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

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

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Objectives: To examine the relationship between endometrial integrin beta 5 level and risk of recurrent pregnancy loss. Method: The descriptive, prospective, observational, case-controlstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from January to May 2022, and comprised women aged up to 35 years with at least 1 live birth delivery beyond 20-week gestation with normal thyroid and prolactin levels. Age-matched normal fertile women were enrolled as controls. All the participants were subjected to detailed history and complete clinical examination. Endometrial integrin beta 5 was assessed using an antibody sandwich enzyme-linked immunosorbent assay. Data was analysed using SPSS 20. RESULTS: Of the 50 subjects, 25(50%) were cases with a mean age of 26.72±2.64 years, and 25(50%) were controls with a mean age of 25.36±2.16 years. The integrin beta 5 level was significantly lower among the cases than the controls (p<0.05). The best cut-off level of serum integrin beta 5 was ≤2.5765 with area under curve 0.886, sensitivity 88%, specificity 76%, positive predictive value 78.6%, negative predictive value 86.4%, and accuracy 82%. CONCLUSIONS: Therewas an inverse correlationbetween endometrial integrinbeta 5 andthe risk ofrecurrentpregnancy loss.

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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)

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Objective:To investigate the clinical efficacy of Yunkang oral liquid combined with dexamethasone and low-molecular-weight heparin in the treatment of recurrent spontaneous abortion (RSA) complicated with pre thrombotic state (PTS), and its effects on thromboelastogram and serum progesterone, β-human chorionic gonadotropin (β- hCG), and helper T cell (Th) 1/Th2 cytokine levels in patients with recurrent spontaneous abortion (RSA).Methods:A prospective selection of 94 RSA patients with PTS admitted to the Baoding Second Central Hospital from January 2015 to December 2020 was conducted. They were randomly divided into two groups using a random number table method, with 47 patients in each group. The control group was treated with dexamethasone combined with low molecular weight heparin, while the observation group was treated with Yunkang oral liquid in addition to the control group. Continuously treat until 12 weeks of pregnancy to evaluate the efficacy of both groups and observe the adverse reactions in both groups. Two sets of thromboelastogram parameters were compared before and after treatment, including clot formation time (K value), clot reaction time (R value), and clot formation rate (α angle), maximum clot strength (MA value), and coagulation comprehensive index (CI), as well as serum progesterone β- hCG, Th1/Th2 cytokine levels. The pregnancy outcomes of the two groups were followed up.Results:The total effective rate of the observation group [95.7%(45/47)] was significantly higher than that of the control group [83.0%(39/47), P<0.05]. After treatment, the K and R values of both groups were significantly prolonged compared to before treatment (all P<0.05), the angle α, MA value, and CI value were significantly reduced compared to those before treatment (all P<0.05); After treatment, the K and R values in the observation group were significantly longer than those in the control group (al P<0.05), The angleα, MA value, and CI value were significantly lower than those of the control group (all P<0.05). After treatment, the levels of β- hCG serum progesterone of the two groups were significantly higher than those before treatment (all P<0.05), and The β-hCG levels of the serum progesterone were all higher than those in the control group (all P<0.05). After treatment, The levels serum Th1 cytokines [interferon-γ (INF- γ), tumor necrosis factor- α (TNF- α)] of both groups were significantly decreased compared to those before treatment (all P<0.05), and the levels of serum Th2 cytokines [interleukin-4, IL-10] were significantly increased compared to those before treatment (all P<0.05); After treatment, the observation group's serum IFN- γ, TNF- α were significantly lower than those of the control group (all P<0.05), and The levels of serum IL-4 and IL-10 were significantly higher than those of the control group all P<0.05). The live birth rate of the observation group was 87.2%(41/47), which was higher than that of the control group [70.2%(33/47)] ( P<0.05). There was no statistically significant difference in the adverse reaction rate between the observation group [6.4%(3/47)] and the control group [4.3%(2/47)] ( P>0.05). Conclusions:The treatment of RSA combined with PTS with Yunkang oral liquid, dexmedroxyprogesterone, and low molecular weight heparin can significantly alleviate blood hypercoagulability, increase reproductive endocrine hormone levels, regulate Th1/Th2 cytokine balance, improve live birth rate and clinical efficacy, and is safe and reliable.

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Objective:To investigate the relationship between uterine artery blood flow parameters detected by ultrasound examination during early pregnancy and pregnancy outcomes in pregnant women who had a history of recurrent spontaneous abortion.Methods:A total of 100 pregnant women with a history of recurrent spontaneous abortion who were at 6-10 weeks of gestation and received treatment in Zhuji Maternal and Child Health Hospital from June 2020 to June 2022 were included in the study group. Using a case-control study method, 100 normal pregnant women who were at 6-10 weeks of gestation who concurrently underwent physical examination were selected and included in the control group. Both groups of pregnant women were tested for uterine artery blood flow parameters using color Doppler ultrasound diagnostic equipment, including peak systolic/diastolic velocity (S/D), resistance index (RI), and pulsatility index (PI). The occurrence of early miscarriage was monitored in both groups. The value of uterine artery blood flow parameters in the prediction of adverse pregnancy outcomes and the correlation between uterine artery blood flow parameters and adverse pregnancy outcomes were analyzed. Multivariate logistic regression was performed to analyze the relationship between uterine artery blood flow parameters and adverse pregnancy outcomes.Results:S/D, RI, and PI in the study group were (3.87 ± 0.43), (0.93 ± 0.16), and (1.73 ± 0.41), respectively, which were significantly higher than (2.54 ± 0.37), (0.64 ± 0.14), and (1.24 ± 0.35) in the control group ( t = 23.44, 13.64, 9.09, all P < 0.05). The early abortion rate in the study group was 57.0% (57/100), which was significantly higher than 2.0% (2/100) in the control group ( χ2 = 72.73, P < 0.05). The receiver operating characteristic curve analysis showed that S/D sensitivity and specificity in the prediction of adverse pregnancy outcomes were 79.1% and 70.2%, respectively, RI sensitivity and specificity were 88.4% and 84.2%, respectively, and PI sensitivity and specificity were 65.1% and 75.4%, respectively. Pearson analysis results showed that S/D, RI, and PI were positively linearly correlated with adverse pregnancy outcomes ( r = 0.587, 0.648, 0.613, all P < 0.05). Conclusion:Uterine artery blood flow parameters S/D, RI, and PI are abnormally high in pregnant women with a history of recurrent spontaneous abortion in the early stage of pregnancy. These parameters are closely associated with adverse pregnancy outcomes and are the independent risk factors of adverse pregnancy outcomes.

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Objective:To investigate the expression and correlation of H19, matrix metalloproteinase (MMP)-2 and MMP-9 in patients with recurrent spontaneous abortion (RSA).Methods:Human extravillous trophoblast cell line HTR-8 was cultured in vitro. Lentivirus was used to infect the HTR-8 cell line to over-express or knockdown the expression of H19. The concentrations of MMP-2 and MMP-9 protein in cell culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of H19, MMP-2 and MMP-9 mRNA in villi of patients with RSA were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Spearman correlation analysis was used to understand the correlation between H19 and the expression levels of MMP-2 and MMP-9. Results:After overexpression of H19, the expression levels of MMP-2 and MMP-9 mRNA and protein concentration in Lv-ph19 group were significantly higher than those in Lv-vector group ( P<0.05); After interfering with the expression of H19, the expression levels of MMP-2 and MMP-9 mRNA and protein concentration in Lv-shH19 group were significantly lower than those in Lv-shcon control group ( P<0.05). The number of spontaneous abortions in patients with recurrent spontaneous abortion was significantly higher than that in the control group ( P<0.05). qRT-PCR showed that the expression levels of H19, MMP-2 and MMP-9 mRNA in villi of patients with RSA were significantly lower than those in the control group ( P<0.05). There was a positive correlation between H19 and the expression levels of MMP-2 and MMP-9 ( P<0.05). Conclusions:H19 regulates the expression of MMP-2 and MMP-9 of trophoblast during early pregnancy, and the abnormal expression of H19, MMP-2, and MMP-9 in human first-trimester villous tissues was related with the incidence of early miscarriage.

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The cause of immune recurrent abortion is closely related to immune abnormalities. At present, the Traditional Chinese Medicine (TCM) syndrome types of immune recurrent abortion mainly include kidney deficiency and blood stasis syndrome, spleen and kidney deficiency syndrome, blood heat syndrome, spleen deficiency syndrome and lung and kidney qi deficiency syndrome; The commonly used TCM compound for treating this disease usually could replenish kidney qi and take effect, so it is considered that the pathogenesis of this disease is mainly kidney deficiency. The mechanism of action of the TCM compound is mainly related to regulating hormone secretion, immune balance and improving local microcirculation.

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Objective:To investigate the effect and mechanism of tumor necrosis factor α (TNF-α) and its inhibitor etanercept (ETA) on the invasion ability of extravillous trophoblast in patients with unexplained recurrent spontaneous abortion (URSA).Methods:(1) Patients were collected from March to June in 2019. They were divided into the URSA group ( n=15) and the normal control group ( n=15), according to whether diagnosed with URSA or not. The mRNA expression levels of TNF-α in villi tissue of patients in the two groups were detected by quantitative real-time PCR (qRT-PCR). (2) The mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2), Slug and CXC chemokine rceptor 4 (CXCR4) in HTR-8/SVneo cells were detected by qRT-PCR or western blot after being stimulated by exogenous TNF-α (0.2, 2, 20 ng/ml) alone or TNF-α along with ETA, or phosphate buffered saline (PBS) as control. (3) The invasion ability of HTR-8/SVneo cells was investigated by transwell test after stimulating by TNF-α alone or TNF-α along with ETA. (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells, which were stimulated by TNF-α (2 ng/ml) alone after nuclear factor-κB (NF-κB) inhibitor, BAY 11-7028, preconditioning, were detected by qRT-PCR or western blot. Results:(1) The mRNA expression level of TNF-α in villi tissue of URSA group (4.10±0.49) was 4.1 times as much as the normal control group ( t=10.51, P<0.05). (2) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells of TNF-α group were significantly lower than those in PBS control group ( P<0.05) and those in TNF-α along with ETA group ( P<0.05). (3) The invasion ability of HTR-8/SVneo cells in TNF-α group was significantly decreased than PBS group and TNF-α along with ETA group (78±14 vs 373±26 vs 227±44, P<0.05). (4) The mRNA and protein expression levels of MMP-2, Slug and CXCR4 in HTR-8/SVneo cells with BAY 11-7028 preconditioning (mRNA: 1.03±0.10, 1.03±0.06, 1.09±0.08; protein: 1.09±0.03, 1.49±0.03, 1.12±0.03) were significantly higher than without preconditioning after being stimulated by TNF-α (all P<0.05). Conclusions:The expression of TNF-α in the villi of URSA patients is much higher than normal early pregnant women. TNF-α could decrease the capacity of invasion by suppressing the expression of MMP-2, Slug and CXCR4 through NF-κB signaling pathway in extravillous trophoblast cells. While ETA could improve the invasiveness capability of extravillous trophoblast cells through inhibiting the negative effect of TNF-α.

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A perda gestacional de repetição (PGR) é definida classicamente como três perdas consecutivas antes de 20 semanas de gestação. Ela afeta aproximadamente 3% dos casais que tentam conceber, quando se consideram pelo menos duas perdas, e cerca de 1%, quando acima de três perdas. A PGR está associada a diferentes fatores causais. Algumas mulheres não terão nenhuma anormalidade identificável nos protocolos investigativos atuais. O aborto pode causar doenças mentais, tais como depressão e ansiedade, e ser responsável por sentimentos como medo, raiva e culpa. Embora existam intervenções já estabelecidas para pacientes com perda gestacional com fator causal determinado, não existe nenhum tratamento comprovadamente efetivo em mulheres com perda gestacional inexplicada. O oferecimento do chamado Tender Loving Care pode levar a melhores resultados gestacionais nessas pacientes. Este artigo irá fazer uma revisão sobre os aspectos psíquicos em PGR e o cuidado suportivo que poderá ser realizado nessas pacientes.(AU)

Recurrent pregnancy loss (RPL) is classically defined as three consecutive losses before 20 weeks of gestation. It affects approximately 3% of couples who try to conceive, when considering at least two losses, and about 1%, when considering three or more. RPL is associated with different causal factors. Some women will have no identificable abnormalities in current investigative protocols. Abortion can cause mental illness, such as depression and anxiety, and be responsible for feelings like fear, anger and guilt. Although there are interventions already established for patients with pregnancy loss with a determined causal factor, there is no proven effective treatment for women with unexplained pregnancy loss. The offer of the so-called Tender Loving Care can lead to better pregnancy results in these patients. This article will review the psychic aspects of recurrent pregnancy losses and the supportive care that can be performed in these patients.(AU)

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Objective To investigate the regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer (dNK) cells during early pregnancy and its association with the incidence of recurrent spontaneous abortion (RSA). Methods Decidua tissues were collected from normal pregnancies (n=16) and RSA cases (n=6) at 6-10 gestational weeks in the Department of Obstetrics and Gynecology of Peking University Third Hospital from October 2018 to May 2019. (1) Expressions of CLEC2D and CD161 in decidua from early pregnancy were detected using immunofluorescence. (2) Primary dNK cells were isolated from decidua from early pregnancy. dNK cells pre-treated with CD161 antibody (blocking CD161, B-CD161) were co-cultured with JEG-3 cells which were knocked-down by CLEC2D small interfering RNA (siCLEC2D), followed by killing capacity assessment of dNK cells by cytotoxicity assay and determination of expressions of related molecules by quantitive real-time polymerase chain reaction. (3) Western blot and flow cytometry were used to detect the expression of CLEC2D and CD161 in decidua tissues. Cytotoxicity assay was performed to analyze the killing capacity of dNK cells. T test was used for statistical analysis between normal and RSA cases. Results (1) CLEC2D was mainly expressed in extravillous trophoblast (EVT) cells and CD161 was mainly detected in dNK cells. CD161-positive dNK cells and CLEC2D-positive EVT cells were adjacently located in decidua tissues allowing their interaction. (2) Cytotoxicity assay suggested that CD161 blocking in dNK cells or CLEC2D knockdown in JEG-3 cells could enhance the cytotoxicity of dNK cells. The target cell lysis rates at the effector-target ratios of 40 ∶ 1, 20 ∶ 1, 10 ∶ 1 and 5 ∶ 1 in B-CD161 group were (59.12±4.56)%, (25.96±5.44)%, (13.60±8.94)% and (12.53±8.94)%, and in IgG control group were (20.01±1.96)%, (8.51±1.32)%, (3.24±0.75)% and (3.82±1.92)%, respectively. There were significant differences between the two groups at the effector-target ratios of 40∶1 (t=13.922, P<0.01) and 20∶1 (t=5.403 P<0.05), but not at 10∶1 or 5∶1 (P>0.05). The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5 ∶ 1 in si-CLEC2D group were (43.37±2.01)%, (32.99±2.08)%, (23.47±1.36)% and (11.48±0.37)%, and in the negative control (NC) group were (15.54±1.46)%, (13.84±1.68)%, (9.94±3.01) and (5.50±0.99)%, respectively. Differences between the two groups at all effector-target ratios were statistically significant (t=19.402, 12.400, 7.093 and 9.842, all P<0.01). Moreover, the expression of dNK killing-related factor granzyme B in the siCLEC2D group was higher than that in the NC group. (3) Compared with the normal pregnancy group, the RSA group showed decreased CD161 expression and increased killing capacity of dNK cells, but no significant difference in CLEC2D expression. Conclusions At early pregnancy, CLEC2D on EVT cells can interact with CD161 on dNK cells, which inhibits the cytotoxicity of dNK cells and induces immune tolerance at the fetal-maternal interface. Decreased expression of CD161 in decidua results in increased cytotoxicity of dNK cells, which may be one of the causes of immune rejection in RSA.

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Objective@#To investigate the regulatory effect of CLEC2D-CD161 interaction on killing capacity of decidual natural killer (dNK) cells during early pregnancy and its association with the incidence of recurrent spontaneous abortion (RSA).@*Methods@#Decidua tissues were collected from normal pregnancies (n=16) and RSA cases (n=6) at 6-10 gestational weeks in the Department of Obstetrics and Gynecology of Peking University Third Hospital from October 2018 to May 2019. (1) Expressions of CLEC2D and CD161 in decidua from early pregnancy were detected using immunofluorescence. (2) Primary dNK cells were isolated from decidua from early pregnancy. dNK cells pre-treated with CD161 antibody (blocking CD161, B-CD161) were co-cultured with JEG-3 cells which were knocked-down by CLEC2D small interfering RNA (siCLEC2D), followed by killing capacity assessment of dNK cells by cytotoxicity assay and determination of expressions of related molecules by quantitive real-time polymerase chain reaction. (3) Western blot and flow cytometry were used to detect the expression of CLEC2D and CD161 in decidua tissues. Cytotoxicity assay was performed to analyze the killing capacity of dNK cells. T test was used for statistical analysis between normal and RSA cases.@*Results@#(1) CLEC2D was mainly expressed in extravillous trophoblast (EVT) cells and CD161 was mainly detected in dNK cells. CD161-positive dNK cells and CLEC2D-positive EVT cells were adjacently located in decidua tissues allowing their interaction. (2) Cytotoxicity assay suggested that CD161 blocking in dNK cells or CLEC2D knockdown in JEG-3 cells could enhance the cytotoxicity of dNK cells. The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5∶1 in B-CD161 group were (59.12±4.56)%, (25.96±5.44)%, (13.60±8.94)% and (12.53±8.94)%, and in IgG control group were (20.01±1.96)%, (8.51±1.32)%, (3.24±0.75)% and (3.82±1.92)%, respectively. There were significant differences between the two groups at the effector-target ratios of 40∶1 (t=13.922, P<0.01) and 20∶1 (t=5.403 P<0.05), but not at 10∶1 or 5∶1 (P>0.05). The target cell lysis rates at the effector-target ratios of 40∶1, 20∶1, 10∶1 and 5∶1 in si-CLEC2D group were (43.37±2.01)%, (32.99±2.08)%, (23.47±1.36)% and (11.48±0.37)%, and in the negative control (NC) group were (15.54±1.46)%, (13.84±1.68)%, (9.94±3.01) and (5.50±0.99)%, respectively. Differences between the two groups at all effector-target ratios were statistically significant (t=19.402, 12.400, 7.093 and 9.842, all P<0.01). Moreover, the expression of dNK killing-related factor granzyme B in the siCLEC2D group was higher than that in the NC group. (3) Compared with the normal pregnancy group, the RSA group showed decreased CD161 expression and increased killing capacity of dNK cells, but no significant difference in CLEC2D expression.@*Conclusions@#At early pregnancy, CLEC2D on EVT cells can interact with CD161 on dNK cells, which inhibits the cytotoxicity of dNK cells and induces immune tolerance at the fetal-maternal interface. Decreased expression of CD161 in decidua results in increased cytotoxicity of dNK cells, which may be one of the causes of immune rejection in RSA.

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ABSTRACT Objective To standardize the investigation and clinical management of women with laboratory and/or clinical abnormalities suggestive of thrombophilia, in order to optimize antithrombotic approach and indication of laboratory tests. Methodology A discussion was carried out among 107 physicians (gynecologists/obstetricians, hematologists and vascular surgeons) present at a forum held at the Hospital Israelita Albert Einstein, in São Paulo (SP), Brazil. As a minimum criterion, 80% agreement was established in the voting to each recommendation of conduct in the final document. The cases in which there was agreement below 80% were discussed again, reaching a consensual agreement of conduct for the document writing. Conclusion The standardization of an institutional consensus of suggestions of clinical approach contributes to a better management of the group to be evaluated and minimizes risks of intercurrent events. This was the first national consensus on the investigation of thrombophilia in women.

RESUMO Objetivo Padronizar a investigação e o manejo clínico de mulheres com anormalidades clínicas e exames laboratoriais sugestivos de trombofilia, para melhorar a abordagem antitrombótica e otimizar a indicação de exames laboratoriais. Metodologia Foi conduzida discussão incluindo 107 médicos (ginecologistas/obstetras, hematologistas e cirurgiões vasculares) participantes de um fórum realizado no Hospital Israelita Albert Einstein, em São Paulo (SP). Como critério mínimo, estabeleceu-se concordância de 80% em votação para cada recomendação de conduta registrada em documento como diretrizes finais. Os casos em que a concordância esteve abaixo de 80% foram rediscutidos, para definir consenso na conduta. Conclusão A padronização e o estabelecimento de consenso institucional, com sugestões para abordagem clínica, contribui para melhorar o manejo do grupo a ser avaliado e minimizar os riscos de intercorrências. Este foi o primeiro consenso nacional sobre investigação de trombofilia em mulheres.

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Objective: To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. Methods: Patients with a history of two or more consecutive clinical miscarriages (≤12 weeks of gestation) consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI) , chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome (APS) . Results: (1) Among 696 patients, the abnormal embryonic karyotypes was 60.6% (422/696) and routine RM etiologies was 32.2% (224/696) , leaving the ratio of unexplained RM was only 29.0% (202/696). (2) A total of 717 embryo karyotype were found in 696 patients, included21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7% (285/717) , while abnormal ones was 60.3% (432/717). Among the types of abnormal karyotype, the most common ones (>10%) were trisomy 16 (19.2%, 83/432) , monosome X (11.3%, 49/432) and trisomy 22 (10.9%, 47/432). (3) Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446 (64.1%, 446/696) and 250 (35.9%, 250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion (P<0.05). But no difference was found in body mass index (BMI) , the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all P>0.05) between two groups. Conclusions: The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.

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O estudo teve por objetivo descrever os fatores de risco para o abortamento no Hospital Nossa Senhora da Conceição, Tubarão-SC, no período de julho de 2010 a julho de 2011. Foi realizado um estudo caso-controle, onde foram analisados 366 prontuários, sendo 122 casos de pacientes que deram entrada com abortamento e 244 controles de pacientes que tiveram seus partos normalmente. Foi realizada análise descritiva, bivariada e regressão logística, relatando-se o OR e respectivo IC95%. No presente estudo 96,7% dos abortos foram classificados como espontâneos e 3,3% como provocados. Foi observado que as mulheres que não tinham relação estável apresentaram duas vezes mais chances de abortamento do que as que possuíam (OR: 1,98) (p=0,037), assim como as com menos de oito anos de escolaridade (OR:2,03) (p=0,0013). As pacientes tabagistas apresentaram uma chance de aborto aproximadamente sete vezes maior do que as não fumantes (OR:6,49) (p=0,0000013), e uma magnitude de chance semelhante foi encontrada nas pacientes que não possuíam religião (OR:6,87) (p=0,000013). Foi encontrada também uma associação de aborto com aborto prévio, sendo que as que o possuíam apresentaram o dobro de chance em comparação à aquelas que não possuíam aborto anterior (OR: 1,88) (p=0,021). Mulheres que não possuíam parceiro fixo e religião, assim como aquelas que tiveram oito anos ou menos de escolaridade, fumantes e com história de abortamento prévio apresentaram um risco maior de abortamento na análise multivariada.

The objective of this study was to describe the risk factors for abortion at Hospital Nossa Senhora da Conceição, Tubarão-SC, from July 2010 to July 2011. A case-control study was carried out, which 366 medical records were analyzed, 122 cases of patients who were admitted with abortion and 244 controls of patients who had their normal deliveries. A descriptive, bivariate and logistic regression analysis was performed, reporting the OR and its 95% CI. In the present study, 96.7% of the abortions were classified as spontaneous and 3.3% as provoked. It was observed that women who had no stable relationship were twice as likely to have an abortion as they had (OR: 1.98) (p = 0.037), as well as those with less than eight years of schooling (OR: 2.03) (p = 0.0013). Smoking patients presented a chance of abortion approximately seven times higher than nonsmokers (OR: 6.49) (p = 0.0000013), and a similar magnitude of chance was found in patients who did not have a religion (OR: 6.87) (p = 0.000013). It was also found an association of abortion with previous abortion, and those who had it presented a double chance compared to those who did not have a previous abortion (OR: 1.88) (p = 0.021). Women who did not have a fixed partner and religion, as well as those who had eight years or less of schooling, smokers and previous history of abortion presented a greater risk of abortion in the multivariate analysis.

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Essentials Inherited factor XIII deficiency is a very rare bleeding disorder. We used recombinant factor XIII-A in a pregnant patient with factor XIII-A subunit deficiency. The patient had a successful pregnancy outcome with no pregnancy related complications. The dose of recombinant factor XIII-A was minimized by using frequent trough level monitoring. SUMMARY: Inherited factor XIII deficiency is a very rare bleeding disorder, and is one of the causes of recurrent pregnancy loss. The use of plasma-derived FXIII to improve pregnancy outcomes has been reported. We report a 26-year-old woman with FXIII A-subunit (FXIII-A) deficiency who was treated with recombinant FXIII-A and had a successful pregnancy outcome with no pregnancy-related complications. Our case illustrates that the dose of recombinant FXIII-A can be minimized and adjusted on the basis of frequent trough level monitoring.

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Objective: To investigate the influence of occupational stress on recurrent spontaneous abortion (RSA) in women of childbearing age. Methods: From January to December, 2017, 75 working women of childbearing age (25-35 years) who were admitted to a provisional hospital in Lanzhou, China and diagnosed with RSA were assigned into patient group. At a 1∶4 ratio, 300 age-matched working women who had normal first pregnancy were randomly selected as controls. A case-control study was conducted by a self-made questionnaire and the effort-reward imbalance scale. The impact of occupational stress on RSA in women of childbearing age was analyzed by evaluation of occupational harmful factors, regularity, effort-reward ratio, and sleep quality. Results: There were significant differences in the distribution of sleep, daily exercise, night shift, extrinsic-effort/low-reward score, and effort/low-reward score between the patient group and the control group (χ(2)=7.867, P<0.05; χ(2)=7.377, P<0.05; χ(2)=3.714, P<0.05; χ(2)=6.651, P<0.05; χ(2)=8.556, P<0.05) . With controlled factors such as general conditions and living habits, logistic regression analysis showed that poor sleep quality and high-effort/low-reward were risk factors for RSA (odds ratio[OR]=1.462, 95% confidence interval[CI]: 1.032~2.073; OR=3.253, 95%CI: 1.169~9.053) . A regular work was a protective factor against RSA (OR=0.644, 95%CI: 0.438-0.946) . Conclusion: In occupational stress, irregular working hours, lack of sleep, and high-effort/low-reward are risk factors for RSA. Working women of childbearing age should ensure adequate sleep, pay attention to effort-reward balance, and make a regular work schedule.

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Objective To explore the relationship between aryl hydrocar-bon receptor (AhR),aryl hydrocarbon receptor nuclear translocator (ARNT),estradiol (E2),estrogen receptor (ER) and recurrent spontaneous abortion (RSA) through observing the level of serum AhR,ARNT,E2,and AhR,ARNT,ER in decidua and chorionic tissues of the patients with recurrent spontaneous abortion.Methods 64 cases of RSA patients who induced abortion at the Shanxi Dayi hospital from May 2015 to September2017 were chosen as RSA group,and 30 cases of healthy abortion women of the same period who had born full-term normal fetus were choosen as the normal group.The serum,villi and decidua of each case were collected during abortion.The level of AhR,ARNT,ER of both groupswere detected by enzyme-linked immunoscrbent assay (ELISA) method.The Serum E2 lever were detected by the method of chemical luminescence.The data of all the patients were analyzed.Results (1) The level of ARNT in peripheral blood of RSA group was significantly higher than that of normal group (P ＜ 0.05),and the levels of AhR and E2 in peripheral blood were not statistically significant between the two groups (P ＞ 0.05).The levels of AhR and ARNT in villi and decidua were significantly higher in RSA group than in normal group (P ＜ 0.05),while the expression of ER in villi and decidua was significantly lower in RSA group than in normal group (P ＜ 0.05).(2) There was no significant difference in the ratio of AhR/ARNT between the two groups (P ＞ 0.05);the ratio of AhR/ER and ARNT/ER in the villi and decidua of the RSA group was higher than that of the normal group (P ＜ 0.05).Conclusions Overexpression of AhR and ARNT and low expression of ER in villi and decidua tissues may be related to the occurrence of RSA.

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Objective@#To investigate the influence of occupational stress on recurrent spontaneous abortion (RSA) in women of childbearing age.@*Methods@#From January to December, 2017, 75 working women of childbearing age (25-35 years) who were admitted to a provisional hospital in Lanzhou, China and diagnosed with RSA were assigned into patient group. At a 1∶4 ratio, 300 age-matched working women who had normal first pregnancy were randomly selected as controls. A case-control study was conducted by a self-made questionnaire and the effort-reward imbalance scale. The impact of occupational stress on RSA in women of childbearing age was analyzed by evaluation of occupational harmful factors, regularity, effort-reward ratio, and sleep quality.@*Results@#There were significant differences in the distribution of sleep, daily exercise, night shift, extrinsic-effort/low-reward score, and effort/low-reward score between the patient group and the control group (χ2=7.867, P<0.05; χ2=7.377, P<0.05; χ2=3.714, P<0.05; χ2=6.651, P<0.05; χ2=8.556, P<0.05) . With controlled factors such as general conditions and living habits, logistic regression analysis showed that poor sleep quality and high-effort/low-reward were risk factors for RSA (odds ratio[OR]=1.462, 95% confidence interval[CI]: 1.032~2.073; OR=3.253, 95%CI: 1.169~9.053) . A regular work was a protective factor against RSA (OR=0.644, 95%CI: 0.438-0.946) .@*Conclusion@#In occupational stress, irregular working hours, lack of sleep, and high-effort/low-reward are risk factors for RSA. Working women of childbearing age should ensure adequate sleep, pay attention to effort-reward balance, and make a regular work schedule.

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Objective To compare the etiological constitution of recurrent miscarriage (RM) between patients with consecutive two and three or more miscarriages through combining the routine examination results and embryonic karyotype. Methods Patients with a history of two or more consecutive clinical miscarriages(≤12 weeks of gestation)consulting in the RM clinic of the First Affiliated Hospital of Sun Yat-sen University from March 2011 to January 2016 were collected. Six hundred and ninety-six with detailed history recorded, routine clinical examinations of RM and at least once embryonic karyotype were ultimately enrolled in this study. Their etiological constitution of RM were analyzed in groups of consecutive two and three or more miscarriage. The etiologies of RM in analysis consisted of women age, body mass index (BMI), chromosome abnormalities of couples, uterine abnormalities, endocrinology abnormalities and antiphospholipid syndrome(APS). Results (1)Among 696 patients, the abnormal embryonic karyotypes was 60.6%(422/696)and routine RM etiologies was 32.2%(224/696), leaving the ratio of unexplained RM was only 29.0%(202/696).(2)A total of 717 embryo karyotype were found in 696 patients, included 21 cases with twice embryo karyotype results the percentage of normal embryo was 39.7%(285/717), while abnormal ones was 60.3%(432/717). Among the types of abnormal karyotype, the most common ones (>10%)were trisomy 16(19.2%, 83/432), monosome X(11.3%, 49/432)and trisomy 22(10.9%, 47/432). (3)Among the 696 RM patients, the number of two and three or more miscarriages were respectively 446(64.1%,446/696)and 250(35.9%,250/696). Comparing groups of three or more miscarriages with two miscarriages, there were significant differencein older age as well as uterine adhesion(P<0.05). But no difference was found in body mass index(BMI), the rates of chromosome abnormalities of couples, uterine abnormalities except uterine adhesion, endocrinology abnormalities and APS (all P>0.05) between two groups. Conclusions The abnormal embryonic karyotype is the most common cause of first-trimester RM. The etiological constitution of two and three or more recurrent miscarriages is accordant, suggesting that routine clinical examination and the embryonic karyotype should be started following two consecutive clinical early miscarriages.