{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:00:58Z","timestamp":1785855658074,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>A randomized sibling-embryo pilot trial investigated whether two ways of laser-assisted hatching result in different blastulation and clinical outcomes after extended <jats:italic>in vitro<\/jats:italic> culture process of highly fragmented day-3 cleavage embryos. From 92 couples, a total of 315 highly fragmented day-3 embryos (the fragmentation &amp;gt;25%) were recruited and randomized into laser-assisted zona thinning (LAT, n=157) and opening (LAO, n=158) groups, and then underwent a blastocyst culture <jats:italic>in vitro<\/jats:italic>. The main endpoint measurements including blastocyst formation and grading as well as the clinical pregnancy after blastocyst transfer were obtained during the treatment procedure of <jats:italic>in vitro<\/jats:italic> fertilization and embryo transfer, and then analyzed with generalized estimating equation (GEE) and\/or time-to blastocyst analysis models. A total of 166 day-3 embryos developed into blastocyst stage (52.70%), of which 97 were viable blastocysts (30.79%), and 42 top-quality ones (13.33%). LAT did not have any inferior or superior to LAO in the endpoints of either total, viable, top-quality or hatched blastocyst formation, with the ORs (95%CI) from GEE model as 0.89 (0.55-1.45), 0.71 (0.42-1.21), 1.12 (0.56-2.25) and 0.68 (0.42-1.12) respectively for LAT treatment. And the time-to-blastocyst analysis showed a similar result. Additionally, no difference in clinical outcomes after blastocyst transfer was found between the two groups. The author concluded that when applying the LAHs during the extended culture of highly fragmented embryos, both LAT and LAO can generate a promising clinical outcome, and the LAT operation be equivalent to the LAO. Future well-designed, multiple-center, larger-sample investigations are required to ascertain above conclusion.<\/jats:p>","DOI":"10.3389\/fendo.2022.927834","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T07:25:42Z","timestamp":1656314742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Thinning or Opening: A Randomized Sibling-Embryo Pilot Trial on the Efficacy of Two Laser-Assisted Hatching Modes During the Extended Culture of Highly Fragmented Cleavage Embryos"],"prefix":"10.3389","volume":"13","author":[{"given":"Ling","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-er","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-jin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-mei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-shi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-yi","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-hai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(01)01904-5","article-title":"Embryo Fragmentation In Vitro and Its Impact on Treatment and Pregnancy Outcome","volume":"76","author":"Ebner","year":"2001","journal-title":"Fertil Steril"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2006.01.048","article-title":"Predictors of Embryo Fragmentation and Outcome After Fragment Removal in In Vitro Fertilization","volume":"86","author":"Keltz","year":"2006","journal-title":"Fertil Steril"},{"key":"B3","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13048-021-00844-7","article-title":"Laser-Assisted Hatching in Lower Grade Cleavage Stage Embryos Improves Blastocyst Formation: Results From a Retrospective Study","volume":"14","author":"Xu","year":"2021","journal-title":"J Ovarian Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1016\/j.ajog.2005.02.048","article-title":"Embryo Fragmentation as a Determinant of Blastocyst Development In Vitro and Pregnancy Outcomes Following Embryo Transfer","volume":"192","author":"Stone","year":"2005","journal-title":"Am J obstet gynecol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.03.014","article-title":"Defragmentation of Low Grade Day 3 Embryos Resulted in Sustained Reduction in Fragmentation, But did Not Improve Compaction or Blastulation Rates","volume":"94","author":"Keltz","year":"2010","journal-title":"Fertil Steril"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-016-0806-1","article-title":"Ultrastructure of Cytoplasmic Fragments in Human Cleavage Stage Embryos","volume":"33","author":"Halvaei","year":"2016","journal-title":"J Assisted Reprod Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2018.12.011","article-title":"Laser Technology in the ART Laboratory: A Narrative Review","volume":"38","author":"Davidson","year":"2019","journal-title":"Reprod BioMed Online."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a138781","article-title":"Fertilization and Early Embryology: Use of Lasers in Assisted Fertilization and Hatching","volume":"9","author":"Obruca","year":"1994","journal-title":"Hum Reproduction."},{"key":"B9","doi-asserted-by":"publisher","first-page":"37","DOI":"10.12891\/ceog16092014","article-title":"A Study Comparing Three Different Laser-Assisted Hatching Techniques","volume":"41","author":"Ma","year":"2014","journal-title":"Clin Exp Obstet Gynecol."},{"key":"B10","article-title":"[Impact of Laser-Assisted Hatching (Quarter Technique) in Poor Prognosis Patients]","volume":"83","author":"Gonz\u00e1lez-Ortega","year":"2015","journal-title":"Ginecologia y obstetricia Mexico"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3892\/br.2016.716","article-title":"Outcomes of Vitrified-Warmed Cleavage-Stage Embryo Hatching After In Vitro Laser-Assisted Zona Pellucida Thinning in Patients","volume":"5","author":"Wang","year":"2016","journal-title":"Biomed Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.5653\/cerm.2015.42.2.51","article-title":"Effect of Laser-Assisted Multi-Point Zona Thinning on Development and Hatching of Cleavage Embryos in Mice","volume":"42","author":"Lee","year":"2015","journal-title":"Clin Exp Reprod Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.5.1331","article-title":"Rescue of Implantation Potential in Embryos With Poor Prognosis by Assisted Zona Hatching","volume":"13","author":"Magli","year":"1998","journal-title":"Hum Reproduction."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.9.1959","article-title":"Laser Zona Pellucida Thinning\u2014an Alternative Approach to Assisted Hatching","volume":"16","author":"Blake","year":"2001","journal-title":"Hum Reproduction."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000016734","article-title":"Zona Hardening, Zona Drilling and Assisted Hatching: New Achievements in Assisted Reproduction","volume":"166","author":"De Vos","year":"2000","journal-title":"Cells Tissues Organs"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.5653\/cerm.2018.45.3.129","article-title":"Thinning and Drilling Laser-Assisted Hatching in Thawed Embryo Transfer: A Randomized Controlled Trial","volume":"45","author":"Le","year":"2018","journal-title":"Clin Exp Reprod Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-019-02787-4","article-title":"Effects of Laser-Assisted Thinning Versus Opening on Clinical Outcomes According to Maternal Age in Patients With Repeated Implantation Failure","volume":"34","author":"Lee","year":"2019","journal-title":"Lasers Med Science"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2007.05.016","article-title":"Randomized Double-Blind Comparison of Laser Zona Pellucida Thinning and Breaching in Frozen Thawed Embryo Transfer at the Cleavage Stage","volume":"89","author":"Ng","year":"2008","journal-title":"Fertil Steril"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.10.2182","article-title":"A Comparison Between Quarter, Partial and Total Laser Assisted Hatching in Selected Infertility Patients","volume":"16","author":"Mantoudis","year":"2001","journal-title":"Hum Reprod (Oxford England)."},{"key":"B20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1477-7827-11-21","article-title":"Effects of Partial or Complete Laser-Assisted Hatching on the Hatching of Mouse Blastocysts and Their Cell Numbers","volume":"11","author":"Chailert","year":"2013","journal-title":"Reprod Biol Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.05.048","article-title":"Use of a Zona Laser Treatment System in Assisted Hatching: Optimal Laser Utilization Parameters","volume":"84","author":"Tinney","year":"2005","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2011.02.001","article-title":"The Istanbul Consensus Workshop on Embryo Assessment: Proceedings of an Expert Meeting\u2020","volume":"26","year":"2011","journal-title":"Hum Reproduction."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0578.2006.00145.x","article-title":"Assisted Hatching Using a 1.48-\u00b5m Diode Laser: Evaluation of Zona Opening and Zona Thinning Techniques in Human Embryos","volume":"5","author":"Yano","year":"2006","journal-title":"Reprod Med Biol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1097\/00001703-199906000-00013","article-title":"Culture and Transfer of Human Blastocysts","volume":"11","author":"Gardner","year":"1999","journal-title":"Curr Opin Obstet Gynec"},{"key":"B25","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1097\/EDE.0b013e31821b5351","article-title":"Analysis of Multiple-Cycle Data From Couples Undergoing In Vitro Fertilization: Methodologic Issues and Statistical Approaches","volume":"22","author":"Missmer","year":"2011","journal-title":"Epidemiology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2007.03.008","article-title":"Weighting Condom Use Data to Account for Nonignorable Cluster Size","volume":"17","author":"Williamson","year":"2007","journal-title":"Ann Epidemiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.11.033","article-title":"Pathogenesis, Developmental Consequences, and Clinical Correlations of Human Embryo Fragmentation","volume":"95","author":"Fujimoto","year":"2011","journal-title":"Fertil Steril"},{"key":"B28","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.fertnstert.2014.10.031","article-title":"Fragmentation of Human Cleavage-Stage Embryos is Related to the Progression Through Meiotic and Mitotic Cell Cycles","volume":"103","author":"Stensen","year":"2015","journal-title":"Fertil Steril"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.12.2634","article-title":"Cleavage Anomalies in Early Human Embryos and Survival After Prolonged Culture in-Vitro","volume":"15","author":"Alikani","year":"2000","journal-title":"Hum Reprod (Oxford England)."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.010090","article-title":"Maintenance of the Inner Cell Mass in Human Blastocysts From Fragmented Embryos","volume":"68","author":"Hardy","year":"2003","journal-title":"Biol Reproduction."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dei242","article-title":"Epithelial Cadherin Distribution in Abnormal Human Pre-Implantation Embryos","volume":"20","author":"Alikani","year":"2005","journal-title":"Hum Reprod"},{"key":"B32","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1093\/humrep\/13.4.998","article-title":"Detection of Reactive Oxygen Species (ROS) and Apoptosis in Human Fragmented Embryos","volume":"13","author":"Yang","year":"1998","journal-title":"Hum Reproduction."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.4.719","article-title":"A Microscopic and Biochemical Study of Fragmentation Phenotypes in Stage-Appropriate Human Embryos","volume":"16","author":"Van Blerkom","year":"2001","journal-title":"Hum Reprod"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gag016","article-title":"Expression of Apoptosis-Related Genes During Human Preimplantation Embryo Development: Potential Roles for the Harakiri Gene Product and Caspase-3 in Blastomere Fragmentation","volume":"9","author":"Jurisicova","year":"2003","journal-title":"Mol Hum Reprod"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.2.429","article-title":"Temporal and Spatial Aspects of Fragmentation in Early Human Embryos: Possible Effects on Developmental Competence and Association With the Differential Elimination of Regulatory Proteins From Polarized Domains","volume":"14","author":"Antczak","year":"1999","journal-title":"Hum Reprod (Oxford England)."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.14.5444","article-title":"Abnormal Development and Dye Coupling Produced by Antisense RNA to Gap Junction Protein in Mouse Preimplantation Embryos","volume":"86","author":"Bevilacqua","year":"1989","journal-title":"Proc Natl Acad Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201407064","article-title":"Getting to Know Your Neighbor: Cell Polarization in Early Embryos","volume":"206","author":"Nance","year":"2014","journal-title":"J Cell Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(99)00092-8","article-title":"Human Embryo Fragmentation In Vitro and its Implications for Pregnancy and Implantation","volume":"71","author":"Alikani","year":"1999","journal-title":"Fertil Steril"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5653\/cerm.2018.45.3.122","article-title":"Early Fragment Removal on In Vitro Fertilization Day 2 Significantly Improves the Subsequent Development and Clinical Outcomes of Fragmented Human Embryos","volume":"45","author":"Kim","year":"2018","journal-title":"Clin Exp Reprod Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s10103-018-2681-8","article-title":"The Impacts of Laser Zona Thinning on Hatching and Implantation of Vitrified-Warmed Mouse Embryos","volume":"34","author":"Huang","year":"2019","journal-title":"Lasers Med Science"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7501","article-title":"Practical Recommendations for Reporting Fine-Gray Model Analyses for Competing Risk Data","volume":"36","author":"Austin","year":"2017","journal-title":"Stat Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840070628","article-title":"Multivariate Survival Analysis Using Cox's Regression Model","volume":"7","author":"Christensen","year":"1987","journal-title":"Hepatology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.927834\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T07:25:45Z","timestamp":1656314745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.927834\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":42,"alternative-id":["10.3389\/fendo.2022.927834"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.927834","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]},"article-number":"927834"}}