基于PGT-A测序数据的端粒评分用于胚胎评估的初步研究
该回顾性队列研究纳入2023年9月至2025年2月间1451对夫妇的5251枚囊胚，从常规PGT-A测序数据中提取端粒评分（Teloscore）。在335个单胚胎移植周期中，Teloscore可独立预测种植（OR 1.096，95%CI 1.011-1.188），并与活检时间共同构建预测模型（AUC 0.668，验证队列0.634）。
要点
- Teloscore每增加1单位，种植几率独立升高（OR 1.096，95%CI 1.011-1.188）。
- 第5天活检与更高种植相关（OR 1.993，95%CI 1.071-3.707）。
- 种植率随Teloscore升高而递增，从36.8%（0-4）至72.4%（≥13）。
核心结论
- Teloscore是从常规PGT-A数据再分析衍生的可行、可重复且成本效益好的胚胎评估生物标志物。
- 现阶段Teloscore并非确定性临床检测，而是提供端粒恢复可能与胚胎发育潜能和种植潜力相关的假设生成框架。
研究设计与样本
- 回顾性队列研究，纳入2023年9月至2025年2月间1451对夫妇的5251枚囊胚（平均母亲年龄36.5岁）。
- 暴露为从常规PGT-A测序数据再分析得出的Teloscore，量化为每百万总reads中的端粒reads。
主要发现
- 335个单胚胎移植周期中206例发生种植（61.5%）。
- 多变量logistic回归中Teloscore独立预测种植（OR 1.096/单位增加，95%CI 1.011-1.188），第5天活检亦独立预测（OR 1.993，95%CI 1.071-3.707）。
- 包含Teloscore、活检时间、BMI和胚胎形态的预测模型AUC为0.668，验证队列为0.634。
- 种植率随Teloscore升高而递增：36.8%（0-4）、63.3%（4-7）、64.6%（7-10）、65.7%（10-13）、72.4%（≥13）。
- 重复测序运行确认技术可重复性（R2=0.756）。
临床怎么用
- 可探索将Teloscore作为现有胚胎选择流程的补充指标，但尚不能作为确定性临床检测。
- Teloscore来源于常规PGT-A数据再分析，无需额外检测成本。
局限性
- 为回顾性队列研究，样本中仅335个单胚胎移植周期可用于种植结局分析。
- 预测模型AUC在开发队列为0.668、验证队列为0.634，区分度有限。
- 作者指出Teloscore为假设生成框架，尚需进一步验证。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVE: To determine whether telomere measurement (Teloscore) derived from sequencing data from preimplantation genetic testing for aneuploidy (PGT-A) improves embryo selection beyond morphology and ploidy assessment alone in assisted reproduction. DESIGN: Retrospective cohort study. SUBJECTS: A total of 5,251 blastocysts from 1,451 couples undergoing in vitro fertilization/PGT-A cycles between September 2023 and February 2025 (mean maternal age, 36.5 years) were included. EXPOSURE: Teloscore, derived from reanalysis of routine PGT-A sequencing data and quantified as telomeric reads per million total reads. MAIN OUTCOME MEASURES: Implantation after single embryo transfer (SET), defined as the presence of a gestational sac. RESULTS: Among 335 SET cycles (development cohort: 234; validation cohort: 101), implantation occurred in 206 cases (61.5%). Teloscore independently predicted implantation in the multivariable logistic regression model (odds ratio [OR]: 1.096 per unit increase, 95% confidence interval [CI]: 1.011-1.188), along with day 5 biopsy (OR: 1.993, 95% CI: 1.071-3.707). Findings were consistent in both the development and validation cohorts. A predictive model incorporating Teloscore, biopsy timing, body mass index, and embryo morphology yielded an area under the curve of 0.668, which was replicated in the validation cohort (0.634). Implantation rates rose progressively with increasing Teloscore, from 36.8% (0-4) to 63.3% (4-7), 64.6% (7-10), 65.7% (10-13), and 72.4% (≥13). Technical reproducibility was confirmed using duplicate sequencing runs (R2 = 0.756). CONCLUSION: The Teloscore, derived from reanalysis of routine PGT-A data, is a feasible, reproducible, and cost-effective biomarker for embryo assessment. At this stage, rather than offering a definitive clinical test, the Teloscore provides a hypothesis-generating framework that suggests telomere recovery may be linked to embryonic competence and implantation potential. Its integration into current workflows offers an opportunity to explore telomere biology as a complementary approach in embryo selection.
引用
- Lo WC, Cheng EH, Shih HH, et al. Postfertilization telomere marker testing in human embryos: a pilot study of a novel embryo evaluation assay. Fertil Steril. 2026. PMID: 41985734. doi:10.1016/j.fertnstert.2026.04.003
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。