			Home About us Contact

Implantation Failures (implantation + failure)

Distribution by Scientific Domains

Medical Sciences	96%

Selected Abstracts

ORIGINAL ARTICLE: Serum Anti-endometrial Antibodies in Infertile Women , Potential Risk Factor for Implantation Failure

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010
Aili Sarapik
Citation Sarapik A, Haller-Kikkatalo K, Utt M, Teesalu K, Salumets A, Uibo R. Serum anti-endometrial antibodies in infertile women , potential risk factor for implantation failure. Am J Reprod Immunol 2010 Problem, Female infertility patients with diverse etiologies show increased production of autoantibodies. Method of study, Immunoblot analysis of sera from patients with endometriosis and tubal factor infertility (TFI) and mass spectrometry identification of candidate antigens. Results, The immunoblot results demonstrated the presence of IgA and IgG anti-endometrial antibodies (AEA) to various antigens at molecular weights ranging from 10 to 200 kDa. Differences were detected in certain AEA reactions between the patients' groups and particular AEA were associated with in vitro fertilization (IVF) implantation failure. IgA AEA to a 47-kDa protein were more prevalent in TFI patients and were associated with unsuccessful IVF treatment. This antigen was subsequently identified as ,-enolase. Conclusion, Determination of the presence and spectra of AEA in patients with endometriosis and TFI undergoing IVF may be a useful marker to predict their pregnancy outcome. [source]

Increasing Circulating T-cell Activation Markers are Linked to Subsequent Implantation Failure After Transfer of In vitro Fertilized Embryos

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2003
Carolyn B. Coulam
Problem: Implantation determines success of in vitro fertilization (IVF) and embryo transfer (ET) cycles. Data are accumulating to support a role of the immune system in implantation. Most of the literature addresses the importance of natural killer (NK) cells in this process. The purpose of the current study is to examine the role of circulating T cells in implantation failure. Method of study: Blood from 22 women undergoing IVF/ET during November, 2001, was drawn on cycle day 9 and analyzed for the percentage of circulating T cells expressing the activation markers CD69+ and human leukocyte antigen (HLA)-DR and the suppressor marker CD11b using immunofluorescence and flow cytometry. These results were compared with total percentage circulating CD3, CD4 and CD8 cells as well as NK cells and pregnancy outcome that cycle. Results: Infertile women had significantly greater expression of the activation marker of CD69+ among CD8+ and CD4+ T cells and HLA-DR among CD4 cells than fertile women. No difference in expression of T cell suppressor marker of CD11b was noted when infertile and fertile women were compared. No correlations were observed when activated T cells were compared with circulating CD3+, CD4+, CD8+, activated NK cells and NK cytotoxicity. CD3+4+HLA-DR+ was expressed significantly less among successfully pregnant compared with unsuccessfully pregnant women. Conclusion: T-cell activation markers CD 69+ and HLA-DR+ are associated with increased implantation failure after IVF/ET. [source]

ORIGINAL ARTICLE: Women with Multiple Implantation Failures and Recurrent Pregnancy Losses have Increased Peripheral Blood T Cell Activation

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2010
Kwang Moon Yang
Citation Yang KM, Ntrivalas E, Cho HJ, Kim NY, Beaman K, Gilman-Sachs A, Kwak-Kim J. Women with multiple implantation failures and recurrent pregnancy losses have increased peripheral blood T cell activation. Am J Reprod Immunol 2010 Problem, We aim to determine whether peripheral blood T cell activation is associated with repeated implantation failures or recurrent pregnancy losses (RPLs). Method of study, Women with a history of repeated implantation failure (n = 18) or RPLs (n = 17) comprise the study group. Normal fertile women (n = 11) are included as controls. Proportion of activated peripheral blood T cells (CD69+, CD154+) and Th1/Th2 cell ratios are measured by flow cytometric analysis. Results, Proportions (%) of CD4+/154+ of CD4+ and CD8+/154+ of CD8+ cells were significantly higher in study group than those of controls. Proportions (%) of CD3+/69+ of CD3+ cells and CD8+/69+ of CD8+ cells were significantly increased in study group compared to controls. Proportion (%) of CD4+/69+ cells significantly correlated with % CD4+/154+ cells (P = 0.003). Activated cytotoxic T cells (CD8+/154+, CD8+/69+) inversely correlated with INF-,/IL-10 producing CD3+/4+ T cell ratios. Proportion of activated CD3+/8+/69 and CD3+/8+/154+ cells was inversely correlated with IFN-,/IL-10 expressing CD3+/4+ T cell ratios. Conclusion, Women with MIFs or RPLs have increased T cell activation in peripheral blood lymphocytes, and T cell suppressor activation seems to be associated with decreased Th1 immunity. Further studies on T cell activation may elucidate molecular mechanisms controlling Th1 effectors. [source]

ORIGINAL ARTICLE: Correlation Between Natural Cytotoxicity Receptors and Intracellular Cytokine Expression of Peripheral Blood NK Cells in Women with Recurrent Pregnancy Losses and Implantation Failures

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009
Atsushi Fukui
Problem, Natural cytotoxicity receptors (NCRs) are unique markers, which regulate NK cell cytotoxicity and cytokine production. We investigated whether women with recurrent pregnancy losses (RPLs) and implantation failures have aberrant correlation between NCRs and intracellular cytokine expression of NK cells. Method of study, Peripheral blood NK cells (CD56dim and CD56bright) were analyzed for NCRs (NKp46, NKp44 and NKp30) and cytokine expression (TNF-,, IFN-,, IL-4, IL-10) using flow cytometry in RPL (n = 22), implantation failures (n = 23) or controls (n = 15). Results, In type 1 cytokine studies, CD56bright/NKp30+ cells in controls (r = 0.696, P < 0.05) were positively correlated with CD56bright/IFN-,+/TNF-,+ cells. CD56bright/NKp46+ cells in implantation failures (r = ,0.76, P < 0.01) were negatively correlated with CD56bright/IFN-,+/TNF-,, cells. RPL did not have any correlation. In type 2 cytokine studies, CD56+/NKp46+ cells (r = 0.758, P < 0.01) and CD56+/NKp30+ cells (r = 0.637, P < 0.05) were positively correlated with CD56bright/IL-4+/IL-10+ cells in controls. CD56+/NKp30+ cells in implantation failures (r = ,0.778, P < 0.05) were negatively correlated with CD56bright/IL-10+/IL-4+ cells. There were no correlations in RPL. Conclusion, Recurrent pregnancy losses and implantation failures have lack of, or negative correlation between NCRs and intracellular cytokines expression. This observation suggests that excessive pro-inflammatory cytokine expression in NK cells in RPL and implantation failures may be exerted through the NCRs or interruption of signal transduction processes. [source]

Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: A randomised clinical trial

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2009
Mohammad Ali KARIMZADEH
Background:, Implantation failure is the most important cause of recurrent in vitro fertilisation (IVF)/intra cytoplasmic sperm injection (ICSI) failure. It has been reported that endometrial injury using a biopsy catheter resulted in a higher pregnancy rate in following cycle of treatment. The local endometrial trauma increases the implantation rate through the release of chemical mediators such as histamine and growth factor. Aims:, To evaluate the influence of endometrial biopsy on increasing implantation rate in patients with recurrent implantation failures. Methods:, In a randomised control trial study, 115 women each with at least two implantation failures were randomly assigned to two groups. In the case group, endometrial biopsy was obtained from patients in the luteal phase of previous cycle, and implantation and clinical pregnancy rates were compared with those of patients in the control group. Results:, The implantation rate was determined as 10.9% in the biopsy group compared to 3.38% in the controls. The clinical pregnancy rate was significantly higher in the case group than in controls (27.1% and 8.9% respectively). Conclusion:, The results suggest that pregnancy outcome increases through IVF or ICSI after endometrial biopsy. [source]

Polar body biopsy and aneuploidy testing by simultaneous detection of six chromosomes

PRENATAL DIAGNOSIS, Issue 10 2005
Markus Montag
Abstract Objectives To simultaneously detect six chromosomes in a single round of fluorescence in situ hybridization (FISH) during polar body diagnosis and aneuploidy testing in human in vitro fertilization (IVF) treatment. Methods A commercially available five-color FISH probe was modified by an additional chromosome probe. This kit was first tested on lymphocyte spreads and then used for polar body diagnosis (PBD) in patients with advanced maternal age and repeated implantation failure. The outcome of IVF treatment was compared with a control group. Results All six chromosomes could be simultaneously detected and easily distinguished by FISH analysis. PBD and aneuploidy testing were performed in 75 treatment cycles and compared with 126 controls. The biochemical pregnancy rate was significantly higher in the PBD group (37.1% vs 22.9%, p < 0.05) and a trend was observed for higher clinical pregnancy and implantation rates (24.22% and 14.4% vs 18.62% and 10.8%, respectively) and lower abortion rates (20% vs 31.8%) following PBD. Conclusions The simultaneous detection of six chromosomes in a single FISH round is possible and can be applied to PBD. This approach may present another step towards increasing the number of chromosomes for aneuploidy testing. Copyright © 2005 John Wiley & Sons, Ltd. [source]

REVIEW ARTICLE: Research on Blastocyst Implantation Essential Factors (BIEFs)

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Koji Yoshinaga
Citation Yoshinaga K. Research on Blastocyst Implantation Essential Factors (BIEFs). Am J Reprod Immunol 2010 Blastocyst implantation is a process of interaction between embryo and the uterus. To understand this process, this review tries to summarize what blastocyst implantation essential factors (BIEFs) play what roles, as well as where in the uterus and at what stage of implantation process. Addition of more new data to this kind of compilation of information will help the development of diagnosis and treatment of infertility caused by implantation failure. The major, important cells of the endometrial cells that interact with invading blastocyst (trophoblast) are luminal epithelial cells, stromal cells (decidual cells) and resident immune cells. BIEFs regulate these cells to successfully maintain pregnancy. [source]

REVIEW ARTICLE: Th1/Th2/Th17 and Regulatory T-Cell Paradigm in Pregnancy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Shigeru Saito
Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010 T-helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)-, and interleukin (IL)-10 or by cell-to-cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms. [source]

ORIGINAL ARTICLE: Serum Anti-endometrial Antibodies in Infertile Women , Potential Risk Factor for Implantation Failure

ORIGINAL ARTICLE: Women with Multiple Implantation Failures and Recurrent Pregnancy Losses have Increased Peripheral Blood T Cell Activation

SHORT COMMUNICATION: CD3, CD56+ CD16+ Natural Killer Cells and Improvement of Pregnancy Outcome in IVF/ICSI Failure After Additional IVIG-Treatment

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010
Lothar Heilmann
Citation Heilmann L, Schorsch M, Hahn T. CD3, CD56+ CD16+ Natural killer cells and improvement of pregnancy outcome in IVF/ICSI failure after additional IVIG-treatment. Am J Reprod Immunol 2010; 63: 263,265 Problem, The purpose of this retrospective, observational study was to investigate whether additional treatment with intravenous immunglobulin (IVIG) increased the rate of successful pregnancies after repeated implantation failure (RIF). The retrospective data were compared with data of patients without IVIG-therapy from the meta-analysis of Clark et al. Method of study, A total of 188 women with 226 treatment cycles between 2007 and 2009 were evaluated for IVIG therapy. The percentage of NK cells was measured two times before a new embryo transfer (only women with NK cell percentages >12% were included) and after embryo transfer at a positive pregnancy test. Results, In comparison with the meta-analysis of Clark et al., we observed a pregnancy rate of 50.5%, an implantation rate of 21% and a miscarriage rate of 16.8%. In 42%/IVIG- patient or 34.9%/embryo transfer, we observed a live born baby. The live born rate per embryo was 16.6%. In accordance with the study of Kwak et al., we indicate a decrease in the NK cells in patients with improved pregnancy outcome. Conclusion, In a subgroup of RIF-patients with high level of CD56+ CD16+ NK-cells the additional application of IVIG leads to a favourable pregnancy outcome. [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]

Increasing Circulating T-cell Activation Markers are Linked to Subsequent Implantation Failure After Transfer of In vitro Fertilized Embryos

Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2003
Gérard Chaouat
Problem: Human in vitro fertilization (IVF) embryo transfer is accompanied by a low implantation rate even after a very successful IVF, and there are a certain number of ,idiopathic sterilities' which are due to repeated implantation failures. In the very same vein, the question of improving implantation rates is of prime importance in agricultural research to improve the management of livestock. Pre-implantation prenatal diagnosis cannot be accomplished in individuals who have a high rate of implantation failure, whether women undergoing IVF, or animals, during genetic cloning. Implantation cytokine networks need to be known in such a perspective. Methods: We review the evolution and theories in reproductive immunology, briefly deal with the complexity of implantation as a step by step developmental event, and then present some of our recent data in mice and human. Conclusions: We conclude that the T helper cell type 1/2 (Th1/Th2) paradigm, as useful as it has been to explain pregnancy, is no longer sufficient in view of the emerging complexity of the cytokine network at the materno-fetal interface. This is peculiarly true for implantation, which, as a step by step developmentally regulated process, involving inflammatory molecules, cannot fit into such a scheme. [source]

Association of p53 polymorphism with ICSI/IVF failure and recurrent pregnancy loss

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009
FIROUZABADI Razieh Dehghani
Background: The p53 tumour suppressor gene is a well-known factor regulating apoptosis in a wide variety of cells. Alterations in the p53 gene are among the most common genetic changes in human cancers. Several polymorphisms of the p53 tumour suppressor gene have been associated with recurrent pregnancy loss (RPL). Aims: To evaluate the association of polymorphisms p53 codon 72 with the response to in vitro fertilisation (IVF) treatment and occurrence of repeated miscarriages. Methods: The homozygous and heterozygous genotypes and allelic frequencies of Arg and Pro p53 at codon 72 were identified by using polymerase chain reaction,restriction fragment length polymorphism technique in 70 infertile women with more than two IVF failures. Each comparison was made with 97 women experiencing RPL and 32 fertile women each with at least two healthy children as the control group. Results: The frequency of homozygous Pro/Pro genotypes was found significantly higher among the women with RPL than the other two groups (P = 0.041). Whereas, Arg/Arg genotype was significantly different in the recurrent implantation failure (RIF) group (P = 0.005). Conclusion: It is concluded that p53 codon 72 polymorphism may serve as a susceptible factor affecting the chances of RPL and RIF. [source]

Elevated NK Cell Cytotoxicity, CD158a Expression in NK Cells and Activated T Lymphocytes in Peripheral Blood of Women with IVF Failures

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Viktor P. Chernyshov
Citation Chernyshov VP, Sudoma IO, Dons'koi BV, Kostyuchyk AA, Masliy YV. Elevated NK cell cytotoxicity, CD158a expression in NK cells and activated T lymphocytes in peripheral blood of women with IVF failures. Am J Reprod Immunol 2010; 64: 58,67 Problem, The aim of this study was to evaluate the role of elevated natural killer cytotoxicity (NKc) in women with multiple implantation failures (IF) in vitro fertilization,embryo transfer (IVF,ET) cycles. Methods of study, Seventy-nine antiphospholipid antibodies-negative women with IF including 33 women with elevated NKc were selected for investigation. K-562 cell line was used to evaluate NKc. Lymphocyte subsets, intracellular cytokines [interferon (IFN)-,, interleukin (IL)-4, tumour necrosis factor, IL-10], expression of activating markers [CD69, human leukocyte antigen (HLA)-DR], CD8, KIR (CD158a), CD95, and chemokine receptors (CXCR3, CCR4) were estimated by flow cytometry. Results, In women with IF, levels of NKc were higher than in IVF successful women. IF was associated with higher expression of CD8, CD158a, and HLA-DR in NK cells, activating markers in T lymphocytes, and lower levels of CCR4+ and IL-4+ T lymphocyte subsets. Predictive value of single elevated NKc for IVF success was 0.85, but addition of two other abnormal parameters resulted in its decrease to <0.39. Conclusions, Elevated NKc is negative factor, though not critical for implantation in IVF cycles. Immune mechanism of IVF failure includes not only elevated NKc but also some other factors, such as elevated expression of CD8 and CD158a on NK cells, T lymphocyte activation, and diminished T helper 2 parameters. [source]

REVIEW ARTICLE: Immunological Modes of Pregnancy Loss

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Joanne Kwak-Kim
Citation Kwak-Kim J, Park JC, Ahn HK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss. Am J Reprod Immunol 2010 During the implantation period, a significant portion of embryos are lost and eventually less than half of clinically established pregnancies end as full-term pregnancies without obstetrical complications. A significant portion of these pregnancy losses is associated with immune etiologies, including autoimmune and cellular immune abnormalities. Although an autoimmune etiology such as anti-phospholipid antibodies (APAs) has been reported to induce placental infarct and thrombosis at maternal,fetal interface, APAs induce inflammatory immune responses as well. Inflammatory immune responses, such as increased proportions of NK cells and Th1/Th2 cell ratios in peripheral blood are related to recurrent pregnancy losses and multiple implantation failures. Systemic and local inflammatory immune responses seem to be induced by activation of Toll-like receptors with infectious agents, fetal cell debris, or gonadotropin-releasing hormone agonist, etc. Cellular activation of T and NK cells leads to pro-inflammatory cytokine storm and consequently, placental infarction and thrombosis. Potential application of anti-inflammatory therapeutic agents for the prevention of pregnancy losses should be explored further. [source]

ORIGINAL ARTICLE: Women with Multiple Implantation Failures and Recurrent Pregnancy Losses have Increased Peripheral Blood T Cell Activation

ORIGINAL ARTICLE: Correlation Between Natural Cytotoxicity Receptors and Intracellular Cytokine Expression of Peripheral Blood NK Cells in Women with Recurrent Pregnancy Losses and Implantation Failures

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]

Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept

Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: A randomised clinical trial