bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Autoimmune Antibodies in Failed Embryo Transfer Cycles
Authors: Birkenfeld A. , Mukaida T. , Minichiello L. , Jackson M. , Kase N.G. , Yemini M. 
Published: May 2013

PROBLEM: The presence of antiphospholipid antibodies lupus anticoagulant (LAC), anticardiolipin antibody (ACA) as well as antinuclear antibody (ANA) has been associated with early spontaneous pregnancy loss and adverse pregnancy outcome. The purpose of this study was to investigate the possible role of autoimmune antibodies (LAC, ACA, and ANA) as a cause of implantation failure following embryo transfer (ET) after in vitro fertilization (IVF).METHOD: Three groups were studied: Group I, 56 patients who failed to conceive following ET; group II, 14 patients who have conceived following IVF‐ET and delivered or are carrying an uncomplicated ongoing pregnancy; and group III, 69 patients who were new candidates for IVF‐ET.RESULTS: Eighteen out of 56 (32.1%) of patients who failed to conceive following previous IVF‐ET cycle (group I) tested positive for one or more of the autoimmune antibodies. None of the 14 patients of group II tested positive for autoimmune antibodies (P<.02). Seven out of the 69 patients (10%) of group III were found positive to one or more of the autoimmune factor. This rate is significantly lower than the rate of positive autoimmune antibodies detected in group I (P<.003). Fifteen patients of the 18 who tested positive for autoimmune antibodies and who had previously failed to conceive following ET underwent a subsequent IVF‐ET cycle while being treated with prednisone and aspirin. Seven out of the 15 (46.6%) conceived and were able to sustain a clinical ongoing pregnancy.CONCLUSIONS: Patients receiving ET are carrying viable embryos within the intrauterine environment. Therefore, in this unique group of patients, failure to demonstrate a positive pregnancy test represents an implantation failure or a very early postimplantation loss. The results of this study suggest that periimplantation events may be affected by autoimmune antibodies. Very early miscarriage or implantation failure may be related to the same pathophysiological mechanism that causes recurrent miscarriages and is diagnosed incorrectly as infertility.
Effect of Epidermal Growth Factor on Mouse Sperm Acrosome Reaction Induced by Zona Pellucida
Authors: Furuya Satoru , Endo Yoshihiro , Oba Mikiko , Matsui Yukari , Suzuki Shuetu , Nozawa Shiro 
Published: May 2013

PROBLEM: The effect of epidermal growth factor (EGF) on the acid‐solubilized zona pellucida (ZP)‐induced acrosome reaction was investigated in mouse sperm.METHOD: Mouse epididymal sperm were capacitated in modified Krebs‐Ringer bicarbonate buffer (m‐KRB) for 120 min and further treated with acid‐solubilized ZP(4 zona/μl) for an additional 60 min to induce the acrosome reaction. The chlortetracycline fluorescence assay was used to monitor the acrosome reaction. The acrosome reacted sperm featured the acrosome reacted (AR) pattern, which demonstrates the lack of fluorescence on the head and bright midpiece.RESULTS: EGF caused an early increase in the AR pattern in response to the acid‐solubilized ZP in a dose‐dependent manner. The EGF‐dependent stimulation of the ZP‐induced acrosome reaction was inhibited by an inhibitor of protein tyrosine kinases, genistein or activators of Ca++ and phospholipid‐dependent protein kinase (protein kinase C). Furthermore, the stimulatory effect of EGF was not attenuated when sperm were capacitated in the presence of islet‐activating protein, an inactivator of inhibitory guanine nucleotide‐binding regulatory protein (Gi protein).CONCLUSION: EGF stimulates the ZP‐induced acrosome reaction in a manner that is independent of the Gi protein. The EGF action is regulated by protein tyrosine kinase and protein kinase C.
Effects of Atrial Natriuretic Peptide on Rat Ovarian Granulosa Cell Steroidogenesis in Vitro
Authors: Johnson K.M. , Hughes F.M. , Fong Y.‐Y. , Mathur R.S. , Williamson H.O. , Gorospe W.C. 
Published: May 2013

PROBLEM: The localization and biological effects of atrial natriuretic peptide (ANP) are not limited to cardiac tissue but extend to a number of extra‐atrial tissues and organs, including the ovary. The objective of the present study was to determine the effects of ANP on granulosa cell steroidogenesis. Hence, the direct effects of ANP on the production of progesterone, 20α‐hydroxpregn‐4‐en‐3‐one (20α‐OH‐P), and estrogen by undifferentiated and differentiated rat ovarian granulosa cells were examined in vitro.METHOD: Undifferentiated granulosa cells obtained from the ovaries of diethylstilbestrol‐primed, immature rats were treated with increasing doses (10−12 to 10−6 M) of rANP for 48 h.RESULTS: ANP evoked a two‐ and threefold increase in progesterone and 20α‐OH‐P production relative to untreated controls, respectively. Increasing doses of ANP in combination with porcine FSH (125 ng/well) resulted in a biphasic response in progesterone production above FSH‐treated controls. Specifically, a maximal inhibition of 35% in progesterone production was achieved at 10−9 M ANP, followed by a stimulation to levels comparable with FSH‐stimulated controls at higher doses examined. Increasing doses of ANP evoked a twofold increase in FSH‐stimulated 20α‐OH‐P production over respective controls. Following pretreatment of granulosa cells with FSH for 48 h to evoke differentiation, ANP caused a significant dose‐dependent inhibition in basal progesterone production that resulted in a 76% suppression at the highest dose examined. In contrast, ANP evoked a 2.8‐fold increase in 20α‐OH‐P production when compared with controls. Finally, in FSH‐stimulated differentiated granulosa cells, ANP evoked a threefold increase in progesterone production and a 65% inhibition in 20α‐OH‐P production. ANP exerted no significant effects on estrogen production by either undifferentiated or differentiated granulosa cells in the presence or absence of FSH.CONCLUSIONS: These data demonstrate that ANP can modulate directly progestin steroidogenesis in both undifferentiated and differentiated rat ovarian granulosa cells in vitro and, therefore, may play an important role in granulosa cell differentiation and follicular maturation.
Functions of Macrophages in Human Decidual Tissue in Early Pregnancy
Authors: Mizuno Masahiko , Aoki Koji , Kimbara Toshihiro 
Published: May 2013

PROBLEM: Roles of decidual macrophages (DMs) in the maintenance of early pregnancy was determined by comparing three of their functions, antigen presentation, immunoregulation, and lymphokine production, with those of peripheral monocytes (PMos) isolated from the same subjects.METHOD: The antigen‐presenting capacity of DMs was examined by the one‐way mixed lymphocyte reaction (MLR) in which accessory cell‐depleted mononuclear cells isolated from pregnant women were used as responders. The effect of DMs on cellular immunity was investigated by inhibition tests of either one‐way MLR or phytohemagglutinin stimulation. The production of interleukin‐1 (IL‐1) and prostaglandin E2 (PGE2) by DMs following lipopolysaccharide stimulation was examined.RESULTS: Addition of increasing concentrations of DMs to the culture resulted in a concentration‐dependent proliferative response, as well as with PMos. In both assays, a stronger suppression was observed in the presence of DMs from normal pregnant women compared with PMos from the same subjects. DMs were found to secrete significantly lower levels of IL‐1 α and IL‐1β than PMos. No difference in PGE2 production was observed between DMs and PMos.CONCLUSIONS: These findings suggest that DMs present in human early decidual tissue have a capacity for allo‐antigen presentation, a higher suppressive activity, and a lower capacity to produce IL‐1 than their peripheral counterparts.
Interleukin‐1 Receptor Antagonist (IL‐1ra) Production by Human Amnion, Chorion, and Decidua
Authors: Fidel P.L. , Romero R. , Ramirez M. , Cutright J. , Edwin S.S. , Lamarche S. , Cotton D.B. , Mitchell M.D. 
Published: May 2013

PROBLEM: This study was conducted to determine whether (1) conditioned media from unstimulated primary cultures of human amnion, chorion, or decidua contain detectable concentrations of IL‐lra in vitro, and (2) bacterial endotoxin (LPS), tumor necrosis factor‐alpha (TNF‐α), or IL‐1‐beta (IL‐1β) stimulate amnion, chorion, or decidua to produce increased amounts of IL‐1ra.METHOD: Placentae were obtained from women at term with intact membranes before the onset of labor. Amnion, chorion, and decidual cells were isolated by standard procedures and grown to confluence. Cells were then cultured in quadruplicate for 16 h in tissue culture medium supplemented with 10% fetal calf serum or, additionally, with various concentrations of Eschrichia coli LPS, TNF‐α, or IL‐1β. Culture supernatants were collected, and concentrations of IL‐1ra were quantitated by a sensitive and specific enzyme‐linked immunosorbent assay for IL‐lra.RESULTS: Results showed that primary cultures of amnion and chorion from 4 of 9 and decidua from 10 of 12 placentae had detectable rates of production of IL‐lra (ranges: 0.08‐6.5, 0.42‐12.1, and 1.55–96.5 pg IL‐1ra/μg protein/16 h, respectively). In addition, LPS (10‐1,000 ng/ml) and IL‐1β (0.1–10 ng/ml), but not TNF‐α (0.01–100 ng/ml), stimulated decidual cells to release/secrete increased amounts of IL‐lra compared with media alone (range: 2.5–400 pg IL‐lra/μg protein/16 h, P < 0.0001). In contrast, neither LPS, TNF‐α, or IL‐1β could stimulate amnion or chorion to release/secrete IL‐1ra.CONCLUSIONS: These results indicate (1) that amnion, chorion, and predominantly decidua, can release or secrete IL‐1ra in vitro, and (2) that LPS and IL‐1β can stimulate decidual cells to produce increased amounts of IL‐lra.
Maternal—Fetal Transport of Immunoglobulin G and Its Subclasses During the Third Trimester of Human Pregnancy
Authors: Malek Antoine , Sager Ruth , Schneider Henning 
Published: May 2013

PROBLEM: We determined the maternal‐fetal transport of immunoglobulin G (IgG) during the third trimester of human pregnancy.METHOD: The concentration of IgG and its subclasses (IgG1–4) was determined in sera of blood samples from 38 pregnancies collected at the time of delivery from a peripheral maternal vein (MV) and from the placental umbilical artery (UA) and vein (UV). Gestational age varied between 28 and 42 weeks (WG).RESULT: Whereas placental weight showed a significant correlation with gestational age, the maternal level of IgG and the ratio of its subclasses did not vary with gestational age. At 28–33 WG (n = 15) the mean values in the UA (5.91 ± 1.53 g/1) and UV (6.41 ± 1.57 g/1) for total IgG concentration were lower than in the MV (10.74 ± 2.55 g/1). At the end of gestation (37–42 WG, n = 12), IgG in both UA (11.21 ± 1.95 g/1) and UV (12.26 ± 2.06 g/1) exceeded the maternal concentration (9.69 ± 1.84 g/1). In addition to the significant positive correlation between IgG concentration in the fetal circulation (UV + UA) and gestational age (28–42 WG), an increase in the positive difference between UV and UA at the end of pregnancy indicates that there is a substantial rise in placental IgG transport capacity.CONCLUSION: All four subclasses IgG1–4 were detectable in the umbilical circulation (28–42 WG). Whereas IgG3 and IgG4 in UA and UV had a similar concentration as in MV and remained unchanged, IgG2 increased with gestation from 0.67/0.74 g/1 (UA/UV, 28–33 WG) to 1.29/1.58 g/1 (UA/UV, 37–42 WG), but nevertheless remained lower than the level found in the MV (2.65 ± 1.12 g/1). The main increase in IgG concentration, however, was due to the substantial rise in the transport of IgG1, which increased from 4.37 ± 1.24 (UA) and 4.94 ± 1.52 g/1 (UV) at 28–33 WG to 8.94 ± 1.66 (UA) and 10.89 ± 1.96 g/1 (UV) at the end of gestation, which was even higher than the overall IgG concentration in MV.
H5D12 Monoclonal Antibody Identifies a 24‐kD Immunosuppressor Factor Produced by Human Chorio Carcinoma Cells
Authors: Bose Ratna , Berczi Anna 
Published: May 2013

PROBLEM: The purpose of this study was to identify and characterize embryo‐associated immunosuppressor factor (EASF) secreted by chorio carcinoma cells with the help of EASF‐specific monoclonal antibody H5D12 (raised against EASF purified from embryo growth media of in vitro fertilized human ova).METHOD: Paraffin‐embedded slides of human chorio carcinoma as well as control cell lines were prepared, and immunohistochemistry was done by the avidin‐biotin‐peroxidase technique. EASF was affinity purified using H5D12‐Sepharose 4B from culture media of cell lines and analyzed for immunosuppressive activity (by Concanavalin‐A‐induced lymphocyte proliferation assay) and molecular weight identity (by metabolic‐labelling studies with 35S‐methionine followed by immunoprecipitation and SDS‐PAGE).RESULTS: H5D12 showed intense immunostaining of BeWo chorio carcinoma cells. Bio‐synthetic labeling studies identifies this factor as a 24‐kD molecule, and EASF bioassay indicates that this factor possesses immunosuppressive activity. No such immunosuppressive activity or similar molecules were identified when control cell lines were analyzed.CONCLUSIONS: Monoclonal antibody H5D12 recognizes a 24‐kD factor with immunosuppressive activity that is secreted by chorio carcinoma cells, which suggests that this is a unique factor and may be one of the key regulators of reproductive functions.
Use of Lymphocyte Platelet Binding Assay for Detecting a Preimplantation Factor: A Quantitative Assay
Authors: Barnea E. R. , Lahijani K. I. , Roussev R. , Barnea J. D. , Coulam C. B. 
Published: May 2013

PROBLEM: To evaluate the ability of the lymphocyte/platelet binding assay to identify a preimplantation factor (PIF).METHOD: Percentages of binding of lymphocytes by platelets in the presence of sera from 30 known pregnant and 30 nonpregnant individuals were compared using a novel lymphocyte/platelet binding assay. The assay is performed using a combination of a heat inactivated sera with donor O+ lymphocytes, activated complement and an antibody against CD2(T11, Ortho Pharmaceuticals).RESULTS: In nonpregnant females (23.6 ± 6.5%) and males (17.7 ± 4.7%) the percentage of lymphocytes bound by platelets was significantly different from pregnant women (56.1 ± 15.9%) (P < 0.0001). Serial sampling of blood in five women undergoing IVF/ET who had normal pregnancies showed the detection of PIF by 4 days after transfer. The lymphocyte/platelet binding assay was not influenced by hCG, progesterone and estradiol. The interassay and intraassay variabilities were <3%.CONCLUSIONS: The lymphocyte/platelet binding assay is a simple, reproducible, specific and cost efficient assay for measurement of PIF. Application of this assay will provide investigative and diagnostic tools for identifying and monitoring early pregnancy events.
Intralipid as Treatment for Recurrent Unexplained Abortion?
Authors: Clark David A. 
Published: May 2013

PROBLEM: Safe, effective, and inexpensive alternatives to partner leukocyte immunotherapy are being sought. Psychotherapy may be effective but it is uncertain what constitutes effective treatment and the form of treatment tested in cohort controlled trials is expensive. IVIG also appears effective, but is expensive.METHOD: A published double blind randomized controlled trial in which Intralipid (Kabi Vitrum, Toronto, Ontario) was used as a control versus trophoblast membrane vesicles was reviewed. A prediction made from this data was then tested using the DBA/2‐mated CBA/ J mouse model of recurrent spontaneous abortion.RESULTS: It can be hypothesized from the human clinical trial data that Intralipid even in small doses could be an effective antiabortion treatment. The number of patients in the published study is too small for the required degree of precision. Intralipid was highly effective in preventing abortion in mice, and protection was prolonged. This may be explained by previous data in the literature showing that Intralipid affects the reticuloendothelial system of the recipient.CONCLUSIONS: The evidence suggests that Intralipid might be an effective treatment for human recurrent miscarriages, and injection into women who may become pregnant has been found ethically acceptable at one university center. Comparison of Intralipid to partner leukocyte immunotherapy or IVIG would be worthwhile. For adequate statistical power, this would require a large, multicenter, prognostically stratified randomized controlled trial and could be accomplished via the Recurrent Miscarriage Immunotherapy Trialists Group network.
The Effectiveness of Allogeneic Leukocyte Immunization in Unexplained Primary Recurrent Spontaneous Abortion
Authors: Daya Salim , Gunby Joanne ,   The Recurrent Miscarriage Immunotherapy Trialists Group
Published: May 2013

PROBLEM: Unexplained primary recurrent spontaneous abortion (RSA) can be viewed as a partner‐specific problem for which immunization with allogeneic leukocytes is being offered as therapy. Published data from randomized controlled trials have produced conflicting results regarding treatment effectiveness. The aim of this study was to perform a subgroup analysis of the data from a recent worldwide collaborative meta‐analysis using the raw data for patients with primary RSA entered into randomized controlled trials of immunotherapy.METHODS: Data from randomized controlled trials in eight centers were included in this analysis. Individual patients were included only if they had had three or more spontaneous abortions, no previous pregnancy beyond 20 weeks' gestation, no identifiable cause for the abortions, and no evidence of antipaternal antibodies. Meta‐analysis by centre and logistic regression analysis were performed to determine the overall effect of treatment in achieving live birth and to identify variables that affect the prognosis for a successful outcome.RESULTS: In the meta‐analysis by center, immunotherapy significantly improved the live birth rate (common odds ratio = 1.94, 95% confidence interval (CI) = 1.20 to 3.12). In the analysis by patient, the likelihood of a successful outcome was also significantly better with treatment (relative risk = 1.46, 95% CI 1.19 to 1.69). The absolute treatment effect was 16.3% producing a number needed to treat of 6. The number of previous abortions had a significant negative correlation with live birth rate, such that for each additional pregnancy loss beyond three, the likelihood of live birth was reduced by 23%.CONCLUSION: Allogeneic leukocyte immunization is an effective treatment for unexplained primary RSA when pretreatment antipaternal antibodies are absent. Better diagnostic tests are required to identify patients who may derive maximal benefit from this therapeutic approach.
Chymotrypsin‐Galactose Treatment of Sperm With Antisperm Antibodies Results in Improved Pregnancy Rates Following in Vitro Fertilization
Authors: KATSOFF DIANE , CHECK JEROME H. , BOLLENDORF ANIELA , BENFER KELLY 
Published: May 2013

PROBLEM: To determine if chymotrypsin‐galactose (CG) treatment of sperm bound with antisperm antibodies (ASA) improves pregnancy rates (PRs) following in vitro fertilization (IVF).METHOD: Patients with >50% ASA who failed to conceive despite six intrauterine insemination (IUI) cycles were included. Initially the sperm treatments were randomized with CG vs culture medium; subsequently only CG treatment was used.RESULTS: There was a significantly lower fertilization rate in those patients inseminated with sperm incubated in culture medium vs CG (27% vs 47%, P<.05 t‐test). Similarly, a higher percentage of patients receiving culture medium treatment of sperm had failed fertilization (45%) compared to CG (11%). Though the clinical PRs were higher with CG (21%) than medium (9.5%), there was no statistical difference.CONCLUSIONS: Though the percentage of sperm bound with antibodies are not reduced, we hypothesize that the CG treatment improves fertility by possibly mitigating the antagonistic action of these antibodies.
Suppression of Natural Killer Cell Activity by Monocytes Following Immunotherapy for Recurrent Spontaneous Aborters
Authors: HIGUCHI KAZUHIRO , AOKI KOJI , KIMBARA TOSHIHIRO , HOSOI NOBUYUKI , YAMAMOTO TAKASHI , OKADA HIDECHIKA 
Published: May 2013

PROBLEM: Natural killer (NK) cell activity has previously been shown to decrease in normal pregnancy as compared with the nonpregnancy state. The purpose of this study was to determine NK cell activity in recurrent aborters and to investigate the kinetics of NK cell activity following immunotherapy.METHODS: Recurrent aborters (N = 17) were immunized with husbands' mononuclear cells (1 × 108) twice during the early stage of current pregnancy. NK cell activity of recurrent aborters as well as that of normal pregnant (N = 12) and nonpregnant (N = 6) women (controls) was determined by 51Cr release assay. Monocytes were depleted from the mononuclear cell fraction and its effect on the NK cell activity was determined as well.RESULTS: At around 5 wk of gestation, NK cell activity in recurrent aborters before treatment was significantly higher (28.0 ± 5.1%) than that in normal pregnancy (18.9 ± 4.3%) (P < 0.01). Following immunotherapy, NK cell activity of recurrent aborters (N = 13) who maintained their pregnancy decreased significantly (21.7 ± 8.9%) (P < 0.05). In contrast, NK cell activity of recurrent aborters (N = 4) who aborted their current pregnancy did not decrease. Depletion of monocytes resulted in a significant increase in NK cell activity (P < 0.05).CONCLUSIONS: This study suggests that the immunotherapy induces suppression of NK cell activity which may contribute for the maintenance of pregnancy. Moreover, monocytes may be involved in this suppression.
Gonadotropin Releasing Hormone (GnRH) Agonist Induces Down‐Regulation of the CD3+CD25+ Lymphocyte Subpopulation in Peripheral Blood
Authors: HO G‐NERNG , CHEN HSIN‐FU , CHEN SHEE‐UAN , CHAO KUAN‐HAN , YANG YU‐SHIH , HUANG SU‐CHENG , LEE TZU‐YAO , GILL THOMAS J. 
Published: May 2013

PROBLEM: To test whether GnRH agonist could alter in vivo human immune cells and whether the alteration is related to the success of pregnancy in an in vitro fertilization‐embryo transfer (IVF‐ET) program.METHODS: Thirty‐six infertile patients were enrolled under the long protocol of GnRH agonist (buserelin acetate) and superovulation with gonadotropin from our IVF‐ET program. Peripheral B cells, NK cells, CD4+ and CD8+ T cells, and the expression of CD69, CD25, HLA‐DR, and CD71 antigens on the T cells were serially examined by dual‐color flow cytometry.RESULTS: B cells, NK cells, CD8+ T cells, and CD71+ T lymphocyte subpopulations were not changed throughout the whole course of treatment. CD4+ T cell and CD25+ T cell sub‐populations were significantly down‐regulated when the GnRH agonist was used for approximately 2 wk. CD3+CD69+, CD3+CD25+, and CD3+DR+ lymphocyte subpopulations were increased at 7 days (during implantation) and at 14 days after embryo transfer in pregnant patients, but not in patients who failed to get pregnant.CONCLUSIONS: The GnRH agonist had a transiently immunosuppressive effect on CD4+ and CD25+ T cells, but CD69+, CD25+, and HLA‐DR+ T cells were activated during and after successful implantation.