{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:08:50Z","timestamp":1790690930293,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale\/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70\u201385%, specificity 88\u201392%) compared to biopsy. Other significant factors include the high rates of amplification failure (10\u201350%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons. Wider Implications: The integration of niPGT with artificial intelligence, time-lapse imaging, and multi-omics profiling underlies a promising future. However, its transition from a predominantly research tool to a clinical standard necessitates various critical undertakings. These include rigorous multicenter RCTs, standardizing international protocol, and tailoring validation for the RPL and RIF subgroups. This review highlights the need for cautious optimism, positing that evidence-based integration, rather than premature adoption, is essential to realizing niPGT\u2019s full potential without compromising patient care in these complex fertility scenarios.<\/jats:p>","DOI":"10.3390\/cells14201591","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T10:37:14Z","timestamp":1760438234000},"page":"1591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Noninvasive Preimplantation Genetic Testing in Recurrent Pregnancy Loss and Implantation Failure: Breakthrough or Overpromise?"],"prefix":"10.3390","volume":"14","author":[{"given":"Grzegorz","family":"Mrugacz","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Bia\u0142ystok Branch, 26 Akademicka St., 15-267 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0833-0197","authenticated-orcid":false,"given":"Aleksandra","family":"Mospinek","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, \u0141\u00f3d\u017a Branch, 157a Piotrkowska St., 90-440 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"G\u0142owacka","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Pozna\u0144 Branch, 77a D\u0105browskiego St., 60-529 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"Sprawski","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Pozna\u0144 Branch, 77a D\u0105browskiego St., 60-529 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Kawa\u0142ek","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Lublin Branch, 26 Relaksowa St., 20-819 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiktoria","family":"G\u0105sior","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Lublin Branch, 26 Relaksowa St., 20-819 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julita","family":"Macha\u0142owska","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Szczecin Branch, 1 Brama Portowa Sq, 70-225 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yekaterina","family":"Sidorova","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Szczecin Branch, 1 Brama Portowa Sq, 70-225 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Borecka","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Bia\u0142ystok Branch, 26 Akademicka St., 15-267 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Bojanowska","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Bia\u0142ystok Branch, 26 Akademicka St., 15-267 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Szczepa\u0144ska","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine Bocian, Gda\u0144sk Branch, 103a Grunwaldzka Ave, 80-236 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e39584","DOI":"10.1016\/j.heliyon.2024.e39584","article-title":"Revolutionized attitude toward recurrent pregnancy loss and recurrent implantation failure based on precision regenerative medicine","volume":"10","author":"Asghari","year":"2024","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1515\/mr-2022-0030","article-title":"Understanding recurrent pregnancy loss: Recent advances on its etiology, clinical diagnosis, and management","volume":"2","author":"Cao","year":"2022","journal-title":"Med. 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