{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:03:12Z","timestamp":1793606592580,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>The meiotic spindle is essential for accurate chromosome segregation during oocyte maturation and fertilization, and its alteration might be considered a major contributor to age-related aneuploidy and reproductive failure. Spindle formation is inherently vulnerable to errors and contributes to the unusually high frequency of chromosome segregation defects observed in human eggs. Human oocytes are particularly prone to aneuploidy; the presence of an abnormal chromosome number, which represents one of the leading causes of infertility, recurrent pregnancy loss, implantation failure, and congenital disorders in neonates. Previous studies have reported a U-shaped relationship between maternal age and aneuploidy rates, with relatively higher rates observed in both very young females and in women of advanced maternal age. Conversely, aneuploidy rates appear comparatively lower during the intervening reproductive-age period, particularly between approximately 25 and 35 years of age. Because most aneuploid embryos fail to develop successfully after fertilization, chromosome segregation errors in oocytes have profound consequences for female reproductive success. Aneuploidy primarily arises from defects during meiotic chromosome segregation. Faithful chromosome segregation depends on the accurate assembly and function of the meiotic spindle, a dynamic microtubule-based structure that aligns and separates homologous chromosomes during meiosis I and sister chromatids during meiosis II. Growing evidence indicates that chromosome mis-segregation results from the combined effects of impaired sister chromatid cohesion, altered kinetochore architecture, defective microtubule dynamics, weakened spindle assembly checkpoint activity, and age-related metabolic decline. Together, these defects compromise spindle integrity and reduce the fidelity of chromosome separation. Furthermore, the intrinsic instability of the acentrosomal spindle increases the likelihood of incorrect microtubule\u2013kinetochore attachments, a defect that becomes more prevalent with maternal aging due to progressive deterioration of chromosome organization and kinetochore function. This review summarizes the current understanding of the molecular mechanisms regulating meiotic spindle assembly and function in human oocytes and examines how their disruption contributes to chromosome segregation errors and embryonic aneuploidy. We discuss the interplay between spindle abnormalities and upstream cellular defects, distinguish meiotic from post-zygotic origins of chromosomal abnormalities, and evaluate the clinical significance of spindle assessment in assisted reproductive technologies. Finally, we critically examine emerging strategies aimed at preserving chromosome segregation fidelity, including approaches targeting mitochondrial function and spindle regulation, while distinguishing interventions supported by mechanistic evidence from those that remain preclinical or speculative.<\/jats:p>","DOI":"10.3390\/medicina62091810","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:25:43Z","timestamp":1789986343000},"page":"1810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Meiotic Spindle, Mechanisms of Chromosome Segregation and Aneuploidy in Aging Human Oocytes: An Update Review"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-8823","authenticated-orcid":false,"given":"Romualdo","family":"Sciorio","sequence":"first","affiliation":[{"name":"Vitrolife-Group, 421 32 V\u00e4stra Fr\u00f6lunda, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4675-3145","authenticated-orcid":false,"given":"Gyongyver","family":"Teglas","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Gynecological Endocrinology, Lucerne Cantonal Hospital, 6004 Lucerne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Tramontano","sequence":"additional","affiliation":[{"name":"Endometriosis and Fertility Center, H\u00f4pital de La Tour, 1217 Meyrin, Switzerland"},{"name":"Departement de Gynecologie-Obstetrique, Reseau Hospitalier Neuch\u00e2telois, 2000 Neuch\u00e2tel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-4528","authenticated-orcid":false,"given":"Laszlo","family":"Nanassy","sequence":"additional","affiliation":[{"name":"Division of Gynecological Endocrinology and Reproductive Medicine, Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Girardi","sequence":"additional","affiliation":[{"name":"Igenomix Italy, Reproductive Genetics, 36063 Marostica, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Fleming","sequence":"additional","affiliation":[{"name":"Discipline of Anatomy & Histology, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/35066065","article-title":"To err (meiotically) is human: The genesis of human aneuploidy","volume":"2","author":"Hassold","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrg3245","article-title":"Human aneuploidy: Mechanisms and new insights into an age-old problem","volume":"13","author":"Nagaoka","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00439-002-0852-x","article-title":"Maternal aging and chromosomal abnormalities: New data drawn from in vitro unfertilized human oocytes","volume":"112","author":"Pellestor","year":"2003","journal-title":"Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.aav7321","article-title":"Chromosome errors in human eggs shape natural fertility over reproductive life span","volume":"365","author":"Gruhn","year":"2019","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1007\/s00439-013-1309-0","article-title":"The origin and impact of embryonic aneuploidy","volume":"132","author":"Fragouli","year":"2013","journal-title":"Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1016\/j.cell.2021.04.013","article-title":"Parental genome unification is highly error-prone in mammalian embryos","volume":"184","author":"Cavazza","year":"2021","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.tcb.2016.09.002","article-title":"Mechanisms of Aneuploidy in Human Eggs","volume":"27","author":"Webster","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/humupd\/dmx035","article-title":"Regulation of chromosome segregation in oocytes and the cellular basis for female meiotic errors","volume":"24","author":"Greaney","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1126\/science.aaa9529","article-title":"Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes","volume":"348","author":"Blayney","year":"2015","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1042\/BST20200043","article-title":"Aneuploidy in human eggs: Contributions of the meiotic spindle","volume":"49","author":"Thomas","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eabj3944","DOI":"10.1126\/science.abj3944","article-title":"Mechanism of spindle pole organisation and instability in human oocytes","volume":"375","author":"So","year":"2022","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1083\/jcb.153.3.517","article-title":"Merotelic Kinetochore Orientation Is a Major Mechanism of Aneuploidy in Mitotic Mammalian Tissue Cells","volume":"153","author":"Cimini","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e11389","DOI":"10.7554\/eLife.11389","article-title":"Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect","volume":"4","author":"Zielinska","year":"2015","journal-title":"eLife"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44001","DOI":"10.1038\/srep44001","article-title":"Loss of Centromere Cohesion in Aneuploid Human Oocytes Correlates with Decreased Kinetochore Localization of the Sac Proteins Bub1 and Bubr1","volume":"7","author":"Ciabrini","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1242\/bio.016394","article-title":"Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities","volume":"5","author":"Patel","year":"2015","journal-title":"Biol. Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00412-015-0536-7","article-title":"How oocytes try to get it right: Spindle checkpoint control in meiosis","volume":"125","author":"Touati","year":"2016","journal-title":"Chromosoma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108320","DOI":"10.1016\/j.mrrev.2020.108320","article-title":"Mechanisms of oocyte aneuploidy associated with advanced maternal age","volume":"785","author":"Mikwar","year":"2020","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s00018-018-2986-6","article-title":"Meiotic spindle assembly checkpoint and aneuploidy in males versus females","volume":"76","author":"Lane","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7217","DOI":"10.1038\/ncomms8217","article-title":"A three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes","volume":"6","author":"Clift","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1091\/mbc.E16-05-0322","article-title":"The sequential activation of the mitotic microtubule assembly pathways favors bipolar spindle formation","volume":"27","author":"Cavazza","year":"2016","journal-title":"Mol. Biol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.cub.2018.08.052","article-title":"Genetic Interactions between the Aurora Kinases Reveal New Requirements for AURKB and AURKC during Oocyte Meiosis","volume":"28","author":"Nguyen","year":"2018","journal-title":"Curr. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e13489","DOI":"10.1111\/acel.13489","article-title":"Age-dependent integrity of the meiotic spindle assembly checkpoint in females requires Aurora kinase B","volume":"20","author":"Blengini","year":"2021","journal-title":"Aging Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1111\/febs.13166","article-title":"The spindle checkpoint and chromosome segregation in meiosis","volume":"282","author":"Gorbsky","year":"2015","journal-title":"FEBS J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2200135","DOI":"10.1002\/bies.202200135","article-title":"Meiotic defects in human oocytes: Potential causes and clinical implications","volume":"44","author":"Wu","year":"2022","journal-title":"BioEssays"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/biolre\/ioab210","article-title":"Acentriolar spindle assembly in mammalian female meiosis and the consequences of its perturbations on human reproduction","volume":"106","author":"Blengini","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6547","DOI":"10.1038\/s41467-021-26826-3","article-title":"CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes","volume":"12","author":"Nabi","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"71987","DOI":"10.18632\/oncotarget.12453","article-title":"Spc24 is required for meiotic kinetochore-microtubule attachment and production of euploid eggs","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"144495","DOI":"10.1016\/j.gene.2020.144495","article-title":"CDCA8 regulates meiotic spindle assembly and chromosome segregation during human oocyte meiosis","volume":"741","author":"Zhang","year":"2020","journal-title":"Gene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nature14568","article-title":"Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes","volume":"524","author":"Pfender","year":"2015","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e202106170","DOI":"10.1083\/jcb.202106170","article-title":"Volumetric morphometry reveals spindle width as the best predictor of mammalian spindle scaling","volume":"221","author":"Kletter","year":"2022","journal-title":"J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"eadd7397","DOI":"10.1126\/sciadv.add7397","article-title":"Initial spindle positioning at the oocyte center protects against incorrect kinetochore-microtubule attachment and aneuploidy in mice","volume":"9","author":"Kincade","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1093\/humrep\/deg447","article-title":"Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development","volume":"18","author":"Cooke","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0015-0282(02)04196-1","article-title":"Prediction of chromosome misalignment among in vitro matured human oocytes by spindle imaging with the PolScope","volume":"78","author":"Wang","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1093\/humrep\/dex083","article-title":"Tri-directional anaphases as a novel chromosome segregation defect in human oocytes","volume":"32","author":"Haverfield","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1080\/15384101.2017.1327488","article-title":"Merotelic kinetochore attachment in oocyte meiosis II causes sister chromatids segregation errors in aged mice","volume":"16","author":"Cheng","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1038\/s41467-020-15470-y","article-title":"Artificially decreasing cortical tension generates aneuploidy in mouse oocytes","volume":"11","author":"Bennabi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8990","DOI":"10.1096\/fj.202000131R","article-title":"Cell division cycle 23 is required for mouse oocyte meiotic maturation","volume":"34","author":"Zhou","year":"2020","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaax3969","DOI":"10.1126\/sciadv.aax3969","article-title":"The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I","volume":"6","author":"Zhou","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.18632\/oncotarget.13684","article-title":"Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20092","DOI":"10.18632\/oncotarget.15383","article-title":"HDAC8 functions in spindle assembly during mouse oocyte meiosis","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e202010106","DOI":"10.1083\/jcb.202010106","article-title":"Dual spindles assemble in bovine zygotes despite the presence of paternal centrosomes","volume":"220","author":"Schneider","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105553","DOI":"10.1016\/j.rbmo.2026.105553","article-title":"Why human embryos are mosaic: The role of the spindle assembly checkpoint in chromosome segregation in the zygote","volume":"52","year":"2026","journal-title":"Reprod. Biomed. Online"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/ng.3306","article-title":"Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates","volume":"47","author":"Ottolini","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.cub.2010.06.069","article-title":"Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes","volume":"20","author":"Chiang","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/j.1474-9726.2012.00866.x","article-title":"Chromosome cohesion decreases in human eggs with advanced maternal age","volume":"11","author":"Duncan","year":"2012","journal-title":"Aging Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1093\/humrep\/dead177","article-title":"Human ovarian aging is characterized by oxidative damage and mitochondrial dysfunction","volume":"38","author":"Smits","year":"2023","journal-title":"Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"a017970","DOI":"10.1101\/cshperspect.a017970","article-title":"Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births","volume":"7","author":"Herbert","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1038\/s41467-024-54659-3","article-title":"Chromosome architecture and low cohesion bias acrocentric chromosomes towards aneuploidy during mammalian meiosis","volume":"15","author":"Bellou","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cub.2023.11.061","article-title":"Age-dependent loss of cohesion protection in human oocytes","volume":"34","author":"Mihalas","year":"2024","journal-title":"Curr. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1262\/jrd.2018-056","article-title":"Destabilization of spindle assembly checkpoint causes aneuploidy during meiosis II in murine post-ovulatory aged oocytes","volume":"65","author":"Shimoi","year":"2019","journal-title":"J. Reprod. Dev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jeon, H.-J., and Oh, J.S. (2020). RASSF1A Regulates Spindle Organisation by Modulating Tubulin Acetylation via SIRT2 and HDAC6 in Mouse Oocytes. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.601972"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/humrep\/deaa300","article-title":"Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and human oocytes","volume":"36","author":"Adhikari","year":"2021","journal-title":"Hum. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e230510","DOI":"10.1530\/REP-23-0510","article-title":"Reproductive Ageing: Metabolic contribution to age-related chromosome missegregation in mammalian oocytes","volume":"168","author":"Mihalas","year":"2024","journal-title":"Reproduction"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1023\/B:JARG.0000046202.00570.1d","article-title":"Visualization and Examination of the Meiotic Spindle in Human Oocytes with Polscope","volume":"21","author":"Konc","year":"2004","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"ESHRE Guideline Group on Good Practice in IVF Labs, De los Santos, M.J., Apter, S., Coticchio, G., Debrock, S., Lundin, K., Plancha, C.E., Prados, F., Rienzi, L., and Verheyen, G. (2016). Revised guidelines for good practice in IVF laboratories (2015). Hum. Reprod., 31, 685\u2013686.","DOI":"10.1093\/humrep\/dew016"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Working Group on the update of the ESHRE\/ALPHA Istanbul Consensus, Coticchio, G., Ahlstr\u00f6m, A., Arroyo, G., Balaban, B., Campbell, A., De Los Santos, M.J., Ebner, T., Gardner, D.K., and Kova\u010di\u010d, B. (2025). The Istanbul consensus update: A revised ESHRE\/ALPHA consensus on oocyte and embryo static and dynamic morphological assessment. Hum. Reprod., 40, 989\u20131035.","DOI":"10.1093\/humrep\/deaf021"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.rbmo.2021.10.023","article-title":"Analysis of parental contribution for aneuploidy detection (APCAD): A novel method to detect aneuploidy and mosaicism in preimplantation embryos","volume":"44","author":"Verdyck","year":"2022","journal-title":"Reprod. Biomed. Online"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Verdyck, P., Berckmoes, V., Fernandez Gallardo, E., Keymolen, K., Olsen, C., and De Rycke, M. (2025). APCAD Part 2: A Novel Method for Detection of Meiotic Aneuploidy in Preimplantation Embryos. Genes, 16.","DOI":"10.3390\/genes16020115"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105704","DOI":"10.1016\/j.rbmo.2026.105704","article-title":"Gain of heterozygosity: An embryo-only, single-nucleotide polymorphism-based method to identify meiotic trisomies in preimplantation genetic testing for aneuploidy","volume":"53","author":"Hornak","year":"2026","journal-title":"Reprod. Biomed. Online"},{"key":"ref_60","first-page":"CD005291","article-title":"Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation","volume":"9","author":"Cornelisse","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1016\/j.fertnstert.2009.12.065","article-title":"Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing or vitrification","volume":"94","author":"Smith","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S0015-0282(02)03117-5","article-title":"Rigorous thermal control during intracytoplasmic sperm injection stabilizes the meiotic spindle and improves fertilization and pregnancy rates","volume":"77","author":"Wang","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1093\/humrep\/dew029","article-title":"Closed oocyte vitrification and storage in an oocyte donation programme: Obstetric and neonatal outcome","volume":"31","author":"Belva","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_64","first-page":"139","article-title":"Oocyte, embryo and blastocyst cryopreservation in ART: Systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance","volume":"23","author":"Rienzi","year":"2017","journal-title":"Hum. Reprod. Update"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1472-6483(10)61296-5","article-title":"Polar body morphology and spindle imaging as predictors of oocyte quality","volume":"11","author":"Cino","year":"2005","journal-title":"Reprod. Biomed. Online"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0015-0282(16)53644-9","article-title":"Transient cooling to room-temperature can cause irreversible disruption of the meiotic spindle in the human oocyte","volume":"54","author":"Pickering","year":"1990","journal-title":"Fertil. Steril."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1093\/humrep\/16.11.2374","article-title":"Limited recovery of meiotic spindles in living human oocytes after cooling-rewarming observed using polarized light microscopy","volume":"16","author":"Wang","year":"2001","journal-title":"Hum. Reprod."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/S1472-6483(10)60231-3","article-title":"Oocyte assessment and embryo viability prediction: Birefringence imaging","volume":"17","author":"Montag","year":"2008","journal-title":"Reprod. Biomed. Online"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.fertnstert.2008.01.076","article-title":"Slow cooling of human oocytes: Ultrastructural injuries and apoptotic status","volume":"91","author":"Gualtieri","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1093\/humrep\/17.7.1885","article-title":"A confocal microscopy analysis of the spindle and chromosome configurations of human oocytes cryopreserved at the germinal vesicle and metaphase II stage","volume":"17","author":"Boiso","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/humrep\/deh101","article-title":"Polscope analysis of meiotic spindle changes in living metaphase II human oocytes during the freezing and thawing procedures","volume":"19","author":"Rienzi","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1095\/biolreprod.113.108167","article-title":"Impact of vitrification on the meiotic spindle and components of the microtubule-organizing center in mouse mature oocytes","volume":"89","author":"Tamura","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S0015-0282(00)01725-8","article-title":"Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes","volume":"75","author":"Cobo","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.fertnstert.2012.04.028","article-title":"Oocyte vitrification does not increase the risk of embryonic aneuploidy or diminish the implantation potential of blastocysts created after intracytoplasmic sperm injection: A novel, paired randomized controlled trial using DNA fingerprinting","volume":"98","author":"Forman","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/acel.12368","article-title":"Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging","volume":"14","author":"Burstein","year":"2015","journal-title":"Aging Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/j.celrep.2020.01.058","article-title":"NAD+ Repletion Rescues Female Fertility during Reproductive Aging","volume":"30","author":"Bertoldo","year":"2020","journal-title":"Cell Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41598-024-81393-z","article-title":"Nicotinamide mononucleotide boosts the development of bovine oocyte by enhancing mitochondrial function and reducing chromosome lagging","volume":"15","author":"Hashimoto","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1007\/s10815-024-03263-x","article-title":"The NAD+ precursor nicotinamide riboside protects against postovulatory aging in vitro","volume":"41","author":"Li","year":"2024","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4137\/CMRH.S14681","article-title":"Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment","volume":"8","author":"Bentov","year":"2014","journal-title":"Clin. Med. Insights Reprod. Health"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1038\/s44318-025-00493-2","article-title":"The proteostatic landscape of healthy human oocytes","volume":"44","author":"Zaffagnini","year":"2025","journal-title":"EMBO J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/humrep\/dead205","article-title":"Human-induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation","volume":"38","author":"Piechota","year":"2023","journal-title":"Hum. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1007\/s10815-019-01551-5","article-title":"Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles","volume":"36","author":"Sanchez","year":"2019","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e12640","DOI":"10.1002\/rmb2.12640","article-title":"Human oocyte capacitation culture: Essential step toward hormone-free assisted reproductive technology","volume":"24","author":"Smitz","year":"2025","journal-title":"Reprod. Med. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nature11647","article-title":"Towards germline gene therapy of inherited mitochondrial diseases","volume":"493","author":"Tachibana","year":"2013","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nature18303","article-title":"Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease","volume":"534","author":"Hyslop","year":"2016","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.rbmo.2017.01.013","article-title":"Live birth derived from oocyte spindle transfer to prevent mitochondrial disease","volume":"34","author":"Zhang","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.fertnstert.2018.09.023","article-title":"Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization\u2014A randomized pilot study","volume":"111","author":"Labarta","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1007\/s43032-020-00371-8","article-title":"Cytoplasmic Transfer Improves Human Egg Fertilization and Embryo Quality: An Evaluation of Sibling Oocytes in Women with Low Oocyte Quality","volume":"28","author":"Sobek","year":"2021","journal-title":"Reprod. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e192","DOI":"10.1016\/j.fertnstert.2025.07.603","article-title":"Preclinical testing of a novel therapeutic for reduction of aneuploidy in oocytes","volume":"124","author":"Webster","year":"2025","journal-title":"Fertil. Steril."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1810\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:28:45Z","timestamp":1789990125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/9\/1810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":89,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["medicina62091810"],"URL":"https:\/\/doi.org\/10.3390\/medicina62091810","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}