囊胚活检相关液滴的遗传学分析及其在PGT-SR患者中的潜在应用
Genetic analysis of biopsy-related droplets and its potential applications in PGT-SR patients
摘要
该研究收集218枚囊胚活检过程中产生的活检、洗涤与暂存三类液滴(合并约15 µL),进行全基因组扩增与CNV测序,以评估活检相关液滴(BRD)在植入前遗传学检测结构重排(PGT-SR)中的辅助价值。69.27%的BRD文库浓度≥0.5 ng/µL,CNV检测成功率为94.04%;142例成功检测者中87.32%与PGT结果倍性一致,结构重排异常囊胚中完全或部分一致率为77.53%。37枚移植的活检整倍体囊胚中,BRD整倍体或不可检出组的临床妊娠率(85.71%、86.96%)明显高于BRD非整倍体组(28.57%)。作者结论:BRD检测可作为PGT-SR常规活检的辅助手段。
原文摘要
PURPOSE: To investigate genetic material in biopsy-related droplets (BRDs) from blastocyst biopsy and its potential applications in preimplantation genetic testing for structural rearrangements (PGT-SR). METHODS: BRDs were collected from 218 blastocysts by combining three types of biopsy-related droplets (biopsy, washing, and temporary storage droplets) into ~15 µL samples. Genomic DNA amplification and copy number variation (CNV) sequencing library preparation were performed. Next-generation sequencing (NGS) was conducted on BRD libraries with concentrations ≥0.5 ng/µL. RESULTS: 69.27% of BRDs had a sequencing library concentration (CSL) ≥ 0.5 ng/µL, with a CNV detection success rate of 94.04%. CSL was significantly higher in biopsy-classified non-euploid than euploid blastocysts (P < 0.0001). Among 142 BRDs with successful CNV detection, 87.32% showed ploidy concordance with PGT findings. Complete or partial concordance was observed in 77.53% of blastocysts with structural rearrangement-related abnormalities. In 37 transferred biopsy-euploid blastocysts, clinical pregnancy rates were higher in the BRD-euploid and undetectable/non-informative BRD groups than in the BRD-non-euploid group (85.71% and 86.96% vs. 28.57%). In seven blastocysts undergoing secondary biopsy after initial testing failure, BRD and secondary biopsy results showed 85.71% ploidy concordance. CONCLUSIONS: BRD-based genetic testing may serve as an adjunct to conventional biopsy-based testing in PGT-SR.
推荐理由:将活检废弃液滴转化为可检测的遗传材料,为PGT-SR提供潜在的无创或补救性验证路径,并首次报告其与临床妊娠结局的关联;但临床结局样本量小(n=37)、单中心,结论需外部验证。
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