{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:19:43Z","timestamp":1790363983648,"version":"4.1.0"},"reference-count":308,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"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>Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed\/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos\u2019 arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field.<\/jats:p>","DOI":"10.3390\/ijms22158353","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T02:16:07Z","timestamp":1628043367000},"page":"8353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research"],"prefix":"10.3390","volume":"22","author":[{"given":"Konstantinos","family":"Sfakianoudis","sequence":"first","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-166X","authenticated-orcid":false,"given":"Evangelos","family":"Maziotis","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"},{"name":"Department of Physiology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Karantzali","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Kokkini","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-8701","authenticated-orcid":false,"given":"Sokratis","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Pantou","sequence":"additional","affiliation":[{"name":"Genesis Genoma Lab, Genetic Diagnosis, Clinical Genetics & Research, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Giannelou","sequence":"additional","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"},{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Petroutsou","sequence":"additional","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Markomichali","sequence":"additional","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fakiridou","sequence":"additional","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koutsilieris","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Asimakopoulos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Pantos","sequence":"additional","affiliation":[{"name":"Centre for Human Reproduction, Genesis Athens Clinic, 14\u201316 Papanikoli, 15232 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-9100","authenticated-orcid":false,"given":"Mara","family":"Simopoulou","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/humrep\/dey091","article-title":"Should Extended Blastocyst Culture Include Day 7?","volume":"33","author":"Hammond","year":"2018","journal-title":"Hum. 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