{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:14:43Z","timestamp":1774286083430,"version":"3.50.1"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health\uff0cCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medi","award":["SKLRM-2022D2"],"award-info":[{"award-number":["SKLRM-2022D2"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030040"],"award-info":[{"award-number":["82030040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oocyte aneuploidy is a major cause of pregnancy failure in women of advanced maternal age (AMA), and current assisted reproductive technologies offer limited effective strategies to prevent age-related decline in oocyte quality. The mevalonate (MVA) pathway in granulosa cells has recently been implicated in supporting meiotic maturation, but its therapeutic potential in humans remains unclear. This randomized controlled trial is designed to evaluate the effects of MVA supplementation on oocyte competence in women of AMA undergoing preimplantation genetic testing for aneuploidy (PGT-A).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study will be conducted as a single-center, prospective, randomized controlled trial. A total of 128 infertile women aged 38\u201342\u00a0years undergoing PGT-A will be enrolled and randomized to either the MVA supplementation group or the control group. Cumulus-oocyte complexes retrieved from each cycle will be allocated according to the randomization protocol, with an estimated 150 cycles analyzed. The primary outcome is the euploidy blastocyst rate, while the secondary outcomes are the clinical pregnancy rate and live birth rate following frozen embryo transfer (FET).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This trial is expected to evaluate the effects of MVA supplementation on euploidy blastocyst rate and clinical pregnancy outcomes in women of AMA undergoing PGT-A. These findings may provide valuable insights into the potential application of MVA supplementation as an adjunct treatment for infertility in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05788822. Registered in March 2023.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-026-09522-9","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:24:32Z","timestamp":1771028672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mevalonate supplementation to enhance euploid embryo formation in women of advanced maternal age: a study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"27","author":[{"given":"Shanshan","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingjuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junshun","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanxin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"9522_CR1","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1016\/S0140-6736(16)31405-2","volume":"388","author":"Y Zeng","year":"2016","unstructured":"Zeng Y, Hesketh T. The effects of China\u2019s universal two-child policy. Lancet. 2016;388:1930\u20138.","journal-title":"Lancet"},{"key":"9522_CR2","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s11427-012-4352-5","volume":"55","author":"Q Li","year":"2012","unstructured":"Li Q, Geng X, Zheng W, Tang J, Xu B, Shi Q. Current understanding of ovarian aging. Sci China Life Sci. 2012;55:659\u201369.","journal-title":"Sci China Life Sci"},{"key":"9522_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.710033","volume":"9","author":"R Beverley","year":"2021","unstructured":"Beverley R, Snook ML, Brie\u00f1o-Enr\u00edquez MA. Meiotic cohesin and variants associated with human reproductive aging and disease. Front Cell Dev Biol. 2021;9:710033.","journal-title":"Front Cell Dev Biol"},{"key":"9522_CR4","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1126\/science.aav7321","volume":"365","author":"JR Gruhn","year":"2019","unstructured":"Gruhn JR, Zielinska AP, Shukla V, Blanshard R, Capalbo A, Cimadomo D, et al. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science. 2019;365:1466\u20139.","journal-title":"Science"},{"key":"9522_CR5","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1126\/science.aaa9529","volume":"348","author":"Z Holubcov\u00e1","year":"2015","unstructured":"Holubcov\u00e1 Z, Blayney M, Elder K, Schuh M. Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science. 2015;348:1143\u20137.","journal-title":"Science"},{"key":"9522_CR6","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1093\/humupd\/dmab038","volume":"28","author":"L Secomandi","year":"2022","unstructured":"Secomandi L, Borghesan M, Velarde M, Demaria M. The role of cellular senescence in female reproductive aging and the potential for senotherapeutic interventions. Hum Reprod Update. 2022;28:172\u201389.","journal-title":"Hum Reprod Update"},{"key":"9522_CR7","unstructured":"Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 2018;109:429\u201336."},{"key":"9522_CR8","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/s43587-023-00419-9","volume":"3","author":"C Liu","year":"2023","unstructured":"Liu C, Zuo W, Yan G, Wang S, Sun S, Li S, et al. Granulosa cell mevalonate pathway abnormalities contribute to oocyte meiotic defects and aneuploidy. Nat Aging. 2023;3:670\u201387.","journal-title":"Nat Aging"},{"key":"9522_CR9","doi-asserted-by":"crossref","unstructured":"Jiang L, Chen Y, Wang Q, Wang X, Luo X, Chen Y, et al. Chinese Society of Reproductive Medicine (CSRM). A Chinese practice guideline of the assisted reproductive technology strategies for women with advanced age. J Evid Based Med. 2019;12:167\u201384.","DOI":"10.1111\/jebm.12346"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-026-09522-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09522-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-026-09522-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T16:44:32Z","timestamp":1774284272000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13063-026-09522-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9522"],"URL":"https:\/\/doi.org\/10.1186\/s13063-026-09522-9","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]},"assertion":[{"value":"10 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Academic Committee of Nanjing Drum Tower Hospital (Approval No. 2023003) and the Ethics Committee of Nanjing Drum Tower Hospital (Approval No. 2022-648-01). Written informed consent will be obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"All authors agree to publish.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"223"}}