{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:35:00Z","timestamp":1785342900756,"version":"3.55.0"},"reference-count":61,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Geburtshilfe Frauenheilkd"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients.<\/jats:p><jats:p>\n          Materials and Methods Ten RIF patients with elevated T-helper 1\/T-helper 2 (Th1\/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-\u03b3) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated.<\/jats:p><jats:p>\n          Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-\u03b3, and the IFN-\u03b3\/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1\/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate.<\/jats:p><jats:p>\n          Conclusions Our findings suggest that RIF patients with a higher Th1\/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.<\/jats:p>","DOI":"10.1055\/a-1056-3148","type":"journal-article","created":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T23:06:49Z","timestamp":1597446409000},"page":"851-862","source":"Crossref","is-referenced-by-count":23,"title":["Tacrolimus Improves the Implantation Rate in Patients with Elevated Th1\/2 Helper Cell Ratio and Repeated Implantation Failure (RIF)"],"prefix":"10.1055","volume":"80","author":[{"given":"Zahra","family":"Bahrami-Asl","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran"},{"name":"Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), ISS LaFe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laya","family":"Farzadi","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran"},{"name":"Women\u02bcs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Fattahi","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran"},{"name":"Women\u02bcs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Quinonero","sequence":"additional","affiliation":[{"name":"Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), ISS LaFe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvin","family":"Hakimi","sequence":"additional","affiliation":[{"name":"Women\u02bcs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Latifi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Reza","family":"Nejabati","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohid","family":"Ghasemnejad","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aydin Raei","family":"Sadigh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hassan","family":"Heidari","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Nouri","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran"},{"name":"Institute for Stem Cell and Regenerative Medicine, Tabriz University of Medical Sciences, Tabriz, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marefat Ghaffari","family":"Novin","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), ISS LaFe, Valencia, 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