{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:45:12Z","timestamp":1792799112256,"version":"4.5.0"},"reference-count":93,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>After more than four decades of assisted reproductive technology (ART) practice worldwide, today more than 60% of women undergoing in vitro fertilization (IVF) treatments fail to become pregnant after the first embryo transfer and nearly 20% of patients are suffering from unexplained recurrent implantation failures (RIFs) and repeated pregnancy loss (RPL). The literature reported different causes of RIF\u2013RPL, mainly multifactorial, endometrial and idiopathic. RIF remains a black box because of the complicated categorization and causes of this physio-pathological dysregulation of implantation and pregnancy process after ovarian stimulation. Many options were suggested as solutions to treat RIF\u2013RPL with controversial results on their usefulness. In this article, we reviewed different possible therapeutic options to improve implantation rates and clinical outcomes. Based on our experience we believe that endometrium immunomodulation after intrauterine insemination of activated autologous peripheral blood mononuclear cells (PBMCs) or platelet-rich plasma (PRP) can be a promising therapeutic solution. On the other hand, peripheral lymphocyte balance typing, specific cytokines and interleukins profiling can be proposed as predictive biomarkers of implantation before embryo transfer.<\/jats:p>","DOI":"10.3390\/ijms232112787","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T06:37:45Z","timestamp":1666593465000},"page":"12787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Endometrium Immunomodulation to Prevent Recurrent Implantation Failure in Assisted Reproductive Technology"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2798-4930","authenticated-orcid":false,"given":"Mustapha","family":"Benkhalifa","sequence":"first","affiliation":[{"name":"HB Laboratory, Tunis TN 1007, Tunisia"},{"name":"Faculty of Sciences of Bizerte, University of Carthage, Bizerte TN 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Joao","sequence":"additional","affiliation":[{"name":"Fertilys Reproductive Center, Laval, QC H7S 1Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Duval","sequence":"additional","affiliation":[{"name":"Fertilys Reproductive Center, Laval, QC H7S 1Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Montjean","sequence":"additional","affiliation":[{"name":"Fertilys Reproductive Center, Laval, QC H7S 1Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-5701","authenticated-orcid":false,"given":"Molka","family":"Bouricha","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Reproductive Biology & Genetics, University Hospital and School of Medicine Picardie University Jules Verne, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Cabry","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Reproductive Biology & Genetics, University Hospital and School of Medicine Picardie University Jules Verne, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Claire","family":"B\u00e9langer","sequence":"additional","affiliation":[{"name":"Fertilys Reproductive Center, Laval, QC H7S 1Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem","family":"Bahri","sequence":"additional","affiliation":[{"name":"HB Laboratory, Tunis TN 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-2369","authenticated-orcid":false,"given":"Pierre","family":"Miron","sequence":"additional","affiliation":[{"name":"Fertilys Reproductive Center, Laval, QC H7S 1Z5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moncef","family":"Benkhalifa","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Reproductive Biology & Genetics, University Hospital and School of Medicine Picardie University Jules Verne, 80054 Amiens, France"},{"name":"PeriTox Laboratory, CURS, Amiens Sud, 80480 Salou\u00ebl, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/14789450.2018.1464915","article-title":"Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?","volume":"15","author":"Benkhalifa","year":"2018","journal-title":"Expert Rev. 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