Skip to main content
Log in

Current Applications and Controversies in Preimplantation Genetic Testing for Aneuploidies (PGT-A) in In Vitro Fertilization

  • Reproductive Genetics: Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) has evolved over recent years, including improvements in embryo culture, biopsy, transfer, and genetic testing. The application of new comprehensive chromosome screening analysis has improved the accuracy in determining the chromosomal status of the analyzed sample, but it has brought new challenges such as the management of partial aneuploidies and mosaicisms. For the past two decades, PGT-A has been involved in a controversy regarding its efficiency in improving IVF outcomes, despite its widespread worldwide implementation. Understanding the impact of embryo aneuploidy in IVF (in vitro fertilization) should theoretically allow improving reproductive outcomes. This review of the literature aims to describe the impact of aneuploidy in human reproduction and how PGT-A was introduced to overcome this obstacle in IVF (in vitro fertilization). The article will try to analyze and summarize the evolution of the PGT-A in the recent years, and its current applications and limitations, as well as the controversy it generates. Conflicting published data could indicate the lacking value of a single biopsied sample to determine embryo chromosomal status and/or the lack of standardized methods for embryo culture and management and genetic analysis among other factors. It has to be considered that PGT-A may not be a universal test to improve the reproductive potential in IVF patients, rather each clinic should evaluate the efficacy of PGT-A in their IVF program based on their population, skills, and limitations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. ESHRE PGT Consortium Steering Committee, Carvalho F, Coonen E, et al. ESHRE PGT Consortium good practice recommendations for the organisation of PGT. Hum Reprod Open. 2020;2020(3):hoaa021. https://doi.org/10.1093/hropen/hoaa021.

  2. Kuliev A, Rechitsky S. Preimplantation genetic testing: current challenges and future prospects. Expert Rev Mol Diagn. 2017;17(12):1071–88. https://doi.org/10.1080/14737159.2017.1394186.

    Article  CAS  PubMed  Google Scholar 

  3. Handyside AH, Kontogianni EH, Hardy K, Winston RML. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990;344:768–70. https://doi.org/10.1038/344768a0.

    Article  CAS  PubMed  Google Scholar 

  4. Munné S, Lee A, Rosenwaks Z, Grifo J, Cohen J. Fertilization and early embryology: diagnosis of major chromosome aneuploidies in human preimplantation embryos. Hum Reprod. 1993;8:2185–91. https://doi.org/10.1093/oxfordjournals.humrep.a138001.

    Article  PubMed  Google Scholar 

  5. Velilla E, Morales C. Relevance of embryo aneuploidy in medically assisted reproduction. In: Allahbadia GN, Ata B, Lindheim SR, Woodward BJ, Bhagavath B (eds.) Textbook of Assisted Reproduction Singapore: Springer; 2020;643–8. https://doi.org/10.1007/978-981-15-2377-9_71.

  6. 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. https://doi.org/10.3390/ijms21124381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kuwayama M. Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method. Theriogenology. 2007;67:73–80. https://doi.org/10.1016/j.theriogenology.2006.09.014.

    Article  CAS  PubMed  Google Scholar 

  8. Viotti M. Preimplantation genetic testing for chromosomal abnormalities: aneuploidy, mosaicism, and structural rearrangements. Genes. 2020;11:E602. https://doi.org/10.3390/genes11060602.

    Article  CAS  Google Scholar 

  9. Alfarawati S, Fragouli E, Colls P, Stevens J, Gutiérrez-Mateo C, Schoolcraft WB, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011;95:520–4. https://doi.org/10.1016/j.fertnstert.2010.04.003.

    Article  PubMed  Google Scholar 

  10. Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014;29:1173–81. https://doi.org/10.1093/humrep/deu033.

    Article  PubMed  Google Scholar 

  11. Ozgur K, Berkkanoglu M, Bulut H, Yoruk GDA, Candurmaz NN, Coetzee K. Single best euploid versus single best unknown-ploidy blastocyst frozen embryo transfers: a randomized controlled trial. J Assist Reprod Genet. 2019;36:629–36. https://doi.org/10.1007/s10815-018-01399-1.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Neal SA, Morin SJ, Franasiak JM, Goodman LR, Juneau CR, Forman EJ, et al. Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage. Fertil Steril. 2018;110:896–904. https://doi.org/10.1016/j.fertnstert.2018.06.021.

    Article  PubMed  Google Scholar 

  13. Tiegs AW, Tao X, Zhan Y, Whitehead C, Kim J, Hanson B, et al. A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy. Fertil Steril. 2021;115:627–37. https://doi.org/10.1016/j.fertnstert.2020.07.052.

    Article  CAS  PubMed  Google Scholar 

  14. Wang L, Wang X, Li M, Liu Y, Ou X, Chen L, et al. PGT-A: the biology and hidden failures of randomized control trials. Prenat Diagn. 2022;42:1211–21. https://doi.org/10.1002/pd.6199.

    Article  PubMed  Google Scholar 

  15. Practice Committee of the American Society for Reproductive Medicine. Electronic address: ASRM@asrm.org, Practice Committee of the Society for Assisted Reproductive Technology. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril. 2017;107:901–3. https://doi.org/10.1016/j.fertnstert.2017.02.107.

    Article  Google Scholar 

  16. Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013;100:100-107.e1. https://doi.org/10.1016/j.fertnstert.2013.02.056.

    Article  PubMed  Google Scholar 

  17. van den Berg MMJ, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta BBA - Mol Basis Dis. 2012;1822:1951–9. https://doi.org/10.1016/j.bbadis.2012.07.001.

    Article  CAS  Google Scholar 

  18. Soler A, Morales C, Mademont-Soler I, Margarit E, Borrell A, Borobio V, et al. Overview of chromosome abnormalities in first trimester miscarriages: a series of 1,011 consecutive chorionic villi sample karyotypes. Cytogenet Genome Res. 2017;152:81–9. https://doi.org/10.1159/000477707.

    Article  CAS  PubMed  Google Scholar 

  19. Klimczak AM, Patel DP, Hotaling JM, Scott RT. Role of the sperm, oocyte, and embryo in recurrent pregnancy loss. Fertil Steril. 2021;115:533–7. https://doi.org/10.1016/j.fertnstert.2020.12.005.

    Article  CAS  PubMed  Google Scholar 

  20. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2:76–83.

    PubMed  PubMed Central  Google Scholar 

  21. Fragouli E, Wells D. Aneuploidy in the human blastocyst. Cytogenet Genome Res. 2011;133:149–59. https://doi.org/10.1159/000323500.

    Article  CAS  PubMed  Google Scholar 

  22. Templado C, Uroz L, Estop A. New insights on the origin and relevance of aneuploidy in human spermatozoa. Mol Hum Reprod. 2013;19:634–43. https://doi.org/10.1093/molehr/gat039.

    Article  CAS  PubMed  Google Scholar 

  23. Penrose LS. Maternal age in familial mongolism. J Ment Sci. 1951;97:738–47. https://doi.org/10.1192/bjp.97.409.738.

    Article  CAS  PubMed  Google Scholar 

  24. Smith A, Record RG. Maternal age and birth rank in the aetiology of mongolism. Br J Prev Soc Med. 1955;9:51–5. https://doi.org/10.1136/jech.9.1.51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of maternal age on oocyte and embryo competence. Front Endocrinol. 2018;9:327.

  26. Moghadam ARE, Moghadam MT, Hemadi M, Saki G. Oocyte quality and aging. JBRA Assist Reprod. 2022;26:105–22. https://doi.org/10.5935/1518-0557.20210026.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kuliev A, Zlatopolsky Z, Kirillova I, Spivakova J, Janzen JC. Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reprod Biomed Online. 2011;22:2–8. https://doi.org/10.1016/j.rbmo.2010.08.014.

    Article  PubMed  Google Scholar 

  28. Sánchez-Castro M, Jiménez-Macedo AR, Sandalinas M, Blanco J. Prognostic value of sperm fluorescence in situ hybridization analysis over PGD. Hum Reprod Oxf Engl. 2009;24:1516–21. https://doi.org/10.1093/humrep/dep037.

    Article  Google Scholar 

  29. Sarrate Z, Vidal F, Blanco J. Role of sperm fluorescent in situ hybridization studies in infertile patients: indications, study approach, and clinical relevance. Fertil Steril. 2010;93:1892–902. https://doi.org/10.1016/j.fertnstert.2008.12.139.

    Article  CAS  PubMed  Google Scholar 

  30. Rodrigo L, Meseguer M, Mateu E, Mercader A, Peinado V, Bori L, et al. Sperm chromosomal abnormalities and their contribution to human embryo aneuploidy. Biol Reprod. 2019;101:1091–101. https://doi.org/10.1093/biolre/ioz125.

    Article  PubMed  Google Scholar 

  31. Harton GL, Tempest HG. Chromosomal disorders and male infertility. Asian J Androl. 2012;14:32–9. https://doi.org/10.1038/aja.2011.66.

    Article  PubMed  Google Scholar 

  32. Stolakis V, Bertero MC. Molecular aspects of aneuploidy in preimplantation human embryos: a mini-review. Ann Res Hosp. 2019;3. https://doi.org/10.21037/arh.2019.02.02.

  33. McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet TIG. 2017;33:448–63. https://doi.org/10.1016/j.tig.2017.04.001.

    Article  CAS  PubMed  Google Scholar 

  34. Taylor TH, Gitlin SA, Patrick JL, Crain JL, Wilson JM, Griffin DK. The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Hum Reprod Update. 2014;20:571–81. https://doi.org/10.1093/humupd/dmu016.

    Article  CAS  PubMed  Google Scholar 

  35. Currie CE, Ford E, Benham Whyte L, Taylor DM, Mihalas BP, Erent M, et al. The first mitotic division of human embryos is highly error prone. Nat Commun. 2022;13:6755. https://doi.org/10.1038/s41467-022-34294-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vera-Rodríguez M, Michel C-E, Mercader A, Bladon AJ, Rodrigo L, Kokocinski F, et al. Distribution patterns of segmental aneuploidies in human blastocysts identified by next-generation sequencing. Fertil Steril. 2016;105:1047-1055.e2. https://doi.org/10.1016/j.fertnstert.2015.12.022.

    Article  PubMed  Google Scholar 

  37. Girardi L, Serdarogullari M, Patassini C, Poli M, Fabiani M, Caroselli S, et al. Incidence, origin, and predictive model for the detection and clinical management of segmental aneuploidies in human embryos. Am J Hum Genet. 2020;106:525–34. https://doi.org/10.1016/j.ajhg.2020.03.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Munné S, Chen S, Colls P, Garrisi J, Zheng X, Cekleniak N, et al. Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos. Reprod Biomed Online. 2007;14:628–34. https://doi.org/10.1016/s1472-6483(10)61057-7.

    Article  PubMed  Google Scholar 

  39. Munné S. Chromosome abnormalities and their relationship to morphology and development of human embryos. Reprod Biomed Online. 2006;12:234–53. https://doi.org/10.1016/s1472-6483(10)60866-8.

    Article  PubMed  Google Scholar 

  40. Fragouli E, Alfarawati S, Spath K, Wells D. Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos. Mol Hum Reprod. 2014;20:117–26. https://doi.org/10.1093/molehr/gat073.

    Article  CAS  PubMed  Google Scholar 

  41. Minasi MG, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31:2245–54. https://doi.org/10.1093/humrep/dew183.

    Article  PubMed  Google Scholar 

  42. Brezina PR, Kutteh WH, Bailey AP, Ke RW. Preimplantation genetic screening (PGS) is an excellent tool, but not perfect: a guide to counseling patients considering PGS. Fertil Steril. 2016;105:49–50. https://doi.org/10.1016/j.fertnstert.2015.09.042.

    Article  PubMed  Google Scholar 

  43. Sachdev NM, Maxwell SM, Besser AG, Grifo JA. Diagnosis and clinical management of embryonic mosaicism. Fertil Steril. 2017;107:6–11. https://doi.org/10.1016/j.fertnstert.2016.10.006.

    Article  PubMed  Google Scholar 

  44. ESHRE PGT-SR/PGT-A Working Group, Coonen E, Rubio C, Christopikou D, Dimitriadou E, Gontar J, et al. ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations†. Hum Reprod Open. 2020;2020:hoaa017. https://doi.org/10.1093/hropen/hoaa017.

    Article  PubMed Central  Google Scholar 

  45. Treff NR, Zimmerman RS. Advances in preimplantation genetic testing for monogenic disease and aneuploidy. Annu Rev Genomics Hum Genet. 2017;18:189–200. https://doi.org/10.1146/annurev-genom-091416-035508.

    Article  CAS  PubMed  Google Scholar 

  46. Chen H-F, Chen M, Ho H-N. An overview of the current and emerging platforms for preimplantation genetic testing for aneuploidies (PGT-A) in in vitro fertilization programs. Taiwan J Obstet Gynecol. 2020;59:489–95. https://doi.org/10.1016/j.tjog.2020.05.004.

    Article  PubMed  Google Scholar 

  47. Friedenthal J, Maxwell SM, Munné S, Kramer Y, McCulloh DH, McCaffrey C, et al. Next generation sequencing for preimplantation genetic screening improves pregnancy outcomes compared with array comparative genomic hybridization in single thawed euploid embryo transfer cycles. Fertil Steril. 2018;109:627–32. https://doi.org/10.1016/j.fertnstert.2017.12.017.

    Article  CAS  PubMed  Google Scholar 

  48. Biezuner T, Raz O, Amir S, Milo L, Adar R, Fried Y, et al. Comparison of seven single cell whole genome amplification commercial kits using targeted sequencing. Sci Rep. 2021;11:17171. https://doi.org/10.1038/s41598-021-96045-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Volozonoka L, Miskova A, Gailite L. Whole genome amplification in preimplantation genetic testing in the era of massively parallel sequencing. Int J Mol Sci. 2022;23:4819. https://doi.org/10.3390/ijms23094819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Capalbo A, Bono S, Spizzichino L, Biricik A, Baldi M, Colamaria S, et al. Sequential comprehensive chromosome analysis on polar bodies, blastomeres and trophoblast: insights into female meiotic errors and chromosomal segregation in the preimplantation window of embryo development. Hum Reprod. 2013;28:509–18. https://doi.org/10.1093/humrep/des394.

    Article  CAS  PubMed  Google Scholar 

  51. Montag M, Köster M, Strowitzki T, Toth B. Polar body biopsy. Fertil Steril. 2013;100:603–7. https://doi.org/10.1016/j.fertnstert.2013.05.053.

    Article  PubMed  Google Scholar 

  52. Scott KL, Hong KH, Scott RT. Selecting the optimal time to perform biopsy for preimplantation genetic testing. Fertil Steril. 2013;100:608–14. https://doi.org/10.1016/j.fertnstert.2013.07.004.

    Article  PubMed  Google Scholar 

  53. Zacchini F, Arena R, Abramik A, Ptak GE. Embryo biopsy and development: the known and the unknown. Reproduction. 2017;154:R143–8. https://doi.org/10.1530/REP-17-0431.

    Article  PubMed  Google Scholar 

  54. ESHRE Working Group on Chromosomal Mosaicism, De Rycke M, Capalbo A, Coonen E, Coticchio G, Fiorentino F, et al. ESHRE survey results and good practice recommendations on managing chromosomal mosaicism†. Hum Reprod Open. 2022;2022:hoac044. https://doi.org/10.1093/hropen/hoac044.

    Article  PubMed Central  Google Scholar 

  55. Gleicher N, Kushnir VA, Barad DH. Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod Biol Endocrinol. 2014;12:22. https://doi.org/10.1186/1477-7827-12-22.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chen L, Sun Q, Xu J, Fu H, Liu Y, Yao Y, et al. A Non-invasive chromosome screening strategy for prioritizing in vitro fertilization embryos for implantation. Front Cell Dev Biol. 2021;9:708322. https://doi.org/10.3389/fcell.2021.708322.

    Article  PubMed  PubMed Central  Google Scholar 

  57. 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.e2. https://doi.org/10.1016/j.fertnstert.2018.03.036.

    Article  CAS  PubMed  Google Scholar 

  58. Huang L, Bogale B, Tang Y, Lu S, Xie XS, Racowsky C. Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy. Proc Natl Acad Sci USA. 2019;116:14105–12. https://doi.org/10.1073/pnas.1907472116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lledo B, Morales R, Ortiz JA, Rodriguez-Arnedo A, Ten J, Castillo JC, et al. Consistent results of non-invasive PGT-A of human embryos using two different techniques for chromosomal analysis. Reprod Biomed Online. 2021;42:555–63. https://doi.org/10.1016/j.rbmo.2020.10.021.

    Article  CAS  PubMed  Google Scholar 

  60. Rubio C, Rienzi L, Navarro-Sánchez L, Cimadomo D, García-Pascual CM, Albricci L, et al. Embryonic cell-free DNA versus trophectoderm biopsy for aneuploidy testing: concordance rate and clinical implications. Fertil Steril. 2019;112:510–9. https://doi.org/10.1016/j.fertnstert.2019.04.038.

    Article  CAS  PubMed  Google Scholar 

  61. 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. https://doi.org/10.1371/journal.pone.0246438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Vera-Rodriguez M, Diez-Juan A, Jimenez-Almazan J, Martinez S, Navarro R, Peinado V, et al. Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development. Hum Reprod Oxf Engl. 2018;33:745–56. https://doi.org/10.1093/humrep/dey028.

    Article  CAS  Google Scholar 

  63. 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;36:1609–21. https://doi.org/10.1007/s10815-019-01517-7.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Navarro-Sánchez L, García-Pascual C, Rubio C, Simón C. Non-invasive preimplantation genetic testing for aneuploidies: an update. Reprod Biomed Online. 2022;44:817–28. https://doi.org/10.1016/j.rbmo.2022.01.012.

    Article  CAS  PubMed  Google Scholar 

  65. ESHRE PGT Consortium and SIG-Embryology Biopsy Working Group, Kokkali G, Coticchio G, Bronet F, Celebi C, Cimadomo D, et al. ESHRE PGT Consortium and SIG Embryology good practice recommendations for polar body and embryo biopsy for PGT†. Hum Reprod Open. 2020;2020:hoaa020. https://doi.org/10.1093/hropen/hoaa020.

    Article  PubMed Central  Google Scholar 

  66. Harper JC, Aittomäki K, Borry P, Cornel MC, de Wert G, Dondorp W, et al. Recent developments in genetics and medically assisted reproduction: from research to clinical applications. Eur J Hum Genet EJHG. 2018;26:12–33. https://doi.org/10.1038/s41431-017-0016-z.

    Article  CAS  PubMed  Google Scholar 

  67. Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Electronic address: ASRM@asrm.org, Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. The use of preimplantation genetic testing for aneuploidy (PGT-A): a committee opinion. Fertil Steril. 2018;109:429–36. https://doi.org/10.1016/j.fertnstert.2018.01.002.

    Article  Google Scholar 

  68. Mehari M, Maeruf H, Robles CC, Woldemariam S, Adhena T, Mulugeta M, et al. Advanced maternal age pregnancy and its adverse obstetrical and perinatal outcomes in Ayder comprehensive specialized hospital, Northern Ethiopia, 2017: a comparative cross-sectional study. BMC Pregnancy Childbirth. 2020;20:60. https://doi.org/10.1186/s12884-020-2740-6.

    Article  PubMed  PubMed Central  Google Scholar 

  69. van Montfoort A, Carvalho F, Coonen E, Kokkali G, Moutou C, Rubio C, et al. ESHRE PGT Consortium data collection XIX–XX: PGT analyses from 2016 to 2017†. Hum Reprod Open. 2021;2021:hoab024. https://doi.org/10.1093/hropen/hoab024.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, et al. The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening. Fertil Steril. 2014;101:656-663.e1. https://doi.org/10.1016/j.fertnstert.2013.11.004.

    Article  PubMed  Google Scholar 

  71. Mazzilli R, Vaiarelli A, Dovere L, Cimadomo D, Ubaldi N, Ferrero S, et al. Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update. Asian J Androl. 2022;24:125. https://doi.org/10.4103/aja.aja_53_21.

    Article  CAS  PubMed  Google Scholar 

  72. Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15:369–84. https://doi.org/10.1038/s41585-018-0003-3.

    Article  CAS  PubMed  Google Scholar 

  73. Rubio C, Gil-Salom M, Simón C, Vidal F, Rodrigo L, Mínguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16:2084–92. https://doi.org/10.1093/humrep/16.10.2084.

    Article  CAS  PubMed  Google Scholar 

  74. Burrello N, Vicari E, Shin P, Agarwal A, De Palma A, Grazioso C, et al. Lower sperm aneuploidy frequency is associated with high pregnancy rates in ICSI programmes. Hum Reprod. 2003;18:1371–6. https://doi.org/10.1093/humrep/deg299.

    Article  PubMed  Google Scholar 

  75. Nicopoullos JDM, Gilling-Smith C, Almeida PA, Homa S, Nice L, Tempest H, et al. The role of sperm aneuploidy as a predictor of the success of intracytoplasmic sperm injection? Hum Reprod. 2008;23:240–50. https://doi.org/10.1093/humrep/dem395.

    Article  CAS  PubMed  Google Scholar 

  76. Rodrigo L. Sperm genetic abnormalities and their contribution to embryo aneuploidy & miscarriage. Best Pract Res Clin Endocrinol Metab. 2020;34:101477. https://doi.org/10.1016/j.beem.2020.101477.

    Article  CAS  PubMed  Google Scholar 

  77. Popescu F, Jaslow CR, Kutteh WH. Recurrent pregnancy loss evaluation combined with 24-chromosome microarray of miscarriage tissue provides a probable or definite cause of pregnancy loss in over 90% of patients. Hum Reprod. 2018;33:579–87. https://doi.org/10.1093/humrep/dey021.

    Article  CAS  PubMed  Google Scholar 

  78. Sato T, Sugiura-Ogasawara M, Ozawa F, Yamamoto T, Kato T, Kurahashi H, et al. Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure. Hum Reprod. 2019;34:2340–8. https://doi.org/10.1093/humrep/dez229.

    Article  PubMed  Google Scholar 

  79. Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018;2018:hoy004. https://doi.org/10.1093/hropen/hoy004.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Thornhill AR, deDie-Smulders CE, Geraedts JP, Harper JC, Harton GL, Lavery SA, et al. ESHRE PGD Consortium “Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS).” Hum Reprod Oxf Engl. 2005;20:35–48. https://doi.org/10.1093/humrep/deh579.

    Article  CAS  Google Scholar 

  81. Bashiri A, Halper KI, Orvieto R. Recurrent Implantation Failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol. 2018;16:121. https://doi.org/10.1186/s12958-018-0414-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ata B, Kalafat E, Somigliana E. A new definition of recurrent implantation failure on the basis of anticipated blastocyst aneuploidy rates across female age. Fertil Steril. 2021;116:1320–7. https://doi.org/10.1016/j.fertnstert.2021.06.045.

    Article  PubMed  Google Scholar 

  83. Sun Y, Zhang Y, Ma X, Jia W, Su Y. Determining diagnostic criteria of unexplained recurrent implantation failure: a retrospective study of two vs three or more implantation failure. Front Endocrinol (Lausanne). 2021;12:619437. https://doi.org/10.3389/fendo.2021.619437.

  84. McCoy RC, Demko ZP, Ryan A, Banjevic M, Hill M, Sigurjonsson S, et al. Evidence of selection against complex mitotic-origin aneuploidy during preimplantation development. PLoS Genet. 2015;11:e1005601. https://doi.org/10.1371/journal.pgen.1005601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Levy B, Hoffmann ER, McCoy RC, Grati FR. Chromosomal mosaicism: origins and clinical implications in preimplantation and prenatal diagnosis. Prenat Diagn. 2021;41:631–41. https://doi.org/10.1002/pd.5931.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Treff NR, Marin D. The, “mosaic” embryo: misconceptions and misinterpretations in preimplantation genetic testing for aneuploidy. Fertil Steril. 2021;116:1205–11. https://doi.org/10.1016/j.fertnstert.2021.06.027.

    Article  PubMed  Google Scholar 

  87. Marin D, Xu J, Treff NR. Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data. Prenat Diagn. 2021;41:545–53. https://doi.org/10.1002/pd.5828.

  88. Kahraman S, Cetinkaya M, Yuksel B, Yesil M, Pirkevi CC. The birth of a baby with mosaicism resulting from a known mosaic embryo transfer: a case report. Hum Reprod Oxf Engl. 2020;35:727–33. https://doi.org/10.1093/humrep/dez309.

    Article  Google Scholar 

  89. Schlade-Bartusiak K, Strong E, Zhu O, Mackie J, Salema D, Volodarsky M, et al. Mosaic embryo transfer—first report of a live born with nonmosaic partial aneuploidy and uniparental disomy 15. FS Rep. 2022;3:192–7. https://doi.org/10.1016/j.xfre.2022.05.003.

    Article  Google Scholar 

  90. Viotti M, Victor AR, Barnes FL, Zouves CG, Besser AG, Grifo JA, et al. Using outcome data from one thousand mosaic embryo transfers to formulate an embryo ranking system for clinical use. Fertil Steril. 2021;115:1212–24. https://doi.org/10.1016/j.fertnstert.2020.11.041.

    Article  CAS  PubMed  Google Scholar 

  91. Capalbo A, Poli M, Rienzi L, Girardi L, Patassini C, Fabiani M, et al. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet. 2021;108:2238–47. https://doi.org/10.1016/j.ajhg.2021.11.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Fragouli E, Munne S, Wells D. The cytogenetic constitution of human blastocysts: insights from comprehensive chromosome screening strategies. Hum Reprod Update. 2019;25:15–33. https://doi.org/10.1093/humupd/dmy036.

    Article  CAS  PubMed  Google Scholar 

  93. Wu L, Jin L, Chen W, Liu JM, Hu J, Yu Q, et al. The true incidence of chromosomal mosaicism after preimplantation genetic testing is much lower than that indicated by trophectoderm biopsy. Hum Reprod. 2021;36:1691–701. https://doi.org/10.1093/humrep/deab064.

    Article  CAS  PubMed  Google Scholar 

  94. CoGEN position statement on chromosomal mosaicism detected in preimplantation blastocyst biopsies. n.d. https://ivf-worldwide.com/cogen/general/cogen-statement.html. Accessed January 19, 2023.

  95. Practice Committee and Genetic Counseling Professional Group (GCPG) of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org. Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil Steril. 2020;114:246–54. https://doi.org/10.1016/j.fertnstert.2020.05.014.

    Article  CAS  Google Scholar 

  96. Leigh D, Cram DS, Rechitsky S, Handyside A, Wells D, Munne S, et al. PGDIS position statement on the transfer of mosaic embryos 2021. Reprod Biomed Online. 2022;45:19–25. https://doi.org/10.1016/j.rbmo.2022.03.013.

    Article  CAS  PubMed  Google Scholar 

  97. Mochizuki L, Gleicher N. The PGS/PGT-A controversy in IVF addressed as a formal conflict resolution analysis. J Assist Reprod Genet. 2020;37:677–87. https://doi.org/10.1007/s10815-020-01688-8.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Cohen J, Munné S. Comment 2 on Staessen et al. (2004). Two-cell biopsy and PGD pregnancy outcome. Hum Reprod. 2005;20:2363–4. https://doi.org/10.1093/humrep/deh880.

    Article  PubMed  Google Scholar 

  99. Mastenbroek S, M MBossuyt P, Heineman MJ, Repping S, van der Veen F. Comment 1 on Staessen et al. (2004). Design and analysis of a randomized controlled trial studying preimplantation genetic screening. Hum Reprod. 2005;20:2362–3. https://doi.org/10.1093/humrep/deh879.

    Article  PubMed  Google Scholar 

  100. Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril. 2005;83:393–7. https://doi.org/10.1016/j.fertnstert.2004.06.071.

    Article  PubMed  Google Scholar 

  101. Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod Oxf Engl. 2004;19:2849–58. https://doi.org/10.1093/humrep/deh536.

    Article  Google Scholar 

  102. Shahine LK, Cedars MI. Preimplantation genetic diagnosis does not increase pregnancy rates in patients at risk for aneuploidy. Fertil Steril. 2006;85:51–6. https://doi.org/10.1016/j.fertnstert.2005.06.045.

    Article  PubMed  Google Scholar 

  103. Staessen C, Verpoest W, Donoso P, Haentjens P, Van der Elst J, Liebaers I, et al. Preimplantation genetic screening does not improve delivery rate in women under the age of 36 following single-embryo transfer. Hum Reprod Oxf Engl. 2008;23:2818–25. https://doi.org/10.1093/humrep/den367.

    Article  CAS  Google Scholar 

  104. Twisk M, Mastenbroek S, Hoek A, Heineman M-J, van der Veen F, Bossuyt PM, et al. No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy. Hum Reprod Oxf Engl. 2008;23:2813–7. https://doi.org/10.1093/humrep/den231.

    Article  Google Scholar 

  105. Meyer LR, Klipstein S, Hazlett WD, Nasta T, Mangan P, Karande VC. A prospective randomized controlled trial of preimplantation genetic screening in the “good prognosis” patient. Fertil Steril. 2009;91:1731–8. https://doi.org/10.1016/j.fertnstert.2008.02.162.

    Article  PubMed  Google Scholar 

  106. Schoolcraft WB, Katz-Jaffe MG, Stevens J, Rawlins M, Munne S. Preimplantation aneuploidy testing for infertile patients of advanced maternal age: a randomized prospective trial. Fertil Steril. 2009;92:157–62. https://doi.org/10.1016/j.fertnstert.2008.05.029.

    Article  PubMed  Google Scholar 

  107. Mastenbroek S, Twisk M, van Echten-Arends J, Sikkema-Raddatz B, Korevaar JC, Verhoeve HR, et al. In vitro fertilization with preimplantation genetic screening. N Engl J Med. 2007;357:9–17. https://doi.org/10.1056/NEJMoa067744.

    Article  CAS  PubMed  Google Scholar 

  108. Scott RT, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril. 2012;97:870–5. https://doi.org/10.1016/j.fertnstert.2012.01.104.

    Article  PubMed  Google Scholar 

  109. Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012;5:24. https://doi.org/10.1186/1755-8166-5-24.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Scott RT, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100:697–703. https://doi.org/10.1016/j.fertnstert.2013.04.035.

    Article  PubMed  Google Scholar 

  111. Rubio C, Bellver J, Rodrigo L, Castillón G, Guillén A, Vidal C, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017;107:1122–9. https://doi.org/10.1016/j.fertnstert.2017.03.011.

    Article  PubMed  Google Scholar 

  112. Sui Y-L, Lei C-X, Ye J-F, Fu J, Zhang S, Li L, et al. In vitro fertilization with single-nucleotide polymorphism microarray-based preimplantation genetic testing for aneuploidy significantly improves clinical outcomes in infertile women with recurrent pregnancy loss: a randomized controlled trial. Reprod Dev Med. 2020;04:32–41. https://doi.org/10.4103/2096-2924.281852.

    Article  Google Scholar 

  113. Rubio C. PGT-A and RCT proof in AMA and SMF couples. Reprod Biomed Online. 2019;38:e8. https://doi.org/10.1016/j.rbmo.2019.03.016.

    Article  Google Scholar 

  114. Munné S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019;112:1071-1079.e7. https://doi.org/10.1016/j.fertnstert.2019.07.1346.

    Article  CAS  PubMed  Google Scholar 

  115. Paulson RJ. Outcome of in vitro fertilization cycles with preimplantation genetic testing for aneuploidies: let’s be honest with one another. Fertil Steril. 2019;112:1013–4. https://doi.org/10.1016/j.fertnstert.2019.11.002.

    Article  PubMed  Google Scholar 

  116. Schattman GL. Preimplantation genetic testing for aneuploidy: it’s déjà vu all over again! Fertil Steril. 2019;112:1046–7. https://doi.org/10.1016/j.fertnstert.2019.08.102.

    Article  PubMed  Google Scholar 

  117. Verpoest W, Staessen C, Bossuyt PM, Goossens V, Altarescu G, Bonduelle M, et al. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial. Hum Reprod Oxf Engl. 2018;33:1767–76. https://doi.org/10.1093/humrep/dey262.

    Article  CAS  Google Scholar 

  118. Kucherov A, Fazzari M, Lieman H, Ball GD, Doody K, Jindal S. PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS. J Assist Reprod Genet. 2023;40:137–49. https://doi.org/10.1007/s10815-022-02667-x.

    Article  PubMed  Google Scholar 

  119. Cheng X, Zhang Y, Deng H, Feng Y, Chong W, Hai Y, et al. Preimplantation genetic testing for aneuploidy with comprehensive chromosome screening in patients undergoing in vitro fertilization: a systematic review and meta-analysis. Obstet Gynecol. 2022;140:769. https://doi.org/10.1097/AOG.0000000000004962.

    Article  CAS  PubMed  Google Scholar 

  120. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, et al. Live birth with or without preimplantation genetic testing for aneuploidy. N Engl J Med 2021;385:2047–58. https://doi.org/10.1056/NEJMoa2103613.

  121. Wilkinson J. Neither relevant, nor randomized: the use of ‘per embryo transferred’ in the analysis of preimplanatation genetic testing for aneuploidy trials. Fertil Steril. 2023;S0015028223002297. https://doi.org/10.1016/j.fertnstert.2023.03.020.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carmen Morales.

Ethics declarations

Ethical Approval

This is not applicable.

Consent to Participate

This is not applicable.

Consent for Publication

This is not applicable.

Conflict of Interest

The author declares no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morales, C. Current Applications and Controversies in Preimplantation Genetic Testing for Aneuploidies (PGT-A) in In Vitro Fertilization. Reprod. Sci. 31, 66–80 (2024). https://doi.org/10.1007/s43032-023-01301-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-023-01301-0

Keywords

Navigation