{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:34:15Z","timestamp":1780569255712,"version":"3.54.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"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:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this retrospective cohort study was to evaluate the clinical and neonatal outcomes between day 4 and day 5 embryo transfer across different fertilization methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study was conducted between January 2018 and March 2023, enrolling a total of 1,245 fresh embryo transfer cycles, including 1,023\n                      <jats:italic>in vitro<\/jats:italic>\n                      fertilization (IVF) cycles and 222 intracytoplasmic sperm injection (ICSI) cycles. Among these, IVF cycles included 793 day 4 transfers and 230 day 5 transfers; ICSI cycles included 179 day 4 transfers and 43 day 5 transfers. The study conducted a comparative analysis of clinical pregnancy outcomes between day 4 and day 5 transfers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In IVF or ICSI cycles, no significant differences were found in clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), or other clinical outcomes between transfers of day 4 and day 5 embryos (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). In IVF cycles with single high-quality embryo transfer, the CPR (62.72%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.026), gestational week of delivery (39 weeks,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.026) of day 4 were significantly higher than day 5 (38 weeks). After controlling for potential confounding factors, the CPR of the day 4 group was also higher than day 5 (OR 0.578, 95% CI 0.352-0.949,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.030). In IVF or ICSI cycles with day 4 high-quality embryo transfer, the LBR (63.06%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006; 70.37%,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006) and multiple pregnancy rate (MPR; 53.29%,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001; 50%,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001) of transferring double high-quality embryo were significantly higher than transferring single high-quality embryo (LBR: 50.87%, 44.23%; MPR: 0%, 3.23%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In IVF or ICSI cycles, day 4 embryo transfer is considered a viable option or alternative to day 5 blastocyst transfer with no difference in clinical and neonatal outcomes. In IVF cycles with single high embryo transfer, day 4 transfer is recommended due to its significantly higher pregnancy rate compared to day 5 transfer. To reducing MPRs and preterm birth rates (PBRs), day 4 single embryo transfer is recommended if embryos achieve high-quality grade (full compaction) on day 4.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1740765","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T07:45:56Z","timestamp":1773647156000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative outcomes of day 4 versus day 5 embryo transfers by fertilization method"],"prefix":"10.3389","volume":"17","author":[{"given":"Lin-Lin","family":"Tao","sequence":"first","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasong","family":"Geng","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Yang","family":"Dai","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Fang","family":"Dai","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-017-0535-6","article-title":"Propensity score-matched study and meta-analysis of cumulative outcomes of day 2\/3 versus day 5\/6 embryo transfers","volume":"11","author":"Yin","year":"2017","journal-title":"Front Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey047","article-title":"Single embryo transfer by Day 3 time-lapse selection versus Day 5 conventional morphological selection: a randomized, open-label, non-inferiority trial","volume":"33","author":"Yang","year":"2018","journal-title":"Hum Reprod"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.8.1781","article-title":"Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro","volume":"15","author":"Magli","year":"2000","journal-title":"Hum Reprod"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(01)01771-x","article-title":"A comparison of day 5 and day\u00a06 blastocyst transfers","volume":"75","author":"Shapiro","year":"2001","journal-title":"Fertil Steril"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew219","article-title":"Cumulative live birth rates after fresh and vitrified cleavage-stage versus blastocyst-stage embryo transfer in the first treatment cycle","volume":"31","author":"De Vos","year":"2016","journal-title":"Hum Reprod"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002118.pub6","article-title":"Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology","volume":"30","author":"Glujovsky","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/332459a0","article-title":"Human gene expression first occurs between the four-and eight-cell stages of preimplantation development","volume":"332","author":"Braude","year":"1988","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2018.08.016","article-title":"Early blastulation (EB) of day 4 embryo is predictive of outcomes in single embryo transfer (SET) cycles","volume":"57","author":"Hsieh","year":"2018","journal-title":"Taiwan J Obstet Gynecol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/4.4.440","article-title":"Uterine junctional zone contractions during assisted reproduction cycles","volume":"4","author":"Lesny","year":"1998","journal-title":"Hum Reprod Upd"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s1472-6483(10)62088-3","article-title":"Effect of culture environment on embryo quality and gene expression - experience from animal studies","volume":"7","author":"Lonergan","year":"2003","journal-title":"Reprod BioMed Online"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/17.6.1513","article-title":"The neglected morula\/compact stage embryo transfer","volume":"17","author":"Tao","year":"2002","journal-title":"Hum Reprod"},{"key":"B12","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.rbmo.2022.03.019","article-title":"Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers","volume":"45","author":"Tartia","year":"2022","journal-title":"Reprod BioMed Onl"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1004-3845.2019.08.007","article-title":"Pregnancy outcomes of day 4 or day 5 embryo transfer in IVF-ET cycles","volume":"28","author":"Xin","year":"2019","journal-title":"J Reprod Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e928737","DOI":"10.12659\/MSM.928737","article-title":"Comparison of pregnancy outcomes between single-Morula embryo transfer and single-blastocyst transfer in fresh IVF\/ICSI Cycles","volume":"27","author":"Zhang","year":"2021","journal-title":"Med Sci Monit"},{"key":"B15","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1186\/s12884-024-06597-7.PMID:38961359","article-title":"Comparison of pregnancy outcomes between 4th day morula and 5th day blastocyst after embryo transfer: a retrospective cohort study","volume":"24","author":"Sun","year":"2024","journal-title":"BMC Preg Childb"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2017.12.008","article-title":"Day 4 good morula embryo transfer provided compatible live birth rate with day 5 blastocyst embryo in fresh IVF\/ET cycles","volume":"57","author":"Li","year":"2018","journal-title":"Taiwan J Obstet Gynecol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14134596","article-title":"Day 4 versus day 5 fresh embryo transfer in in vitro fertilization: is it all about timing","volume":"14","author":"\u015ei\u015fmano\u011flu","year":"2025","journal-title":"J Clin Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der037","article-title":"The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting","volume":"26","year":"2011","journal-title":"Hum Reprod"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/3.4.367","article-title":"Culture and selection of viable blastocysts: a feasible proposition for human IVF","volume":"3","author":"Gardner","year":"1997","journal-title":"Hum Reprod Update"},{"key":"B20","article-title":"Evaluation of day 4 embryonic development potential and its application in assisted reproduction","volume":"32","author":"Dai","year":"2023","journal-title":"J Reprod Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1016\/j.fertnstert.2011.09.015","article-title":"Prediction of human blastocyst development from morulas with delayed and\/or incomplete compaction","volume":"96","author":"Ivec","year":"2011","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2015.09.016","article-title":"Should we be promoting embryo transfer at blastocyst stage","volume":"32","author":"Maheshwari","year":"2016","journal-title":"Reprod BioMed Online"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoab010","article-title":"Endometrial Receptivity Analysis (ERA) test: an unproven technology","volume":"2021","author":"Ben Rafael","year":"2021","journal-title":"Hum Reprod Open"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab123","article-title":"Global transcriptomic changes occur in uterine fluid-derived extracellular vesicles during the endometrial window for embryo implantation","volume":"36","author":"Giacomini","year":"2021","journal-title":"Hum Reprod"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00298","article-title":"Novel techniques of sperm selection for improving IVF and ICSI outcomes","volume":"7","author":"Oseguera-L\u00f3pez","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-018-1358-3","article-title":"In assisted reproduction by IVF or ICSI, the rate at which embryos develop to the blastocyst stage is influenced by the fertilization method used: a split IVF\/ICSI study","volume":"36","author":"Speyer","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/srep03894","article-title":"Uterine selection of human embryos at implantation","volume":"4","author":"Brosens","year":"2014","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1095\/biolreprod.114.122846","article-title":"The human endometrium as a sensor of embryo quality","volume":"91","author":"Macklon","year":"2014","journal-title":"Biol Reprod"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e10258","DOI":"10.1371\/journal.pone.0010258","article-title":"Natural selection of human embryos: decidualizing endometrial stromal cells serve as sensors of embryo quality upon implantation","volume":"5","author":"Teklenburg","year":"2010","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e41424","DOI":"10.1017\/S2040174417000228","article-title":"Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high-and low-quality human embryos","volume":"7","author":"Weimar","year":"2012","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1017\/S2040174417000228","article-title":"The health outcomes of human offspring conceived by assisted reproductive technologies (ART)","volume":"8","author":"Chen","year":"2017","journal-title":"J Dev Orig Health Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2020.06.013","article-title":"Reduction of multiple pregnancy: counselling and techniques","volume":"70","author":"Sebghati","year":"2021","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2019.03.203","article-title":"A meta-analysis of pregnancy-related outcomes and complications in women with polycystic ovary syndrome undergoing IVF","volume":"39","author":"Sha","year":"2019","journal-title":"Reprod BioMed Onl"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn101441-20200702-00374","article-title":"Research progress of pregnancy complications,pregnancy outcomes and offspring health of women with polycystic ovary syndrome","volume":"42","author":"Zhou","year":"2022","journal-title":"Chin J Reprod Contracept"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6909a1","article-title":"Assisted reproductive technology surveillance-United States, 2017","volume":"69","author":"Sunderam","year":"2020","journal-title":"MMWR Surveill Summ"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-020-01708-7","article-title":"Morula transfer achieves better clinical outcomes than post-thawed cleavage embryos after overnight culture in frozen embryo transfer (FET) cycles","volume":"37","author":"Hui","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.02.107","article-title":"Guidance on the limits to the number of embryos to transfer: a committee opinion","volume":"107","year":"2017","journal-title":"Fertil Steril"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaf028","article-title":"Effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from the UK HFEA registry","volume":"40","author":"Tighe","year":"2025","journal-title":"Hum Reprod"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-12-54","article-title":"Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles","volume":"12","author":"Desai","year":"2014","journal-title":"Reprod Biol Endocrinol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2018.05.016","article-title":"Time-lapse imaging algorithms rank human preimplantation embryos according to the probability of live birth","volume":"37","author":"Fishel","year":"2018","journal-title":"Reprod BioMed Onl"},{"key":"B41","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1093\/humrep\/deaf021","article-title":"The Istanbul consensus update: a revised ESHRE\/ALPHA consensus on oocyte and embryo static and dynamic morphological assessment","volume":"40","author":"Coticchio","year":"2025","journal-title":"Hum Reprod"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1740765\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:58:59Z","timestamp":1773766739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1740765\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":41,"alternative-id":["10.3389\/fendo.2026.1740765"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1740765","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]},"article-number":"1740765"}}