Technically feasible solutions to challenges in preimplantation genetic testing for thalassemia: experiences of multiple centers between 2019 and 2022

IF 3.2 3区医学 Q2 GENETICS & HEREDITY Journal of Assisted Reproduction and Genetics Pub Date : 2024-09-10 DOI:10.1007/s10815-024-03240-4

Zi Ren, Peng Huang, Yong Wang, Yaxin Yao, Jun Ren, Linan Xu, Jinhui Shu, Liang Zhou, Dunmei Zhao, Xiaolan Li, Zhiqiang Zhang, Chunhui Zhang, Bolan Sun, Sijia Lu, Weiping Qian, Hong Zhou, Cong Fang

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Abstract

Purpose

In clinical practice, the success of preimplantation genetic testing for monogenic diseases (PGT-M) for thalassemia was hindered by the absence of probands, incomplete family members, or failure in detecting embryonic gene mutation sites. This study aimed to address these issues.

Methods

This retrospective study included 342 couples undergoing PGT-M for α- or β-thalassemia at three reproductive medicine centers from 2019 to 2022. Various methods were used to construct parental haplotypes. A total of 1778 embryos were analyzed and selected for transfer based on chromosomal ploidy and PGT-M results. Follow-up involved amniocentesis results and clinical outcomes.

Results

Haplotypes were established using DNA samples from probands or parents, as well as sibling blood samples, single sperm, and affected embryos, achieving an overall success rate was 99.4% (340/342). For α-thalassemia and β-thalassemia, the concordance between embryo single nucleotide polymorphism (SNP) haplotype analysis results and mutation loci detection results was 93.8% (1011/1078) and 98.2% (538/548), respectively. Multiple annealing and looping-based amplification cycles (MALBAC) showed a higher whole genome amplification success rate than multiple displacement amplification (MDA) (98.8% (1031/1044) vs. 96.2% (703/731), p < 0.001). Amniocentesis confirmed PGT-M outcomes in 100% of cases followed up (99/99).

Conclusion

This study summarizes feasible solutions to various challenging scenarios encountered in PGT-M for thalassemia, providing valuable insights to enhance success rate of PGT-M in clinical practice.

Graphical Abstract

Abstract Image

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地中海贫血植入前基因检测挑战的技术可行解决方案：2019 年至 2022 年期间多个中心的经验

目的在临床实践中，地中海贫血症的单基因疾病植入前基因检测（PGT-M）的成功率因缺乏原型、家庭成员不完整或未能检测到胚胎基因突变位点而受到阻碍。这项回顾性研究纳入了2019年至2022年期间在三家生殖医学中心接受α或β地中海贫血PGT-M检查的342对夫妇。采用各种方法构建亲本单倍型。根据染色体倍性和PGT-M结果，共分析并选择了1778个胚胎进行移植。随访内容包括羊膜腔穿刺结果和临床结果。结果单倍型的建立使用了来自原核或父母、同胞血样、单精子和受影响胚胎的 DNA 样本，总体成功率为 99.4%（340/342）。对于α地中海贫血和β地中海贫血，胚胎单核苷酸多态性（SNP）单体型分析结果与突变位点检测结果的一致性分别为93.8%（1011/1078）和98.2%（538/548）。基于多重退火和循环扩增循环（MALBAC）的全基因组扩增成功率高于多重位移扩增（MDA）（98.8% (1031/1044) vs. 96.2% (703/731)，p < 0.001）。结论本研究总结了地中海贫血 PGT-M 中遇到的各种挑战性情况的可行解决方案，为提高临床实践中 PGT-M 的成功率提供了宝贵的见解。

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来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.