{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:53Z","timestamp":1787008913183,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":244,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Scientific Program of CITIC Group","award":["2023ZXKYB34100, to Ge.L."],"award-info":[{"award-number":["2023ZXKYB34100, to Ge.L."]}]},{"name":"Hunan Provincial Grant for Innovative Province Construction","award":["2019SK4012"],"award-info":[{"award-number":["2019SK4012"]}]},{"name":"Hunan Xiangjiang New District (Changsha High-tech Zone) key core technology research project in 2023, and Science Foundation of Hunan Province","award":["2023JJ30422"],"award-info":[{"award-number":["2023JJ30422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Can ultra-low-coverage whole-genome sequencing (ulc-WGS) accurately identify abnormal ploidy during preimplantation genetic testing (PGT)?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>The artificial intelligence (AI)-based PGT-Plus model demonstrates high accuracy in ploidy detection, offering a cost-effective solution that enhances clinical utility of PGT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>The predominant PGT for aneuploidy can identify chromosomal aneuploidies but cannot determine ploidy status. Transferring embryos with ploidy abnormalities can result in miscarriage and molar pregnancy. On the other hand, in ART, fertilization is assessed by morphological pronuclear assessment at the zygote stage. However, it has a low specificity in the prediction of abnormal ploidy status and embryos deemed abnormally fertilized can yield healthy pregnancies. Accurately identified abnormal ploidy in PGT-A can resolve current limitations and expand the utility range of PGT-A. Several studies have identified ploidy abnormalities; however, they were mainly based on single-nucleotide polymorphism (SNP) arrays or needed to combine additional targeted-next-generation sequencing (NGS) information. Studies based on ulc-WGS remain scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>The study consisted of two stages: methodology establishment and validation. An AI model, named PGT-Plus, was developed using 653 samples with known ploidy status, which was further validated using 792 different ploidy status samples. In the clinical application stage, the approach was used to analyse the ploidy status of 19\u2009103 normally fertilized PGT blastocysts and 140 single pronucleus (1PN)-derived blastocysts collected between May 2022 and December 2023. All blastocysts were tested using trophectoderm biopsy and NGS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>The methodology is based on the ulc-WGS data. First, based on samples with known ploidy status: the heterozygosity rate of high-frequency biallelic SNPs, the likelihood ratio (LLR) of alleles was calculated under different assumptions (\u2018both parental homologs\u2019 [BPH] from a single parent, \u2018single parental homolog\u2019 [SPH] from each parent, disomy, and monosomy) by leveraging allele frequencies and linkage disequilibrium (LD) measured in the 1000 genomes project database. Twenty-three continuous candidate features derived from heterozygosity rates and LLRs of chromosomes or selected windows were included to establish the ploidy prediction AI model. Gini importance analysis and multicollinearity mitigation was performed for feature selection, then the performance of Random Forest (RF), Support Vector Machine (SVM), and Logistic Regression for modelling was compared. Subsequently, the parameter optimization was performed based on the RF model. Ploidy constitution concordance was evaluated in known ploidy status samples. The frequency of abnormal ploidy in normal fertilized PGT blastocysts and 1PN-derived blastocysts (including conventional IVF and ICSI) was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Eleven features were collected for model architecture compared to SVM and Logistic Regression; RF achieved superior performance for ploidy detection. The AI model achieved an AUC of 1 for genome-wide-uniparental diploidy (GW-UPD), 1 for triploidy, and 0.99 for diploidy. For the 792 validation samples, 99.5% of samples were successfully detected using the AI model, and the model showed 100% accuracy for ploidy classification. In the clinical application stage, out of 19\u2009103 PGT samples, 19\u2009069 were successfully analysed using the model, with 110 (0.57%) identified as having abnormal ploidy embryos. Among these, 12.7% (14\/110) were identified as GW-UPD, and 87.3% (96\/110) were triploid. Among 5563 diploid blastocysts transferred, 3478 clinical pregnancies were achieved. Subsequent ploidy analysis was performed for 217 spontaneous abortion and 935 prenatal diagnostic samples, and no abnormal ploidy was identified. Furthermore, of the 140 1PN embryos tested, 40 (28.6%) exhibited GW-UPD, 3 (2.1%) exhibited triploidy, and 97 (69.3%) were determined to be biparental and normally fertilized. Among the 97 biparental embryos, 46 were diploid, 11 were mosaic, and 40 were aneuploid. In terms of the insemination pattern, the percentage of abnormal ploidy in ICSI was significantly higher than in conventional IVF (P\u2009&amp;lt;\u20090.01, 37.1% vs. 2.9%, respectively). With full informed consent, 20 patients without euploidy from normal fertilization chose 1PN-derived biparental and diploid blastocysts to transfer, resulting in 10 clinical pregnancies and 9 ongoing pregnancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LARGE-SCALE DATA<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Some rare ploidy abnormalities, such as polyploidy with an equal number of identical sets of chromosomes and ploidy mosaicism cannot be accurately identified. Moreover, the origin of abnormal ploidy was not identified due to the unavailability of DNA from both parents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>The PGT-Plus AI model provides a ploidy evaluation method based on the conventional PGT-A data and integrates directly into standard PGT-A workflows. Clinical utility results suggest that the model is a valuable tool for identifying embryos with abnormal ploidy in PGT-A and rescuing normal diploid embryos from abnormally fertilized embryos. These findings demonstrate that PGT-Plus significantly enhances the diagnostic accuracy of PGT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This study was supported by grants from Major Scientific Program of CITIC Group (No. 2023ZXKYB34100, to Ge.L.), Hunan Provincial Grant for Innovative Province Construction (2019SK4012), Hunan Xiangjiang New District (Changsha High-tech Zone) key core technology research project in 2023, and Science Foundation of Hunan Province (Grant 2023JJ30422). All authors declared no conflicts of interest..<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/hropen\/hoaf054","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:39:57Z","timestamp":1756467597000},"source":"Crossref","is-referenced-by-count":2,"title":["Accurate identification of abnormal ploidy using an artificial intelligence model in preimplantation genetic testing"],"prefix":"10.1093","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0865-9526","authenticated-orcid":false,"given":"Pingyuan","family":"Xie","sequence":"first","affiliation":[{"name":"Hunan Guangxiu Hospital, Hunan Normal University Health Science Center , Changsha,","place":["China"]},{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya , Changsha,","place":["China"]},{"name":"National Engineering and Research Center of Human Stem Cells , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rijing","family":"Pang","sequence":"additional","affiliation":[{"name":"Hunan Guangxiu Hospital, Hunan Normal University Health Science Center , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Hunan Guangxiu Hospital, Hunan Normal University Health Science Center , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6866-7675","authenticated-orcid":false,"given":"Shuoping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya , Changsha,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Peking Jabrehoo Med Tech Co. 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