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When embryology meets genetics: the definition of developmentally incompetent preimplantation embryos (DIPE)—the consensus of two Italian scientific societies

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Abstract

A clear definition of developmentally incompetent preimplantation embryo (DIPE) in literature is still missing, while several scientific societies are discussing this challenging topic. From both a clinical and scientific perspective, the identification of embryos unfit for reproductive purpose is crucial. This aim should be pursued in light of all diagnostic technologies for embryo evaluation, encompassing also genetic analyses, of recent implementation in IVF. The Italian context is characterized by an unusual scenario: embryos can be discarded only if not viable and cannot be used for research purposes either. Therefore, thousands of embryos, diagnosed as affected and/or aneuploid as resulting from preimplantation genetic testing (PGT) and clinically not utilizable, are cryopreserved and stored indefinitely, with important psychological, legal, and financial implications. With the aim of updating the definition of DIPE, also on the basis of the embryo genetic status, the Italian Society of Embryology, Reproduction and Research (SIERR) and the Italian Society of Human Genetic (SIGU) reviewed the literature on this topic, found a consensus, and produced a list of relevant criteria.

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References

  1. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Hum Reprod. 2017;32(9):1786–801. https://doi.org/10.1093/humrep/dex234.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The international glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108(3):393–406. https://doi.org/10.1016/j.fertnstert.2017.06.005.

    Article  PubMed  Google Scholar 

  3. Alpha SIRM, ESHRE SIGE. Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reprod BioMed Online. 2011;22(6):632–46. https://doi.org/10.1016/j.rbmo.2011.02.001.

    Article  Google Scholar 

  4. Alpha SiRM, ESHRE SIGoE. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26(6):1270–83. https://doi.org/10.1093/humrep/der037.

    Article  Google Scholar 

  5. ASRM. Blastocyst culture and transfer in clinically assisted reproduction: a committee opinion. Fertil Steril. 2018;110(7):1246–52. https://doi.org/10.1016/j.fertnstert.2018.09.011.

    Article  Google Scholar 

  6. Hammond ER, Cree LM, Morbeck DE. Should extended blastocyst culture include day 7? Hum Reprod. 2018;33(6):991–7. https://doi.org/10.1093/humrep/dey091.

    Article  PubMed  Google Scholar 

  7. Tiegs AW, Sun L, Patounakis G, Scott RT. Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as day 5 and day 6 blastocysts. Hum Reprod. 2019;34(9):1632–9. https://doi.org/10.1093/humrep/dez138.

    Article  CAS  PubMed  Google Scholar 

  8. Alikani M, Munne S. Nonviable human pre-implantation embryos as a source of stem cells for research and potential therapy. Stem Cell Rev. 2005;1(4):337–43. https://doi.org/10.1385/SCR:1:4:337.

    Article  PubMed  Google Scholar 

  9. Gavrilov S, Prosser RW, Khalid I, MacDonald J, Sauer MV, Landry DW, et al. Non-viable human embryos as a source of viable cells for embryonic stem cell derivation. Reprod BioMed Online. 2009;18(2):301–8. https://doi.org/10.1016/s1472-6483(10)60270-2.

    Article  PubMed  Google Scholar 

  10. Morbeck DE. Blastocyst culture in the era of PGS and FreezeAlls: is a ‘C’ a failing grade? Hum Reprod Open. 2017;2017(3):hox017. https://doi.org/10.1093/hropen/hox017.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cimadomo D, Soscia D, Vaiarelli A, Maggiulli R, Capalbo A, Ubaldi FM, et al. Looking past the appearance: a comprehensive description of the clinical contribution of poor-quality blastocysts to increase live birth rates during cycles with aneuploidy testing. Hum Reprod. 2019;34(7):1206–14. https://doi.org/10.1093/humrep/dez078.

    Article  PubMed  Google Scholar 

  12. Hammond ER, Foong AKM, Rosli N, Morbeck DE. Should we freeze it? Agreement on fate of borderline blastocysts is poor and does not improve with a modified blastocyst grading system. Hum Reprod. 2020;35:1045–53. https://doi.org/10.1093/humrep/deaa060.

    Article  PubMed  Google Scholar 

  13. Gardner DK, Schoolcraft B. In vitro culture of human blastocysts. In: Jansen R, Mortimer D, editors. Toward reproductive certainty: fertility and genetics beyond. London: Parthenon Publishing; 1999. p. 378–88.

    Google Scholar 

  14. Lagalla C, Tarozzi N, Sciajno R, Wells D, Di Santo M, Nadalini M, et al. Embryos with morphokinetic abnormalities may develop into euploid blastocysts. Reprod BioMed Online. 2017;34(2):137–46. https://doi.org/10.1016/j.rbmo.2016.11.008.

    Article  CAS  PubMed  Google Scholar 

  15. Coticchio G, Lagalla C, Sturmey R, Pennetta F, Borini A. The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART. Hum Reprod Update. 2019;25(4):422–38. https://doi.org/10.1093/humupd/dmz008.

    Article  CAS  PubMed  Google Scholar 

  16. McCollin A, Swann RL, Summers MC, Handyside AH, Ottolini CS. Abnormal cleavage and developmental arrest of human preimplantation embryos in vitro. Eur J Med Genet. 2020;63(2):103651. https://doi.org/10.1016/j.ejmg.2019.04.008.

    Article  PubMed  Google Scholar 

  17. Ottolini CS, Kitchen J, Xanthopoulou L, Gordon T, Summers MC, Handyside AH. Tripolar mitosis and partitioning of the genome arrests human preimplantation development in vitro. Sci Rep. 2017;7(1):9744. https://doi.org/10.1038/s41598-017-09693-1.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zaninovic N, Zhan Q, Norberg C, Ye Z, Clarke R, Rosenwaks Z. Blastomere extrusion and abnormal cleavage behavior in human embryos under time-lapse monitoring: possible way of embryo “self-correction”? Fertil Steril. 2016;106(3, SUPPLEMENT):E353. https://doi.org/10.1016/j.fertnstert.2016.07.1003.

    Article  Google Scholar 

  19. 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(6):1173–81. https://doi.org/10.1093/humrep/deu033.

    Article  PubMed  Google Scholar 

  20. Baumann CG, Morris DG, Sreenan JM, Leese HJ. The quiet embryo hypothesis: molecular characteristics favoring viability. Mol Reprod Dev. 2007;74(10):1345–53. https://doi.org/10.1002/mrd.20604.

    Article  CAS  PubMed  Google Scholar 

  21. Leese HJ, Sturmey RG, Baumann CG, McEvoy TG. Embryo viability and metabolism: obeying the quiet rules. Hum Reprod. 2007;22(12):3047–50. https://doi.org/10.1093/humrep/dem253.

    Article  PubMed  Google Scholar 

  22. Betts DH, Madan P. Permanent embryo arrest: molecular and cellular concepts. Mol Hum Reprod. 2008;14(8):445–53. https://doi.org/10.1093/molehr/gan035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hardy K, Spanos S, Becker D, Iannelli P, Winston RM, Stark J. From cell death to embryo arrest: mathematical models of human preimplantation embryo development. Proc Natl Acad Sci U S A. 2001;98(4):1655–60. https://doi.org/10.1073/pnas.98.4.1655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Heffner LJ. Advanced maternal age--how old is too old? N Engl J Med. 2004;351(19):1927–9. https://doi.org/10.1056/NEJMp048087.

    Article  CAS  PubMed  Google Scholar 

  25. Alfarawati S, Fragouli E, Colls P, Stevens J, Gutierrez-Mateo C, Schoolcraft WB, et al. The relationship between blastocyst morphology, chromosomal abnormality, and embryo gender. Fertil Steril. 2011;95(2):520–4. https://doi.org/10.1016/j.fertnstert.2010.04.003.

    Article  PubMed  Google Scholar 

  26. Bruno C, Dudkiewicz-Sibony C, Berthaut I, Weil E, Brunet L, Fortier C, et al. Survey of 243 ART patients having made a final disposition decision about their surplus cryopreserved embryos: the crucial role of symbolic embryo representation. Hum Reprod. 2016;31(7):1508–14. https://doi.org/10.1093/humrep/dew104.

    Article  CAS  PubMed  Google Scholar 

  27. Faustini F, Forte M, Capalbo A, Cimadomo D, Ubaldi FM, Rienzi L. The main will of the patients of a private Italian IVF clinic for their aneuploid/affected blastocysts would be donation to research: a currently forbidden choice. J Assist Reprod Genet. 2019;36(8):1555–60. https://doi.org/10.1007/s10815-019-01465-2.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Capalbo A, Hoffmann ER, Cimadomo D, Ubaldi FM, Rienzi L. Human female meiosis revised: new insights into the mechanisms of chromosome segregation and aneuploidies from advanced genomics and time-lapse imaging. Hum Reprod Update. 2017;23(6):706–22. https://doi.org/10.1093/humupd/dmx026.

    Article  CAS  PubMed  Google Scholar 

  29. Bebbere D, Masala L, Albertini DF, Ledda S. The subcortical maternal complex: multiple functions for one biological structure? J Assist Reprod Genet. 2016;33(11):1431–8. https://doi.org/10.1007/s10815-016-0788-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Leese HJ, Guerif F, Allgar V, Brison DR, Lundin K, Sturmey RG. Biological optimization, the goldilocks principle, and how much is lagom in the preimplantation embryo. Mol Reprod Dev. 2016;83(9):748–54. https://doi.org/10.1002/mrd.22684.

    Article  CAS  PubMed  Google Scholar 

  31. McCoy RC, Newnham LJ, Ottolini CS, Hoffmann ER, Chatzimeletiou K, Cornejo OE, et al. Tripolar chromosome segregation drives the association between maternal genotype at variants spanning PLK4 and aneuploidy in human preimplantation embryos. Hum Mol Genet. 2018;27(14):2573–85. https://doi.org/10.1093/hmg/ddy147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Apter S, Ebner T, Freour T, Guns Y, Kovacic B, Le Clef N, et al. Eshre Working group on Time-lapse technology: Good practice recommendations for the use of time-lapse technology. Hum Reprod Open. 2020;2020(2):hoaa008. https://doi.org/10.1093/hropen/hoaa008.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pennetta F, Lagalla C, Borini A. Embryo morphokinetic characteristics and euploidy. Curr Opin Obstet Gynecol. 2018;30(3):185–96. https://doi.org/10.1097/GCO.0000000000000453.

    Article  PubMed  Google Scholar 

  34. Zhan Q, Ye Z, Clarke R, Rosenwaks Z, Zaninovic N. Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome. PLoS One. 2016;11(12):e0166398. https://doi.org/10.1371/journal.pone.0166398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cimadomo D, Rienzi L, Capalbo A, Rubio C, Innocenti F, Garcia-Pascual CM, et al. The dawn of the future: 30 years from the first biopsy of a human embryo. The detailed history of an ongoing revolution. Hum Reprod Update. 2020;26:453–73. https://doi.org/10.1093/humupd/dmaa019.

    Article  CAS  PubMed  Google Scholar 

  36. Kokkali G, Coticchio G, Bronet F, Celebi C, Cimadomo D, Goossens V, et al. ESHRE PGT consortium and SIG embryology good practice recommendations for polar body and embryo biopsy for PGT. Hum Reprod Open. 2020;2020(3):hoaa020. https://doi.org/10.1093/hropen/hoaa020.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Scott RT Jr, Upham KM, Forman EJ, Zhao T, Treff NR. Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial. Fertil Steril. 2013;100(3):624–30. https://doi.org/10.1016/j.fertnstert.2013.04.039.

    Article  PubMed  Google Scholar 

  38. Capmany G, Taylor A, Braude PR, Bolton VN. The timing of pronuclear formation, DNA synthesis and cleavage in the human 1-cell embryo. Mol Hum Reprod. 1996;2(5):299–306. https://doi.org/10.1093/molehr/2.5.299.

    Article  CAS  PubMed  Google Scholar 

  39. Nagy ZP, Liu J, Joris H, Devroey P, Van Steirteghem A. Time-course of oocyte activation, pronucleus formation and cleavage in human oocytes fertilized by intracytoplasmic sperm injection. Hum Reprod. 1994;9(9):1743–8. https://doi.org/10.1093/oxfordjournals.humrep.a138786.

    Article  CAS  PubMed  Google Scholar 

  40. Payne D, Flaherty SP, Barry MF, Matthews CD. Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography. Hum Reprod. 1997;12(3):532–41. https://doi.org/10.1093/humrep/12.3.532.

    Article  CAS  PubMed  Google Scholar 

  41. Coticchio G, Mignini Renzini M, Novara PV, Lain M, De Ponti E, Turchi D, et al. Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability. Hum Reprod. 2018;33(1):23–31. https://doi.org/10.1093/humrep/dex344.

    Article  CAS  PubMed  Google Scholar 

  42. Meseguer M, Herrero J, Tejera A, Hilligsoe KM, Ramsing NB, Remohi J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011;26(10):2658–71. https://doi.org/10.1093/humrep/der256.

    Article  PubMed  Google Scholar 

  43. Scott LA, Smith S. The successful use of pronuclear embryo transfers the day following oocyte retrieval. Hum Reprod. 1998;13(4):1003–13.

    Article  CAS  Google Scholar 

  44. Tesarik J, Greco E. The probability of abnormal preimplantation development can be predicted by a single static observation on pronuclear stage morphology. Hum Reprod. 1999;14(5):1318–23. https://doi.org/10.1093/humrep/14.5.1318.

    Article  CAS  PubMed  Google Scholar 

  45. Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod. 2000;15(11):2394–403. https://doi.org/10.1093/humrep/15.11.2394.

    Article  CAS  PubMed  Google Scholar 

  46. Machtinger R, Racowsky C. Morphological systems of human embryo assessment and clinical evidence. Reprod BioMed Online. 2013;26(3):210–21. https://doi.org/10.1016/j.rbmo.2012.10.021.

    Article  PubMed  Google Scholar 

  47. Balaban B, Urman B, Isiklar A, Alatas C, Aksoy S, Mercan R, et al. The effect of pronuclear morphology on embryo quality parameters and blastocyst transfer outcome. Hum Reprod. 2001;16(11):2357–61. https://doi.org/10.1093/humrep/16.11.2357.

    Article  CAS  PubMed  Google Scholar 

  48. Rienzi L, Ubaldi F, Iacobelli M, Ferrero S, Minasi MG, Martinez F, et al. Day 3 embryo transfer with combined evaluation at the pronuclear and cleavage stages compares favourably with day 5 blastocyst transfer. Hum Reprod. 2002;17(7):1852–5. https://doi.org/10.1093/humrep/17.7.1852.

    Article  PubMed  Google Scholar 

  49. Zollner U, Zollner KP, Hartl G, Dietl J, Steck T. The use of a detailed zygote score after IVF/ICSI to obtain good quality blastocysts: the German experience. Hum Reprod. 2002;17(5):1327–33. https://doi.org/10.1093/humrep/17.5.1327.

    Article  CAS  PubMed  Google Scholar 

  50. Nagy ZP, Dozortsev D, Diamond M, Rienzi L, Ubaldi F, Abdelmassih R, et al. Pronuclear morphology evaluation with subsequent evaluation of embryo morphology significantly increases implantation rates. Fertil Steril. 2003;80(1):67–74. https://doi.org/10.1016/s0015-0282(03)00569-7.

    Article  PubMed  Google Scholar 

  51. Wittemer C, Bettahar-Lebugle K, Ohl J, Rongieres C, Nisand I, Gerlinger P. Zygote evaluation: an efficient tool for embryo selection. Hum Reprod. 2000;15(12):2591–7. https://doi.org/10.1093/humrep/15.12.2591.

    Article  CAS  PubMed  Google Scholar 

  52. Montag M, van der Ven H, German pronuclear morphology study G. Evaluation of pronuclear morphology as the only selection criterion for further embryo culture and transfer: results of a prospective multicentre study. Hum Reprod. 2001;16(11):2384–9. https://doi.org/10.1093/humrep/16.11.2384.

    Article  CAS  PubMed  Google Scholar 

  53. De los Santos MJ, Apter S, Coticchio G, Debrock S, Lundin K, Plancha CE, et al. Revised guidelines for good practice in IVF laboratories (2015). Hum Reprod. 2016;31(4):685–6. https://doi.org/10.1093/humrep/dew016.

    Article  PubMed  Google Scholar 

  54. Liu J, Wang XL, Zhang X, Shen CY, Zhang Z. Live births resulting from 0PN-derived embryos in conventional IVF cycles. J Assist Reprod Genet. 2016;33(3):373–8. https://doi.org/10.1007/s10815-015-0644-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Destouni A, Dimitriadou E, Masset H, Debrock S, Melotte C, Van Den Bogaert K, et al. Genome-wide haplotyping embryos developing from 0PN and 1PN zygotes increases transferrable embryos in PGT-M. Hum Reprod. 2018;33(12):2302–11. https://doi.org/10.1093/humrep/dey325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Hondo S, Arichi A, Muramatsu H, Omura N, Ito K, Komine H, et al. Clinical outcomes of transfer of frozen and thawed single blastocysts derived from nonpronuclear and monopronuclear zygotes. Reprod Med Biol. 2019;18(3):278–83. https://doi.org/10.1002/rmb2.12275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Basile N, Morbeck D, Garcia-Velasco J, Bronet F, Meseguer M. Type of culture media does not affect embryo kinetics: a time-lapse analysis of sibling oocytes. Hum Reprod. 2013;28(3):634–41. https://doi.org/10.1093/humrep/des462.

    Article  CAS  PubMed  Google Scholar 

  58. Staessen C, Van Steirteghem AC. The chromosomal constitution of embryos developing from abnormally fertilized oocytes after intracytoplasmic sperm injection and conventional in-vitro fertilization. Hum Reprod. 1997;12(2):321–7.

    Article  CAS  Google Scholar 

  59. Kang HJ, Rosenwaks Z. Triploidy--the breakdown of monogamy between sperm and egg. Int J Dev Biol. 2008;52(5–6):449–54. https://doi.org/10.1387/ijdb.082602hk.

    Article  PubMed  Google Scholar 

  60. Mateo S, Vidal F, Parriego M, Rodriguez I, Montalvo V, Veiga A, et al. Could monopronucleated ICSI zygotes be considered for transfer? Analysis through time-lapse monitoring and PGS. J Assist Reprod Genet. 2017;34(7):905–11. https://doi.org/10.1007/s10815-017-0937-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bradley CK, Traversa MV, Hobson N, Gee AJ, McArthur SJ. Clinical use of monopronucleated zygotes following blastocyst culture and preimplantation genetic screening, including verification of biparental chromosome inheritance. Reprod BioMed Online. 2017;34(6):567–74. https://doi.org/10.1016/j.rbmo.2017.03.013.

    Article  PubMed  Google Scholar 

  62. Capalbo A, Treff N, Cimadomo D, Tao X, Ferrero S, Vaiarelli A, et al. Abnormally fertilized oocytes can result in healthy live births: improved genetic technologies for preimplantation genetic testing can be used to rescue viable embryos in in vitro fertilization cycles. Fertil Steril. 2017;108:1007–1015.e3. https://doi.org/10.1016/j.fertnstert.2017.08.004.

    Article  PubMed  Google Scholar 

  63. Staessen C, Janssenswillen C, Devroey P, Van Steirteghem AC. Cytogenetic and morphological observations of single pronucleated human oocytes after in-vitro fertilization. Hum Reprod. 1993;8(2):221–3. https://doi.org/10.1093/oxfordjournals.humrep.a138026.

    Article  CAS  PubMed  Google Scholar 

  64. Munne S, Tang YX, Grifo J, Cohen J. Origin of single pronucleated human zygotes. J Assist Reprod Genet. 1993;10(4):276–9. https://doi.org/10.1007/BF01204942.

    Article  CAS  PubMed  Google Scholar 

  65. Nagy ZP, Janssenswillen C, Janssens R, De Vos A, Staessen C, Van de Velde H, et al. Timing of oocyte activation, pronucleus formation and cleavage in humans after intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and after ICSI or in-vitro fertilization on sibling oocytes with ejaculated spermatozoa. Hum Reprod. 1998;13(6):1606–12. https://doi.org/10.1093/humrep/13.6.1606.

    Article  CAS  PubMed  Google Scholar 

  66. Capalbo A, Ottolini CS, Griffin DK, Ubaldi FM, Handyside AH, Rienzi L. Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte. Fertil Steril. 2016;105(3):807–14.e2. https://doi.org/10.1016/j.fertnstert.2015.11.017.

    Article  CAS  PubMed  Google Scholar 

  67. Jacobs PA, Angell RR, Buchanan IM, Hassold TJ, Matsuyama AM, Manuel B. The origin of human triploids. Ann Hum Genet. 1978;42(1):49–57. https://doi.org/10.1111/j.1469-1809.1978.tb00930.x.

    Article  CAS  PubMed  Google Scholar 

  68. McFadden DE, Robinson WP. Phenotype of triploid embryos. J Med Genet. 2006;43(7):609–12. https://doi.org/10.1136/jmg.2005.037747.

    Article  CAS  PubMed  Google Scholar 

  69. Joergensen MW, Labouriau R, Hindkjaer J, Stougaard M, Kolevraa S, Bolund L, et al. The parental origin correlates with the karyotype of human embryos developing from tripronuclear zygotes. Clin Exp Reprod Med. 2015;42(1):14–21. https://doi.org/10.5653/cerm.2015.42.1.14.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Li M, Xue X, Zhao W, Li W, Shi J. Effects of high three pro-nuclei (3PN) proportion incidence on clinical outcomes in the fresh cleavage-stage and blastocyst-stage embryo transfer (ET) cycles. Gynecol Endocrinol. 2017;33(1):53–6. https://doi.org/10.1080/09513590.2016.1190817.

    Article  PubMed  Google Scholar 

  71. Yao G, Xu J, Xin Z, Niu W, Shi S, Jin H, et al. Developmental potential of clinically discarded human embryos and associated chromosomal analysis. Sci Rep. 2016;6:23995. https://doi.org/10.1038/srep23995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Grau N, Escrich L, Galiana Y, Meseguer M, Garcia-Herrero S, Remohi J, et al. Morphokinetics as a predictor of self-correction to diploidy in tripronucleated intracytoplasmic sperm injection-derived human embryos. Fertil Steril. 2015;104(3):728–35. https://doi.org/10.1016/j.fertnstert.2015.05.024.

    Article  PubMed  Google Scholar 

  73. Xu J, Zhang M, Niu W, Yao G, Sun B, Bao X, et al. Genome-wide uniparental disomy screen in human discarded morphologically abnormal embryos. Sci Rep. 2015;5:12302. https://doi.org/10.1038/srep12302.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Grati FR, Gallazzi G, Branca L, Maggi F, Simoni G, Yaron Y. An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening. Reprod BioMed Online. 2018;36(4):442–9. https://doi.org/10.1016/j.rbmo.2018.01.005.

    Article  PubMed  Google Scholar 

  75. Gueye NA, Devkota B, Taylor D, Pfundt R, Scott RT Jr, Treff NR. Uniparental disomy in the human blastocyst is exceedingly rare. Fertil Steril. 2014;101(1):232–6. https://doi.org/10.1016/j.fertnstert.2013.08.051.

    Article  PubMed  Google Scholar 

  76. Gardner RJM, Sutherland GR, Schaffer LG. Chromosome abnormalities and genetic counseling. 4th ed. New York: Oxford University Press; 2012.

    Google Scholar 

  77. McFadden DE, Kwong LC, Yam IY, Langlois S. Parental origin of triploidy in human fetuses: evidence for genomic imprinting. Hum Genet. 1993;92(5):465–9. https://doi.org/10.1007/BF00216452.

    Article  CAS  PubMed  Google Scholar 

  78. McFadden DE, Langlois S. Parental and meiotic origin of triploidy in the embryonic and fetal periods. Clin Genet. 2000;58(3):192–200. https://doi.org/10.1034/j.1399-0004.2000.580306.x.

    Article  CAS  PubMed  Google Scholar 

  79. Gruhn JR, Zielinska AP, Shukla V, Blanshard R, Capalbo A, Cimadomo D, et al. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science. 2019;365(6460):1466–9. https://doi.org/10.1126/science.aav7321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Thornhill AR, Handyside AH, Ottolini C, Natesan SA, Taylor J, Sage K, et al. Karyomapping-a comprehensive means of simultaneous monogenic and cytogenetic PGD: comparison with standard approaches in real time for Marfan syndrome. J Assist Reprod Genet. 2015;32(3):347–56. https://doi.org/10.1007/s10815-014-0405-y.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 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 

  82. 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. 2020. https://doi.org/10.1016/j.fertnstert.2020.07.052.

  83. Popovic M, Dhaenens L, Boel A, Menten B, Heindryckx B. Chromosomal mosaicism in human blastocysts: the ultimate diagnostic dilemma. Hum Reprod Update. 2020;26:313–34. https://doi.org/10.1093/humupd/dmz050.

    Article  CAS  PubMed  Google Scholar 

  84. Scott RT Jr, 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(4):870–5. https://doi.org/10.1016/j.fertnstert.2012.01.104.

    Article  PubMed  Google Scholar 

  85. Popovic M, Dhaenens L, Taelman J, Dheedene A, Bialecka M, De Sutter P, et al. Extended in vitro culture of human embryos demonstrates the complex nature of diagnosing chromosomal mosaicism from a single trophectoderm biopsy. Hum Reprod. 2019;34(4):758–69. https://doi.org/10.1093/humrep/dez012.

    Article  CAS  PubMed  Google Scholar 

  86. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2(4):280–91. https://doi.org/10.1038/35066065.

    Article  CAS  PubMed  Google Scholar 

  87. Ottolini CS, Newnham LJ, Capalbo A, Natesan SA, Joshi HA, Cimadomo D, et al. Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nat Genet. 2015;47(7):727–35. https://doi.org/10.1038/ng.3306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Goodrich D, Tao X, Bohrer C, Lonczak A, Xing T, Zimmerman R, et al. A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy in a cell line mixture model of blastocyst biopsy mosaicism. J Assist Reprod Genet. 2016;33(11):1473–80. https://doi.org/10.1007/s10815-016-0784-3.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Capalbo A, Rienzi L. Mosaicism between trophectoderm and inner cell mass. Fertil Steril. 2017;107(5):1098–106. https://doi.org/10.1016/j.fertnstert.2017.03.023.

    Article  PubMed  Google Scholar 

  90. Capalbo A, Ubaldi FM, Rienzi L, Scott R, Treff N. Detecting mosaicism in trophectoderm biopsies: current challenges and future possibilities. Hum Reprod. 2017;32(3):492–8. https://doi.org/10.1093/humrep/dew250.

    Article  CAS  PubMed  Google Scholar 

  91. Forman EJ. Demystifying “mosaic” outcomes. Fertil Steril. 2019;111(2):253. https://doi.org/10.1016/j.fertnstert.2018.12.012.

    Article  PubMed  Google Scholar 

  92. Paulson RJ, Treff N. Isn’t it time to stop calling preimplantation embryos “mosaic”? F&S Reports. 2020. https://doi.org/10.1016/j.xfre.2020.10.009.

  93. Besser AG, Blakemore JK, Grifo JA, Mounts EL. Transfer of embryos with positive results following preimplantation genetic testing for monogenic disorders (PGT-M): experience of two high-volume fertility clinics. J Assist Reprod Genet. 2019;36(9):1949–55. https://doi.org/10.1007/s10815-019-01538-2.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank Attilio Anastasi, Emanuele Licata, and Francesca Gioia Klinger for their help in drafting the manuscript and discussing its content. We thank also Dr. Giovanni Coticchio for the constructive comments and general revision of the manuscript.

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DC, AC, CS, and LSF contributed equally to this work. All authors participated in drafting the manuscript, discussed the results, and contributed to the final article. LR, RC, MGM, and AN revised the article critically. RC, LR, and LDS coordinated the working group on behalf of SIERR and DZ on behalf of SIGU.

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Correspondence to Danilo Cimadomo.

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Danilo Cimadomo, Antonio Capalbo, Catello Scarica, Laura Sosa Fernandez, Laura Rienzi, Rosanna Ciriminna, Maria Giulia Minasi, and Lucia De Santis on behalf of the Italian Society of Embryology, Reproduction and Research (SIERR)

Antonio Capalbo, Antonio Novelli and Daniela Zuccarello on behalf of the Italian Society of Human Genetics (SIGU)

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Cimadomo, D., Capalbo, A., Scarica, C. et al. When embryology meets genetics: the definition of developmentally incompetent preimplantation embryos (DIPE)—the consensus of two Italian scientific societies. J Assist Reprod Genet 38, 319–331 (2021). https://doi.org/10.1007/s10815-020-02015-x

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