{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:52:14Z","timestamp":1781869934317,"version":"3.54.5"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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>To evaluate the impact of day 4 double embryo transfer (DET) with a fully compacted morula (FCM) and a partially compacted morula (PCM) versus day 4 single embryo transfer (SET) with an FCM on clinical and neonatal outcomes in fresh cycles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a retrospective cohort study including 889 fresh day 4 embryo transfer cycles conducted between October 2018 and December 2024. Propensity score matching (PSM) was applied to control for potential confounders and compare the clinical outcomes between SET with FCM and DET with FCM and PCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After PSM, logistic regression analysis showed no significant differences in clinical pregnancy rate (CPR), miscarriage rate, live birth rate (LBR), cumulative live birth rate (CLBR), monozygotic twin rate, stillbirth rate, and cesarean section rate (CSR) (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). However, the DET with FCM and PCM group was associated with a significantly higher multiple pregnancy rate (MPR) (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and preterm delivery rate (PDR) (OR 4.02, 95% CI 1.75\u20139.22;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001) after matching. Among patients aged&amp;lt;35 years or undergoing IVF, the pregnancy and neonatal outcomes were consistent with the overall data presented above. Specifically, following logistic regression analysis, there were no significant differences in CPR, LBR, and CLBR between the two groups(all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05), but the MPR in the DET with FCM and PCM group was significantly higher(all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt;0.001). Furthermore, after excluding early-stage blastocysts, the clinical and neonatal outcomes remained consistent with the main study findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In fresh cycles, there were no significant differences in CPR, LBR and CLBR following day 4 DET with FCM and PCM compared with SET with FCM. However, the MPR was significantly higher in the DET group. SET with FCM may be a preferable strategy for balancing clinical and multiple pregnancy rates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1776207","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:19:24Z","timestamp":1780287564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical outcomes of co-transfer of partially and fully compacted morulae versus a fully compacted morula alone on day 4"],"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, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, 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, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Song","family":"Geng","sequence":"additional","affiliation":[{"name":"Reproductive Center, Xingtai Meihe Reproductive and Genetic Hospital","place":["Xingtai, Hebei, 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, Hebei, 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, Hebei, 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, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital","place":["Shijiazhuang, Hebei, 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":"Lingyin","family":"Kong","sequence":"additional","affiliation":[{"name":"Basecare Medical Device Co., Ltd.","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoaa034","article-title":"A stepwise approach to move from a cleavage-stage to a blastocyst-stage transfer policy for all patients in the IVF clinic","volume":"2020","author":"De Croo","year":"2020","journal-title":"Hum Reprod Open"},{"key":"B3","doi-asserted-by":"publisher","first-page":"CD002118","DOI":"10.1002\/14651858.cd002118.pub4","article-title":"Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology","volume":"2016","author":"Glujovsky","year":"2016","journal-title":"Cochrane Database Syst Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00247-x","article-title":"Pregnancy outcomes of single\/double blastocysts and cleavage embryo transfers: a retrospective cohort study of 24,422 frozen-thawed cycles","volume":"27","author":"Long","year":"2020","journal-title":"Reprod Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2016.11.008","article-title":"Embryos with morphokinetic abnormalities may develop into euploid blastocysts","volume":"34","author":"Lagalla","year":"2017","journal-title":"Reprod BioMed Online"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu018","article-title":"Metabolic heterogeneity during preimplantation development: the missing link","volume":"20","author":"Brison","year":"2014","journal-title":"Hum Reprod Update"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1242\/dev.064741","article-title":"Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development","volume":"138","author":"Vassena","year":"2011","journal-title":"Development"},{"key":"B8","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":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1186\/s12884-024-06597-7","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 Pregnancy Childbirth"},{"key":"B11","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":"B12","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":"B13","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":"B14","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 Online"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.8.1856","article-title":"Multiple gestation pregnancy","volume":"15","year":"2000","journal-title":"Hum Reprod (Oxford England)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/s0029-7844(02)01986-5","article-title":"Guidance on the limits to the number of embryos to transfer: a committee opinion","volume":"116","year":"2021","journal-title":"Fertil Steril"},{"key":"B17","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":"B18","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":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/aog.0000000000000106","article-title":"Number of embryos transferred after in vitro fertilization and good perinatal outcome","volume":"123","author":"Kissin","year":"2014","journal-title":"Obstet Gynecol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"20(1):20","DOI":"10.1186\/s12958-022-00899-1","article-title":"Comparisons of benefits and risks of single embryo transfer versus double embryo transfer: a systematic review and meta-analysis","volume":"27","author":"Ma","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd003416.pub5","article-title":"Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection","volume":"8","author":"Kamath","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12097","article-title":"Morphologically poor blastocysts could affect the implantation rate of a morphologically good blastocyst during a double-blastocyst transfer for patients who have experienced repeated implantation failures","volume":"17","author":"Ohgi","year":"2018","journal-title":"Reprod Med Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hox020","article-title":"The addition of a low-quality embryo as part of a fresh day 3 double embryo transfer does not improve ongoing pregnancy rates","volume":"2017","author":"Berkhout","year":"2017","journal-title":"Hum Reprod Open"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2022.08.848","article-title":"Transfer of a poor-quality along with a good-quality embryo on in vitro fertilization\/intracytoplasmic sperm injection-embryo transfer clinical outcomes: a systematic review and meta-analysis","volume":"118","author":"Xiao","year":"2022","journal-title":"Fertil Steril"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.05.010","article-title":"Effect of transfer of a poor quality embryo along with a top quality embryo on the outcome during fresh and frozen in vitro fertilization cycles","volume":"110","author":"Dobson","year":"2018","journal-title":"Fertil Steril"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00930","article-title":"The association between embryo quality, number of transferred embryos and live birth rate after vitrified cleavage-stage embryos and blastocyst transfer","volume":"11","author":"Zhu","year":"2020","journal-title":"Front Physiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s12958-020-00656-2","article-title":"Does the transfer of a poor quality embryo with a good quality embryo benefit poor prognosis patients","volume":"18","author":"Wang","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmz008","article-title":"The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART","volume":"25","author":"Coticchio","year":"2019","journal-title":"Hum Reprod Update"},{"key":"B29","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":"B30","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":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2023.103729","article-title":"Blastocysts from partial compaction morulae are not defined by their early mistakes","volume":"48","author":"Parriego","year":"2024","journal-title":"Reprod BioMed Online"},{"key":"B32","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\u2020,\u2021","volume":"40","author":"Coticchio","year":"2025","journal-title":"Hum Reprod"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2026.1740765","article-title":"Comparative outcomes of day 4 versus day 5 embryo transfers by fertilization method","volume":"17","author":"Tao","year":"2026","journal-title":"Front Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1186\/s12884-024-06976-0","article-title":"Effect of day 3 embryo cell number on the pregnancy and neonatal outcomes of day 4 single embryo transfer from fresh cycles","volume":"24","author":"Tao","year":"2024","journal-title":"BMC Pregnancy Childbirth"},{"key":"B35","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","volume":"26","year":"2011","journal-title":"Hum Reprod"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn101441-20230327-00125","article-title":"Comparison of clinical outcomes and maternal and fetal outcomes between different transplantation schemes on day 4 in fresh cycle","volume":"44","author":"Tao","year":"2024","journal-title":"Chin J Reprod Contracep"},{"key":"B37","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":"B38","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":"B39","doi-asserted-by":"publisher","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":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041424","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":"B41","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":"B42","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12958-024-01194-x","article-title":"Effect of frozen-thawed embryo transfer with a poor-quality embryo and a good-quality embryo on pregnancy and neonatal outcomes","volume":"22","author":"Zeng","year":"2024","journal-title":"Reprod Biol Endocrinol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1186\/s12884-020-03353-5","article-title":"Live birth rate and neonatal outcomes of different quantities and qualities of frozen transferred blastocyst in patients requiring whole embryo freezing stratified by age","volume":"20","author":"Chen","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"B44","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":"B45","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.14424","article-title":"Comparison of frozen-thawed embryo transfer strategies for the treatment of infertility in young women: a retrospective study","volume":"10","author":"Wu","year":"2022","journal-title":"PeerJ"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1141605","article-title":"Comparison of frozen-thaw blastocyst transfer strategies in women aged 35\u201340 years: a retrospective study","volume":"14","author":"Wu","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq352","article-title":"Reducing the incidence of twins from IVF treatments: predictive modelling from a retrospective cohort","volume":"26","author":"Roberts","year":"2011","journal-title":"Hum Reprod"},{"key":"B48","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"}],"updated-by":[{"DOI":"10.3389\/fendo.2026.1900682","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000}}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1776207\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:07:13Z","timestamp":1781867233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1776207\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":48,"alternative-id":["10.3389\/fendo.2026.1776207"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1776207","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"article-number":"1776207"}}