| 405 | 5 | 60 |
| 下载次数 | 被引频次 | 阅读次数 |
胚胎植入前遗传学检测(PGT)是辅助生殖与遗传学检测技术相结合的一种胚胎诊断检测技术，在移植前筛查胚胎染色体以排除染色体异常的胚胎。但是由于目前该技术复杂昂贵，且有创操作可能存在安全风险，所以该技术在临床的应用受到一定限制。因此，人们开始探索利用囊胚腔液和胚胎培养液中发现的游离DNA进行无创PGT。作为更加安全和便捷的基因检测技术，目前无创PGT已经在胚胎染色体检测等方面取得了一定进展，但现有的研究结果之间差异较大，临床应用的有效性仍存在争议。本文就游离DNA的来源及产生机制、无创PGT的临床研究现状进行综述，为无创PGT应用于临床实践提供参考。
Abstract：Preimplantation genetic testing(PGT) is a diagnostic testing technique that combines assisted reproduction and genetic testing techniques to screen embryo chromosomes before implantation to exclude embryos with chromosomal abnormalities. However, due to the complexity and cost of this technology and the potential safety implications of invasive procedures, its widespread clinical application is limited. Therefore, researchers began to explore the use of free DNA found in blastocoel fluid and embryo culture fluid for non-invasive PGT. As a safer and more convenient genetic testing technology, non-invasive PGT has made some progress in embryonic chromosome detection, but there are significant differences in existing research results, and the effectiveness of its clinical application remains controversial. This article summarizes the sources and mechanisms of free DNA and the current status of clinical research on noninvasive PGT,providing a reference for the application of noninvasive PGT in clinical practice.
[1] 张晓翠，赵琼珍，伊江燕，等.51 057例患者外周血染色体核型与生殖异常关系的研究[J].生殖医学杂志，2023,32:220-227.
[2] Tocci A.The unknown human trophectoderm:implication for biopsy at the blastocyst stage[J].J Assist Reprod Genet,2020,37:2699-2711.
[3] Vera-Rodriguez M,Diez-Juan A,Jimenez-Almazan J,et al.Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development[J].Hum Reprod,2018,33:745-756.
[4] Leaver M,Wells D.Non-invasive preimplantation genetic testing(niPGT):the next revolution in reproductive genetics?[J].Hum Reprod Update,2020,26:16-42.
[5] Winiarczyk D,Piliszek A,Sampino S,et al.Embryo structure reorganisation reduces the probability of apoptosis in preimplantation mouse embryos[J].Reprod Fertil Dev,2021,33:725-735.
[6] Huang L,Bogale B,Tang Y,et al.Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy[J].Proc Natl Acad Sci U S A,2019,116:14105-14112.
[7] Gleicher N,Barad DH.Not even noninvasive cell-free DNA can rescue preimplantation genetic testing[J].Proc Natl Acad Sci U S A,2019,116:21976-21977.
[8] Capalbo A,Romanelli V,Patassini C,et al.Diagnostic efficacy of blastocoel fluid and spent media as sources of DNA for preimplantation genetic testing in standard clinical conditions[J].Fertil Steril,2018,110:870-879.
[9] Xie P,Zhang S,Gu Y,et al.Non-invasive preimplantation genetic testing for conventional IVF blastocysts[J].J Transl Med,2022,20:396.
[10] Chen Y,Gao Y,Jia J,et al.DNA methylome reveals cellular origin of cell-free DNA in spent medium of human preimplantation embryos[J].J Clin Invest,2021,131:e146051.
[11] Cai L,Zeng Q,Gao C,et al.Majority of transferred mosaic embryos developed healthy live births revealed by a preclinical study using embryonic morphology assessment and noninvasive PGT-A on cell-free DNA in blastocoel fluid[J].J Assist Reprod Genet,2022,39:2483-2504.
[12] Sialakouma A,Karamasiliotis I,Ntala V,et al.Embryonic cell-free DNA in spent culture medium:a non-invasive tool for aneuploidy screening of the corresponding embryos[J].In Vivo,2021,35:3449-3457.
[13] Rubio C,Rienzi L,Navarro-Sánchez L,et al.Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing:concordance rate and clinical implications[J].Fertil Steril,2019,112:510-519.
[14] Franco JG Jr,Vagnini LD,Petersen CG,et al.Noninvasive preimplantation genetic testing for aneuploidy(niPGT-A):The first Brazilian baby[J].JBRA Assist Reprod,2020,24:517-520.
[15] Huang J,Rong L,Zeng L,et al.Embryo selection through non-invasive preimplantation genetic testing with cell-free DNA in spent culture media:a protocol for a multicentre,double-blind,randomised controlled trial[J].BMJ Open,2022,12:e057254.
[16] Cheng YF,Zhang CL,Liu Y,et al.Effect of noninvasive embryo viability testing versus conventional IVF on the live birth rate in IVF/ICSI patients:a study protocol for a double-blind,multicenter,randomized controlled trial[J].BMC Pregnancy Childbirth,2023,23:641.
[17] Ho JR,Arrach N,Rhodes-Long K,et al.Pushing the limits of detection:investigation of cell-free DNA for aneuploidy screening in embryos[J].Fertil Steril,2018,110:467-475,e2.
[18] Hanson BM,Tao X,Hong KH,et al.Noninvasive preimplantation genetic testing for aneuploidy exhibits high rates of deoxyribonucleic acid amplification failure and poor correlation with results obtained using trophectoderm biopsy[J].Fertil Steril,2021,115:1461-1470.
[19] Hammond ER,Shelling AN,Cree LM.Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium:evidence and potential clinical use[J].Hum Reprod,2016,31:1653-1661.
[20] Magli MC,Pomante A,Cafueri G,et al.Preimplantation genetic testing:polar bodies,blastomeres,trophectoderm cells,or blastocoelic fluid?[J].Fertil Steril,2016,105:676-683,e5.
[21] Magli MC,Albanese C,Crippa A,et al.Deoxyribonucleic acid detection in blastocoelic fluid:a new predictor of embryo ploidy and viable pregnancy[J].Fertil Steril,2019,111:77-85.
[22] Tomic M,Vrtacnik Bokal E,Stimpfel M.Non-invasive preimplantation genetic testing for aneuploidy and the mystery of genetic material:A review article[J].Int J Mol Sci,2022,23:3568.
[23] Tobler KJ,Zhao Y,Ross R,et al.Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis[J].Fertil Steril,2015,104:418-425.
[24] Wu H,Ding C,Shen X,et al.Medium-based noninvasive preimplantation genetic diagnosis for human alpha-thalassemias-SEA[J].Medicine(Baltimore),2015,94:e669.
[25] Liu W,Liu J,Du H,et al.Non-invasive pre-implantation aneuploidy screening and diagnosis of beta thalassemia IVSII654 mutation using spent embryo culture medium[J].Ann Med,2017,49:319-328.
[26] Ou Z,Deng Y,Liang Y,et al.Improved non-invasive preimplantation genetic testing for beta-thalassemia using spent embryo culture medium containing blastocoelic fluid[J].Front Endocrinol(Lausanne),2021,12:793821.
[27] Jiao J,Shi B,Sagnelli M,et al.Minimally invasive preimplantation genetic testing using blastocyst culture medium[J].Hum Reprod,2019,34:1369-1379.
[28] 胡静，张琼芬，凡姝.NICS与PGD检测胚胎染色体罗氏易位一致性的研究[J].中国妇幼健康研究，2022,33:152-157.
[29] Lane M,Zander-Fox DL,Hamilton H,et al.Ability to detect aneuploidy from cell free DNA collected from media is dependent on the stage of development of the embryo[J].Fertil Steril,2017,108:e61.
[30] Veraguas D,Aguilera C,Henriquez C,et al.Evaluation of extracellular vesicles and gDNA from culture medium as a possible indicator of developmental competence in human embryos[J].Zygote,2021,29:138-149.
[31] Segura-Benítez M,Carbajo-García MC,Corachán A,et al.Proteomic analysis of extracellular vesicles secreted by primary human epithelial endometrial cells reveals key proteins related to embryo implantation[J].Reprod Biol Endocrinol,2022,20:3.
[32] Rosenbluth EM,Shelton DN,Wells LM,et al.Human embryos secrete microRNAs into culture media--a potential biomarker for implantation[J].Fertil Steril,2014,101:1493-1500.
[33] Fang F,Li Z,Yu J,et al.MicroRNAs secreted by human embryos could be potential biomarkers for clinical outcomes of assisted reproductive technology[J].J Adv Res,2021,31:25-34.
[34] Kuznyetsov V,Madjunkova S,Antes R,et al.Evaluation of a novel non-invasive preimplantation genetic screening approach[J/OL].PLoS One,2018,13:e0197262.
[35] Shamonki MI,Jin H,Haimowitz Z,et al.Proof of concept:preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media[J].Fertil Steril,2016,106:1312-1318.
基本信息:
中图分类号:R714.8
引用信息:
[1]王嘉祥,田甜,张楠,等.无创胚胎植入前遗传学检测技术进展研究[J].生殖医学杂志,2024,33(07):965-970.
基金信息:
国家重点研发计划课题(2021YFC2700605); 北京市科技计划(Z191100006619085); 国家自然科学基金项目(82171632)
2023-10-04
2023
2024-01-17
2024-05-28
2024
1
2024-07-15
2024-07-15