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Recurrent Spontaneous Abortion (recurrent + spontaneous_abortion)

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Medical Sciences93%

Selected Abstracts

ORIGINAL ARTICLE: A High Dose of Intravenous Immunoglobulin Increases CD94 Expression on Natural Killer Cells in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Shigeki Shimada
Problem, A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy. Method of study, By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8). Results, Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 ± 21.4% versus 71.0 ± 17.6%). Conclusion, Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity. [source]

SHORT COMMUNICATION: Gender Ratio Distortion in Abortuses and Live Births From Patients with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009
Takashi Kano
Problem, Gender ratio of live birth in humans is approximately 1.05 and males are born a slightly more, while gender ratio of fertilization should be 1.00, suggesting that female fetus might be more sensitive to abortion than male fetus during pregnancy. Method of study, We examined karyotype of abortuses from patients with recurrent spontaneous abortion (RSA), who had at least one live birth before or after the treatment of RSA. Results, Chromosomal abnormality was not frequent (14.6%) in the abortuses from the RSA patients. Among abortuses without chromosomal abnormality, male karyotype was rare (9.2%), and this gender ratio distortion was more prominent in RSA cases not carrying autoantibodies (3.5%) than that in the RSA cases carrying autoantibodies (26.3%), with statistical significance (P = 0.009). Conclusion, These observations suggested that the aborted fetuses from RSA of unknown etiology, i.e. no chromosomal abnormality and no autoantibody, were preferentially female. [source]

ORIGINAL ARTICLE: The Role of TSP-1 on Decidual Macrophages Involved in the Susceptibility to Unexplained Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009
Yan Jin
Problem, To investigate the role of TSP-1 on decidual macrophages (DM,) in unexplained recurrent spontaneous abortion (RSA). Method of study, A total of 20 women undergoing artificial abortion in the first trimester and 10 patients with RSA were selected. (i) The expression of TSP-1 mRNA in deciduas was detected by real-time polymerase chain reaction; (ii) Flow cytometry was used to detect the percentage of positive TSP-1, CD36, CD47 markers on macrophages. (iii) Cytokine expression was measured by enzyme-linked immunosorbent spot-forming (ELISPOT) cell assay. Results, (i) The expression of TSP-1 mRNA on DM, in RSA was significantly decreased (P < 0.05). (ii) The increased expression of CD36 (P < 0.01) and the decreased expression of TSP1 (P < 0.01) were found on DM, of RSA. No different CD47 expression level on DM, was observed between two groups. (iii)The expression of IL-10 in DM, of RSA patients was decreased significantly compared with that of controls (P < 0.05). When adding TSP1 into culture medium, there was no change in IFN-, expression, but increased IL-10 (P < 0.05) expression in DM, of RSA patients was observed. The expression of IL-10 was decreased significantly in DM, from controls when adding anti-TSP-1 antibody to culture medium (P < 0.05). Conclusion, TSP-1 on DM, could influence IL-10 expression as Th2 cytokines. The abnormal expression of TSP-1 could make some women undergo pregnancy loss. [source]

The Investigation on the Value of Repeat and Combination Test of ACA and Anti-,2 -GPI Antibody in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2008
Shi Hua Bao
Problem In order to investigate the value of anticardiolipin antibodies (ACA) and anti-,2 -GPI antibodies detection in screening autoimmune type recurrent spontaneous abortion and its clinic application in antiphospholipid syndrome diagnosis, we adopt repeat combined ACA and anti-,2 -GPI antibodies detection in this study. Method of study Sera were collected from patients and work-up was done for detection of ACA and anti-,2 -GPI antibodies by enzyme-linked immunosorbent assay (ELISA). The work-up was done for detection of antibodies once in every 6 weeks for 14 times consecutively. Results The repeated and combined detection of ACA and anti-,2 -GPI antibodies detection could raise the positivity rate up to 21.8% (P < 0.05) in comparison with positive for ACA alone (14.1%), positive for anti-,2 -GPI alone (3.1%), and concurrently positive for both ACA and anti-,2 -GPI antibodies (4.6%). In 91 confirmed positive antiphospholipid antibodies (APA) patients, with more frequent screening for ACA and anti-,2 -GPI antibodies, more patients with APA were found. The positive rate of five and more screenings was over 81.32%, which was statistically significant (P < 0.05), in comparison with that of four or less screenings (68.13%). Conclusion Our data implied that it would be appropriate to take over five or more screenings of combined ACA and anti-,2 -GPI antibodies detection in suspect patients to facilitate the positive diagnostic rate for autoimmune type RSA. [source]

ORIGINAL ARTICLE: Genetic Predisposition to Idiopathic Recurrent Spontaneous Abortion: Contribution of Genetic Variations in IGF-2 and H19 Imprinted Genes

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2008
a Ostoji
Problem, Recurrent spontaneous abortion (RSA) is a common clinical problem with a complex etiology of genetic and non-genetic causes, which remains to be fully determined. IGF-2 stimulates trophoblast invasion, proliferation and maturation of placenta, while H19 RNA suppresses growth. As genomic imprinting plays a critical role in the development of placenta and embryo, our aim was to evaluate the possible role of variations in IGF-2 and H19 imprinted genes as factors of predisposition for RSA. Method of study, A case,control study was conducted to determine the association between IGF-2 and H19 gene polymorphisms and the susceptibility to RSA in 113 couples with RSA and 226 controls. PCR/RFLP were performed to analyze IGF-2 ApaI and H19 HhaI polymorphisms. Results, We found a statistically significant difference in the genotype frequency distribution of IGF-2 ApaI polymorphism between males from couples with RSA and healthy males (,2(2) = 45.12; P < 0.0001). There were no differences in the genotype and allele distribution of H19 polymorphism frequencies, or for the IGF-2 ApaI polymorphism between female groups. Conclusion, The presence of IGF-2 ApaI polymorphism in partners of RSA women could affect IGF-2 level of expression in placenta and embryo and represent a risk factor for RSA susceptibility. [source]

ORIGINAL ARTICLE: Treatment with Tumor Necrosis Factor Inhibitors and Intravenous Immunoglobulin Improves Live Birth Rates in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2008
Edward E. Winger
Problem, The purpose of this study was to investigate whether treatment with tumor necrosis factor (TNF) inhibitors combined with intravenous immunoglobulin (IVIG) increases live birth rates among women with recurrent spontaneous abortion (RSA) concurrently treated with anticoagulants (AC). Method of study, Seventy-five pregnancies in patients with a history of RSA were retrospectively evaluated. The population was divided into three groups: group I: 21 patients treated with AC (anticoagulants), group II: 37 patients treated with AC and IVIG, and group III: 17 patients treated with AC, IVIG and the TNF inhibitor Etanercept (Enbrel®) or Adalimumab (Humira®). In groups II and III, IVIG was administered at least once during the cycle of conception and/or at least once after a positive pregnancy test. In group III, either Adalimumab or Etanercept was administered by subcutaneous injection according to standard protocols. Statistical analysis of pregnancy outcome was performed using Fisher's exact test. Results, Patient populations in the three treatment groups were similar in terms of age, past miscarriages, inherited thrombophilia and autoimmunity. The live birth rate was 19% (4/21) in group I, 54% (20/37) in group II, and 71% (12/17) in group III. There was significant improvement in pregnancy outcome in group II versus group I (P = 0.0127) and in group III versus group I (P = 0.0026). The live birth rate in group III compared to group II was not significantly different (P = 0.3723). Side effects of AC, IVIG and TNF inhibitor treatment were minimal in these patients, and no birth defects were identified in their offspring. Conclusion, In women with RSA, addition of either IVIG or a TNF inhibitor + IVIG to the AC regimen appears to improve live birth rates compared to the treatment with AC alone. The positive effect of IVIG and TNF inhibitor therapy on pregnancy outcome merits further study in prospective clinical trials. [source]

Polymorphisms in the Interleukin-12/18 Genes and Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2007
a Ostoji
Problem Interleukin (IL) IL-12/IL-18 are involved in uterine NK cells control of uterine vascular development. Polymorphisms in the IL-12/IL-18 genes could modify the cytokine balance, which might result in an increased susceptibility to recurrent spontaneous abortion (RSA). Method of Study A case,control study was conducted to determine the association between the IL12 (I/D) and IL18 (,607C>A, ,137G>C) gene polymorphisms and the risk of RSA in 125 women with RSA and in 136 controls. Results The frequencies of DD, ID, II for IL-12 were, 25.6%, 52.8% and 21.6% respectively, in patients versus 21.3%, 51.5% and 27.2% respectively in controls; the frequencies of CC, CA, AA genotypes for IL-18 (,607) were, 34.4%, 54.4% and 11.2% respectively in patients versus 30.1%, 58.1% and 11.8% respectively in controls; the frequencies of GG, GC, CC genotypes for IL-18(,137) were 47.2%, 43.2% and 9.6% respectively in patients and 45.6%, 46.3% and 8.1% respectively in controls. Conclusion IL-12B and IL-18 promoter gene polymorphisms were not associated with RSA in our women. [source]

Thrombophilic Gene Mutations and Recurrent Spontaneous Abortion: Prothrombin Mutation Increases the Risk in the First Trimester

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2001
Rudolf Pihusch
PROBLEM: Thrombophilic predisposition may be one of the underlying causes of recurrent spontaneous abortions (RSA). We studied the prevalence of five thrombophilic gene mutations in patients with RSA. METHOD OF STUDY: 102 patients with two or more consecutive abortions and 128 women without miscarriage were analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM), C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, glycoprotein IIIa (GPIIIa) C1565T polymorphism, and ,-fibrinogen G-455A polymorphism by polymerase chain reaction (PCR) techniques. RESULTS: No differences in the prevalence of FVL, MTHFR T/T, GPIIIa and ,-fibrinogen polymorphism were detected. Heterozygous PTM occurred more often in patients with RSA. This effect was significant in a subgroup with abortions exclusively in the first trimester (6.7% vs. 0.8%, P=0.027, OR 8.5). CONCLUSIONS: In contrast to the other mutations and polymorphisms, heterozygous PTM is more common in patients with abortions in the first trimester. This might reflect an influence of PTM on pathogenesis of early pregnancy loss. [source]

Is the Paternal Mononuclear Cells' Immunization a Successful Treatment for Recurrent Spontaneous Abortion?

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000
R. RAMHORST
PROBLEM: Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. The present study was conducted to compare the live birth rate in the presence or absence of immunotherapy. METHOD OF STUDY: Ninety-two women with RSA (79 primary [PA] and 13 secondary aborters[SA]) received immunotherapy. Thirty-seven RSA couples not receiving paternal alloimmunization, constituted the "control" group. RESULTS: The pregnancy rate in alloimmunized was 58 vs 46% in the control group. The live birth increased from 71% in the controls to 88% after immunotherapy. The alloimmunization induced mixed lymphocyte reaction blocking factors (MLR BFs) in 79% of women. However, they were also present in 83% of immunized women experiencing a new abortion. CONCLUSION: These results indicate that alloimmunization may be useful in the treatment of RSA. [source]

Vasoconstrictively Acting AT1R A1166C and NOS3 4/5 Polymorphisms in Recurrent Spontaneous Abortions (RSA),

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2004
Tina Buchholz
Problem:, Inadequate uteroplacental perfusion is one of the main reasons for recurrent spontaneous abortions (RSA). Coagulation, fibrinolysis, and vasoconstriction affect tissue perfusion. These systems are regulated by different gene products. Polymorphisms can modulate the expression levels of the respective genes and can thereby affect perfusion. Vasoconstriction is influenced by the expression of endothelial nitric oxide synthase (eNOS) and of the angiotensinogen II type 1 receptor (AT1R). Method:, The aim of our study was to investigate, whether two polymorphisms in the AT1R and NOS3 genes shown to result in maternal vasoconstriction are associated with an increased risk for RSA. Results:, Our data indicate that the vasoconstrictively acting genotypes AT1R C/C and NOS3 4/4 are of similar prevalence in RSA patients and in controls. Conclusion:, Results do not show any influence of the polymorphisms studied on early pregnancy development. This is in concordance with the concept of an independent regulation of placental perfusion. [source]

Proteomic analysis of recurrent spontaneous abortion: Identification of an inadequately expressed set of proteins in human follicular fluid

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2006
Yong-Soo Kim
Abstract Recurrent spontaneous abortion (RSA), defined as the loss of three or more consecutive pregnancies prior to the 20th,week of gestation, affects up to 5% of the child-bearing population. To investigate the proteins associated with RSA, the protein expression in human follicular fluid was analyzed using 2-DE. Follicular fluid contains a variety of biologically important proteins for oocyte fertilization and follicle maturation in the mammalian reproductive process. Therefore, it can be used as a provisional source for identifying proteins involved in RSA. In this study, we identified five aberrantly expressed proteins (complement component,C3c chain,E, fibrinogen,,, antithrombin, angiotensinogen, and hemopexin precursor) in follicular fluid from RSA patients with MALDI-TOF-MS and nano-LC MS/MS. Western blot analysis confirmed that the protein expression level of fibrinogen,, and antithrombin was less in follicular fluid from RSA patients than those from normal controls. Semiquantitative RT-PCR and real-time PCR analyses revealed that mRNA level of these coagulation factors was also decreased significantly in chorionic villi of RSA patients compared with normal samples. Taken all together, it is likely that coagulation factors (fibrinogen,, and antithrombin) play an important role in maintaining the normal pregnancy. [source]

ORIGINAL ARTICLE: Genetic Predisposition to Idiopathic Recurrent Spontaneous Abortion: Contribution of Genetic Variations in IGF-2 and H19 Imprinted Genes

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2008
a Ostoji
Problem, Recurrent spontaneous abortion (RSA) is a common clinical problem with a complex etiology of genetic and non-genetic causes, which remains to be fully determined. IGF-2 stimulates trophoblast invasion, proliferation and maturation of placenta, while H19 RNA suppresses growth. As genomic imprinting plays a critical role in the development of placenta and embryo, our aim was to evaluate the possible role of variations in IGF-2 and H19 imprinted genes as factors of predisposition for RSA. Method of study, A case,control study was conducted to determine the association between IGF-2 and H19 gene polymorphisms and the susceptibility to RSA in 113 couples with RSA and 226 controls. PCR/RFLP were performed to analyze IGF-2 ApaI and H19 HhaI polymorphisms. Results, We found a statistically significant difference in the genotype frequency distribution of IGF-2 ApaI polymorphism between males from couples with RSA and healthy males (,2(2) = 45.12; P < 0.0001). There were no differences in the genotype and allele distribution of H19 polymorphism frequencies, or for the IGF-2 ApaI polymorphism between female groups. Conclusion, The presence of IGF-2 ApaI polymorphism in partners of RSA women could affect IGF-2 level of expression in placenta and embryo and represent a risk factor for RSA susceptibility. [source]

TH1/TH2,3 Imbalance due to Cytokine-Producing NK, ,, T and NK-,, T Cells in Murine Pregnancy Decidua in Success or Failure of Pregnancy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001
DAVID A. CLARK
PROBLEM: Recurrent spontaneous abortion in DBA/2-mated CBA/J mice has been attributed to the production of Th1 cytokines (tumor necrosis factor [TNF]-, and interferon [IFN]-,) by asialoGM1+ natural killer (NK) cells and V,1.1,6.3+ T cells that infiltrate decidua by day 6.5, during the peri-implantation period. Abortions can be prevented by a second population of V,1.1,6.3 cells, which infiltrate on day 8.5 of gestation, and produce the Th2 cytokine interleukin (IL)-10 and Th3 cytokine transforming growth factor (TGF)-,2. In low abortion rate immunocompetent mice, most of the TGF-,2 is derived from ,, T cells. However, TGF-,2-producing cells are present in the decidua of pregnant severe combined immune deficient (SCID) mice, which lack ,, T cells. METHODS: The cells in day 13.5 decidua of CBA×DBA/2 matings and SCID×SCID matings were identified using flow cytometry and combined surface staining for ,, and/or asialoGM1, and intracellular cytokine staining for TNF-,, IFN-,, and TGF-,2,3. RESULTS: TGF-,2 and TNF-, were found in asialoGM1+ NK cells in SCID mouse decidua. In CBA×DBA/2 mated mice, two major and one minor subsets of cytokine-positive cells were identified: -,,-only T cells, double positive asialoGM1+,,+ (NK-,, T) cells, and a small number of asialoGM1+,,, NK-only cells. The NK-only and NK-,, T subsets showed a greater Th1/Th2,3 pattern of intracellular staining compared with the ,,-only subset. In the CBA×DBA/2 and SCID×SCID systems, Th1/Th2,3 ratios could not predict actual observed abortion rates but did correlate with susceptibility to abortions (if exposed to an additional stimulus such as stress). The known effect of in vivo administration of anti-asialoGM1 antibody on abortion rates within groups of mice exposed to such stresses could also be predicted. CONCLUSION: ,,+ cells in decidua (e.g. V,1+ cells which can recognize trophoblasts) differ based on the presence or absence of the NK marker-asialo-GM1. NK-,, T cells may be quite important in the Th1 response in early pregnancy that predisposes to abortions in CBA×DBA/2 matings, whereas ,, T-only cells appear to be protective. In pregnant SCID mice, the TNF-,+/TGF-,2+ NK population is greatly expanded. An activating stimulus (such as stress or endotoxin) appears to be as important in triggering abortions, as is the Th1/Th2,3 ratio at the feto,maternal interface. [source]

IL-1 receptor antagonist gene polymorphism in idiopathic recurrent spontaneous abortion in a Chinese Han population

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2010
M. Z. Dai
Summary Interleukin-1 receptor antagonist (IL-1Ra) has been supposed to play important roles in pregnancy. The purpose of this study was to evaluate the association between the polymorphisms of IL-1Ra gene (IL1RN) variable number tandem repeat (VNTR) in intron 2 with idiopathic recurrent spontaneous abortion (RSA). Ninety-two RSA patients and hundred normal women with at least one live birth and no history of miscarriage were included in the study. Frequencies of the IL1RN alleles and genotypes were determined. Data revealed that the prevalence of IL1RN allele and genotype was not significant between the RSA and control group (all P > 0.05). Our finding indicated that the polymorphism VNTR of IL1RN gene in intron 2 may not be a risk factor for RSA in the Chinese Han population. [source]

HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006
W. H. Yan
Summary Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal,fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal,maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA. [source]

Proteomic analysis of recurrent spontaneous abortion: Identification of an inadequately expressed set of proteins in human follicular fluid

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2006
Yong-Soo Kim
Abstract Recurrent spontaneous abortion (RSA), defined as the loss of three or more consecutive pregnancies prior to the 20th,week of gestation, affects up to 5% of the child-bearing population. To investigate the proteins associated with RSA, the protein expression in human follicular fluid was analyzed using 2-DE. Follicular fluid contains a variety of biologically important proteins for oocyte fertilization and follicle maturation in the mammalian reproductive process. Therefore, it can be used as a provisional source for identifying proteins involved in RSA. In this study, we identified five aberrantly expressed proteins (complement component,C3c chain,E, fibrinogen,,, antithrombin, angiotensinogen, and hemopexin precursor) in follicular fluid from RSA patients with MALDI-TOF-MS and nano-LC MS/MS. Western blot analysis confirmed that the protein expression level of fibrinogen,, and antithrombin was less in follicular fluid from RSA patients than those from normal controls. Semiquantitative RT-PCR and real-time PCR analyses revealed that mRNA level of these coagulation factors was also decreased significantly in chorionic villi of RSA patients compared with normal samples. Taken all together, it is likely that coagulation factors (fibrinogen,, and antithrombin) play an important role in maintaining the normal pregnancy. [source]

ORIGINAL ARTICLE: A High Dose of Intravenous Immunoglobulin Increases CD94 Expression on Natural Killer Cells in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Shigeki Shimada
Problem, A high dose of intravenous immunoglobulin (HIVIg) therapy is effective in various diseases such as autoimmune diseases, and also is expected to have efficacy in recurrent spontaneous abortion (RSA). The aim of this study was to understand immunological mechanisms of this therapy. Method of study, By flowcytometric analyses, we examined phenotypic changes of a variety of immunological cells including natural killer (NK) cells, cytotoxic T cells, regulatory T cells and macrophages in peripheral blood of RSA women with HIVIg therapy (n = 8). Results, Expression percentages of inhibitory CD94 on NK cells significantly (P = 0.01) increased after the therapy (58.8 ± 21.4% versus 71.0 ± 17.6%). Conclusion, Mechanisms of possible efficacy of HIVIg therapy for RSA may include enhancement of CD94 expression and subsequent suppression of NK cell cytotoxicity. [source]

SHORT COMMUNICATION: Gender Ratio Distortion in Abortuses and Live Births From Patients with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009
Takashi Kano
Problem, Gender ratio of live birth in humans is approximately 1.05 and males are born a slightly more, while gender ratio of fertilization should be 1.00, suggesting that female fetus might be more sensitive to abortion than male fetus during pregnancy. Method of study, We examined karyotype of abortuses from patients with recurrent spontaneous abortion (RSA), who had at least one live birth before or after the treatment of RSA. Results, Chromosomal abnormality was not frequent (14.6%) in the abortuses from the RSA patients. Among abortuses without chromosomal abnormality, male karyotype was rare (9.2%), and this gender ratio distortion was more prominent in RSA cases not carrying autoantibodies (3.5%) than that in the RSA cases carrying autoantibodies (26.3%), with statistical significance (P = 0.009). Conclusion, These observations suggested that the aborted fetuses from RSA of unknown etiology, i.e. no chromosomal abnormality and no autoantibody, were preferentially female. [source]

ORIGINAL ARTICLE: The Role of TSP-1 on Decidual Macrophages Involved in the Susceptibility to Unexplained Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2009
Yan Jin
Problem, To investigate the role of TSP-1 on decidual macrophages (DM,) in unexplained recurrent spontaneous abortion (RSA). Method of study, A total of 20 women undergoing artificial abortion in the first trimester and 10 patients with RSA were selected. (i) The expression of TSP-1 mRNA in deciduas was detected by real-time polymerase chain reaction; (ii) Flow cytometry was used to detect the percentage of positive TSP-1, CD36, CD47 markers on macrophages. (iii) Cytokine expression was measured by enzyme-linked immunosorbent spot-forming (ELISPOT) cell assay. Results, (i) The expression of TSP-1 mRNA on DM, in RSA was significantly decreased (P < 0.05). (ii) The increased expression of CD36 (P < 0.01) and the decreased expression of TSP1 (P < 0.01) were found on DM, of RSA. No different CD47 expression level on DM, was observed between two groups. (iii)The expression of IL-10 in DM, of RSA patients was decreased significantly compared with that of controls (P < 0.05). When adding TSP1 into culture medium, there was no change in IFN-, expression, but increased IL-10 (P < 0.05) expression in DM, of RSA patients was observed. The expression of IL-10 was decreased significantly in DM, from controls when adding anti-TSP-1 antibody to culture medium (P < 0.05). Conclusion, TSP-1 on DM, could influence IL-10 expression as Th2 cytokines. The abnormal expression of TSP-1 could make some women undergo pregnancy loss. [source]

The Investigation on the Value of Repeat and Combination Test of ACA and Anti-,2 -GPI Antibody in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2008
Shi Hua Bao
Problem In order to investigate the value of anticardiolipin antibodies (ACA) and anti-,2 -GPI antibodies detection in screening autoimmune type recurrent spontaneous abortion and its clinic application in antiphospholipid syndrome diagnosis, we adopt repeat combined ACA and anti-,2 -GPI antibodies detection in this study. Method of study Sera were collected from patients and work-up was done for detection of ACA and anti-,2 -GPI antibodies by enzyme-linked immunosorbent assay (ELISA). The work-up was done for detection of antibodies once in every 6 weeks for 14 times consecutively. Results The repeated and combined detection of ACA and anti-,2 -GPI antibodies detection could raise the positivity rate up to 21.8% (P < 0.05) in comparison with positive for ACA alone (14.1%), positive for anti-,2 -GPI alone (3.1%), and concurrently positive for both ACA and anti-,2 -GPI antibodies (4.6%). In 91 confirmed positive antiphospholipid antibodies (APA) patients, with more frequent screening for ACA and anti-,2 -GPI antibodies, more patients with APA were found. The positive rate of five and more screenings was over 81.32%, which was statistically significant (P < 0.05), in comparison with that of four or less screenings (68.13%). Conclusion Our data implied that it would be appropriate to take over five or more screenings of combined ACA and anti-,2 -GPI antibodies detection in suspect patients to facilitate the positive diagnostic rate for autoimmune type RSA. [source]

ORIGINAL ARTICLE: Treatment with Tumor Necrosis Factor Inhibitors and Intravenous Immunoglobulin Improves Live Birth Rates in Women with Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2008
Edward E. Winger
Problem, The purpose of this study was to investigate whether treatment with tumor necrosis factor (TNF) inhibitors combined with intravenous immunoglobulin (IVIG) increases live birth rates among women with recurrent spontaneous abortion (RSA) concurrently treated with anticoagulants (AC). Method of study, Seventy-five pregnancies in patients with a history of RSA were retrospectively evaluated. The population was divided into three groups: group I: 21 patients treated with AC (anticoagulants), group II: 37 patients treated with AC and IVIG, and group III: 17 patients treated with AC, IVIG and the TNF inhibitor Etanercept (Enbrel®) or Adalimumab (Humira®). In groups II and III, IVIG was administered at least once during the cycle of conception and/or at least once after a positive pregnancy test. In group III, either Adalimumab or Etanercept was administered by subcutaneous injection according to standard protocols. Statistical analysis of pregnancy outcome was performed using Fisher's exact test. Results, Patient populations in the three treatment groups were similar in terms of age, past miscarriages, inherited thrombophilia and autoimmunity. The live birth rate was 19% (4/21) in group I, 54% (20/37) in group II, and 71% (12/17) in group III. There was significant improvement in pregnancy outcome in group II versus group I (P = 0.0127) and in group III versus group I (P = 0.0026). The live birth rate in group III compared to group II was not significantly different (P = 0.3723). Side effects of AC, IVIG and TNF inhibitor treatment were minimal in these patients, and no birth defects were identified in their offspring. Conclusion, In women with RSA, addition of either IVIG or a TNF inhibitor + IVIG to the AC regimen appears to improve live birth rates compared to the treatment with AC alone. The positive effect of IVIG and TNF inhibitor therapy on pregnancy outcome merits further study in prospective clinical trials. [source]

Polymorphisms in the Interleukin-12/18 Genes and Recurrent Spontaneous Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2007
a Ostoji
Problem Interleukin (IL) IL-12/IL-18 are involved in uterine NK cells control of uterine vascular development. Polymorphisms in the IL-12/IL-18 genes could modify the cytokine balance, which might result in an increased susceptibility to recurrent spontaneous abortion (RSA). Method of Study A case,control study was conducted to determine the association between the IL12 (I/D) and IL18 (,607C>A, ,137G>C) gene polymorphisms and the risk of RSA in 125 women with RSA and in 136 controls. Results The frequencies of DD, ID, II for IL-12 were, 25.6%, 52.8% and 21.6% respectively, in patients versus 21.3%, 51.5% and 27.2% respectively in controls; the frequencies of CC, CA, AA genotypes for IL-18 (,607) were, 34.4%, 54.4% and 11.2% respectively in patients versus 30.1%, 58.1% and 11.8% respectively in controls; the frequencies of GG, GC, CC genotypes for IL-18(,137) were 47.2%, 43.2% and 9.6% respectively in patients and 45.6%, 46.3% and 8.1% respectively in controls. Conclusion IL-12B and IL-18 promoter gene polymorphisms were not associated with RSA in our women. [source]

High NK Cell Activity in Early Pregnancy Correlates with Subsequent Abortion with Normal Chromosomes in Women with Recurrent Abortion

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2001
Hideto Yamada
PROBLEM: The aim of this study was to assess the role of natural killer (NK) cells in pregnant women with a history of recurrent spontaneous abortion (RSA). METHOD OF STUDY: Consecutive 66 pregnant women with a history of RSA were prospectively assessed for peripheral NK cell activity, percentage of the NK cell subsets, and subsequent pregnancy outcome. RESULTS: NK cell activity in women with subsequent live birth (group I) at 4,5 gestational weeks (GW) (mean±SD, 32.5±12.3%) significantly decreased at 6,7 GW (28.1±12.1%) and at 8,9 GW (28.0±11.8%). NK cell activity in women with subsequent abortion with normal chromosomes (group II) at 6,7 GW (41.2±19.0%) was significantly higher than that in group I women, while NK cell activity at 6,7 GW in women with subsequent abortion with abnormal chromosomes (group III) was the same as the level in group I women. CONCLUSIONS: High NK cell activity at 6,7 GW correlates with subsequent abortion with normal chromosomes. [source]

Is the Paternal Mononuclear Cells' Immunization a Successful Treatment for Recurrent Spontaneous Abortion?

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000
R. RAMHORST
PROBLEM: Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. The present study was conducted to compare the live birth rate in the presence or absence of immunotherapy. METHOD OF STUDY: Ninety-two women with RSA (79 primary [PA] and 13 secondary aborters[SA]) received immunotherapy. Thirty-seven RSA couples not receiving paternal alloimmunization, constituted the "control" group. RESULTS: The pregnancy rate in alloimmunized was 58 vs 46% in the control group. The live birth increased from 71% in the controls to 88% after immunotherapy. The alloimmunization induced mixed lymphocyte reaction blocking factors (MLR BFs) in 79% of women. However, they were also present in 83% of immunized women experiencing a new abortion. CONCLUSION: These results indicate that alloimmunization may be useful in the treatment of RSA. [source]

HLA-G polymorphism in a Chinese Han population with recurrent spontaneous abortion

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006
W. H. Yan
Summary Reproduction is an important biological phenomenon posing an immunological paradox because the semiallogeneic fetus survives by evading maternal immune recognition. The detailed mechanisms behind this maternal,fetal immunotolerance remain elusive. Human leucocyte antigen (HLA)-G, a non-classical HLA class I antigen, initially identified as a molecule selectively expressed on extravillous cytotrophoblasts and first studied in the context of pregnancy, has long been supposed to play a critical role in fetal,maternal immunotolerance. To investigate the role of HLA-G polymorphism in this process and whether the HLA-G genotype is associated with an increased risk for a subsequent miscarriage, 69 women with three or more recurrent spontaneous abortions (RSA) and 146 fertile control women were genotyped for the HLA-G locus in this study. To our knowledge, this is the first report on HLA-G polymorphism in RSA and in normal fertile women from a Chinese Han population. Nine HLA-G alleles were detected in the fertile control group; however, the allele HLA-G*0103 was absent in the RSA group. No statistical significance was observed in the distribution of HLA-G alleles between the two groups. The frequency of the null allele HLA-G*0105 N in the RSA group and in normal fertile women is 0.7% and 1.4%, respectively. Our data suggested that there was no association of HLA-G polymorphism with RSA. [source]

REVIEW ARTICLE: Clinical Implication of Natural Killer Cells and Reproduction

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2008
Joanne Kwak-Kim
The regulation of natural killer (NK) cells in the peripheral blood and endometrial layers has been associated with reproductive immunopathology such as recurrent spontaneous abortions (RSA), infertility of implantation failures, or pre-eclampsia. The placenta has a complex anatomical structure and different subsets of NK cells with various functional roles can directly interact with trophoblasts. NK cell subpopulations and their functions, putative roles of NK cells in peripheral blood and endometrium are reviewed in relation to RSA and infertility. An increase in NK cell numbers and /or activity in pre- or post-conceptional period in women with RSA or infertility with multiple implantation failures are a significant clinical concern. In addition, immuno-phenotypic characteristics of NK cells in these women support the changes for their increased activity status. Further studies are needed to explore underlying mechanism of NK cells in RSA, infertility, and other reproductive immunopathologies. Possible neurological and hormonal control of NK cells and NK cell interaction with various leukocyte populations need further investigation in women with reproductive failures. [source]

1141154113 Expression of natural cytotoxicity receptors in peripheral blood NK cell subsets of women with recurrent spontaneous abortions (RSA) or implantation failures

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006
A Fukui
Problem:, Natural Cytotoxicity Receptors (NCRs) are unique markers of NK cells and regulate NK cell cytotoxicity and cytokine production. a2V-ATPase is expressed in the cell membrane and can regulate the pH of the extracellular environment, which might facilitate NK cell killing or cytokine secretion. In this preliminary study we evaluated the expression of NCRs and a2V-ATPase in peripheral blood NK cells of women with RSA or implantation (IVF-ET) failures. Method of Study:, Peripheral blood was obtained from women with RSA (n = 10), or IVF-ET failures (n = 9). CD56dim and CD56bright NK cells were analyzed for the expression of NCRs (NKp46, NKp44 and NKp30) and a2V-ATPase using flow cytometry. Results:, For women with RSA, there were significant differences in the expression of NKp46 between CD56dim (36.9 ± 30.2) and CD56bright (76.0 ± 27.5) (P < 0.01), of NKp30 between CD56dim (30.9 ± 25.7) and CD56bright (55.8 ± 29.5) (P < 0.01), and of a2V-ATPase between CD56dim (1.0 ± 0.9) and CD56bright (23.2 ± 15.1) (P < 0.01) NK cells. For women with IVF-ET failures, there were significant differences in the expression of NKp46 between CD56dim (39.5 ± 21.5) and CD56bright (78.8 ± 26.0) (P < 0.01), of NKp30 between CD56dim (27.2 ± 17.9) and CD56bright (45.2 ± 29.8) (P < 0.05), and of a2V-ATPase between CD56dim (1.6 ± 1.4) and CD56bright (21.2 ± 16.5) (P < 0.01) NK cells. Conclusions:, The differential expression of NCRs and a2V-ATPase in NK cell subsets of women with RSA and IVF-ET failures may have an effect in cytotoxicity and cytokine production. Additional studies are currently in effect to evaluate these activities. We suggest that the analysis of NCRs and a2V-ATPase expression in peripheral blood NK cell subsets may contribute to a better understanding in the biology of NK cells in women with RSA or IVF-ET failures. [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]

Vasoconstrictively Acting AT1R A1166C and NOS3 4/5 Polymorphisms in Recurrent Spontaneous Abortions (RSA),

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2004
Tina Buchholz
Problem:, Inadequate uteroplacental perfusion is one of the main reasons for recurrent spontaneous abortions (RSA). Coagulation, fibrinolysis, and vasoconstriction affect tissue perfusion. These systems are regulated by different gene products. Polymorphisms can modulate the expression levels of the respective genes and can thereby affect perfusion. Vasoconstriction is influenced by the expression of endothelial nitric oxide synthase (eNOS) and of the angiotensinogen II type 1 receptor (AT1R). Method:, The aim of our study was to investigate, whether two polymorphisms in the AT1R and NOS3 genes shown to result in maternal vasoconstriction are associated with an increased risk for RSA. Results:, Our data indicate that the vasoconstrictively acting genotypes AT1R C/C and NOS3 4/4 are of similar prevalence in RSA patients and in controls. Conclusion:, Results do not show any influence of the polymorphisms studied on early pregnancy development. This is in concordance with the concept of an independent regulation of placental perfusion. [source]

Thrombophilic Gene Mutations and Recurrent Spontaneous Abortion: Prothrombin Mutation Increases the Risk in the First Trimester

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2001
Rudolf Pihusch
PROBLEM: Thrombophilic predisposition may be one of the underlying causes of recurrent spontaneous abortions (RSA). We studied the prevalence of five thrombophilic gene mutations in patients with RSA. METHOD OF STUDY: 102 patients with two or more consecutive abortions and 128 women without miscarriage were analyzed for factor V Leiden mutation (FVL), prothrombin G20210A mutation (PTM), C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, glycoprotein IIIa (GPIIIa) C1565T polymorphism, and ,-fibrinogen G-455A polymorphism by polymerase chain reaction (PCR) techniques. RESULTS: No differences in the prevalence of FVL, MTHFR T/T, GPIIIa and ,-fibrinogen polymorphism were detected. Heterozygous PTM occurred more often in patients with RSA. This effect was significant in a subgroup with abortions exclusively in the first trimester (6.7% vs. 0.8%, P=0.027, OR 8.5). CONCLUSIONS: In contrast to the other mutations and polymorphisms, heterozygous PTM is more common in patients with abortions in the first trimester. This might reflect an influence of PTM on pathogenesis of early pregnancy loss. [source]