{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:54:23Z","timestamp":1793321663495,"version":"4.5.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22gk0110056h0001"],"award-info":[{"award-number":["JP22gk0110056h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>This large multi-center retrospective study examined whether artificial oocyte activation (AOA) using Ca<jats:sup>2+<\/jats:sup> ionophore following ICSI improves the live birth rate for couples with previous ICSI cycles of unexplained low fertilization rate. In this large-scale multi-center retrospective study conducted in Japan, data were collected from Keio University and 17 collaborating institutions of the Japanese Institution for Standardizing Assisted Reproductive Technology. Between January 2015 and December 2019, 198 couples were included in this study. Oocytes for both the intervention and control groups were procured from the same pool of couples. Oocytes obtained from ICSI cycles with no or low fertilization rate (&amp;lt;50%) with unknown causes were included in the control (conventional ICSI) group while oocytes procured from ICSI cycles followed by performing AOA were assigned to the intervention (ICSI-AOA) group. Those fertilized with surgically retrieved sperm were excluded. ICSI-AOA efficacy and safety were evaluated by comparing these two groups. Live birth rate was the primary outcome. The ICSI-AOA group (2,920 oocytes) showed a significantly higher live birth per embryo transfer rate (18.0% [57\/316]) compared to that of the conventional ICSI group with no or low fertilization rate (1,973 oocytes; 4.7% [4\/85]) (odds ratio 4.5, 95% confidence interval 1.6\u201312.6; P&amp;lt;0.05). A higher live birth rate was observed in younger patients without a history of oocyte retrieval. Miscarriage, preterm delivery, and fetal congenital malformation rates were similar between the two groups. ICSI-AOA may reduce fertilization failure without increasing risks during the perinatal period. AOA may be offered to couples with an ICSI fertilization rate &amp;lt; 50%.<\/jats:p>","DOI":"10.3389\/fendo.2023.1131808","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T07:12:06Z","timestamp":1678345926000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Artificial oocyte activation using Ca2+ ionophores following intracytoplasmic sperm injection for low fertilization rate"],"prefix":"10.3389","volume":"14","author":[{"given":"Kazuhiro","family":"Akashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsutoshi","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Chik","family":"Jwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Utsuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Kamijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Osuga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Kuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)92425-f","article-title":"Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte","volume":"340","author":"Palermo","year":"1992","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hox011","article-title":"The Vienna consensus: Report of an expert meeting on the development of art laboratory performance indicators","volume":"2017","year":"2017","journal-title":"Hum Reprod Open"},{"key":"B3","article-title":"Complete failed fertilization after intracytoplasmic sperm injection\u2013analysis of 10 years' data","volume":"50","author":"Esfandiari","year":"2005","journal-title":"Int J Fertil Womens Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/13.suppl_1.155","article-title":"Fertilization failures and abnormal fertilization after intracytoplasmic sperm injection","author":"Flaherty","year":"1998","journal-title":"Hum Reprod"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a135757","article-title":"Aetiology of failed and abnormal fertilization after intracytoplasmic sperm injection","volume":"10","author":"Flaherty","year":"1995","journal-title":"Hum Reprod"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/6.6.510","article-title":"Cytoskeletal organization defects and abortive activation in human oocytes after ivf and icsi failure","volume":"6","author":"Rawe","year":"2000","journal-title":"Mol Hum Reprod"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s1472-6483(10)61027-9","article-title":"Successful pregnancy after icsi with strontium oocyte activation in low rates of fertilization","volume":"13","author":"Yanagida","year":"2006","journal-title":"Reprod BioMed Online"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des097","article-title":"Assisted oocyte activation is not beneficial for all patients with a suspected oocyte-related activation deficiency","volume":"27","author":"Vanden Meerschaut","year":"2012","journal-title":"Hum Reprod"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.04.006","article-title":"Assisted oocyte activation significantly increases fertilization and pregnancy outcome in patients with low and total failed fertilization after intracytoplasmic sperm injection: A 17-year retrospective study","volume":"112","author":"Bonte","year":"2019","journal-title":"Fertil Steril"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(02)03291-0","article-title":"Use of a modified intracytoplasmic sperm injection technique to overcome sperm-borne and oocyte-borne oocyte activation failures","volume":"78","author":"Tesarik","year":"2002","journal-title":"Fertil Steril"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.01.020","article-title":"Genome transfer prevents fragmentation and restores developmental potential of developmentally compromised postovulatory aged mouse oocytes","volume":"8","author":"Yamada","year":"2017","journal-title":"Stem Cell Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.08.013","article-title":"A successful pregnancy and live birth after intracytoplasmic sperm injection with globozoospermic sperm and electrical oocyte activation","volume":"92","author":"Egashira","year":"2009","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.751905","article-title":"Assisted oocyte activation with calcium ionophore improves pregnancy outcomes and offspring safety in infertile patients: A systematic review and meta-analysis","volume":"12","author":"Shan","year":"2021","journal-title":"Front Physiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3109\/19396368.2014.900832","article-title":"Successful pregnancy after Srcl2 oocyte activation in couples with repeated low fertilization rates following calcium ionophore treatment","volume":"60","author":"Kim","year":"2014","journal-title":"Syst Biol Reprod Med"},{"key":"B15","unstructured":"Survey and research project for the promotion of child and child rearing support in Fy2020. final report 2021: Survey on the actual situation of infertility treatment"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoac003","article-title":"Oocyte activation deficiency and assisted oocyte activation: Mechanisms, obstacles and prospects for clinical application","volume":"2022","author":"Kashir","year":"2022","journal-title":"Hum Reprod Open"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2012.02.002","article-title":"The benefit of artificial oocyte activation is dependent on the fertilization rate in a previous treatment cycle","volume":"24","author":"Montag","year":"2012","journal-title":"Reprod BioMed Online"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2014.11.012","article-title":"Live birth after artificial oocyte activation using a ready-to-Use ionophore: A prospective multicentre study","volume":"30","author":"Ebner","year":"2015","journal-title":"Reprod BioMed Online"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(00)00518-5","article-title":"Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer","volume":"73","author":"Gardner","year":"2000","journal-title":"Fertil Steril"},{"key":"B20","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.fertnstert.2015.11.007","article-title":"Effect of two assisted oocyte activation protocols used to overcome fertilization failure on the activation potential and calcium releasing pattern","volume":"105","author":"Nikiforaki","year":"2016","journal-title":"Fertil Steril"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.17296","article-title":"Live-birth rate associated with repeat in vitro fertilization treatment cycles","volume":"314","author":"Smith","year":"2015","journal-title":"Jama"},{"key":"B22","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1016\/j.fertnstert.2017.06.029","article-title":"Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? a meta-analysis","volume":"108","author":"Murugesu","year":"2017","journal-title":"Fertil Steril"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dem135","article-title":"Morphometric characteristics of the primordial to primary follicle transition in the human ovary in relation to age","volume":"22","author":"Westergaard","year":"2007","journal-title":"Hum Reprod"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/14647273.2016.1240374","article-title":"Artificial oocyte activation after intracytoplasmic morphologically selected sperm injection: A prospective randomized sibling oocyte study","volume":"19","author":"Aydinuraz","year":"2016","journal-title":"Hum Fertil (Camb)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/s1472-6483(10)60423-3","article-title":"Artificial oocyte activation using calcium ionophore in icsi cycles with spermatozoa from different sources","volume":"18","author":"Borges","year":"2009","journal-title":"Reprod BioMed Online"},{"key":"B26","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/humrep\/deu285","article-title":"Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: A prospective multicenter study","volume":"30","author":"Ebner","year":"2015","journal-title":"Hum Reprod"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-011-0955-0","article-title":"Alterations in calcium oscillatory activity in vitrified mouse eggs impact on egg quality and subsequent embryonic development","volume":"461","author":"Kim","year":"2011","journal-title":"Pflugers Arch"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.08.041","article-title":"Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term","volume":"300","author":"Ozil","year":"2006","journal-title":"Dev Biol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/humupd\/dmv040","article-title":"Oocyte activation deficiency: A role for an oocyte contribution","volume":"22","author":"Yeste","year":"2016","journal-title":"Hum Reprod Update"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nature13287","article-title":"Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells","volume":"510","author":"Yamada","year":"2014","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature10397","article-title":"Human oocytes reprogram somatic cells to a pluripotent state","volume":"478","author":"Noggle","year":"2011","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12958-020-00680-2","article-title":"Risk of birth defects in children conceived by artificial oocyte activation and intracytoplasmic sperm injection: A meta-analysis","volume":"18","author":"Long","year":"2020","journal-title":"Reprod Biol Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/252041a0","article-title":"Is calcium ionophore a universal activator for unfertilised eggs","volume":"252","author":"Steinhardt","year":"1974","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2015.06.013","article-title":"Assisted yes, but where do we draw the line","volume":"31","author":"Santella","year":"2015","journal-title":"Reprod BioMed Online"},{"key":"B35","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.fertnstert.2015.11.017","article-title":"Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte","volume":"105","author":"Capalbo","year":"2016","journal-title":"Fertil Steril"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nature11800","article-title":"Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants","volume":"493","author":"Paull","year":"2013","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.07.1134","article-title":"Application of a ready-to-Use calcium ionophore increases rates of fertilization and pregnancy in severe Male factor infertility","volume":"98","author":"Ebner","year":"2012","journal-title":"Fertil Steril"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2018.1452311","article-title":"Artificial oocyte activation with calcium ionophore for frozen sperm cycles","volume":"64","author":"Karabulut","year":"2018","journal-title":"Syst Biol Reprod Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cryobiol.2016.12.004","article-title":"Effects of trehalose vitrification and artificial oocyte activation on the development competence of human immature oocytes","volume":"74","author":"Zhang","year":"2017","journal-title":"Cryobiology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey258","article-title":"Artificial oocyte activation with Srcl2 or calcimycin after icsi improves clinical and embryological outcomes compared with icsi alone: Results of a randomized clinical trial","volume":"33","author":"Fawzy","year":"2018","journal-title":"Hum Reprod"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deaa028","article-title":"No effect of ovarian stimulation and oocyte yield on euploidy and live birth rates: An analysis of 12 298 trophectoderm biopsies","volume":"35","author":"Irani","year":"2020","journal-title":"Hum Reprod"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1131808\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T07:12:11Z","timestamp":1678345931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1131808\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":41,"alternative-id":["10.3389\/fendo.2023.1131808"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1131808","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]},"article-number":"1131808"}}