Recurrent Miscarriage (recurrent + miscarriage)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


The Expression of Th1- and Th2-Related Chemokine Receptors in Women with Recurrent Miscarriage: the Impact of Lymphocyte Immunotherapy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Nasim Kheshtchin
Citation Kheshtchin N, Gharagozloo M, Andalib A, Ghahiri A, Maracy MR, Rezaei A. The Expression of Th1- and Th2-Related chemokine receptors in women with recurrent miscarriage: the impact of lymphocyte Immunotherapy. Am J Reprod Immunol 2010; 64: 104,112 Problem, Recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The aim of this study was to investigate the expression of T helper (Th)1- and Th2-related chemokine receptors on CD4+ T helper and CD8+ T cytotoxic (Tc) cells in RM and control subjects. The effects of lymphocyte immunotherapy on the balance of Th1/Th2 and Tc1/Tc2 chemokine receptors were further evaluated in RM women. Method of study, The expression of Th1-related (CCR5 and CXCR3) and Th2-related (CCR3 and CCR4) chemokine receptors on CD4+ or CD8+ T cells from RM women were analyzed and compared with controls using flow cytometry. The expression of chemokine receptors in RM women was also compared before and after lymphocyte immunotherapy. Results, The ratios of Th1/Th2 and Tc1/Tc2 chemokine receptors were higher in RM women compared to controls. The ratio of Th1/Th2 chemokine receptors was decreased in RM women after immunotherapy, while no significant change was identified in the Tc1/Tc2 after immunotherapy. Conclusion, This study indicates the Th1 dominant immune responses in circulation of RM women compared to controls. Moreover, lymphocyte immunotherapy might influence pregnancy outcome via a shift in the balance of the Th1/Th2 chemokine receptors. [source]


ORIGINAL ARTICLE: Activating Killer Cell Immunoglobulin-Like Receptor Genes' Association with Recurrent Miscarriage

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009
Rafael Gustavo Vargas
Problem, Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. Method of study A matched case,control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23,6.01)]. Conclusion Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes. [source]


Searching for Links between Endotoxin Exposure and Pregnancy Loss: CD14 Polymorphism in Idiopathic Recurrent Miscarriage

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2003
Jari Karhukorpi
Problem: Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of abortions in mice. In addition it has been proposed that gut-derived LPS of gram-negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD14 is one of the key molecules that mediates the effects of LPS. Promoter region polymorphism (,159C/T) in the CD14 gene is functionally important by regulating CD14 levels. High-producing CD14 genotype (TT) associates with deleterious effects of gut-derived LPS in hepatic cirrhosis in humans. It is not known whether women with IRM are genetically more prone to suffer from toxic effects of LPS. Method of study: By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal controls of Finnish origin. Results: There were no significant differences in the CD14(,159C/T) allele or the genotype frequencies between the IRM women and the controls. However, there was a trend associating the presence of the T allele with increased odds of miscarriage. Conclusions: Although we were not able to find a statistically significant association between CD14 genotypes and IRM in our relatively small study population, a further study with a larger sample size is warranted to explore the role of high-producing CD14 genotypes in IRM. Also studies highlighting environmental LPS triggers and other intrinsic mediators of LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans. [source]


ORIGINAL ARTICLE: Peripheral Blood NK Cells Reflect Changes in Decidual NK Cells in Women With Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Dong Wook Park
Citation Park DW, Lee HJ, Park CW, Hong SR, Kwak-Kim J, Yang KM. Peripheral blood NK cells reflect changes in decidual NK cells in women with recurrent miscarriages. Am J Reprod Immunol 2010; 63: 173,180 Problem, We aimed to investigate if peripheral blood natural killer (pNK) cell levels are correlated with decidual NK (dNK) cell levels, and if chemokine expression has any role in dNK cell regulation. Method of study, Decidual tissues of women having two or more miscarriages with normal karyotype were collected after miscarriage and an immuno-histochemisty study was made. pNK cells were evaluated using flow cytometric analysis. Results, The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed a significant correlation with mean number of CD56+ dNK cells. The number of decidual CD16+ cells was significantly higher in women with elevated pNK (,15%) than that of normal pNK (<15%). The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed an inverse correlation with duration of gestation. The CCL3+ and CXCL12+ cells were present in the decidua; however, staining intensity was not correlated with number of dNK cells. Conclusion, The pNK cell levels reflect changes in dNK cell levels. This implicates that pNK cell level is a clinically useful marker to predict pregnancy outcome. Further study is needed to examine if elevated pNK cells enhance recruitment of dNK cells in the decidua. [source]


SHORT COMMUNICATION: STAT3 Polymorphisms Linked with Idiopathic Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Ramzi R. Finan
Problem, We investigated the association of signal transducers and activators of transcription (STAT)3 gene variants with idiopathic recurrent miscarriage (RM). Method of Study, A case,control study involving 189 RM patients and 244 control women was carried out. STAT3 (rs1053004 and rs1023023) genotyping was performed by allelic discrimination/real-time PCR method. Results,STAT3 rs1053004 C allele [OR (95% CI) = 1.60 (1.22,2.10)] and C/C genotype [OR (95% CI) = 3.42 (1.70,6.92)] were positively associated with RM. Two-locus (rs1053004/rs1053023) haplotype analysis revealed increased frequency of CG and CA haplotypes in RM patients, of which only CA haplotype (Pc = 0.020) remained positively associated with RM after applying the Bonferroni correction. This was confirmed by multivariate regression analysis (OR = 1.70; 95% CI = 1.17,2.46) after adjusting for a number of covariates. Conclusion,STAT3 rs1053004 variant is significantly associated with idiopathic RM. Replication studies on other racial groups and other STAT3 gene variants are warranted. [source]


ORIGINAL ARTICLE: Live Birth Rate According to Maternal Age and Previous Number of Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Mayumi Sugiura-Ogasawara
Problem, In Japan, marital age and women's age at the first pregnancy are continuing to increase year by year. However, information concerning subsequent live birth rate according to maternal age and number of previous recurrent miscarriages is limited. Method of study, We studied a total of 1250 unexplained patients suffering two or more consecutive miscarriages. We examined the live birth rate at the first pregnancy and the cumulative success rate for birth of at least one child after examination. Results, The live birth rate of women in their 40s was 58.1%, which was similar to that of women who were 35,39 years old (58.4%) at the first pregnancy, as found after examination. From logistic regression, women's age and the number of previous miscarriages independently decreased the live birth rate in subsequent pregnancies (ps) as well as cumulative pregnancies (pc), as follows: Conclusion, The information concerning the live birth rate can be given to each patient before subsequent pregnancy. [source]


ORIGINAL ARTICLE: The Polycystic Ovary Syndrome Does Not Predict Further Miscarriage in Japanese Couples Experiencing Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009
Mayumi Sugiura-Ogasawara
Problem, It has been a matter of controversy whether the polycystic ovary syndrome (PCOS) is actually a causal factor of miscarriages because of the absence of internationally established criteria. We, therefore, in this study investigated whether PCOS and a polycystic ovary (PCO) morphology have predictive value for subsequent miscarriages using new International and Japanese criteria. Method of study, A total of 195 patients with a history of two consecutive first trimester miscarriages and without abnormal chromosomes in either partner, antiphospholipid antibodies or uterine anomalies, were examined. The prospective pregnancy outcome was compared between patients with and without PCOS, PCO morphology, elevated luteinizing hormone (LH), hyperandrogenism and obesity. Results, Of a total of 195 patients, 56 (28.7%) miscarried subsequently. Three (1.5%) and 12 (6.2%) were diagnosed as suffering from PCOS by Japanese and International criteria respectively. There was no relation between a diagnosis of PCOS, PCO morphology, elevated LH, free testosterone or obesity and the subsequent miscarriage rate. Conclusion, A routine test for diagnosis of PCOS is not necessary in patients experiencing recurrent miscarriages because none of the related parameters examined in this study predicted subsequent miscarriage. [source]


The Expression of Th1- and Th2-Related Chemokine Receptors in Women with Recurrent Miscarriage: the Impact of Lymphocyte Immunotherapy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Nasim Kheshtchin
Citation Kheshtchin N, Gharagozloo M, Andalib A, Ghahiri A, Maracy MR, Rezaei A. The Expression of Th1- and Th2-Related chemokine receptors in women with recurrent miscarriage: the impact of lymphocyte Immunotherapy. Am J Reprod Immunol 2010; 64: 104,112 Problem, Recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The aim of this study was to investigate the expression of T helper (Th)1- and Th2-related chemokine receptors on CD4+ T helper and CD8+ T cytotoxic (Tc) cells in RM and control subjects. The effects of lymphocyte immunotherapy on the balance of Th1/Th2 and Tc1/Tc2 chemokine receptors were further evaluated in RM women. Method of study, The expression of Th1-related (CCR5 and CXCR3) and Th2-related (CCR3 and CCR4) chemokine receptors on CD4+ or CD8+ T cells from RM women were analyzed and compared with controls using flow cytometry. The expression of chemokine receptors in RM women was also compared before and after lymphocyte immunotherapy. Results, The ratios of Th1/Th2 and Tc1/Tc2 chemokine receptors were higher in RM women compared to controls. The ratio of Th1/Th2 chemokine receptors was decreased in RM women after immunotherapy, while no significant change was identified in the Tc1/Tc2 after immunotherapy. Conclusion, This study indicates the Th1 dominant immune responses in circulation of RM women compared to controls. Moreover, lymphocyte immunotherapy might influence pregnancy outcome via a shift in the balance of the Th1/Th2 chemokine receptors. [source]


Endocrinological and endometrial factors in recurrent miscarriage

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2000
T. C. Li Consultant Gynaecologist
Objective To investigate the endocrinological and endometrial factors in women with unexplained recurrent miscarriage Design Prospective, case study Setting Recurrent miscarriage clinic, Jessop Hospital for Women, Sheffield Participants One hundred and forty-four women with unexplained recurrent (, 3) miscarriages Methods A blood sample was obtained in early follicular phase (day 3,5) to measure follicle stimulating hormone, luteinising hormone, prolactin, androgens and thyroid function; daily blood/urine samples were obtained from mid-follicular phase to measure luteinising hormone until the luteinising hormone surge was identified; endometrial biopsy and a further blood sample for progesterone measurement were obtained in the mid-luteal phase. A transvaginal ultrasonography was performed to evaluate ovarian morphology. Results Hypersecretion of luteinising hormone or ultrasonographic features of polycystic ovarian disease was present in 8% and 7.8% of women, respectively. The free androgen index was elevated in 14.6% of subjects. In the mid-luteal phase, low progesterone level was found in 17.4% and delayed endometrial development was noted in 27.1% of women. Although women with recurrent miscarriage women and delayed endometrium had significantly lower progesterone levels than those with normal endometrial development, only 8/24 had mid-luteal progesterone levels below 30 nmol/L. Recurrent miscarriage was not associated with hyperprolactinaemia or abnormal thyroid function test. Conclusions Endocrinological and endometrial abnormalities are present in about a quarter of women with unexplained recurrent miscarriage. [source]


Pregnancy and rare bleeding disorders

HAEMOPHILIA, Issue 5 2009
R. KADIR
Summary., Rare bleeding disorders include deficiency of fibrinogen, prothrombin, factor V, factor VII, factor X, factor XI and factor XIII together with combined deficiency disorders, factor V+VIII deficiency, and deficiency of the vitamin K-dependent factors (factor II, VII, IX and X). They account for 3,5% of all inherited coagulation disorders. Due to their rarity, information about pregnancy complications and management is limited and mostly derived from case reports. Deficiency of fibrinogen and FXIII are both found to be strongly associated with increased risk of recurrent miscarriage and placental abruption. Factor replacement is used to reduce these risks. However, the risk of miscarriage and ante-partum complications is less clear in women with other bleeding disorders. Haemostatic abnormalities in women with rare bleeding disorders seem to persist throughout pregnancy especially if the defect is severe. Therefore women affected with these disorders are at risk of post-partum haemorrhage. The fetus can also be affected and potentially at risk of bleeding complications. Specialised multidisciplinary management is essential to minimise the potential maternal and neonatal complications and ensure an optimal outcome. This paper presents literature review for pregnancy complications in each of the rare bleeding disorders. In addition general principles for management of pregnancy, labour and delivery are discussed. [source]


The Expression of Th1- and Th2-Related Chemokine Receptors in Women with Recurrent Miscarriage: the Impact of Lymphocyte Immunotherapy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Nasim Kheshtchin
Citation Kheshtchin N, Gharagozloo M, Andalib A, Ghahiri A, Maracy MR, Rezaei A. The Expression of Th1- and Th2-Related chemokine receptors in women with recurrent miscarriage: the impact of lymphocyte Immunotherapy. Am J Reprod Immunol 2010; 64: 104,112 Problem, Recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The aim of this study was to investigate the expression of T helper (Th)1- and Th2-related chemokine receptors on CD4+ T helper and CD8+ T cytotoxic (Tc) cells in RM and control subjects. The effects of lymphocyte immunotherapy on the balance of Th1/Th2 and Tc1/Tc2 chemokine receptors were further evaluated in RM women. Method of study, The expression of Th1-related (CCR5 and CXCR3) and Th2-related (CCR3 and CCR4) chemokine receptors on CD4+ or CD8+ T cells from RM women were analyzed and compared with controls using flow cytometry. The expression of chemokine receptors in RM women was also compared before and after lymphocyte immunotherapy. Results, The ratios of Th1/Th2 and Tc1/Tc2 chemokine receptors were higher in RM women compared to controls. The ratio of Th1/Th2 chemokine receptors was decreased in RM women after immunotherapy, while no significant change was identified in the Tc1/Tc2 after immunotherapy. Conclusion, This study indicates the Th1 dominant immune responses in circulation of RM women compared to controls. Moreover, lymphocyte immunotherapy might influence pregnancy outcome via a shift in the balance of the Th1/Th2 chemokine receptors. [source]


ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 Activity

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010
Melissa J. Mulla
Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010 Problem Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to ,2 -glycoprotein I (,2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration. Method of study First trimester trophoblast cells were treated with anti-,2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot. Results Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-,2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-,2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration. Conclusion This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia. [source]


SHORT COMMUNICATION: STAT3 Polymorphisms Linked with Idiopathic Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Ramzi R. Finan
Problem, We investigated the association of signal transducers and activators of transcription (STAT)3 gene variants with idiopathic recurrent miscarriage (RM). Method of Study, A case,control study involving 189 RM patients and 244 control women was carried out. STAT3 (rs1053004 and rs1023023) genotyping was performed by allelic discrimination/real-time PCR method. Results,STAT3 rs1053004 C allele [OR (95% CI) = 1.60 (1.22,2.10)] and C/C genotype [OR (95% CI) = 3.42 (1.70,6.92)] were positively associated with RM. Two-locus (rs1053004/rs1053023) haplotype analysis revealed increased frequency of CG and CA haplotypes in RM patients, of which only CA haplotype (Pc = 0.020) remained positively associated with RM after applying the Bonferroni correction. This was confirmed by multivariate regression analysis (OR = 1.70; 95% CI = 1.17,2.46) after adjusting for a number of covariates. Conclusion,STAT3 rs1053004 variant is significantly associated with idiopathic RM. Replication studies on other racial groups and other STAT3 gene variants are warranted. [source]


ORIGINAL ARTICLE: Are Polymorphisms in the ACE and PAI-1 Genes Associated with Recurrent Spontaneous Miscarriages?

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009
Chelsi Goodman
Problem, To determine whether the ACE D/D genotype or the combination of PAI-1 4G/4G and ACE D/D genotypes may serve as a risk factor for recurrent pregnancy loss. Method of study, Buccal swabs were obtained from 120 women experiencing recurrent pregnancy loss and from 84 fertile control women. DNA was extracted from the buccal swab samples using the Qiagen DNA Mini Kit (Qiagen), followed by multiplex polymerase chain reaction (PCR). PCR products were analyzed for the ACE gene polymorphism, which consists of the insertion or deletion (I/D) of a 287-bp fragment in intron 16, and the PAI-1 4G/4G genotype. Results, No significant differences in specific ACE gene mutations were observed when patients experiencing recurrent miscarriage were compared with control women. When the frequencies of homozygous mutations for ACE D/D and PAI-I 4G/4G were compared between recurrent aborters and controls, again no significant differences in the prevalence of the combination of these gene mutations were noted. Conclusion, Homozygosity for the D allele of the ACE gene and the combination of the D/D genotype with two 4G alleles of the PAI-1 promoter gene are not associated with a significant increase in the risk of recurrent miscarriage. [source]


ORIGINAL ARTICLE: Antiphospholipid Antibodies Induce a Pro-Inflammatory Response in First Trimester Trophoblast Via the TLR4/MyD88 Pathway

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009
Melissa J. Mulla
Problem, Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre-eclampsia, and pre-term labor. aPL target the placenta directly by binding to beta2 -glycoprotein I (,2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved. Method of study, First trimester trophoblast cells were treated with anti-,2GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated. Results, We report that anti-,2GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)-8, MCP-1, GRO-,, and IL-1,, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspase-mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-,2GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/paracrine manner. Enhanced IL-8, GRO-,, and IL-1, secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-,2GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations. Conclusion, These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients. [source]


ORIGINAL ARTICLE: Activating Killer Cell Immunoglobulin-Like Receptor Genes' Association with Recurrent Miscarriage

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009
Rafael Gustavo Vargas
Problem, Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. Method of study A matched case,control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23,6.01)]. Conclusion Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes. [source]


1141478081 Cleavage of integrin by calpain in patients with recurrent miscarriage

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006
K Nozawa
Problem:, In our previous study, we have been reported that calpain, a calcium-dependent cysteine protease, activated by increasing intracellular calcium-ion concentration in endometrial cell, cause endometrial dysfunction for implantation. In this study, we investigated the existence and contribution of calpains, their endogenous inhibitor calpastatin, and their substrate such as integrin ,3 and ,-fodrin in deciduas of patients with recurrent miscarriage. Method of Study:, Deciduas were surgically collected from 31 patients with recurrent miscarriage and 23 healthy women with informed consent. Immunohistochemistry, SDS-PAGE and western blot analysis were performed using antibodies against calpain, calpastatin, integrin ,3 and ,-fodrin. Results:, Staining of ,-calpain, m-calpain, capastatin, integrin ,3 and ,-fodrin were observed in the cytoplasm of stromal and epithelial cells in deciduas using immunohistochemistry. No significant differences were observed in staining patterns. Western blot analysis shows no significant differences in m-calpain, calpastatin and ,-fodrin, while ,-calpain was significantly higher and integrin ,3 was lower in subject. Conclusions:, The result provided that cleavage of integrin ,3 by ,-calpain may cause adverse effect in the mechanism of early pregnancy. [source]


Searching for Links between Endotoxin Exposure and Pregnancy Loss: CD14 Polymorphism in Idiopathic Recurrent Miscarriage

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2003
Jari Karhukorpi
Problem: Lipopolysaccharide (LPS) (endotoxin) is a well-known inducer of abortions in mice. In addition it has been proposed that gut-derived LPS of gram-negative bacteria may play a role in triggering idiopathic recurrent miscarriage (IRM) in humans. CD14 is one of the key molecules that mediates the effects of LPS. Promoter region polymorphism (,159C/T) in the CD14 gene is functionally important by regulating CD14 levels. High-producing CD14 genotype (TT) associates with deleterious effects of gut-derived LPS in hepatic cirrhosis in humans. It is not known whether women with IRM are genetically more prone to suffer from toxic effects of LPS. Method of study: By using polymerase chain reaction we analyzed the CD14 promoter region polymorphism in 38 women with IRM and in 127 normal controls of Finnish origin. Results: There were no significant differences in the CD14(,159C/T) allele or the genotype frequencies between the IRM women and the controls. However, there was a trend associating the presence of the T allele with increased odds of miscarriage. Conclusions: Although we were not able to find a statistically significant association between CD14 genotypes and IRM in our relatively small study population, a further study with a larger sample size is warranted to explore the role of high-producing CD14 genotypes in IRM. Also studies highlighting environmental LPS triggers and other intrinsic mediators of LPS signalling are needed to solve the enigmatic role of LPS in IRM in humans. [source]


Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 11 2005
Article first published online: 17 OCT 200
No abstract is available for this article. [source]


Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2005
Raj Raghupathy
Objective To examine the effects of dydrogesterone on the production of Th1 and Th2 cytokines by lymphocytes from women undergoing unexplained recurrent spontaneous miscarriage (RSM). Design Controlled prospective, clinical study conducted in a maternity hospital and a university-based immunology laboratory. Setting Faculty of Medicine, Kuwait University and Kuwait Maternity Hospital. Sample Thirty women with unexplained RSM. Methods Peripheral blood mononuclear cells (PBMC) from women with unexplained RSM were isolated from venous blood by density gradient sedimentation and stimulated with phytohaemagglutinin (PHA). Culture supernatants assayed for interferon (IFN)-,, tumour necrosis factor (TNF)-,, interleukin (IL)-4, IL-6 and IL-10 by ELISA. Levels of the progesterone-induced blocking factor (PIBF) were also measured. Main outcome measures Cytokine production in the presence and absence of progesterone and dydrogesterone. Results Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN-, (P= 0.0001) and TNF-, (P= 0.005) and induced an increase in the levels of the Th2 cytokines IL-4 (P= 0.03) and IL-6 (P= 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. The effect of dydrogesterone was blocked by the addition of the progesterone-receptor antagonist mifepristone, indicating that dydrogesterone was acting via the progesterone receptor. Dydrogesterone induced the production of PIBF. Conclusion Dydrogesterone inhibits the production of the Th1 cytokines IFN-, and TNF-, from lymphocytes and up-regulates the production of the Th2 cytokines IL-4 and IL-6, inducing a Th1 to Th2 cytokine shift. [source]


Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2001
M.F. Reznikoff-Etiévant
Objective To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. Design A prospective study. Setting Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. Population Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n=260) and control healthy women without a previous history of thromboembolism (n=240). Methods Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. Results Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1,5) and 2.7 (95% CI 1,7), respectively. Similar results were found whether or not women had had a previous live birth. Conclusions Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages. [source]


Endocrinological and endometrial factors in recurrent miscarriage

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 12 2000
T. C. Li Consultant Gynaecologist
Objective To investigate the endocrinological and endometrial factors in women with unexplained recurrent miscarriage Design Prospective, case study Setting Recurrent miscarriage clinic, Jessop Hospital for Women, Sheffield Participants One hundred and forty-four women with unexplained recurrent (, 3) miscarriages Methods A blood sample was obtained in early follicular phase (day 3,5) to measure follicle stimulating hormone, luteinising hormone, prolactin, androgens and thyroid function; daily blood/urine samples were obtained from mid-follicular phase to measure luteinising hormone until the luteinising hormone surge was identified; endometrial biopsy and a further blood sample for progesterone measurement were obtained in the mid-luteal phase. A transvaginal ultrasonography was performed to evaluate ovarian morphology. Results Hypersecretion of luteinising hormone or ultrasonographic features of polycystic ovarian disease was present in 8% and 7.8% of women, respectively. The free androgen index was elevated in 14.6% of subjects. In the mid-luteal phase, low progesterone level was found in 17.4% and delayed endometrial development was noted in 27.1% of women. Although women with recurrent miscarriage women and delayed endometrium had significantly lower progesterone levels than those with normal endometrial development, only 8/24 had mid-luteal progesterone levels below 30 nmol/L. Recurrent miscarriage was not associated with hyperprolactinaemia or abnormal thyroid function test. Conclusions Endocrinological and endometrial abnormalities are present in about a quarter of women with unexplained recurrent miscarriage. [source]


Double inherited thrombophilias and adverse pregnancy outcomes: Fashion or science?

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2010
Giovanni Larciprete
Abstract Aim:, To determine to what extent double inherited thrombophilias are associated with adverse obstetric complications correlated with fetoplacental insufficiency, such as preeclampsia, hemolytic anemia elevated liver enzymes and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction (FGR), intrauterine death (ID), abruptio placentae and disseminated intravascular coagulopathy. Methods:, Pregnant women coming to delivery were retrospectively divided into two groups: group A (controls) and group B (cases). Patients belonging to group B had one of the following: severe preeclampsia, HELLP syndrome, gestational hypertension, FGR, intrauterine death, abruptio placentae of disseminated intravascular coagulopathy. We detected methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, plasma homocysteine, antithrombin III, protein S and activated protein C resistance. Normal pregnant women or pregnant women with double defects were enrolled in this study. Results:, The combination of MTHFR C677T mutation with PAI-1 (5G/5G) mutation was significantly linked with the occurrence of ID. HELLP syndrome was significantly related to the simultaneous presence of factor VIII and X mutations. The combination of MTHFR C677T with factor VIII mutation and the combination of factor II and V mutations were significantly related to the occurrence of abruptio placentae. We found an association between double isoforms MTHFR mutation and FGR. Conclusion:, It seems that some thrombophilias and a combination of thrombophilic factors carry a greater risk than others for a given adverse outcome. Further studies are needed to check the link between thrombophilic gene mutations and adverse pregnancy outcomes, such as recurrent miscarriages and deep venous thrombosis. [source]


Gender-medicine aspects in allergology

ALLERGY, Issue 5 2008
E. Jensen-Jarolim
Despite the identical immunological mechanisms activating the release of mediators and consecutive symptoms in immediate-type allergy, there is still a clear clinical difference between female and male allergic patients. Even though the risk of being allergic is greater for boys in childhood, almost from adolescence onwards it seems to be a clear disadvantage to be a woman as far as atopic disorders are concerned. Asthma, food allergies and anaphylaxis are more frequently diagnosed in females. In turn, asthma and hay fever are associated with irregular menstruation. Pointing towards a role of sex hormones, an association of asthma and intake of contraceptives, and a risk for asthma exacerbations during pregnancy have been observed. Moreover, peri- and postmenopausal women were reported to increasingly suffer from asthma, wheeze and hay fever, being even enhanced by hormone replacement therapy. This may be on account of the recently identified oestradiol-receptor-dependent mast-cell activation. As a paradox of nature, women may even become hypersensitive against their own sex hormones, resulting in positive reactivity upon intradermal injection of oestrogen or progesterone. More importantly, this specific hypersensitivity is associated with recurrent miscarriages. Even though there is a striking gender-specific bias in IgE-mediated allergic diseases, public awareness of this fact still remains minimal today. [source]


Prevalence of factor V G1691A (factor V-Leiden) and prothrombin G20210A gene mutations in a recurrent miscarriage population

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2002
Ramzi R. Finan
Abstract Factor V G1691A (FV-Leiden) and prothrombin G20210A mutations are major inherited risk factors for venous thrombosis. Recently, it was suggested that both mutations, through stimulation of venous and placental thrombosis events, were strongly associated with recurrent idiopathic miscarriages, although other studies disputed such a link. The aim of this study was to determine the prevalence of prothrombin G20210A and factor V G1691A (R506Q, FV-Leiden) mutations in women with recurrent idiopathic abortions and to recommend management for high-risk mutation carriers. One hundred ten women with two or more consecutive unexplained first-trimester miscarriages (mean age ± SD, 32.3 ± 5.3) were compared to 67 parous women with uncomplicated pregnancies (mean age ± SD, 33.9 ±7.3) (P = 0.134) from the same ethnic background. The presence or absence of the prothrombin G20210A and FV-Leiden mutations was assessed by PCR and RFLP analysis, using HindIII and MnlI digestion, respectively. In women with primary habitual abortion, 45 (40.91%) carried the FV-Leiden mutation, of whom 7 were in the homozygote and 38 were in the heterozygote states, and 15 (13.64%) carried the prothrombin G20210A mutation all as heterozygotes, compared to 16.42% and 2.99% carrier rates among controls, respectively, all of whom were heterozygote carriers. Of the other risk factors analyzed, smoking (OR 1.76; 95% CI = 0.79,3.94) was more prevalent in habitual aborters compared to controls. Both FV-Leiden and factor II G20210A mutations are major inherited risk factor associated with primary recurrent miscarriages. Women with a family or personal history of thrombosis should be screened before or early in the pregnancy for FV-Leiden and factor II G20210A mutations. Am. J. Hematol. 71:300,305, 2002. © 2002 Wiley-Liss, Inc. [source]


ORIGINAL ARTICLE: Peripheral Blood NK Cells Reflect Changes in Decidual NK Cells in Women With Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010
Dong Wook Park
Citation Park DW, Lee HJ, Park CW, Hong SR, Kwak-Kim J, Yang KM. Peripheral blood NK cells reflect changes in decidual NK cells in women with recurrent miscarriages. Am J Reprod Immunol 2010; 63: 173,180 Problem, We aimed to investigate if peripheral blood natural killer (pNK) cell levels are correlated with decidual NK (dNK) cell levels, and if chemokine expression has any role in dNK cell regulation. Method of study, Decidual tissues of women having two or more miscarriages with normal karyotype were collected after miscarriage and an immuno-histochemisty study was made. pNK cells were evaluated using flow cytometric analysis. Results, The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed a significant correlation with mean number of CD56+ dNK cells. The number of decidual CD16+ cells was significantly higher in women with elevated pNK (,15%) than that of normal pNK (<15%). The %CD3,/56+ and %CD3,/56+/16+ pNK cells showed an inverse correlation with duration of gestation. The CCL3+ and CXCL12+ cells were present in the decidua; however, staining intensity was not correlated with number of dNK cells. Conclusion, The pNK cell levels reflect changes in dNK cell levels. This implicates that pNK cell level is a clinically useful marker to predict pregnancy outcome. Further study is needed to examine if elevated pNK cells enhance recruitment of dNK cells in the decidua. [source]


ORIGINAL ARTICLE: Live Birth Rate According to Maternal Age and Previous Number of Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Mayumi Sugiura-Ogasawara
Problem, In Japan, marital age and women's age at the first pregnancy are continuing to increase year by year. However, information concerning subsequent live birth rate according to maternal age and number of previous recurrent miscarriages is limited. Method of study, We studied a total of 1250 unexplained patients suffering two or more consecutive miscarriages. We examined the live birth rate at the first pregnancy and the cumulative success rate for birth of at least one child after examination. Results, The live birth rate of women in their 40s was 58.1%, which was similar to that of women who were 35,39 years old (58.4%) at the first pregnancy, as found after examination. From logistic regression, women's age and the number of previous miscarriages independently decreased the live birth rate in subsequent pregnancies (ps) as well as cumulative pregnancies (pc), as follows: Conclusion, The information concerning the live birth rate can be given to each patient before subsequent pregnancy. [source]


ORIGINAL ARTICLE: The Polycystic Ovary Syndrome Does Not Predict Further Miscarriage in Japanese Couples Experiencing Recurrent Miscarriages

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009
Mayumi Sugiura-Ogasawara
Problem, It has been a matter of controversy whether the polycystic ovary syndrome (PCOS) is actually a causal factor of miscarriages because of the absence of internationally established criteria. We, therefore, in this study investigated whether PCOS and a polycystic ovary (PCO) morphology have predictive value for subsequent miscarriages using new International and Japanese criteria. Method of study, A total of 195 patients with a history of two consecutive first trimester miscarriages and without abnormal chromosomes in either partner, antiphospholipid antibodies or uterine anomalies, were examined. The prospective pregnancy outcome was compared between patients with and without PCOS, PCO morphology, elevated luteinizing hormone (LH), hyperandrogenism and obesity. Results, Of a total of 195 patients, 56 (28.7%) miscarried subsequently. Three (1.5%) and 12 (6.2%) were diagnosed as suffering from PCOS by Japanese and International criteria respectively. There was no relation between a diagnosis of PCOS, PCO morphology, elevated LH, free testosterone or obesity and the subsequent miscarriage rate. Conclusion, A routine test for diagnosis of PCOS is not necessary in patients experiencing recurrent miscarriages because none of the related parameters examined in this study predicted subsequent miscarriage. [source]


Transfusion-Related Risks of Intradermal Allogeneic Lymphocyte Immunotherapy: Single Cases in a Large Cohort and Review of the Literature

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2006
Christiane Kling
Problem, Lymphocyte immunotherapy (LIT) is applied in infertility treatment. Moreover, it has been suggested for prevention of rhesus D-hemolytic disease and as a vaccine for reduction of human immunodeficiency virus-1 susceptibility. Although transfusion-related problems have been rarely reported they were a matter of debate. Here we discuss extensive single-center experience with intradermal LIT for implantation failure and recurrent miscarriages. Method of study, Retrospective 2- to 3-year follow-up of in vitro fertilization couples treated during 1996,2002 (feedback 2848/3041 = 93%), registering 930 deliveries. Prospective survey for acute reactions for 2000,2003 (feedback 2687/3246 = 83%). Review of the literature. Results, Infections of the patient and transplant rejection later in life are minor residual risks. Post-transfusion purpura was suspected once but not verified. Anaphylaxis or malignancy were not promoted. Fetal/newborn alloimmune disease (severe hemolytic disease, thrombocytopenia, neutropenia) were not observed. Conclusion, Based on microbiological, immunological, and hematological testing the risks of intradermal LIT are low. [source]


1141424444 Detection of a2V-ATPase in T regulatory cells of women with recurrent spontaneous abortions or implantation failures

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006
EI Ntrivalas
Problem:, T regulatory cells (Tregs) have recently been shown to play a critical role in maternal tolerance to the fetus. Tregs are decreased in women with recurrent miscarriages. a2V-ATPase (previously referred to as Regeneration and Tolerance Factor) is expressed in activated lymphocytes and plays a role in immune regulation. The aim of this study was to investigate the expression of a2V-ATPase on CD4+/CD25bright Tregs. Method of Study:, Whole blood from women with RSA or implantation failures was reacted with anti-CD4 and anti-CD25 mAbs for the identification of CD4+/CD25bright and CD4+/CD25neg T cells by flow cytometric analysis. Subsequently, these two T-cell populations were analyzed for the expression of a2V-ATPase using PE-conjugated 2C1 mAb (specific for the membrane portion of a2V-ATPase). These two cell populations were also analyzed for the expression of CD71, CD62L, CD45RO and CD58 (Treg markers). Results:, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (22.8 ± 16.4%) than on CD4+/CD25neg T cells (2.4 ± 3.8%) in women with RSA (P < 0.0001). Additionally, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (18.0 ± 18.2%) than on CD4+/CD25neg T cells (1.5 ± 1.4%) in women with implantation failures (P < 0.0001). a2V-ATPase expression also coincided with the expression of CD71, CD62L, CD45RO and CD58 in Tregs, as opposed to the conventional CD4+/CD25neg T cells. Conclusions:, The expression of a2V-ATPase in Tregs of women with RSA or implantation failures is a novel finding and suggests that this vacuolar ATPase plays an important role in suppression. a2V-ATPase may be a unique molecule in the identification of Tregs among peripheral blood lymphocytes and may also explain the tolerogenic activity of these cells. [source]