{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:00:52Z","timestamp":1789506052072,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>In women with unexplained infertility (UI) and recurrent in vitro fertilization (IVF) failures, the etiology is often unclear. Endometrial immune perturbations and the use of immune markers associated with these dysregulations are of great interest in the diagnosis and treatment of UI. However, reliable biomarkers and standardized quantification methods are lacking. Here, to address endometrial immune dysregulation in UI patients with recurrent IVF failures, we performed endometrial tissue sampling and immunostaining of CD56 (uNK), CD138, and BCL-6. Of these cases, 57.9% had positive CD56 in the endometrial stroma, while 46.1% had positive BCL-6 in the glandular epithelium, and 14.5% of the cases were found to be positive for CD138. Combined staining rates were 60.5%, 68.4%, and 71.05% for (CD56 or BCL-6), (CD56 or CD138), and (CD56, BCL-6, or CD138), respectively. There was a significant correlation between CD56 and BCL-6 positivity, while CD138 positivity was an independent parameter. After the recommended targeted therapy, pregnancy rates were found to increase from 58.5% to 61.6% and 73.8% in CD56-positive, (CD56- or BCL-6-positive), and (CD56-, BCL-6-, or CD138-positive) cases, respectively. Notably, a retrospective evaluation of digital pathology and light microscopy results showed a significant correlation. This study suggests that the examination of CD56, BCL-6, and CD138 in the same endometrial sample may be an effective method in determining the etiology of UI and reaching an early diagnosis and treatment options. Moreover, digital pathology can be used in the evaluation of CD56 and BCL-6 to provide objective, rapid, and reliable results.<\/jats:p>","DOI":"10.3390\/diagnostics13091557","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T01:28:28Z","timestamp":1682558908000},"page":"1557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7135-0233","authenticated-orcid":false,"given":"Suheyla","family":"Ekemen","sequence":"first","affiliation":[{"name":"Vocational School of Health Services, Kerem Ayd\u0131nlar Campus, Ac\u0131badem University, Istanbul 34752, Turkey"},{"name":"Acibadem Central Pathology Laboratory, Kerem Aydinlar Campus, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1083-7042","authenticated-orcid":false,"given":"Cem","family":"Comunoglu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dr. Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cavit Kerem","family":"Kayhan","sequence":"additional","affiliation":[{"name":"Acibadem Central Pathology Laboratory, Kerem Aydinlar Campus, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5997-9861","authenticated-orcid":false,"given":"Ebru","family":"Bilir","sequence":"additional","affiliation":[{"name":"School of Medicine, Bahcesehir University, Istanbul 34349, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilkay","family":"Cavusoglu","sequence":"additional","affiliation":[{"name":"Women\u2019s Health and Gynecological Nursing, Institute of Health Sciences, Biruni University, Istanbul 34010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5711-3733","authenticated-orcid":false,"given":"Nilay","family":"Etiler","sequence":"additional","affiliation":[{"name":"Department of Public Health, School of Medicine, Istanbul Okan University, Istanbul 34947, Turkey"},{"name":"Public Health Department, University of Nevada, Reno, NV 89509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selcuk","family":"Bilgi","sequence":"additional","affiliation":[{"name":"Acibadem Central Pathology Laboratory, Kerem Aydinlar Campus, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umit","family":"Ince","sequence":"additional","affiliation":[{"name":"Acibadem Central Pathology Laboratory, Kerem Aydinlar Campus, Istanbul 34752, Turkey"},{"name":"Department of Digital Pathology, School of Medicine, Ac\u0131badem University, Istanbul 34752, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-7799","authenticated-orcid":false,"given":"Cevayir","family":"Coban","sequence":"additional","affiliation":[{"name":"Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halit Firat","family":"Erden","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Infertility Clinic, Zorlu Center, Istanbul 34340, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","first-page":"69","article-title":"Diagnosis and treatment of unexplained infertility","volume":"1","author":"Quaas","year":"2008","journal-title":"Rev. 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