Preimplantation genetic testing for aneuploidy mosaicism reporting lacks clinical predictive value for live birth in a multisite, double-blinded study with independent validation

作者：Pavan Gill, Xin Tao, Yiping Zhan, Francesca Mulas, Christian Simon Ottolini, Ludovica Picchetta, Silvia Caroselli, D Babariya, Dagan Wells, Georgina Jane Clark, Elena Fernandez Marcos, Carlos Marin Vallejo, Vaidehi Jobanputra, Marie M. Werner, Richard H. Scott, Thomas A. Molinaro, J Pla Victori, Vanessa Vergara Bravo, Antonio Requena Miranda, Juan Antonio García-Velasco, António Pellicer, Emily L. Mounts, Chaim Jalas, Antonio Capalbo · 发表于：American Journal of Obstetrics and Gynecology · 年份：2025 · DOI：10.1016/j.ajog.2025.12.033 · 被引用次数：7 · 研究领域：Prenatal Screening and Diagnostics、Genetic Syndromes and Imprinting、Assisted Reproductive Technology and Twin Pregnancy

BACKGROUND: Preimplantation genetic testing for aneuploidy is used to improve in vitro fertilization outcomes by identifying embryos with lethal chromosomal abnormalities that impair development or lead to pregnancy loss. The adoption of next-generation sequencing has enabled detection of intermediate copy number deviations, often interpreted as putative mosaicism, whose clinical significance remains uncertain. OBJECTIVE: To determine whether reporting putative mosaicism based on intermediate copy number improves the prediction of reproductive outcomes and should influence embryo selection in clinical practice. STUDY DESIGN: We conducted a large, multisite, double-blinded, nonselection study across US fertility clinics (February 2020-October 2022), including 9828 single-embryo transfers from 7564 in vitro fertilization cycles. Findings were independently validated using 5487 euploid single-embryo transfers from European clinics (May 2022-March 2024). Intermediate copy number status was unblinded only after embryo transfer, allowing unbiased comparison between embryos that would have been classified as euploid or mosaic with our platform. The primary outcome for investigation in the study was live birth rate, defined as delivery after 24 weeks (gestational age). RESULTS: After unblinding the intermediate copy number status post-transfer, 84.7% (n=8328) of embryos were negative for intermediate copy number (euploid), while 8.8% (n=864) exhibited segmental intermediate copy numb...