{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T20:19:17Z","timestamp":1785788357213,"version":"3.56.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T00:00:00Z","timestamp":1560816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Previously, we reported the clinical efficacy of tacrolimus in women with repeated implantation failures (RIF) of immune etiologies. Safety of tacrolimus in pregnant women has been reported in women with organ transplantations. However, the safety of tacrolimus for women with RIF undergoing assisted reproductive technology cycles and their babies has not been reported prior.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>This study is a prospective observational study of 109 women with RIF or recurrent pregnancy losses (RPL) who showed elevated peripheral blood Th1\/Th2 (CD4<jats:sup>+<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup>IL\u20104<jats:sup>+<\/jats:sup>) cell ratios (\u226510.3). All received tacrolimus before and during pregnancy (1\u20104\u00a0mg\/d) and delivered a live\u2010born infant(s). Blood concentrations of tacrolimus were measured. Neuromotor development of the babies was also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total 113 babies were born from 109 women, including four twin pregnancies. Nine pregnancies including four twins were delivered prematurely (8.3%). Two of 109 women showed obstetric complications, such as hypertensive disorder of pregnancy, and only one baby (0.9%) had a congenital abnormality. There were no differences in babies' birthweight, placental weight, and lymphocyte proportion (%) of the umbilical cord among the women with different tacrolimus dosing. Tacrolimus was detected in the maternal plasma, and its concentration did not significantly fluctuate during pregnancy while on daily administration regimen. Neuromotor development of the babies exposed to tacrolimus in utero was comparable with that of babies from the general population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>According to our data, tacrolimus treatment for women with RIF and RPL was not associated with obstetrical and perinatal complications. A large size study is needed to confirm this finding.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13142","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T15:05:15Z","timestamp":1557759915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Obstetric and perinatal outcome of the women with repeated implantation failures or recurrent pregnancy losses who received pre\u2010 and post\u2010conception tacrolimus treatment"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-5894","authenticated-orcid":false,"given":"Koji","family":"Nakagawa","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine and Implantation Research Sugiyama Clinic Shinjuku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Kwak\u2010Kim","sequence":"additional","affiliation":[{"name":"Reproductive Medicine and Immunology, Department of Obstetrics and Gynecology Chicago Medical School at Rosalind Franklin University of Medicine and Science Vernon Hills Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michi","family":"Hisano","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2010Fetal Biology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimitsu","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Division of Obstetrics Sugiyama Clinic Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Implantation Research Sugiyama Clinic Shinjuku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikikazu","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Implantation Research Sugiyama Clinic Shinjuku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9471-1078","authenticated-orcid":false,"given":"Koushi","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2010Fetal Biology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deg156"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12338"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12040"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12234"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2012.01116.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000117564.50117.FB"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000084823.89528.89"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14737"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.12328"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12682"},{"issue":"1","key":"e_1_2_7_12_1","first-page":"i117","article-title":"T helper I cell is associated with reproductive outcome of women with repeated implantation failures who received Tacrolimus treatment","volume":"33","author":"Nakagawa K","year":"2018","journal-title":"Hum Reprod"},{"key":"e_1_2_7_13_1","first-page":"905","article-title":"Safety of tacrolimus in pregnancy","volume":"60","author":"Nevers W","year":"2014","journal-title":"Can Fam Physician"},{"key":"e_1_2_7_14_1","first-page":"1381","volume-title":"Drugs in Pregnancy and Lactation","author":"Briggs GG","year":"2011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2015.04.041"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12137"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00829.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13097"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-015-3815-x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13518"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2017.10.048"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(97)70200-2"},{"key":"e_1_2_7_23_1","unstructured":"Notional growth survey on preschool children in 2010. 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