bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Frequency of Antisperm Antibodies in the Cervical Mucus of Women With Poor Postcoital Tests and Their Effect on Pregnancy Rates
Authors: Check J.H. , Bollendorf A. , Katsoff D. , Kozak J. 
Published: May 2013

PROBLEM: To determine the impact of the presence of antisperm antibodies (ASAs) in the cervical mucus of female partners in couples with unexplained poor postcoital tests (PCT). Furthermore, the efficacy of intrauterine insemination (IUI) in these same patients was determined by pregnancy rates (PRs).METHOD: Pregnancy rates following IUI in patients with infertility and poor postcoital tests, whether the cervical mucus was positive or negative for ASAs, were evaluated.RESULTS: The 6‐month PRs were similar in the ASA negative (40.5%) versus the positive (42.4%) group.CONCLUSIONS: It appears that the antifertility effect of ASA may be mainly the immobilization of sperm in the cervical mucus, and thus, performing IUI may effectively correct the problem.
Immunization of Mice Against a Synthetic N‐Terminal Extracellular Domain Gonadotropin‐Releasing Hormone Receptor Peptide: Evidence for a Direct Uterine Effect
Authors: Asirvatham Angela L. , Johnson Gregory A. , Belden E. Lee , Kirk Edward A. Van , Moss Gary E. , Murdoch William J. 
Published: May 2013

PROBLEM: Immature male and female mice were immunized with a synthetic peptide corresponding to amino acids 5–17 (ASLEQDPNHCSAI) of the mouse hypophyseal gonadotropin‐releasing hormone (GnRH) receptor.METHOD: Effect of immunization (postpuberal) was restricted to the uterus. Pituitary‐go‐nadal functions were not altered.RESULTS: The endometrial lining of immunized females was thin and lacked glandular development. These observations were corroborated in actively immunized and passively immunized adult females.CONCLUSIONS: Apparently endometrial cells express a unique surface antigen, though reactive with antipeptide antibodies, that differs from the prototype pituitary GnRH receptor. Antibodies that selectively inhibit endometrial maturation might be used to treat proliferative diseases of the uterus.
Interleukin‐6 Does Not Stimulate Rat Myometrial Contractions in an In Vitro Model
Authors: Dajani Nafisa , Idriss Edo , Collins Patricia L. 
Published: May 2013

PROBLEM: Interleukin‐6 (IL‐6) is increased in culture‐positive amniotic fluid in women with preterm labor. IL‐6 stimulates the production of prostaglandins leading to increased uterine activity.METHODS: We tested the hypothesis that IL‐6 increases myometrial activity through release of uterotonic mediators. We studied the effect of IL‐6 on uterine contractions in the absence and presence of fetal membranes to determine if the effect was on myometrium alone or was mediated through fetal membranes/decidua. IL‐6 in concentrations of 100, 10, 0.1 or 0 ng/ml was added to the maternal side of the dual chamber‐fetal membrane‐uterine muscle in vitro model.RESULTS: We found that 10 ng/ml of IL‐6 alone, without fetal membranes, caused a significant decrease in uterine contractions over time (P≤0.01). This decrease was not observed with the addition of term, nonlabored fetal membranes.CONCLUSIONS: IL‐6 in the presence or absence of membranes, over a four log fold dose range, did not stimulate uterine contractions.
Alternative Treatment to Lymphocyte Immunization for Treatment of Recurrent Spontaneous Abortion: Immunotherapy With Intravenous Immunoglobulin for Prevention of Recurrent Pregnancy Loss: European Experience
Authors: Mueller‐Eckhardt Gertrud 
Published: May 2013

PROBLEM: Due to its strong “immunomodulating” effect in several well established disorders, high‐dose intravenous immunoglobulins (IVIG) has been proposed as an alternative for immunotherapy with allogeneic leucocytes in patients with unexplained recurrent spontaneous abortion. This paper is intended to provide an overview on the European experience in this field.METHOD: Five European pilot studies with a total of 172 patients as well as one controlled double‐blind multicenter study including 64 patients were considered. In the latter, 5% human albumin was used as placebo.RESULTS: Success rates of the pilot studies varied from 68 to 87%. In the German controlled study, a significant specific effect of IVIG could not be verified. However, success rates for both IVIG and albumin were in the same range as for allogeneic leucocytes.CONCLUSION: At present, it is not sufficiently proven that IVIG is an appropriate tool for immunotherapy of recurrent spontaneous abortions. It is suggested that success rates of both IVIG and albumin are due to a placebo effect. However, we cannot exclude that albumin itself provides immunomodulating capacity.
Inhibition of Induced Lymphocyte Proliferation by Lipid and Protein Components of the Syncytiotrophoblast Plasma Membrane
Authors: GIRARD ANNE‐CHRISTINE LALMANACH , GUILLAUMIN JEAN‐MAURICE , THIBAULT GILLES , RUPIN ALAIN , DE RUSSÉ JEANNE , BARDOS PIERRE 
Published: May 2013

PROBLEM: The aim of this work was to define the respective responsibilities of the lipid and protein components of syncytiotrophoblast plasma membranes on the inhibition of lymphocyte proliferation induced in vitro.METHOD: A fractionation method using octyl‐β‐D‐glucopyranoside enabled lipoprotein, lipid, and protein fractions to be isolated from the membrane. RESULTS: The lipid fraction was shown nonspecifically to inhibit lymphocyte proliferation, to a lower extent compared with the native membrane. Alternatively, the protein fraction used as a proteoliposome contained the totality of the cytostatic effect of the native fraction.CONCLUSION: These results are discussed generally in the context of the immunoregulatory role of membrane lipids and proteins and in relation to the local properties of syncytiotrophoblast plasma membrane components in fetal graft tolerance.
Alloimmunization Against Well Defined Polymorphic Major Histocompatibility or Class I MHC Transfected L Cells Antigens Can Prevent Poly IC Induced Fetal Death in Mice
Authors: MENU ELIZABETH , CHAOUAT GÉRARD , KINSKY RADOSLAV , DELAGE GENEVIÉVE , KAPOVIC MILJENCO , THANG M.N. , JAULIN CHRISTIAN , KOURILSKY PHILIPPE , WEGMANN THOMAS G. 
Published: May 2013

METHOD: It is possible to induce increased fetal resorption in a number of inbred murine matings by injecting Poly (I) Poly (C12U) 3.5 days postconception, a maneuver associated with natural killer‐mediated damage to the feto placental unit such as occurs in spontaneous fetal resorptions.RESULTS: We show here that alloimmunization can block this effect. In addition, maternal immune responses induced by alloimmunization against isolated mutant class I or class II, as well as by immunization with class I MHC alloantigens (Kd) transfected L cells are sufficient to restore normal fetal viability. It is not necessary that the maternal immune response be specifically directed against paternal alloantigens fr the fetal protecton to ensue, since the effect occurs in inbred matings when the mother is immunized against unrelated class I or class II alloantigens. As in previous studies conducted in the murine species, not all MHC alloimmunizations are protective. In addition, as control, immunization with a monomorphic class I MHC molecular (37), transfected L cells, sheep red blood cells or hen egg lysozyme is without effect.CONCLUSION: These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.
Embryo‐Associated Immunosuppressor Factor is Produced at the Maternal‐Fetal Interface in Human Pregnancy
Authors: BOSE RATNA , LACSON ATILANO G. 
Published: May 2013

PROBLEM: To study whether embryo associated immunosuppressor factor (EASF) is synthesized at the maternal‐fetal interface.METHOD: Anti‐EASF monoclonal antibody H5D12 was used to identify EASF. Paraffin‐embedded sections were prepared from placental and fetal tissues and immunohistochemistry was done by the avidin‐biotin‐peroxidase technique. EASF was affinity purified using H5D12‐Sepharose 4B from culture media of placental villi and analyzed for immunosuppressive activity (by Concanavalin A‐induced lymphocyte proliferation assay) and molecular weight identity (by metabolic labeling studies with 35S‐methionine followed by immunoprecipitation and SDS‐PAGE).RESULTS: Immunohistochemical studies demonstrates intense immunostaining of villous syncytiotrophoblast and cytotrophoblast cells of first trimester placental tissues. Hoffbauer cells and decidual cells stained positive. The same cells in second and third trimester placental tissues stained weakly. However, the endothelium and smooth muscle cells of fetal blood vessels, fetal ovarian stroma and primordial follicles, kidney epithelium, cerebral neurons, and glial cells all stained negative. The affinity‐purified EASF from the conditioned media of placental villi (less than 12 wk gestational age) was identified as a 37‐kDa molecule with immunosuppressive activity. Metabolic labeling studies revealed that placental villi from early gestational age secretes a major factor of 37‐kDa and minor factors of 41‐kDa and 47‐kDa molecular weight.CONCLUSIONS: Monoclonal antibody H5D12 identifies a factor that is produced by the pre‐implantation embryo and also synthesized by decidua and trophoblast cells.
Sperm Immobilizing Antibodies Interfere With Sperm Migration From the Uterine Cavity through the Fallopian Tubes
Authors: SHIBAHARA HIROAKI , SHIGETA MINORU , TOJI HIDEAKI , KOYAMA KOJI 
Published: May 2013

PROBLEM: It is well known that sperm migration in cervical mucus is impaired by sperm immobilizing antibodies secreted in the mucus. However, it is not clear yet whether sperm migration from the uterine cavity through the fallopian tubes to the peritoneal cavity is impaired by sperm immobilizing antibodies. To test the possible impairment of sperm migration in the tubes, laparoscopic examinations were carried out and the presence of motile sperm in the peritoneal fluid after intra‐uterine insemination was investigated.METHOD: Peritoneal sperm recovery tests were performed in 28 infertile women with sperm immobilizing antibodies in their sera, and the results were compared with those in 322 infertile women without the antibodies. Both the sperm immobilizing antibody titers (SI50) and complement activities (C'H50) in peritoneal fluid were compared with those in patients' sera. In some experiments, the supernatant of the peritoneal fluid was used as a source of complement for the sperm immobilization tests instead of guinea pig serum.RESULTS: Among couples with normal semen characteristics by the criteria of WHO, sperm recovery in the peritoneal fluid was observed in only 3 (11.1%) of 27 patients with sperm immobilizing antibodies, compared with 72 (34.0%) of 212 patients without the antibodies (P<0.025). The antibody titers of the patients with the sperm recovery were very low by the quantitative sperm immobilization test. In most patients, a similar amount of sperm immobilizing antibodies was present in the peritoneal fluid and the sera. Though the complement activities in the peritoneal fluid were less than those in sera, the former were still found to be sufficient to immobilize sperm in vivo.CONCLUSIONS: These results suggest that the complement‐dependent sperm immobilizing antibodies could interfere with sperm migration in the female genital tract at the level of the fallopian tubes.
Standardization of Flow Cytometric Crossmatch (FCXM) for Investigation of Unexplained Habitual Abortion
Authors: Stephenson Mary D. , Wu Vivian , Mackinnon Murray , Sadoway Janet , Keown Paul A. 
Published: May 2013

PROBLEM: To define a positive flow cytometric crossmatch (FCXM), in terms of channel shift, for maternal IgG and IgM (n=28) against paternal T and B lymphocytes.METHOD: A reference range study. Mononuclear cells were obtained from 28 healthy volunteers using density gradient separation of heparinized blood, followed by pre‐incubation with goat immunoglobulin. A total of twelve tubes were prepared for each volunteer. Primary incubation was with negative control serum, positive control sera (either IgG or IgM) and individual AB sera. Secondary incubation was with four combinations of fluorochromes; CD3 PE/IgG‐Fc F(ab′)2FITC, CD3 PE/IgM F(ab′)2FITC, CD20 PE/IgG‐Fc F(ab′)2FITC and CD20 PE/IgM F(ab′)2FITC. The cells were then analyzed with an EPICS Profile flow cytometer, using 256‐channels and a four decade log scale.RESULTS: The linear mean channel fluorescence of the negative control serum was subtracted from the individual AB sera (channel shift) for each of the four combinations of fluorochromes. By determining the 95% one‐sided upper reference limits of the negative control serum for each of the four trimmed data sets, we clinically defined a positive FCXM for bound IgG or IgM to T lymphocytes as a shift of 10 or more channels, and for bound IgG or IgM to B lymphocytes as a shift of 25 or more channels, above the linear mean channel shift of the negative control serum.CONCLUSION: Positive FCXMs were defined for maternal IgG and IgM against T and B lymphocytes, in terms of channel shift above the linear mean channel fluorescence of the negative control serum. By standardizing the dual‐color FCXM methodology, the clinical significance of alloantibodies in the maintenance of pregnancy could be addressed in a collaborative manner.
A Comparison of Flow Cytometry and Microcytotoxicity for the Evaluation of Alloimmune Therapy in Patients With Recurrent Spontaneous Abortions
Authors: Matzner W. , Chong P. , Xu G. , Ching W. 
Published: May 2013

PROBLEM: There is substantial data that support the efficacy of paternal leukocyte immunization (PLI) for the treatment of alloimmune mediated miscarriage; however, there is confusion regarding the laboratory test that should be performed to determine levels of maternal anti‐paternal leukocyte antibodies (MAPLA).METHOD: Popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Cell flow cytometry crossmatch correlates well with the more difficult MLC assay although the former proves the more sensitive study. This work compares the MCX assays with FCXM. The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (<10%) of MAPLA as measured by FCXM. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM.RESULTS: Although all ten patients had very high levels of MAPLA by FCXM during pregnancy, five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. Furthermore, all patients who were positive by MCX to paternal Class I antigens were also positive to Class I antigens not seen in either parent. Both patients who were positive by MCX to paternal Class II antigens were also positive to maternal Class II antigens. Notable is that all ten women eventually delivered healthy infants.CONCLUSION: Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.
Alloantibody Responses to Antigens Recognized by Rabbit Antitrophoblast Antisera in Trophoblast and Mononuclear Cell (MNC) Membranes by Primary Aborting Women Before and After Paternal Leukocyte Immunization
Authors: Goldberg Janet S. , Haynes Mark K. , Cowchock F. Susan , Mcintyre John A. , Smith J. Bruce 
Published: May 2013

PROBLEM: Because shared allogeneic antigens are expressed on peripheral blood lymphocytes, as well as trophoblasts, it has been proposed that lymphocyte transfusions may appropriately sensitize recurrent spontaneous aborters (RSA) to trophoblast and lead to pregnancy conservation. The degree to which these responses are affected by this treatment, however, has not been defined.METHOD: SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) and Western blot analyses were used to study the alloantibody responses in RSA patients both before and after immunization with paternal leukocytes (MNC) against membrane proteins isolated from peripheral blood mononuclear cells (MNC), first trimester and full term chorionic villi (CV).RESULTS: A distinct set of antigens with apparent molecular weights of 32, 36, 41, 63, 65, and 85 kDa was identified in both MNC and trophoblast membranes by rabbit anti‐trophoblast antisera. In addition, a 55 kDa protein was recognized by MNC membranes. Thirty‐eight percent of primary RSA sera recognized this 55 kDa protein. After paternal MNC immunization, all primary RSA samples displayed increased reactivity or produced antibodies to this 55 kDa protein when compared with preimmunization sera. The protein was identified as MCP using a rabbit polyclonal anti‐MCP antisera. In contrast, reactivity to the other antigens present in the membrane preparations decreased after paternal MNC immunization.CONCLUSION: Changes in immune reactivity in RSA patients after paternal MNC immunization suggest that immunization alters serum immune reactivity to MNC and trophoblast shared antigens.
Lymphocyte Subsets and Autoantibodies in Pregnancies Complicated by Placental Disorders
Authors: Matthiesen Leif , Berg Göran , Ernerudh Jan , Skogh Thomas 
Published: May 2013

PROBLEM: The survival of the fetoplacental unit might partly depend on down‐regulation of rejection reactions. Pathological maternal cellular immune response mechanisms could therefore be of pathogenic importance in pregnancies complicated by placental disorders.METHOD: A flow‐cytometric analysis of T‐cell subsets and B‐cell, as well as serological tests for anticardiolipin antibodies (aCL), antinuclear antibodies (ANA), and rheumatoid factor (RF) were done on 90 women with complicated pregnancies. The results were compared with that of nonpregnant women (n=5), and normal pregnant women (n=5) in the third trimester.RESULTS: Two women, suffering from severe preeclampsia and eclampsia respectively, had aCL on 12 and 13 units, respectively. ANA occurred in 11 patients with moderate and severe preeclampsia and intrauterine growth retardation. All women had negative RF tests. Within the CD4 T‐helper subpopulations, the proportion of suppressor/inducer T‐cell population (CD4+CD45RA+) significantly increased, while the memory and helper/inducer T‐cells (CD4+CD45RO+ and CD4+CD29+) significantly decreased during normal pregnancy compared to nonpregnant controls. This deviation of CD4 subpopulations was not found, or was less pronounced, in complicated pregnancies. The proportion of cytotoxic T cells (CD8+S6F1+) was significantly reduced during normal pregnancy. This reduction was less pronounced in complicated pregnancies.CONCLUSION: Systemic immunological deviations toward suppression or decreased activity of the immunological response as seen in normal pregnancies, was not observed in preeclampsia, intrauterine growth retardation, intrauterine fetal death, and abruptio placentae. This lack of suppression or increased T‐cell activity may have a primary pathogenic role in some women with a complicated pregnancy, or it may be secondary to the placental disorders.
Systemic CD56+ Cells Can Predict Pregnancy Outcome
Authors: Coulam C.B. , Goodman C. , Roussev R.G. , Thomason E.J. , Beaman K.D. 
Published: May 2013

PROBLEM: To evaluate differences in circulating CD56+ cells between successful and unsuccessful pregnancies, 114 pregnant women were studied prospectively.METHOD: Seventy women had a history of infertility (INF) and 44 had two or more previous spontaneous abortions (RSA). Among the infertile women, 12 were donor egg recipients (DER) and 15 underwent intracytoplasmic sperm injection (ICSI) for treatment of male factor infertility. Nineteen women were carrying multiple gestations (MG) and 55 had singleton gestations (SG). Thirteen additional women were receiving intravenous immunoglobulin (IVIg).RESULTS: The percentage of CD56+ cells was determined in 310 blood samples from 114 pregnant women by flow cytometry. The prevalence of women with persistent elevation of percent of 56+ cells (>12%) was 58% among DER, 73% among ICSI, 37% among MG, 22% among SG, 18% among RSA, and 39% among INF. Thirteen women with SG received IVIG, 10 had CD56+ cells greater than 12% and all 13 experienced live births. Women with percentage CD56+ cells persistently greater than 12% who were not DER, not ICSI, not receiving IVIg, and not carrying MG had a live birth rate of 11%. Women with greater than 12% CD56+ cells had normal karyotype in 78% of concepti studied in contrast to women less than 12% CD56+ cells who had 68% abnormal karyotypes (P=0.04).CONCLUSION: Elevated CD56+ cells in pregnant women who are not DER, not ICSI, not receiving IVIg, and not carrying MG predicts loss of a karyotypically normal conceptus with a specificity of 87% and positive predictive value of 78%. While the specificity value of this test is high in both infertile and RSA populations, the sensitivity is 86% in RSA and only 54% in INF suggesting this test does not identify all losses among INF. It may identify a subset of pregnancies at risk for loss of a karyotypically normal embryo that may respond to treatment with IVIg.
Production of Mouse Monoclonal Antibodies Directed Against the Oolemma of Human and Hamster Oocytes by Intra‐splenic Injection of Oocytes
Authors: Fusi F.M. , Gasparri A.M. , Pelagi M. , Tamburini C. , Santis L. De , Grieco S.E. , Siccardi A.G. , Ferrari A. 
Published: May 2013

PROBLEM: To develop an additional approach for the study of oolemmal surface moieties involved in gamete interactions, we decided to obtain monoclonal antibodies by intrasplenic injection of human and hamster oocytes in Balb/c mice.METHOD: Two Balb/c males were injected three times intrasplenically at 15‐day intervals with approximately 40 zona‐free hamster and 3–5 zona‐free human oocytes. After the third injection, spleen cells were fused and hybridomas developed. We used a novel screening system based upon the use of sections of frozen human and hamster eggs, tested by means of indirect immunofluorescence. The antibodies that we produced were evaluated for their ability to interfere with the zona‐free hamster eggs penetration by human spermatozoa. The B2B5 antibody was also developed as ascitic fluid and further characterized.RESULTS: Seven antibodies reactive with hamster oocytes were produced. Six of them also reacted with human oolemmas. The binding was confined to the oolemma, and no staining of the zona nor the cytoplasm was present. One of these antibodies reduced the penetration of zona‐free hamster eggs by human spermatozoa. This antibody, B2B5, an IgM kappa, was confirmed to interact with the oolemma by means of indirect immunofluorescence of fresh eggs and Covasphere binding. B2B5 did not react with other human or hamster tissues except capacitated human spermatozoa. The reactivity with the oolemma of hamster oocytes was not lost after egg penetration by human sperm.CONCLUSIONS: Intrasplenic immunization using zona‐free human and hamster oocytes allows the production of anti‐oolemma antibodies. A system of screening based upon the use of sections of frozen eggs also allows an easy and quick scoring of many supernatants. B2B5 monoclonal anti‐oolemma antibody deserves further studies in that is able to interfere with fertilization and its antigen appears to be confined to the gametes surface.