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.

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), ß2-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, ß2-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.

Effectiveness of the use of Low Molecular Heparin in patients with repetition abortion history: Systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of using low molecular weight heparin (LMWH) in women with a history of recurrent abortion without an identified cause. METHODS: To develop a systematic review to select the studies. Total found 437 papers. Seven studies were completed or requested. The following variables were analyzed: clinical pregnancy, implantation rate, live births, abortion, premature birth, pregnancy, continuous pregnancy, beyond the 20th gestational week, congenital abnormality, hemorrhage, preeclampsia, placental premature detachment. RESULTS: The LMWH group had a higher incidence of continuous pregnancy after the 20th week of gestation and there was no significant difference between the LMWH group and the expectant management group in the analysis of other variables. CONCLUSIONS: There was no data showing risk and/or less use of LMWH compared to expectant management; on the contrary, LMWH use increased the incidence of evolutionary pregnancy after the 20th gestational week. LMWH has some influence on prophylactic treatment of repeat abortion for unknown cause.

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.

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)

Using autologous intrauterine platelet-rich plasma to improve the reproductive outcomes of women with recurrent implantation failure.

OBJECTIVE: Reproductive clinics are often faced with cases of repeated implantation failure (RIF). This study evaluated whether platelet-rich plasma (PRP) might improve the implantation outcomes of patients suffering from RIF. METHODS: Thirty women with RIF submitted to frozen-thawed embryo transfers were included in the study. Intrauterine infusions of autologous purified platelet preparations were administered 48 hours prior to embryo transfer. Differences in implantation, clinical pregnancy, and miscarriage rates of cycles with and without PRP infusions were analyzed. RESULTS: The implantation rate seen in the PRP group was 6.7%. No significant difference was found the between the implantation, clinical pregnancy, ongoing pregnancy, and miscarriage rates of frozen-thawed embryo transfers with and without PRP infusion. However, the effect size of PRP infusion (Cohen's d=0.39) on implantation rates revealed a relationship in medium strength. CONCLUSION: Platelet-rich plasma might potentially yield beneficial effects as a safe therapeutic option offered alongside other treatments designed to improve the reproductive outcomes of women with repeated implantation failure.

Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium.

OBJECTIVE: To improve endometrial quality and implantation rates after the administration of platelet-rich plasma in patients with refractory endometrium. METHODS: 19 patients undergoing in vitro fertilization, aged between 33 and 45 years with a history of refractory endometrium, to whom platelet rich plasma was given by infusion with a catheter into the uterine cavity on the tenth day of the hormone replacement therapy, and then 72 hours after the first administration. RESULTS: Endometrial thicknesses >7mm was reported with the first use; and in all cases, endometrial thicknesses >9mm were evident after the second administration. The entire study group qualified for Embryo Transfer at the blastocyst stage. We had 73.7% of positive pregnancy tests, of which 26.3% yielded live births; 26.3% ongoing pregnancies; 10.5% biochemical pregnancies; 5.3% anembryonic pregnancies and 5.3% had fetal death (16 weeks). CONCLUSIONS: Platelet-rich plasma and its biostimulation effects on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Thus, we recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred.

Lymphocyte immunotherapy in the treatment of recurrent miscarriage: systematic review and meta-analysis.

PURPOSE: Recurrent miscarriage (RM) affects up to 2-3% of couples of reproductive age. There are several causes for this condition, including immunologic. The embryo is considered an allograft, subject to the rejection mechanisms of the maternal immune system. Immunotherapy involving immunization with lymphocytes is considered in cases of idiopathic RM. However, there is still no consensus regarding the efficacy and safety of this therapy. METHODS: This systematic review and meta-analysis evaluated the data available in the literature regarding the efficacy and safety of the use of immunotherapy with lymphocytes in couples with history of RM. Searches in PubMed/Medline, SCOPUS, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "meta-analysis." Statistical analyses were performed using Review Manager 5.3 (RevMan), version 5.3. RESULTS: Six published meta-analysis were retrieved; two found no improvements in the rate of live births after the use of immunization with lymphocytes in the treatment of RM, and four found a beneficial effect of the use of immunotherapy with lymphocytes in cases of RM, with significant improvements in the rate of live births. CONCLUSION: Data available in the literature supports the efficacy and safety of immunotherapy with lymphocytes in cases of RM without an identified cause.

Trombofilias: a prevenção direcionada a uma gravidez bem-sucedida / Thrombophilia: prevention targeted to a successful pregnancy

Vários efeitos adversos na gravidez, como pré-eclampsia, deslocamento de placenta, prematuridade e até mesmo perdas fetais recorrentes vêm sendo amplamente associados a estados trombofílicos. Uma vez que o número de trombofilias herdadas tem crescido rapidamente nos últimos anos com a identificação de vários fatores genéticos predispondo ao desenvolvimento de trombose venosa ou arterial, cada vez mais se torna de grande interesse a identificação de mulheres de risco, na tentativa de minimizar os problemas na gravidez e, principalmente, instituir regimes terapêuticos para a prevenção de perdas fetais. Esta revisão aborda os riscos associados à presença de alterações genéticas predispondo à trombose e a importância de um monitoramento adequado.

Many adverse effects during pregnancy, like preeclampsia, placental abruptions, prematurity and recurrent fetal loss have been widely associated with thrombophilic states. The number of inherited thrombophilias has grown rapidly in recent years with the identification of many predisponent genetic factors to the development of venous and/or arterial thrombosis. Therefore, the identification of women of risk becomes of great interest in the attempt to minimize the problems during pregnancy and mainly to institute therapeutical regimens for fetal loss prevention. This review approaches the risk associated to the presence of genetic alterations predisposing to thrombosis, and the importance of an adequate follow up.

Comparative immunological effect of anticoagulant and antioxidant therapy in the prevention of abortion in mice.

PROBLEM: Considering the potential adverse effects of anticoagulation in abortion treatment, we investigate whether antioxidants might exert the same immunoprotection. Although the fertility properties of Vitamin E have been associated with its antioxidant capacity, its effect on cytokine balance during pregnancy is still unknown. METHOD OF STUDY: Pregnant females from CBA/J × DBA/2 abortion model were orally supplemented with Vitamin E or inoculated intraperitoneally with enoxaparin. Foeto-placental units were scored at 14.5 days of pregnancy, and abortion rate was calculated. Cytokine placental levels were determined by enzyme-linked immunosorbent assay. RESULTS: Vitamin E (15 mg/day) has been able to decrease abortion rate and to increase IL-6 placental levels, while both treatments increased vascular endothelial growth factor (VEGF) placental levels. CONCLUSION: Vitamin E and enoxaparin are able not only to prevent foetal wastage but also to balance IL-6 and VEGF placental levels, presenting a new potential therapeutic alternative for patients with recurrent abortion not associated with thrombophilias.

Técnicas emergentes en medicina reproductiva: diagnóstico cromosómico del primer corpúsculo polar del ovocito / Emerging techniques in reproductive medicine: chromosomal diagnosis of the oocyte first polar body

El Diagnóstico Genético Preimplantacional (PGD) se ha convertido en una herramienta de rutina para la detección de anormalidades cromosómicas o genéticas, en muchos países del mundo. Se han reportado más de 20.000 ciclosde PGD, desde su desarrollo hace más de 20 años, habiendo nacido más de 4.000 niños hasta el año 2007. En Chile, esta técnica es realizada por la Unidad de Medicina Reproductiva de Clínica Las Condes, y se realiza sólo en la variante previa a la fecundación, en donde se biopsia el primer corpúsculo polar y sólo se insemina a los ovocitos encontrados cromosómicamente sanos. Las indicaciones más comunes para este tratamiento son: 1) evitar el aborto en pacientes con aborto recurrente sin explicación anatómica ni clínica; 2) mejorar las tasas de implantación en mujeres mayores de 37 años con antecedentesde procedimientos anteriores en los que se transfirieron embriones de buena calidad; 3) evitar el nacimiento deniños con enfermedades de origen cromosómico en mujeres mayores de 39 años.

Pre-implantational Genetic Diagnosis has become a common tool in most countries of the world. In almost 20 years since its development, it has been reported more than 20,000 cycles of PGD and till 2007, more than 4,000 children have been born. In Chile, this technique is done by the Unit of Reproductive Medicine of Clínica Las Condes. It is done only in the mode previous to fertilization. In where we study polar bodies and only chromosomically healthy oocytes are inseminated. The most common indications for this treatment are: 1) to avoid abortions in patients with recurrent abortion without anatomical nor clinical explanation; 2) to improve implantation rates in women older than 37 years of age, with previous procedures in which good quality embryos were transferred; 3) to avoid birth of children with diseases of chromosomal origin in women over 39 year of age.

Abortamento habitual I: Fatores endócrinos / Habitual abortion I: Endocrine factors

Distúrbios hormonais que podem levar a perdas fetais recorrentes. Vários estudos têm mostrado aumento na incidência de auto-anticorpos e doenças auto-imunes tireoidianas entre as mulheres com perdas fetais de repetição. A perda fetal de repetição associada à SOP parece estar relacionada aos efeitos endometriais da hiperinsulinemia. Entretanto, a eficácia do uso da metformina para prevenção de perdas fetais em mulheres com SOP ainda carece de comprovação. A progesterona é um hormônio chave durante a gravidez e parece ter inúmeras funções, tais como a indução de alterações secretórias no endométrio e imunotolerância seletiva, embrião-específica, absolutamente essenciais para o desenvolvimento embrionário adequado. Avaliações clínicas têm mostrado que os critérios diagnósticos dos defeitos de fase lútea, como a avaliação histológica endometrial, dosagem de progesterona sérica, ultra-sonografia pélvica com doppler das artérias uterinas e ovarianas têm limitada acurácia, com significativa variabilidade inter e intra-observador. Embora dados preliminares sejam promissores em relação ao uso da progesterona na prevenção da perda fetal recorrente, as evidências ainda são insuficientes para o uso rotineiro.

Endocrine dysfunction might contribute to recurrent pregnancy loss (RPL) in some women. Many studies have correlated thyroid auto-antibodies and auto-immune diseases to recurrent abortion. Pregnancy loss in women with polycystic ovarian syndrome seems to be related to endometrial effects of hyperinsulinemia. Nevertheless, routine use of metformin to prevent miscarriage is not warranted. Progesterone is a key hormone in pregnancy maintenance and appears to have many functions such as inducing secretory changes in the endometrium and embryo-specific immunotolerance, which are absolutely essential to adequate early embryonic development. Clinical studies have shown that the diagnostic criteria for luteal comprising endometrial hystological evaluation, plasmatic progesterone measurement or uterine and ovary arteries Doppler velocimetry have limited accuracy and significant inter and intra observer variability. Althoug some studies have revealed a remarkable improvement in pregnancy outcome after progesterone supplementation in women suffering from recurrent miscariage, further research is required for routine use.

[Antiphospholipid syndrome and human reproduction]. / Síndrome antifosfolipídico y reproducción humana.

Recurrent pregnancy loss is secondary to multiple illnesses. An important cause sometimes undiagnosed is the antiphospholipid syndrome, an autoimmune disease with various clinical alterations (miscarriage, hypertensive disorders, preterm delivery, vascular thrombosis, intrauterine retard growth, death intrauterine, abruption placentae). There are major and minor clinical criteria and precise indications that guide the physician to its recognition. Antibodies related with the syndrome are anticardiolipin and lupic anticoagulant, but other phospholipids seems to be implicated on this pathology and its participation on trombotic events is even unknown. Opportune diagnosis is of vital importance for fetomaternal morbidity and mortality. The repercussions are important during gestational stage, but effects c an persist o r even appear during the puerperium, predisposing t o trombotic events. The antiphospholipid s yndrome th at accompanies gestation, requires of efficient valuation and a special treatment, with a narrow prenatal surveillance. The best therapy for reproductive future which has less undesirable effects, is with heparin and acetylsalicylic acid administration; prednisone (steroids) is used in cases of active illness. The current knowledge about this disease makes possible that a pregnancy at term can be achieved with the least as possible number of complications.

Dendritic cells therapy confers a protective microenvironment in murine pregnancy.

The fetal-placental unit is a semi-allograft and immunological recognition of pregnancy, together with the subsequent response of the maternal immune system, is necessary for a successful pregnancy. Dendritic cells (DC) show a biological plasticity that confers them special characteristics regulating both immunity and tolerance. Therapy employing DC proved to diminish the abortion in the DBA/2J-mated CBA/J females; however, the underlying mechanisms remain unknown. Here, we evaluated whether DC therapy influences the presence of immunoregulatory populations of cells at the fetal-maternal interface. To address this hypothesis, we analysed the pregnancy-protective CD8, gammadelta cell populations as well as transforming growth factor (TGF)-beta1 and progesterone-induced blocking factor (PIBF) expression at the fetal-maternal interface from abortion-prone female mice that had previously received adoptive transfer of syngeneic DC. Syngeneic DC therapy induced an increase in the number of CD8 and gammadelta cells. Additionally, an upregulation of TGF-beta1 and PIBF expression could be detected after DC transfer. We suggest that DC therapy differentially upregulates a regulatory/protective population of cells at the fetal-maternal interface. It is reasonable to assure that this mechanism would be responsible for the lower abortion rate.

Repetitive miscarriages in a patient with a high level of anticardiolipin antibodies and myocardial infarction.

Antiphospholipid antibodies consist of a group of heterogeneous autoantibodies against anionic phospholipids. We describe the case of a 19-year-old patient who was consulted in the obstetrics service after her second miscarriage. She was a smoker and six months after this consultation she developed diabetes mellitus. At 21 years of age she suffered from myocardial infarction, when high anticardiolipin antibody levels were evidenced. Some months later the patient again became pregnant and prophylaxis against miscarriages was performed using low doses (5000 IU) heparin administered subcutaneously at 12-hour intervals. She evolved with preeclampsia, however, the baby was born in good health. One year after she again became pregnant and prophylaxis against miscarriage was again performed using low doses of heparin. The pregnancy successfully resulted with the birth of her second child.

Enoxaparina y aspirina a bajas dosis en el tratamiento de los síndromes antifosfolípicos del embarazo. Seguridad y utilidad / Low dose enoxaparine and aspirin in the therapy of antiphospholipid syndromes in pregnancy. Safety and usefulness

La pérdida recurrente de embarazo constituye una complicación de los síndromes antifosfolipídicos, con graves consecuencias para las parejas, su entorno familiar y la sociedad. El objetivo de este estudio fue: determinar la efectividad de la heparina de bajo peso molecular (enoxaparina) asociada a bajas dosis de aspirinas, en mujeres con pérdidas recurrentes de embarazo (PRE) vinculada a la presencia de anticuerpos antifosfolípidos (aPL). Determinar la seguridad de estos tratamientos en la madre y en el feto vigilando la aparición de sangrado o plaquetopenia vinculada a la heparina. Para ello se identificó a una población de 76 mujeres con síndrome antifosfolipídico y PRE. Todas cursaron por lo menos un nuevo embarazo tratado con las drogas mencionadas. De 76 nuevos embarazos, 69 llegaron a término con por lo menos un hijo vivo. En la historia previa de las pacientes se registra un 3,8 por ciento de embarazos con hijos vivos mientras que cuando son tratadas 89,5 por ciento de los embarazos resultan exitosos (IC al 95 por ciento para la probabilidad de éxito del tratamiento indica que la misma está comprometida entre el 82,6 por ciento y el 92,4 por ciento). La comparación de proporciones indica que la diferencia es altamente significativa (p-valor del orden 10 a la -8). En relación a los efectos secundarios no se observaron sangrados fetales ni maternos ni plaquetopenias inducidas por heparina. Concluimos que el tratamiento con Enoxaparina y aspirina a bajas dosis es altamente efectivo y seguro para tratar los síndromes antifosfolipícos del embarazo y por lo tanto no debería esperarse PRE sino que las deberían estudiarse siempre que se sospeche el diagnóstico para poder tratarlas en forma adecuada. (AU)

Trombofilia y pérdida recurrente de embarazo / Thrombophilia and recurrent pregnancy loss

La búsqueda de factores pro trombóticos que incidan en la pérdida recurrente de embarazo, ha adquirido en los últimos años un especial interés para hematólogos y obstetras. La identificación progresiva de las diferentes enfermedades trombofílicas constituye un desafío en el diagnóstico de nuevas causas que puedan ser responsables de la pérdida recurrente de la gestación. Se estudió una población de 115 mujeres con pérdida recurrente de embarazo en quienes se descartaron previamente causas hormonales, anatómicas, infecciosas o genéticas. En ellas se buscaron diferentes causas trrombofílicas y se comparó con una población control. Dentro de los factores pro trombóticos estudiados se encontró una prevalencia significativamente mayor en los anticuerpos antifosfolípidos/anticoagulante lúpico, (p<0,0001, OR=8,85, IC95 por ciento 3,8-20,8), la lipoproteína (a) (p<0,0001, OR=6,05, IC95 por ciento 5,5-14,3), el factor V leiden (p<0,005, OR=5, IC95 or ciento 1,5-21), el factor II G20210A (p<0,005, OR=4, IC95 por ciento 1,4-11,5) y la variante homocigota de la MTHFR C677T (p=0,0002, OR=2,4, IC95 por ciento 1,1-5,1). La asociación de 2 o más factores de riesgo trombótico se observa en 65 por ciento de las pacientes por lo cual el estudio trombofílico de las mismas debe ser completo. (AU)

Estudo das alterações placentárias de gestantes com síndrome antifosfolípide: correlações anátomo-clínicas / Placental changes study in pregnant women with antiphospholipid syndrome: anatomic clinic correlation

A sindrome antifosfolípide é caracterizada pela ocorrência de eventos clínicos tromboembólicos associados a persistência laboratorial de anticorpos antifosfolípides. Na gravidez, está associada à perda fetal de repetição atribuída às tromboses placentárias e aumento de morbidades materno-fetais. Este estudo centrado numa amostra de gestantes com síndrome antifosfolípide, submetidas a protocolo terapêutico de anticoagulação, teve como objetivo avaliar as lesões placentárias encontradas nas placentas resultantes dessas gestações e correlacionar com as intercorrências maternas e repercussões perinatais./The antiphospholipid syndrome is characterized by the occurrence of clinical events thromboembolic associated with the persistence laboratorial of antiphospholipid antibodies. In the pregnancy it is associated with the fetal loss attribuited by the placental thromboses and increase of fetal-maternal complications. This study centered in a sample of pregnant women with the antiphospholipid syndrome, submitted to a therapeutic protocol of anticoagulation, it has as an objective to evaluate the in these pregnant women and correlate with the maternal morbidity and pre-birth repercutions...

[Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia]. / Tratamiento con enoxaparina adaptado a los programas de fertilidad en mujeres con aborto recurrente y trombofilia.

Acquired and inherited thrombophilia are associated with recurrent pregnancy loss (RPL). Antithrombotic therapy could restore hemostatic balance and improve early placentation and gestational outcome. We evaluated the efficacy of enoxaparin adapted to the fertility program for prevention of pregnancy loss in 35 women (W) with early RPL and thrombophilia. Previous to the diagnosis of thrombophilia, they had had a total of 105 gestations of which 89 (85%) ended in early pregnancy loss. After diagnosis of thrombophilia, 35 subsequent pregnancies were treated with enoxaparin. In 5 cases assisted reproductive techniques were necessary to achieve pregnancy due to couple infertility. In 17 W who had had at least one preclinical pregnancy loss, enoxaparin (20 mg/d/s.c.) was started previous to conception and adapted to the fertility program. All the women continued with the gestational regime. Eighteen W with only clinical pregnancy loss started enoxaparin (20 mg twice per day s.c.) after biochemical pregnancy diagnosis. During gestations heparin dose was adjusted with anti Xa test, maintaining a range between 0.3 at 0.6 u/ml. With antithrombotic therapy, 30/35 (85%) of the pregnancies ended in live birth versus 16/105 (15%) of the pregnancies without treatment (p < 0.001). These results suggest that enoxaparin adapted to the fertility program can be effective in the prevention of preclinical and clinical abortion in women with thrombophilia.

Tratamiento con enoxaparina adaptado a los programs de fertilidad em mujeres con aborto recurrente y trombofilia / Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia

Las trombofilias adquiridas y hereditarias se asocian con pérdidas embrio-fetales recurrentes. La terapéutica antitrombótica puede reestablecer el balance hemostático y mejorar la fase temprana de la placentación y el pronóstico gestacional. Nosotros evaluamos la eficacia del tratamiento con enoxaparina adaptado a los programas de fertilidad, para prevenir las pérdidas embrio-fetales en 35 mujeres con antecedente de aborto recurrente temprano y trombofilia. Previo al diagnóstico de trombofilia ellas tuvieron un total de 105 embarazos, de los cuales 89 (85%) terminaron en aborto temprano. Luego del diagnóstico de trombofilia, los 35 embarazos subsiguientes fueron tratados con enoxaparina. En 5 casos fue necesario emplear técnicas de reproducción asistida para lograr el embarazo debido a infertilidad de pareja. Diecisiete mujeres con antecedente de al menos un aborto preclínico recibieron enoxaparina (20 mg./día/sc.) previo a la concepción, adaptado al programa de fertilidad. Al lograr el embarazo continuaron con esquema gestacional. Dieciocho mujeres con antecedente únicamente de abortos clínicos ingresaron de novo al esquema gestacional (enoxaparina 20 mg. cada 12 hs/sc) al obtener un test de embarazo positivo Durante la gestación la dosis de heparina se ajustó mediante estudio de Anti Xa, manteniendo un rango entre 0.3 a 0.6 u/ml. Con tratamiento antitrombótico 30/35 (85%) de los embarazos terminaron con nacido vivo, comparado con 16/105 (15%) de los embarazos previos no tratados (p<0.001). Estos resultados sugieren que el tratamiento con enoxaparina adaptado a los programas de fertilidad podría ser efectivo en prevenir los abortos tempranos en mujeres con trombofilia