{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:33:05Z","timestamp":1793313185082,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-18764-7","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:52:53Z","timestamp":1759845173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extended blastocyst culture improves DNA yield in non-invasive preimplantation genetic testing for aneuploidy but diagnostic specificity remains limited"],"prefix":"10.1038","volume":"15","author":[{"given":"Ting-Feng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-I","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Hsin","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Hui","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Chia","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Hsien","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maw-Sheng","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Yao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"e1077","key":"18764_CR1","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.fertnstert.2019.07.1346","volume":"112","author":"S Munne","year":"2019","unstructured":"Munne, S. et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: A multicenter randomized clinical trial. Fertil. Steril. 112(e1077), 1071\u20131079. https:\/\/doi.org\/10.1016\/j.fertnstert.2019.07.1346 (2019).","journal-title":"Fertil. Steril."},{"key":"18764_CR2","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1055\/s-0042-1744291","volume":"44","author":"BR Carvalho","year":"2022","unstructured":"Carvalho, B. R. Great challenges remain for niPGT-A reliability. Rev. Bras. Ginecol. Obstet. 44, 721\u2013722. https:\/\/doi.org\/10.1055\/s-0042-1744291 (2022).","journal-title":"Rev. Bras. Ginecol. Obstet."},{"key":"18764_CR3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.fertnstert.2024.08.326","volume":"123","author":"S Mumusoglu","year":"2025","unstructured":"Mumusoglu, S., Telek, S. B. & Ata, B. Preimplantation genetic testing for aneuploidy in unexplained recurrent pregnancy loss: A systematic review and meta-analysis. Fertil. Steril. 123, 121\u2013136. https:\/\/doi.org\/10.1016\/j.fertnstert.2024.08.326 (2025).","journal-title":"Fertil. Steril."},{"key":"18764_CR4","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.fertnstert.2013.07.004","volume":"100","author":"KL Scott","year":"2013","unstructured":"Scott, K. L., Hong, K. H. & Scott, R. T. Jr. Selecting the optimal time to perform biopsy for preimplantation genetic testing. Fertil. Steril. 100, 608\u2013614. https:\/\/doi.org\/10.1016\/j.fertnstert.2013.07.004 (2013).","journal-title":"Fertil. Steril."},{"key":"18764_CR5","doi-asserted-by":"publisher","unstructured":"Zhang, W. Y. et al. Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertil Steril 112, 283\u2013290 e282, (2019). https:\/\/doi.org\/10.1016\/j.fertnstert.2019.03.033","DOI":"10.1016\/j.fertnstert.2019.03.033"},{"key":"18764_CR6","doi-asserted-by":"publisher","first-page":"819963","DOI":"10.3389\/fendo.2022.819963","volume":"13","author":"S Li","year":"2022","unstructured":"Li, S. et al. Non-Assisted hatching trophectoderm biopsy does not increase the risks of most adverse maternal and neonatal outcome and May be more practical for busy clinics: Evidence from China. Front. Endocrinol. (Lausanne) 13, 819963. https:\/\/doi.org\/10.3389\/fendo.2022.819963 (2022).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"18764_CR7","doi-asserted-by":"publisher","first-page":"14105","DOI":"10.1073\/pnas.1907472116","volume":"116","author":"L Huang","year":"2019","unstructured":"Huang, L. et al. Noninvasive preimplantation genetic testing for aneuploidy in spent medium May be more reliable than trophectoderm biopsy. Proc. Natl. Acad. Sci. U S A 116, 14105\u201314112. https:\/\/doi.org\/10.1073\/pnas.1907472116 (2019).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"18764_CR8","doi-asserted-by":"publisher","unstructured":"De Vos, A. & De Munck, N. Trophectoderm biopsy: Present state of the Art. Genes (Basel) 16 https:\/\/doi.org\/10.3390\/genes16020134 (2025).","DOI":"10.3390\/genes16020134"},{"key":"18764_CR9","doi-asserted-by":"publisher","first-page":"e0185747","DOI":"10.1371\/journal.pone.0185747","volume":"12","author":"HH Chen","year":"2017","unstructured":"Chen, H. H. et al. Optimal timing of blastocyst vitrification after trophectoderm biopsy for preimplantation genetic screening. PLoS One 12, e0185747. https:\/\/doi.org\/10.1371\/journal.pone.0185747 (2017).","journal-title":"PLoS One"},{"key":"18764_CR10","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/j.fertnstert.2021.01.028","volume":"115","author":"BM Hanson","year":"2021","unstructured":"Hanson, B. M. et al. Noninvasive preimplantation genetic testing for aneuploidy exhibits high rates of deoxyribonucleic acid amplification failure and poor correlation with results obtained using trophectoderm biopsy. Fertil. Steril. 115, 1461\u20131470. https:\/\/doi.org\/10.1016\/j.fertnstert.2021.01.028 (2021).","journal-title":"Fertil. Steril."},{"key":"18764_CR11","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.fertnstert.2024.02.030","volume":"122","author":"G Nakhuda","year":"2024","unstructured":"Nakhuda, G., Rodriguez, S., Tormasi, S. & Welch, C. A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media. Fertil. Steril. 122, 42\u201351. https:\/\/doi.org\/10.1016\/j.fertnstert.2024.02.030 (2024).","journal-title":"Fertil. Steril."},{"key":"18764_CR12","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s10815-023-03015-3","volume":"41","author":"JFC Chow","year":"2024","unstructured":"Chow, J. F. C. et al. Optimizing non-invasive preimplantation genetic testing: Investigating culture conditions, sample collection, and IVF treatment for improved non-invasive PGT-A results. J. Assist. Reprod. Genet. 41, 465\u2013472. https:\/\/doi.org\/10.1007\/s10815-023-03015-3 (2024).","journal-title":"J. Assist. Reprod. Genet."},{"key":"18764_CR13","doi-asserted-by":"publisher","unstructured":"Bednarska-Czerwi\u0144ska, A. et al. Comparison of Non-Invasive and minimally invasive preimplantation genetic testing for aneuploidy using samples derived from the same embryo culture. J. Clin. Med. 14 https:\/\/doi.org\/10.3390\/jcm14010033 (2024).","DOI":"10.3390\/jcm14010033"},{"key":"18764_CR14","doi-asserted-by":"publisher","unstructured":"Rubio, C. et al. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am. J. Obstet. Gynecol. 223, 751 e751\u2013751 e713. https:\/\/doi.org\/10.1016\/j.ajog.2020.04.035 (2020).","DOI":"10.1016\/j.ajog.2020.04.035"},{"key":"18764_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s43032-024-01698-2","volume":"32","author":"EC de Albornoz","year":"2025","unstructured":"de Albornoz, E. C. et al. Non invasive preimplantation testing for aneuploidies in assisted reproduction: A SWOT analysis. Reprod. Sci. 32, 1\u201314. https:\/\/doi.org\/10.1007\/s43032-024-01698-2 (2025).","journal-title":"Reprod. Sci."},{"key":"18764_CR16","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1093\/humrep\/deae151","volume":"39","author":"M Volovsky","year":"2024","unstructured":"Volovsky, M., Scott, R. T. Jr. & Seli, E. Non-invasive preimplantation genetic testing for aneuploidy: Is the promise real? Hum. Reprod. 39, 1899\u20131908. https:\/\/doi.org\/10.1093\/humrep\/deae151 (2024).","journal-title":"Hum. Reprod."},{"key":"18764_CR17","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1097\/gco.0000000000000881","volume":"35","author":"B Lledo","year":"2023","unstructured":"Lledo, B., Morales, R., Antonio Ortiz, J., Bernabeu, A. & Bernabeu, R. Noninvasive preimplantation genetic testing using the embryo spent culture medium: An update. Curr. Opin. Obstet. Gynecol. 35, 294\u2013299. https:\/\/doi.org\/10.1097\/gco.0000000000000881 (2023).","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"18764_CR18","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s10815-016-0784-3","volume":"33","author":"D Goodrich","year":"2016","unstructured":"Goodrich, D. et al. A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy in a cell line mixture model of blastocyst biopsy mosaicism. J. Assist. Reprod. Genet. 33, 1473\u20131480. https:\/\/doi.org\/10.1007\/s10815-016-0784-3 (2016).","journal-title":"J. Assist. Reprod. Genet."},{"key":"18764_CR19","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.rbmo.2019.05.020","volume":"39","author":"CI Lee","year":"2019","unstructured":"Lee, C. I. et al. Embryo morphokinetics is potentially associated with clinical outcomes of single-embryo transfers in preimplantation genetic testing for aneuploidy cycles. Reprod. Biomed. Online 39, 569\u2013579. https:\/\/doi.org\/10.1016\/j.rbmo.2019.05.020 (2019).","journal-title":"Reprod. Biomed. Online"},{"key":"18764_CR20","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1093\/humrep\/deae156","volume":"39","author":"D Sakkas","year":"2024","unstructured":"Sakkas, D. et al. The impact of implementing a non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) embryo culture protocol on embryo viability and clinical outcomes. Hum. Reprod. 39, 1952\u20131959. https:\/\/doi.org\/10.1093\/humrep\/deae156 (2024).","journal-title":"Hum. Reprod."},{"key":"18764_CR21","doi-asserted-by":"publisher","first-page":"e12604","DOI":"10.1002\/rmb2.12604","volume":"23","author":"H Takeuchi","year":"2024","unstructured":"Takeuchi, H. et al. Conditions for improved accuracy of noninvasive preimplantation genetic testing for aneuploidy: Focusing on the Zona pellucida and early blastocysts. Reprod. Med. Biol. 23, e12604. https:\/\/doi.org\/10.1002\/rmb2.12604 (2024).","journal-title":"Reprod. Med. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18764-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18764-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18764-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T13:52:54Z","timestamp":1759845174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-18764-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["18764"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-18764-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"1 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval was obtained from the Institutional Review Board of Chung Shan Medical University Hospital (IRB number: CS1-21005). Written informed consent to participate in this study was obtained from all individual participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants provided written consent for the publication of anonymized data related to this study. No identifying information is included in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"34906"}}