Volume 22, Issue 3 (March 2024)                   IJRM 2024, 22(3): 177-190 | Back to browse issues page

‎ 10.18502/ijrm.v22i3.16161

XML Persian Abstract Print

Comparing the advantages, disadvantages and diagnostic power of different non-invasive pre-implantation genetic testing: A literature review
Noorodin Karami1 , Farzaneh Iravani1 , Sareh Bakhshandeh Bavarsad1 , Samira Asadollahi2 , Seyed Mehdi Hoseini3 , Fateme Montazeri * 4, Seyed Mehdi Kalantar5
1- Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2- Department of Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3- Biotechnology Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Science, Yazd, Iran.
4- Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. , f_montazeri@outlook.com
5- Abortion Research Centre, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Abstract:   (331 Views)
To improve embryo transfer success and increase the chances of live birth in assisted reproductive methods, there is a growing demand for the use of pre-implantation genetic testing (PGT). However, the invasive approaches used in PGT have led to in vitro fertilization failure and abortions, increasing anxiety levels for parents. To address this, non-invasive PGT methods have been introduced, such as the detection of DNA in blastocoel fluid of blastocysts and spent culture media (SCM). These methods have proven to be minimally invasive and effective in detecting aneuploidy in the chromosomes of human embryos. This review aims to explore the different approaches to pre-implantation diagnosis, including invasive and non-invasive methods, with a particular focus on non-invasive PGT (niPGT). The search strategy involved gathering data from scientific databases such as PubMed, Google Scholar, and Science Direct using relevant keywords. The search was conducted until January 2023. In total, 22 studies have successfully reported the detection and amplification of cell-free DNA in the embryonic SCM. It is important to note that niPGT has some limitations, which include differences in indicators such as cell-free DNA amplification rate, concordance, level of maternal DNA contamination, sensitivity, and specificity between SCM samples and biopsied cells. Therefore, more extensive and detailed research is needed to fully understand niPGT's potential for clinical applications.

Keywords: Spent culture media, Non-invasive pre-implantation genetic testing, Biopsy methods, Cell-free embryonic DNA.
Full-Text [PDF 1300 kb]   (409 Downloads) |   |   Full-Text (HTML)  (36 Views)  
Type of Study: Review Article | Subject: Assisted Reproductive Technologies
References
1. Cheng W-L, Hsiao Ch-H, Tseng H-W, Lee T-P. Noninvasive prenatal diagnosis. Taiwan J Obstet Gynecol 2015; 54: 343-349. [DOI:10.1016/j.tjog.2015.05.002] [PMID]
2. Nguyen MTM, Knoppers BM. Prenatal and preimplantation diagnosis: International policy perspectives. In: Milunsky A, Milunsky JM. Genetic disorders and the fetus: Diagnosis, prevention, and treatment. 8th Ed. US: Wiley-Blackwell Publisher; 2015. [DOI:10.1002/9781118981559.ch33] [PMID] [PMCID]
3. Fleddermann L, Hashmi SS, Stevens B, Murphy L, Rodriguez-Buritica D, Friel LA, et al. Current genetic counseling practice in the United States following positive non-invasive prenatal testing for sex chromosome abnormalities. J Genet Couns 2019; 28: 802-811. [DOI:10.1002/jgc4.1122] [PMID]
4. Dahdouh EM, Balayla J, García-Velasco JA. Comprehensive chromosome screening improves embryo selection: A meta-analysis. Fertil Steril 2015; 104: 1503-1512. [DOI:10.1016/j.fertnstert.2015.08.038] [PMID]
5. El Hachem H, Crepaux V, May-Panloup P, Descamps P, Legendre G, Bouet P-E. Recurrent pregnancy loss: Current perspectives. Int J Womens Health 2017; 9: 331-345. [DOI:10.2147/IJWH.S100817] [PMID] [PMCID]
6. Schmutzler AG. Theory and practice of preimplantation genetic screening (PGS). Eur J Med Genet 2019; 62: 103670. [DOI:10.1016/j.ejmg.2019.103670] [PMID]
7. Sullivan-Pyke Ch, Dokras A. Preimplantation genetic screening and preimplantation genetic diagnosis. Obstet Gynecol Clin 2018; 45: 113-125. [DOI:10.1016/j.ogc.2017.10.009] [PMID]
8. Chen H-F, Chen S-U, Ma G-C, Hsieh S-T, Tsai H-D, Yang Y-S, et al. Preimplantation genetic diagnosis and screening: Current status and future challenges. J Formos Med Assoc 2018; 117: 94-100. [DOI:10.1016/j.jfma.2017.08.006] [PMID]
9. Munné S. Status of preimplantation genetic testing and embryo selection. Reprod Biomed Online 2018; 37: 393-396. [DOI:10.1016/j.rbmo.2018.08.001] [PMID]
10. Greco E, Litwicka K, Minasi MG, Cursio E, Greco PF, Barillari P. Preimplantation genetic testing: Where we are today. Int J Mol Sci 2020; 21: 4381. [DOI:10.3390/ijms21124381] [PMID] [PMCID]
11. Fesahat F, Montazeri F, Hoseini SM. Preimplantation genetic testing in assisted reproduction technology. J Gynecol Obstet Hum Reprod 2020; 49: 101723. [DOI:10.1016/j.jogoh.2020.101723] [PMID]
12. Chada AR, Crawford S, Hipp HS, Kawwass JF. Trends and outcomes for preimplantation genetic testing for monogenic disorders in the United States, 2014-2018. Fertil Steril 2022; 118: 1190-1193. https://doi.org/10.1016/j.fertnstert.2022.08.100 [DOI:10.1016/j.fertnstert.2022.08.854] [PMID]
13. Parikh FR, Athalye AS, Kulkarni DK, Sanap RR, Dhumal SB, Warang DJ, et al. Evolution and utility of preimplantation genetic testing for monogenic disorders in assisted reproduction: A narrative review. J Hum Reprod Sci 2021; 14: 329-339. [DOI:10.4103/jhrs.jhrs_148_21] [PMID] [PMCID]
14. De Rycke M, Berckmoes V. Preimplantation genetic testing for monogenic disorders. Genes (Basel) 2020; 11: 871. [DOI:10.3390/genes11080871] [PMID] [PMCID]
15. Mateu-Brull E, Rodrigo L, Peinado V, Mercader A, Campos-Galindo I, Bronet F, et al. Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR). J Assist Reprod Genet 2019; 36: 2547-2555. [DOI:10.1007/s10815-019-01593-9] [PMID] [PMCID]
16. Wu TF, Chen MJ, Lee MS, Huang CC, Ho ST, Cheng EH, et al. Comparison of clinical outcome between day 5 and day 6 single blastocyst transfers in cycles undergoing preimplantation genetic testing for aneuploidy. Taiwan J Obstet Gynecol 2023; 62: 429-433. [DOI:10.1016/j.tjog.2023.03.005] [PMID]
17. Dong Z, Wang H, Chen H, Jiang H, Yuan J, Yang Z, et al. Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 genomes project: Implications for interpretation of structural variation in genomes and the future of clinical cytogenetics. Genet Med 2018; 20: 697-707. [DOI:10.1038/gim.2017.170] [PMID] [PMCID]
18. Kakourou G, Mamas T, Vrettou C, Traeger-Synodinos J. An update on non-invasive approaches for genetic testing of the preimplantation embryo. Curr Genomics 2022; 23: 337-352. [DOI:10.2174/1389202923666220927111158] [PMID] [PMCID]
19. Li X, Hao Y, Chen D, Ji D, Zhu W, Zhu X, et al. Non-invasive preimplantation genetic testing for putative mosaic blastocysts: A pilot study. Hum Reprod 2021; 36: 2020-2034. [DOI:10.1093/humrep/deab080] [PMID]
20. Treff NR, Zimmerman R, Bechor E, Hsu J, Rana B, Jensen J, et al. Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform. Eur J Med Genet 2019; 62: 103647. [DOI:10.1016/j.ejmg.2019.04.004] [PMID]
21. Farra C, Choucair F, Awwad J. Non-invasive pre-implantation genetic testing of human embryos: An emerging concept. Hum Reprod 2018; 33: 2162-2167. [DOI:10.1093/humrep/dey314] [PMID]
22. Xu J, Fang R, Chen L, Chen D, Xiao J-P, Yang W, et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci 2016; 113: 11907-11912. [DOI:10.1073/pnas.1613294113] [PMID] [PMCID]
23. Valeriy K, Svetlana M, Ran A, Rina A, Gelareh M, Zenon I, et al. Non-invasive preimplantation genetic testing for aneuploidy (NIPGT-A). Reprod BioMed Online 2019; 38: e41-e42. [DOI:10.1016/j.rbmo.2019.03.068]
24. Leaver M, Wells D. Non-invasive preimplantation genetic testing (niPGT): The next revolution in reproductive genetics? Hum Reprod Update 2020; 26: 16-42. [DOI:10.1093/humupd/dmz033] [PMID]
25. De Rycke M, Goossens V, Kokkali G, Meijer-Hoogeveen M, Coonen E, Moutou C. ESHRE PGD consortium data collection XIV-XV: Cycles from January 2011 to December 2012 with pregnancy follow-up to October 2013. Hum Reprod 2017; 32: 1974-1994. [DOI:10.1093/humrep/dex265] [PMID]
26. Montag M, Van der Ven K, Rösing B, Van der Ven H. Polar body biopsy: A viable alternative to preimplantation genetic diagnosis and screening. Reprod Biomed Online 2009; 18 (Suppl.): 6-11. [DOI:10.1016/S1472-6483(10)60109-5] [PMID]
27. Piyamongkol W, Bermúdez MG, Harper JC, Wells D. Detailed investigation of factors influencing amplification efficiency and allele drop‐out in single cell PCR: Implications for preimplantation genetic diagnosis. Mol Hum Reprod 2003; 9: 411-420. [DOI:10.1093/molehr/gag051] [PMID]
28. Alteri A, Cermisoni GC, Pozzoni M, Gaeta G, Cavoretto PI, Vigano P. Obstetric, neonatal, and child health outcomes following embryo biopsy for preimplantation genetic testing. Hum Reprod Update 2023; 29: 291-306. [DOI:10.1093/humupd/dmad001] [PMID] [PMCID]
29. Kuznyetsov V, Madjunkova S, Abramov R, Antes R, Ibarrientos Z, Motamedi G, et al. Minimally invasive cell-free human embryo aneuploidy testing (miPGT-A) utilizing combined spent embryo culture medium and blastocoel fluid-towards development of a clinical assay. Sci Rep 2020; 10: 7244. [DOI:10.1038/s41598-020-64335-3] [PMID] [PMCID]
30. Jiao J, Shi B, Sagnelli M, Yang D, Yao Y, Li W, et al. Minimally invasive preimplantation genetic testing using blastocyst culture medium. Hum Reprod 2019; 34: 1369-1379. [DOI:10.1093/humrep/dez075] [PMID]
31. Shitara A, Takahashi K, Goto M, Takahashi H, Iwasawa T, Onodera Y, et al. Cell-free DNA in spent culture medium effectively reflects the chromosomal status of embryos following culturing beyond implantation compared to trophectoderm biopsy. PLoS One 2021; 16: e0246438. [DOI:10.1371/journal.pone.0246438] [PMID] [PMCID]
32. Hammond ER, Shelling AN, Cree LM. Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: Evidence and potential clinical use. Hum Reprod 2016; 31: 1653-1661. [DOI:10.1093/humrep/dew132] [PMID]
33. Zhang Y, Li N, Wang L, Sun H, Ma M, Wang H, et al. Molecular analysis of DNA in blastocoele fluid using next-generation sequencing. J Assist Reprod Genet 2016; 33: 637-645. [DOI:10.1007/s10815-016-0667-7] [PMID] [PMCID]
34. Bolton H, Graham SJ, Van der Aa N, Kumar P, Theunis K, Fernandez Gallardo E, et al. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential. Nat Commun 2016; 7: 11165. [DOI:10.1038/ncomms11165] [PMID] [PMCID]
35. Gombos K, Galik B, Kalacs KI, Godony K, Varnagy A, Alpar D, et al. NGS-based application for routine non-invasive pre-implantation genetic assessment in IVF. Int J Mol Sci 2021; 22: 2443. [DOI:10.3390/ijms22052443] [PMID] [PMCID]
36. Homer HA. Preimplantation genetic testing for aneuploidy (PGT-A): The biology, the technology and the clinical outcomes. Aust N Z J Obstet Gynaecol 2019; 59: 317-324. [DOI:10.1111/ajo.12960] [PMID]
37. Lledo B, Ortiz JA, Morales R, Garcia-Hernandez E, Ten J, Bernabeu A, et al. Comprehensive mitochondrial DNA analysis and IVF outcome. Hum Reprod Open 2018; 2018: hoy023. [DOI:10.1093/hropen/hoy023] [PMID] [PMCID]
38. Zhang WY, von Versen-Höynck F, Kapphahn KI, Fleischmann RR, Zhao Q, Baker VL. Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertil Steril 2019; 112: 283-290. https://doi.org/10.1016/j.fertnstert.2019.07.834 [DOI:10.1016/j.fertnstert.2019.03.033] [PMID] [PMCID]
39. Assou S, Aït-Ahmed O, El Messaoudi S, Thierry AR, Hamamah S. Non-invasive pre-implantation genetic diagnosis of X-linked disorders. Med Hypotheses 2014; 83: 506-508. [DOI:10.1016/j.mehy.2014.08.019] [PMID]
40. Wu H, Ding C, Shen X, Wang J, Li R, Cai B, et al. Medium-based noninvasive preimplantation genetic diagnosis for human α-thalassemias-SEA. Medicine (Baltimore) 2015; 94: e669. [DOI:10.1097/MD.0000000000000669] [PMID] [PMCID]
41. Fang Q, Yuan Z, Hu H, Zhang W, Wang G, Wang X. Genome-wide discovery of circulating cell-free DNA methylation biomarkers for colorectal cancer detection. Clin Epigenetics 2023; 15: 119. [DOI:10.1186/s13148-023-01518-5] [PMID] [PMCID]
42. Shamonki MI, Jin H, Haimowitz Z, Liu L. Proof of concept: Preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media. Fertil Steril 2016; 106: 1312-1318. [DOI:10.1016/j.fertnstert.2016.07.1112] [PMID]
43. Hanson BM, Tao X, Hong KH, Comito CE, Pangasnan R, Seli E, 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. Fertil Steril 2021; 115: 1461-1470. [DOI:10.1016/j.fertnstert.2021.01.028] [PMID]
44. Rubio C, Navarro-Sanchez L, Garcia-Pascual CM, Ocali O, Cimadomo D, Venier W, et al. Multicenter prospective study of concordance between embryonic cell-free DNA and trophectoderm biopsies from 1301 human blastocysts. Am J Obstet Gynecol 2020; 223: 751. [DOI:10.1016/j.ajog.2020.04.035] [PMID]
45. Farra C, Choucair F, Awwad J. Corrigendum. Non-invasive pre-implantation genetic testing of human embryos: An emerging concept. Hum Reprod 2019; 34: 590. [DOI:10.1093/humrep/dey385] [PMID]
46. Biricik A, Cotroneo E, Minasi MG, Greco PF, Bono S, Surdo M, et al. Cross-validation of next-generation sequencing technologies for diagnosis of chromosomal mosaicism and segmental aneuploidies in preimplantation embryos model. Life (Basel) 2021; 11: 340. [DOI:10.3390/life11040340] [PMID] [PMCID]
47. Rubio C, Rienzi L, Navarro-Sanchez L, Cimadomo D, Garcia-Pascual CM, Albricci L, et al. Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing: Concordance rate and clinical implications. Fertil Steril 2019; 112: 510-519. [DOI:10.1016/j.fertnstert.2019.04.038] [PMID]
48. Yin B, Zhang H, Xie J, Wei Y, Zhang C, Meng L. Validation of preimplantation genetic tests for aneuploidy (PGT-A) with DNA from spent culture media (SCM): Concordance assessment and implication. Reprod Biol Endocrinol 2021; 19: 41. [DOI:10.1186/s12958-021-00714-3] [PMID] [PMCID]
49. Yang L, Shi W, Li Y, Tong J, Xue X, Zhao Z, et al. SCM is potential resource for non-invasive preimplantation genetic testing based on human embryos single-cell sequencing. Gene 2023; 882: 147647. [DOI:10.1016/j.gene.2023.147647] [PMID]
50. Xu J, Fang R, Chen L, Chen D, Xiao JP, Yang W, et al. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci U S A 2016; 113: 11907-11912. [DOI:10.1073/pnas.1613294113] [PMID] [PMCID]
51. Huang J, Rong L, Zeng L, Hu L, Shi J, Cai 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. BMJ Open 2022; 12: e057254. [DOI:10.1136/bmjopen-2021-057254] [PMID] [PMCID]
52. Yeung QSY, Zhang YX, Chung JPW, Lui WT, Kwok YKY, Gui B, et al. A prospective study of non-invasive preimplantation genetic testing for aneuploidies (NiPGT-A) using next-generation sequencing (NGS) on spent culture media (SCM). J Assist Reprod Genet 2019; 36: 1609-1621. [DOI:10.1007/s10815-019-01517-7] [PMID] [PMCID]
53. Chen D, Xu Y, Ding C, Wang Y, Fu Y, Cai B, et al. The inconsistency between two major aneuploidy-screening platforms-single-nucleotide polymorphism array and next-generation sequencing-in the detection of embryo mosaicism. BMC Genomics 2022; 23: 62. [DOI:10.1186/s12864-022-08294-1] [PMID] [PMCID]
54. Brouillet S, Martinez G, Coutton C, Hamamah S. Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review. Reprod Biomed Online 2020; 40: 779-796. [DOI:10.1016/j.rbmo.2020.02.002] [PMID]
55. Tsai NC, Chang YC, Su YR, Lin YC, Weng PL, Cheng YH, et al. Validation of non-invasive preimplantation genetic screening using a routine IVF laboratory workflow. Biomedicines 2022; 10: 1386. [DOI:10.3390/biomedicines10061386] [PMID] [PMCID]
56. Xu Z, Pan W. Binomial mixture model based association testing to account for genetic heterogeneity for GWAS. Genet Epidemiol 2016; 40: 202-209. [DOI:10.1002/gepi.21954] [PMID] [PMCID]
57. Feichtinger M, Vaccari E, Carli L, Wallner E, Madel U, Figl K, et al. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: A proof-of-concept pilot study. Reprod Biomed Online 2017; 34: 583-589. [DOI:10.1016/j.rbmo.2017.03.015] [PMID]
58. Vera-Rodriguez M, Rubio C. Assessing the true incidence of mosaicism in preimplantation embryos. Fertil Steril 2017; 107: 1107-1112. [DOI:10.1016/j.fertnstert.2017.03.019] [PMID]
59. Liu YL, Yu TN, Wang PH, Tzeng CR, Chen CH, Chen CH. Could PGT-A pick up true abnormalities that have clinical relevance? Retrospective analysis of 1043 embryos. Taiwan J Obstet Gynecol 2020; 59: 496-501. [DOI:10.1016/j.tjog.2020.05.005] [PMID]
60. Ho JR, Arrach N, Rhodes-Long K, Ahmady A, Ingles S, Chung K, et al. Pushing the limits of detection: Investigation of cell-free DNA for aneuploidy screening in embryos. Fertil Steril 2018; 110: 467-475. [DOI:10.1016/j.fertnstert.2018.03.036] [PMID]
61. Cinnioglu C, Glessner H, Jordan A, Bunshaft S. A systematic review of noninvasive preimplantation genetic testing for aneuploidy. Fertil Steril 2023; 120: 235-239. [DOI:10.1016/j.fertnstert.2023.06.013] [PMID]
62. Lane M, Zander-Fox D, Hamilton H, Jasper M, Hodgson B, Fraser M, et al. Ability to detect aneuploidy from cell free DNA collected from media is dependent on the stage of development of the embryo. Fertil Steril 2017; 108 (Suppl.): e61. [DOI:10.1016/j.fertnstert.2017.07.192]
63. Huang J, Yao Y, Jia J, Zhu X, Ma J, Wang J, et al. Chromosome screening of human preimplantation embryos by using spent culture medium: Sample collection and chromosomal ploidy analysis. J Vis Exp 2021; 175: e62619. [DOI:10.3791/62619]
64. Zong C, Lu S, Chapman AR, Xie XS. Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 2012; 338: 1622-1626. [DOI:10.1126/science.1229164] [PMID] [PMCID]
65. Tomic M, Vrtacnik Bokal E, Stimpfel M. Non-invasive preimplantation genetic testing for aneuploidy and the mystery of genetic material: A review article. Int J Mol Sci 2022; 23: 3568. [DOI:10.3390/ijms23073568] [PMID] [PMCID]
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.