention of unexplained recurrent miscarriage: a systematic review and meta-analysis.

The etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: ( https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433 ).

Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

The safety and efficacy of tumor necrosis factor-alpha inhibitor on pregnancy outcomes in patients with unexplained recurrent miscarriage.

OBJECTIVES: Although tumor necrosis factor-alpha inhibitor (TNFi) treatment may improve pregnancy outcomes in unexplained recurrent miscarriage (URM) patients, evidence for its efficacy and safety is still insufficient. The goal of this study was to evaluate the efficacy and safety of TNFi on pregnancy outcomes in patients with URM. METHODS: This retrospective study was conducted at a single institution in China, involving 121 patients treated with TNFi for URM from 2019 to 2022. Patients enrolled were divided into treatment group (receiving TNFi and heparin therapy) and control group (receiving heparin therapy). The outcome variables were the 24-week live birth rate, miscarriage rate, ectopic pregnancy rate, neonatal outcomes, and adverse events. RESULTS: In our study, patients receiving TNFi treatment exhibited a significant increase in live birth rates, achieving 71.2 % compared to the 50.9 % observed in the control group (OR 2.507, 95 % CI: 1.127-5.579). Concurrently, there was a discernible reduction in the miscarriage rate within the TNFi-treated group, marking 24.2 %, in contrast to 43.6 % in the control group (OR 0.387, 95 % CI: 0.170-0.884). Subgroup analyses further illuminated that those under the age of 35 benefitted remarkably from TNFi treatment, with live birth rates soaring to 62.5 % (OR 2.525, 95 % CI: 1.041-6.125). For patients with a history of two miscarriages, the TNFi regimen significantly augmented the live birth rate to 58.9 % (OR 3.044, 95 % CI: 1.039-8.921). Patients with a normal weight range registered a 58.4 % live birth rate post-TNFi treatment (OR 4.261, 95 % CI: 1.539-11.397). Notably, an evident interaction between BMI and TNFi treatment was identified, suggesting a potential modulatory role of BMI on the therapeutic efficacy of TNFi. About safety assessments, neither the TNFi-treated group nor the control manifested any significant disparities in liver function abnormalities, platelet count anomalies, or other pregnancy-related complications. CONCLUSIONS: TNFi, alongside basic therapy, notably enhances the live birth rate in URM patients under 35, with two prior miscarriages or a normal BMI, without increasing adverse event risk. Further prospective studies are essential to validate these observations.

Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Prognostic model on pregnancy outcomes for women with recurrent spontaneous abortions treated with cyclosporin A: A single-institution experience.

BACKGROUND: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. METHODS: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. RESULTS: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693‒0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079‒0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-ß2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176‒409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735‒0.880). CONCLUSIONS: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.

Zishen Yutai Pills Promote Angiogenesis at the Maternal-Fetal Interface in Recurrent Spontaneous Abortion Mice by Regulating miR-187/VEGF Axis.

Ethnopharmacological Relevance: Zishen Yutai pills (ZYP), a traditional Chinese patent medicine, was listed in China in 1981. It is composed of 15 traditional Chinese medicines and has the effects of regulating menstruation, helping pregnancy, and preventing abortion. In clinical practice, it is effective in preventing habitual and threatened miscarriages, and continuing to explore its mechanism of action is very meaningful research. Aim of the Study: To explore the possible mechanism of ZYP promoting angiogenesis at the maternal-fetal interface in recurrent spontaneous abortion (RSA). Materials and Methods: In vitro experiments, placental trophoblast cells (PTCs) were isolated from the placental tissue of RSA mice and divided into six groups: Control group, Model group, ZYP group, miR-187 inhibitor NC group, miR-18 7 inhibitor group, and miR-187 inhibitor+ZYP group. Cell viability and cell cycle were measured using CCK8 and flow cytometry, respectively. The expression levels of miR-187, VEGF, VEGF-R1, and VEGF-R2 were measured using RT-qPCR, WB, and IF staining. Animal experiments first establish an RSA mice model (CBA/J × DBA/2) and then randomly divide the mice into four groups (n=10): normal pregnancy group, RSA model group, ZYP group, and progesterone capsule group. Observed the changes in embryo absorption rate, pathological morphology of decidual tissue, and ultrastructure of vascular endothelial cells in each group of mice. RT-qPCR, WB, and IF staining methods were used to determine the expression of miR-187, VEGF, VEGF-R1, and VEGF-R2. Results: In vitro, ZYP promoted the viability of PTCs and regulated their cell cycle, and ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2 levels. miR-187 inhibitor showed the same effects, and further ZYP intervention enhanced the effects. In vivo, ZYP remarkably reduced embryo resorption rates, and improved the pathological morphology of decidual tissues and ultrastructure of vascular endothelial cells. Moreover, ZYP down-regulated miR-187, up-regulated VEGF, VEGF-R1 and VEGF-R2. Conclusion: In summary, ZYP can regulate the expression of VEGF via miR-187, then promote the angiogenesis at the maternal-fetal interface, and playing a therapeutic role in RSA.

Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research.

ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.

Network pharmacology analysis of Yi-Shen-Gu-Ta i-Ke-Li for recurrent spontaneous abortion in female fitness and athletic populations

Background: Yi-Shen-Gu-Tai-Ke-Li (YSGTKL), a renowned traditional herbal formula, has demonstrated clinical efficacy in addressing recurrent spontaneous abortion (RSA). Despite its widespread utilization in China, the current body of evidence regarding the effectiveness of its herbal components remains insufficient, and the underlying mechanisms of action remain enigmatic. This study endeavors to unravel the mechanisms responsible for the therapeutic effectiveness of YSGTKL in treating RSA, particularly within the context of female fitness and athletic populations. Methods: YSGTKL comprises various herbal plants, selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Specific drug targets associated with RSA were meticulously identified and corroborated using multiple reputable sources, including DrugBank, GeneCards, and Online Mendelian Inheritance in Man. The GEO database was leveraged to pinpoint differentially expressed genes (DEGs) relevant to RSA within female fitness and athletic populations. Subsequently, a comprehensive drug-compound-gene-disease network was meticulously constructed and visualized using Cytoscape software. Functional insights were gleaned through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Within this network, a subset of hub genes was discerned through a protein-protein interaction (PPI) network analysis, specifically tailored to female fitness and athletic populations. To validate key active ingredients and core targets, molecular docking analyses were meticulously performed, taking into account the unique physiological aspects of female athletes and fitness enthusiasts. (AU).

Perda gestacional de repetição e o papel dos progestagênios: evidências atuais / Recurrent pregnancy loss and the role of progestagens: current evidence

Objetivo: Discutir o uso dos progestagênios em mulheres com perda gestacional de repetição (PGR) sem causa aparente, abordando tipos de progestagênios e resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publicados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando-se os seguintes descritores: "progesterone", "dydrogesterone", "recurrent pregnancy loss" e "recurrent abortion". Resultados: Duas grandes metanálises encontraram uma redução da taxa de abortamento e aumento da taxa de nascidos vivos com o uso do progestágeno sintético em pacientes com PGR inexplicada, porém essa conclusão foi contestada em uma metanálise mais recente. Entretanto, a progesterona vaginal micronizada poderia aumentar a taxa de nascidos vivos em mulheres com ameaça de aborto e com história de um ou mais abortos anteriores (risco relativo [RR]: 1,08, intervalo de confiança [IC] de 95%: 1,02-1,15). O benefício foi maior no subgrupo de mulheres com três ou mais perdas anteriores. Conclusão: Ainda restam dúvidas sobre o uso de "progesterona" nas pacientes com PGR inexplicada. Sua administração deve ser discutida individualmente com cada mulher, levando-se em conta especialmente a idade materna, o número de abortos prévios e a história de sangramento na gestação em curso, evitando-se tratamentos que trazem custos e não são isentos de efeitos colaterais.(AU)

Objective: To discuss the use of progestins in women with recurrent pregnancy loss (RPL) with no apparent cause, addressing types of progestins, and results of clinical trials, systematic reviews, and meta-analyses. Methods: This is a non-systematic review of articles published in the PubMed, Cochrane, SciELO electronic databases in the last five years, using the following descriptors: "progesterone", "dydrogesterone", "recurrent pregnancy loss", and "recurrent abortion". Results: Two large meta-analyses found a reduction in the rate of miscarriage, and an increase in the rate of live births with the use of synthetic progestin in patients with unexplained RPL, but this conclusion was challenged in a more recent meta-analysis. However, micronized vaginal progesterone could increase the rate of live births in women with a threatened miscarriage and a history of one or more previous miscarriages (RR: 1.08, 95% CI: 1.02-1.15). The benefit was greatest in the subgroup of women with three or more previous losses. Conclusion: There are still doubts about the use of "progesterone" in patients with unexplained RPL. Its administration should be discussed individually with each woman, taking into account especially the maternal age, number of previous abor tions, and history of bleeding during pregnancy, avoiding treatments that bring costs and are not free from side effects.(AU)

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

Tratamiento con corticoides en abortos espontáneos de repetición: revisión sistemática de la literatura / Corticosteroid treatment in recurrent pregnancy losses: systematic literature review

Antecedentes: el tratamiento de los abortos espontáneos de repetición es controvertido dada la escasez de evidencia disponible al respecto. El objetivo de este trabajo es hacer una revisión sistemática de la literatura acerca del uso de corticoides como terapia de los abortos espontáneos de repetición. Material y métodos: revisión sistemática de la literatura incluyendo 76 artículos clasificados en tres grupos: estudios realizados en pacientes con abortos espontáneos de repetición idiopáticos, abortos espontáneos de repetición asociados a síndrome antifosfolípido y pacientes con fallos de técnicas de fecundación in vitro. Resultados: la revisión de la literatura muestra resultados heterogéneos en cuanto a la contribución de los corticoides en la mejora del desenlace gestacional. Su administración ha demostrado ser beneficiosa en los casos de abortos espontáneos de repetición idiopáticos y posiblemente en aquellos asociados a síndrome antifosfolípido. Los resultados son contradictorios en el caso de las mujeres sometidas a fecundación in vitro, no existiendo metaanálisis concluyentes al respecto. En cuanto a la seguridad, los corticoides han demostrado no producir teratogenicidad. La administración de dosis altas durante largo tiempo se asocia con morbilidad materno-fetal, principalmente crecimiento intrauterino retardado, preeclampsia, diabetes gestacional, hipertensión gestacional, rotura prematura de membranas y parto pretérmino. Sin embargo, el empleo de dosis bajas durante periodos cortos no se ha asociado con efectos adversos maternos ni fetales. Conclusiones: la revisión de la literatura apoya el uso de los corticoides a dosis bajas durante las primeras semanas de embarazo en las pacientes con abortos espontáneos de repetición idiopáticos y posiblemente en los asociados a síndrome antifosfolípido, mientras que su utilidad en pacientes sometidas a técnicas de fecundación in vitro es controvertida

Background: Management of recurrent pregnancy losses is controversial due to the scarcity of literature available. Our aim is to perform a systematic review of the literature about the use of corticoids as therapy for recurrent pregnancy losses. Material and methods: Systematic literature review including 76 papers classified in three groups: idiopathic recurrent pregnancy losses, antiphospholipid syndrome related recurrent pregnancy losses, and patients with failure of in vitro fertilisation. Results: Literature review shows heterogeneous results regarding the effect of corticosteroids in pregnancy outcome. They have been proved to be beneficial in idiopathic recurrent pregnancy losses and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Results are controversial in women undergoing in vitro fertilisation, and conclusive metaanalysis are lacking.Regarding safety, corticosteroids have been shown to be non teratogenic. Long term high dose treatment is associated with maternal and fetal morbitidies, particularly intrauterine growth restriction, preeclampsia, gestational diabetes, gestational hypertension, premature rupture of membranes and premature birth. However, low dose corticosteroids during short periods of time have not been associated with maternal or fetal complications. Conclusions: The literature review supports the use of low dose corticosteroids during the first weeks of pregnancy in patients with idiopathic recurrent pregnancy losses, and possibly in antiphospholipid syndrome related recurrent pregnancy losses. Their efficacy in patients undergoing in vitro fertilisation is controversial

Abortamento de causa aloimune: diagnóstico e tratamento / Alloimmune abortion: diagnosis and treatment

Abortamento espontâneo recorrente (AER) é definido, usualmente, como a perda de três ou mais gestações, até a 20ª semana de gravidez, e afeta aproximadamente 5 % dos casais. Em boa parte dos casos, a causa é desconhecida e muitas hipóteses foram levantadas, dentre elas, a imunológica. Diversos trabalhos vêm tentando mostrar a fisiopatologia da causa aloimune e seu possível diagnóstico e tratamento. Apesar de não haver, até hoje, a liberação por parte de instituições de saúde, como a Food and Drug Administration (FDA) e a Agência Nacional de Vigilância Sanitária (Anvisa), os tratamentos são oferecidos em diversas clínicas ao redor do mundo. Por meio do levantamento dos últimos artigos acerca do assunto, foi possível observar que um método diagnóstico específico que detecte a perda gestacional precoce imune mediada e um método confiável que determine quais mulheres se beneficiariam da manipulação do sistema imune materno são urgentes. Para estabelecer definitivamente ou avaliar a eficácia de qualquer suposto tratamento para o AER, são necessários novos estudos randomizados, com adequado número de amostra.

Recurrent spontaneous abortion (RSA) is usually defined as three or more consecutive pregnancy losses prior to the 20th week of gestation, and affects approximately 5 % of the couples. The etiology of recurrent spontaneous abortion is often unclear and may be multifactorial. However, the majority of cases of RSA remain unexplained and some studies have been attempting to associate it with autoimmune and alloimmune antibodies. Although until today there is no release by health institutions such as Food and Drug Administration (FDA) and Agência Nacional de Vigilância Sanitária (Anvisa), these treatments are offered at various clinics around the world. Through the survey of recent articles on this subject, it was possible to see that a specific diagnostic method to detect the early pregnancy loss imune mediated as well as a reliable method to determine which women would benefit from the manipulaton of the maternal immune system are more than necessary. To definitively establish or evaluate the effectiveness of any treatment for RSA, further randomized studies with adequate number of sample are needed.

Abortamento habitual III - Trombofilias e fatores imunológicos / Habitual abortion III - Thrombophilia and imunologic factors

A associação dos anticorpos antifosfolípides, em particular o anticorpo anticardiolipina e o anticoagulante lúpico, com o abortamento habitual, bem como a eficácia do tratamento com a associação de heparina e ácido acetilsalicílico em baixa dose durante a gravidez estão respaldadas em fortes evidências clínicas. A participação e a eficácia do tratamento de outras trombofilias, tais como o fator V de Leiden, resistância à proteína C ativada, mutação do gene da protrombina e deficiência de proteína S, embora sugerida em alguns estudos, ainda não estão claramente estabelecidas. Não existe até o momento indicações de que alterações aloimunes possam ser causa de abortamento habitual. O tratamento empírico dessas alterações com imunoglobulina endovenosa ou transfusão de linfócitos paternos não tem melhorado os resultados obstétricos das mulheres com perdas recorrentes.

The association of antiphopholipid antibodies, specially the anticardiolipin antibody and lupus anticoagulant, with habitual abortion, as well as the efficacy of the treatment with heparin and low-dose aspirin during pregnancy are based in strong clinical evidence. The role and efficacy of the treatment of other thrombophilias, such as factor V Leiden, resistance to activated C protein, mutation of prothrombin gene and deficiency of protein S, althrough suggested in some studies, are not clearly established. There is no evidence, so far, that aloimmune alterations can be cause of habitual abortion. The empirical treatment of these alterations with IV immunoglobulin of paternal leukocyte transfusion have not improved obstetrical results in women with recurrent miscarriage.