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      Association of IL-1 and TNF-αLevels in Endometrial Secretion and Success of Embryo Transfer in IVF/ICSI Cycles

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          Abstract

          Background

          In this work, we have determined the levels of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), which function as cytokines in endometrial receptivity, through the endometrial secretion within the eligible individuals and thus studied their relationships with the success or failure of pregnancy in in vitro fertilization/intra cytoplasmic sperm injection (IVF/ICSI) cycles.

          Materials and Methods

          In this prospective study, 76 women were selected for their first IVF/ICSI and met the study inclusion criteria. All of the patients have undergone the endometrial secretion aspiration prior to performing the oocyte collection. The levels of IL-1and TNF-α were analyzed by the means of enzyme-linked immunosorbent assay method, using special standard kits. The patients were requested to undergo the serum human chorionic gonadotropin measurements and ultrasound evaluation for the purpose of detecting successful implantations and pregnancies.

          Results

          Among the 76 subjects of the study, 33 (43.4%) patients had a positive beta-human chorionic gonadotropin (β-hCG) and 44 (56.6%) resulted in a negative β-hCG. It should be also noted that through the patients with positive β-hCG, 23 (30.3%) of them displayed fetal heart rate in their transvaginal sonography (TVS). Compared to the group with failed pregnancies and their cytokine levels, we perceived a higher concentration of IL-1 in the group containing successful chemical pregnancies (P=0.00). However, there was no significant difference in terms of clinical pregnancy in the IL-1 levels between the two groups (P=0.06). In addition, there was not any notable difference in the levels of TNF-α between the two groups, neither in terms of chemical nor clinical pregnancy (P=0.8 and P=0.6, respectively).

          Conclusion

          The current study suggests that higher concentrations of IL-1 in endometrial secretions could be as- sociated with improved endometrial receptivity and IVF outcome. With regards to TNF-α, no statistically significant difference was observed between the groups of with and without successful pregnancies.

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          Most cited references15

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          Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates.

          To explore the possibility that local injury to the endometrium in controlled ovarian hyperstimulation cycle improves the incidence of embryo implantation and to analyze the gene expression profile in the endometria of pregnant and nonpregnant patients in in vitro fertilization/embryo transfer (IVF-ET). Prospective study. A clinical assisted reproductive center of a university hospital. Women undergoing fresh IVF-ET cycles (n = 121), treated with a long protocol for controlled ovarian hyperstimulation, whose endometrium were diagnosed by B-ultrasound showing irregular echo. Local injury to the endometrium of 60 patients in controlled ovarian hyperstimulation cycle, who were randomly selected from a total of 121 patients. Seven endometrial biopsies samples from day 10 were analyzed by Affymetrix U133 plus 2.0 gene chip. Outcomes of IVF-ET and gene expression assayed by gene chip technology. Transfer of the same number of embryos (135 in the experimental and control patients, respectively) resulted in rates of implantation (33.33% vs. 17.78%), clinical pregnancy (48.33% vs. 27.86%), and ongoing or live births per ET (41.67% vs. 22.96%) that were higher in the experimental group compared with controls. Statistically significant differences of the expression level of 218 genes (41 up-regulated and 177 down-regulated) were detected in the endometrial biopsy samples from clinical pregnant patients and nonpregnant patients. The results suggested local injury to the endometrium during a COH cycle improved the rates of embryo implantation, clinical pregnancy and live birth in ART. We also demonstrated a statistically significant difference in the messenger RNA (mRNA) expression profiles in the endometrium of pregnant and nonpregnant patients. Further studies on the genes identified herein will assist in predicting implantation competence.
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            Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes.

            The responses of lymphocytes to six CC chemokines--MCP-1, MCP-2, MCP-3, MIP-1 alpha, MIP-1 beta, and RANTES--were studied using cloned human CD4+ and CD8+ T cells. All CC chemokines tested induced migration of both types of lymphocytes, whereas two CXC chemokines used as controls, IL-8 and IP-10, were inactive. The monocyte chemotactic proteins (MCP-1, MCP-2, and MCP-3) showed a typically bimodal concentration dependence, and were considerably more effective than MIP-1 alpha, MIP-1 beta, or RANTES. All CC chemokines also induced a rapid and transient rise in cytosolic free Ca2+ in either type of T cell. The rise was prevented by Bordetella pertussis toxin treatment, indicating that G-protein-coupled receptors are involved in signaling. It was most pronounced with MCP-1 and MCP-3, which is in agreement with the efficacy of these chemokines as chemoattractants. The responses to MCP-2, MIP-1 alpha, MIP-1 beta, and RANTES were weaker, and no changes were obtained on stimulation with IL-8 or IP-10. Freshly isolated human blood lymphocytes were also tested, but neither migration nor Ca2+ changes were observed. Low numbers of high-affinity receptors for MCP-1 were found on CD4+ and CD8+ cells ( < 900 per cell, Kd < 1 nM), and desensitization experiments showed that MCP-1, MCP-2, and MCP-3 share receptors. Owing to their superior effectiveness on CD4+ and CD8+ T cells, the monocyte chemotactic proteins could play a major role in the recruitment of activated T lymphocytes.
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              Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates.

              Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels. We used a multiplex, suspension-array-based immunoassay method to measure 10 proinflammatory (interleukin-1beta [IL-1beta], IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-gamma], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens collected via ophthalmic sponge from 72 healthy, nonpregnant women and correlate their levels with biologic and behavioral covariates in a cross-sectional design. Proinflammatory and immunoregulatory cytokines were readily detected, although proinflammatory cytokines were present at markedly higher levels than were immunoregulatory cytokines. Among the covariates examined, the most striking finding was the significant (P < or = 0.05) association between depressed levels of the cytokines IFN-gamma, IL-1beta, IL-6, and IL-10 and cigarette smoking. Also, nonsignificant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomic site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.
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                Author and article information

                Journal
                Int J Fertil Steril
                Int J Fertil Steril
                Royan Institute
                International Journal of Fertility & Sterility
                Royan Institute
                2008-076X
                2008-0778
                Oct-Dec 2019
                14 July 2019
                : 13
                : 3
                : 236-239
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, Mashhad University of Medical Sciences, Mashhad, Iran
                [2 ]Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                [* Corresponding Address: ]P.O.Box: 91778-99191Department of Obstetrics and GynecologyMashhad University of Medical Sciences MashhadIran Email: matin82a@ 123456gmail.com
                Article
                Int-J-Fertil-Steril-13-236
                10.22074/ijfs.2019.5668
                6642431
                31310079
                fdca9ecb-a2a5-42a3-ba7a-dad07409842e
                The Cell Journal (Yakhteh) is an open access journal which means the articles are freely available online for any individual author to download and use the providing address. The journal is licensed under a Creative Commons Attribution-Non Commercial 3.0 Unported License which allows the author(s) to hold the copyright without restrictions that is permitting unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 July 2018
                : 24 December 2018
                Categories
                Original Article
                Cellular and Molecular Biology
                Embryology
                Custom metadata
                Khadem N, Mansoori M, Attaran M, Attaranzadeh A, Zohdi E. Association of IL-1 and TNF-α levels in endometrial secretion and success of embryo transfer in IVF/ICSI cycles. Int J Fertil Steril. 2019; 13(3): 236-239. doi: 10.22074/ijfs.2019.5668.

                embryo transfer,endometrium,il-1/tnf-α,ivf/icsi,receptivity

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