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Embryo drop-out rates in preimplantation genetic testing for aneuploidy (PGT-A): a retrospective data analysis from the DoLoRes study

  • Assisted Reproduction Technologies
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Abstract

Purpose

To evaluate the decline in transferable embryos in preimplantation genetic testing for aneuploidy (PGT-A) cycles due to (a) non-biopsable blastocyst quality, (b) failure of genetic analysis, (c) diagnosis of uniform numerical or structural chromosomal aberrations, and/or (d) chromosomal aberrations in mosaic constitution.

Methods

This retrospective multicenter study comprised outcomes of 1562 blastocysts originating from 363 controlled ovarian stimulation cycles, respectively, 226 IVF couples in the period between January 2016 and December 2018. Inclusion criteria were PGT-A cycles with trophectoderm biopsy (TB) and next generation sequencing (NGS).

Results

Out of 1562 blastocysts, 25.8% were lost due to non-biopsable and/or non-freezable embryo quality. In 10.3% of all biopsied blastocysts, genetic analysis failed. After exclusion of embryos with uniform or chromosomal aberrations in mosaic, only 18.1% of those originally yielded remained as diagnosed euploid embryos suitable for transfer. This translates into 50.4% of patients and 57.6% of stimulated cycles with no euploid embryo left for transfer. The risk that no transfer can take place rose significantly with a lower number of oocytes and with increasing maternal age. The chance for at least one euploid blastocyst/cycle in advanced maternal age (AMA)-patients was 33.3% compared to 52.1% in recurrent miscarriage (RM), 59.8% in recurrent implantation failure (RIF), and 60.0% in severe male factor (SMF).

Conclusions

The present study demonstrates that PGT-A is accompanied by high embryo drop-out rates. IVF-practitioners should be aware that their patients run a high risk of ending up without any embryo suitable for transfer after (several) stimulation cycles, especially in AMA patients. Patients should be informed in detail about the frequency of inconclusive or mosaic results, with the associated risk of not having an euploid embryo available for transfer after PGT-A, as well as the high cost involved in this type of testing.

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Data availability

The data presented in this manuscript are not publicly available due to data protection restrictions.

References

  1. Munne S. Status of preimplantation genetic testing and embryo selection. Reprod BioMed Online. 2018;37:393–6.

    Article  PubMed  Google Scholar 

  2. Twisk M, Mastenbroek S, van Wely M, Heineman MJ, Van der Veen F, Repping S. Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilisation or intracytoplasmic sperm injection. Cochrane Database Syst Rev. 2006;1:CD005291.

    Google Scholar 

  3. Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020;9:CD005291.

    PubMed  Google Scholar 

  4. 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;100:624–30.

    Article  PubMed  Google Scholar 

  5. Magli MC, Gianaroli L, Fortini D, Ferraretti AP, Munné S. Impact of blastomere biopsy and cryopreservation techniques on human embryo viability. Hum Reprod. 1999;14:770–3.

    Article  PubMed  CAS  Google Scholar 

  6. Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, Kokocinski F, Michel CE. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014;101:1375–82.

    Article  PubMed  CAS  Google Scholar 

  7. Capalbo A, Rienzi L. Mosaicism between trophectoderm and inner cell mass. Fertil Steril. 2017;107:1098–106.

    Article  PubMed  Google Scholar 

  8. Lai HH, Chuang TH, Wong LK, Lee MJ, Hsieh CL, Wang HL, Chen SU. Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization. Mol Cytogenet. 2017;10:14.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Munné S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M, Wells D, Gordon T, Stock-Myer S, Willman S, STAR Study Group. 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;112:1071–79.e7.

    Article  PubMed  Google Scholar 

  10. Yan J, Qin Y, Zhao H, Sun Y, Gong F, Li R, Sun X, Ling X, Li H, Hao C, Tan J, Yang J, Zhu Y, Liu F, Chen D, Wei D, Lu J, Ni T, Zhou W, 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.

    Article  PubMed  CAS  Google Scholar 

  11. Orvieto R, Gleicher N. Preimplantation genetic testing for aneuploidy (PGT-A)—finally revealed. J Assist Reprod Genet. 2020;37:669–72.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Schattman GL. Preimplantation genetic testing for aneuploidy: it’s déjà vu all over again! Fertil Steril. 2019;112:1046–7.

    Article  PubMed  Google Scholar 

  13. Gleicher N, Albertini DF, Barad DH, Homer H, Modi D, Murtinger M, Patrizio P, Orvieto R, Takahashi S, Weghofer A, Ziebe S, Noyes N, International Do No Harm Group in IVF (IDNHG-IVF). The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A. Reprod Biol Endocrinol. 2020;18:57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Homer HA. Preimplantation genetic testing for aneuploidy (PGT-A): the biology, the technology and the clinical outcomes. Aust N Z J Obstet Gynaecol. 2019;59:317–24.

    Article  PubMed  Google Scholar 

  15. Zhang YX, Chen JJ, Nabu S, Yeung QSY, Li Y, Tan JH, Suksalak W, Chanchamroen S, Quangkananurug W, Wong PS, Chung JPW, Choy KW. The pregnancy outcome of mosaic embryo transfer: a prospective multicenter study and meta-analysis. Genes (Basel). 2020;11:973.

    Article  PubMed  CAS  Google Scholar 

  16. Wirleitner B, Okhowat J, Vištejnová L, Králíčková M, Karlíková M, Vanderzwalmen P, Ectors F, Hradecký L, Schuff M, Murtinger M. Relationship between follicular volume and oocyte competence, blastocyst development and live-birth rate: optimal follicle size for oocyte retrieval. Ultrasound Obstet Gynecol. 2018;51:118–25.

    Article  PubMed  CAS  Google Scholar 

  17. Gardner DK, Schoolcraft WB. Culture and transfer of human blastocysts. Curr Opin Obstet Gynecol. 1999;11:307–11.

    Article  PubMed  CAS  Google Scholar 

  18. Wirleitner B, Vanderzwalmen P, Stecher A, Murtinger M. Aseptic vitrification of blastocysts after trophectoderm (TE) biopsy. Reprod BioMed Online. 2018;36(Suppl 1):e13.

    Google Scholar 

  19. Chuang TH, Chang YP, Lee MJ, Wang HL, Lai HH, Chen SU. The incidence of mosaicism for individual chromosome in human blastocysts is correlated with chromosome length. Front Genet. 2021;11:565348.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cimadomo D, Rienzi L, Romanelli V, Alviggi E, Levi-Setti PE, Albani E, Dusi L, Papini L, Livi C, Benini F, Smeraldi A, Patassini C, Ubaldi FM, Capalbo A. Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience. Hum Reprod. 2018;33:1839–46.

    Article  PubMed  Google Scholar 

  21. Bundesministerium für Digitalisierung und Wirtschaftsstandort. Bundesrecht konsolidiert: Gesamte Rechtsvorschrift für Fortpflanzungsmedizingesetz, Fassung vom 19.11.2022. Available from: https://www.ris.bka.gv.at/GeltendeFassung.wxe?Abfrage=Bundesnormen&Gesetzesnummer=10003046 Accessed 20 Nov 2022.

  22. Gleicher N, Metzger J, Croft G, Kushnir VA, Albertini DF, Barad DH. A single trophectoderm biopsy at blastocyst stage is mathematically unable to determine embryo ploidy accurately enough for clinical use. Reprod Biol Endocrinol. 2017;15:33.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Yang H, DeWan AT, Desai MM, Vermund SH. Preimplantation genetic testing for aneuploidy: challenges in clinical practice. Hum Genomics. 2022;16:69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Takahashi S, Johnston J, Patrizio P. Lessons from the premature adoption of preimplantation embryo testing. Genet Med. 2019;21:1038–40.

    Article  PubMed  Google Scholar 

  25. ESHRE Working Group on Chromosomal Mosaicism, De Rycke M, Capalbo A, Coonen E, Coticchio G, Fiorentino F, Goossens V, Mcheik S, Rubio C, Sermon K, Sfontouris I, Spits C, Vermeesch JR, Vermeulen N, Wells D, Zambelli F, Kakourou G. ESHRE survey results and good practice recommendations on managing chromosomal mosaicism. sHum Reprod Open. 2022;2022:hoac044. https://doi.org/10.1093/hropen/hoac044.

    Article  Google Scholar 

  26. Cram DS, Leigh D, Handyside A, Rechitsky L, Xu K, Harton G, Grifo J, Rubio C, Fragouli E, Kahraman S, Forman E, Katz-Jaffe M, Tempest H, Thornhill A, Strom C, Escudero T, Qiao J, Munne S, Simpson JL, Kuliev A. PGDIS position statement on the transfer of mosaic embryos 2019. Reprod BioMed Online. 2019;39(Suppl 1):e1–4.

    PubMed  Google Scholar 

  27. Xie P, Liu P, Zhang S, Cheng D, Chen D, Tan YQ, Hu L, Qiu Y, Zhou S, Ou-Yang Q, Luo K, Lu G, Zhang S, Gong F, Lin G. Segmental aneuploidies with 1 Mb resolution in human preimplantation blastocysts. Genet Med. 2022;24:2285–95. https://doi.org/10.1016/j.gim.2022.08.008.

    Article  PubMed  CAS  Google Scholar 

  28. McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet. 2017;33:448–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Abhari S, Kawwass JF. Pregnancy and neonatal outcomes after transfer of mosaic embryos: a review. J Clin Med. 2021;10:1369.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shahbazi MN, Wang T, Tao X, Weatherbee BAT, Sun L, Zhan Y, Keller L, Smith GD, Pellicer A, Scott RT Jr, Seli E, Zernicka-Goetz M. Developmental potential of aneuploid human embryos cultured beyond implantation. Nat Commun. 2020;11:3987.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Singla S, Iwamoto-Stohl LK, Zhu M, Zernicka-Goetz M. Autophagy-mediated apoptosis eliminates aneuploid cells in a mouse model of chromosome mosaicism. Nat Commun. 2020;11:2958.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Yang M, Rito T, Metzger J, Naftaly J, Soman R, Hu J, Albertini DF, Barad DH, Brivanlou AH, Gleicher N. Depletion of aneuploid cells in human embryos and gastruloids. Nat Cell Biol. 2021;23:314–21.

    Article  PubMed  CAS  Google Scholar 

  33. Gleicher N, Kushnir VA, Barad DH. How PGS/PGT-A laboratories succeeded in losing all credibility. Reprod BioMed Online. 2018;37:242–5.

    Article  PubMed  Google Scholar 

  34. Murtinger M, Wirleitner B, Schuff M. Scoring of mosaic embryos after preimplantation genetic testing: a rollercoaster ride between fear, hope and embryo wastage. Reprod BioMed Online. 2018;37:120–1.

    Article  PubMed  Google Scholar 

  35. Braude P. The emperor still looks naked. Reprod BioMed Online. 2018;37:133–5.

    Article  PubMed  Google Scholar 

  36. Wirleitner B, Schuff M, Stecher A, Murtinger M, Vanderzwalmen P. Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. Hum Reprod. 2016;31:1685–95.

    Article  PubMed  CAS  Google Scholar 

  37. Gleicher N, Barad DH, Ben-Rafael Z, Glujovsky D, Mochizuki L, Modi D, Murtinger M, Patrizio P, Orvieto R, Takahashi S, Weghofer A, Ziebe S, International Do No Harm Group in IVF (IDNHG-IVF). Commentary on two recently published formal guidelines on management of “mosaic” embryos after preimplantation genetic testing for aneuploidy (PGT-A). Reprod Biol Endocrinol. 2021;19:23. https://doi.org/10.1186/s12958-021-00716-1.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Murtinger M, Schuff M, Wirleitner B, Miglar S, Spitzer D. Comment on the recent PGDIS position statement on the transfer of mosaic embryos 2021. J Assist Reprod Genet. 2022; https://doi.org/10.1007/s10815-022-02620-y.

  39. Lin J, Vitek W, Scott EL. Order from chaos: a case report of a healthy live birth from a genetically “chaotic” embryo. F S Rep. 2022;3:301–4. https://doi.org/10.1016/j.xfre.2022.10.003.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Listorti I, Ronsini C, Greco PF, Victor A, Barnes F, Zouves C, Spinella F, Viotti M. Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism. Hum Reprod. 2023:deac263. https://doi.org/10.1093/humrep/deac263.

  41. Gleicher N, Patrizio P, Mochizuki L, Barad DH. Previously reported and here added cases demonstrate euploid pregnancies followed by PGT-A as “mosaic” as well as “aneuploid” designated embryos. Reprod Biol Endocrinol. 2023;21:25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  43. Franasiak JM. Mosaic embryo transfer: a cautionary tale. F S Rep. 2022;3:179–80. https://doi.org/10.1016/j.xfre.2022.07.005.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tocci A. The unknown human trophectoderm: implication for biopsy at the blastocyst stage. J Assist Reprod Genet. 2020;37:2699–711.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Konstantinidis M, Prates R, Goodall NN, Fischer J, Tecson V, Lemma T, Chu B, Jordan A, Armenti E, Wells D, Munné S. Live births following Karyomapping of human blastocysts: experience from clinical application of the method. Reprod BioMed Online. 2015;31:394–403.

    Article  PubMed  Google Scholar 

  47. Osman EK, Neal SA, Tiegs AW, Hanson BM, Kim JG, Franasiak JM, Scott RT Jr. Consistency in rates of diagnosis of embryonic mosaicism, segmental abnormalities, and “no call” results among experienced embryologists performing preimplantation genetic testing for aneuploidy. F S Rep. 2020;1:119–24.

    PubMed  PubMed Central  Google Scholar 

  48. Lee H, McCulloh DH, Olivares R, Goldstein-Tufaro A, McCaffrey C, Grifo J. Live births after transfer of rebiopsy and revitrification of blastocyst that had “no diagnosis” following trophectoderm biopsy. Fertil Steril. 2016;106:e164.

    Article  Google Scholar 

  49. Brower M, Hill D, Danzer H, Surrey M, Ghadir S, Chang W, Wambach C, Alexander C, Barritt J. “No diagnosis” embryos after PGS should not be discarded: rebiopsy and reanalysis demonstrate the majority are euploid. Fertil Steril. 2014;102:e31.

    Article  Google Scholar 

  50. Kaing A, Kroener L, Brower M, Hill D, Danzer H, Barritt J. Rebiopsy and preimplanation genetic screening (PGS) reanalysis demonstrate the majority of originally “no diagnosis” embryos are euploid with comparable pregnancy rates. Fertil Steril. 2015;104:e277.

    Article  Google Scholar 

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Correspondence to Barbara Wirleitner.

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Wirleitner, B., Hrubá, M., Schuff, M. et al. Embryo drop-out rates in preimplantation genetic testing for aneuploidy (PGT-A): a retrospective data analysis from the DoLoRes study. J Assist Reprod Genet 41, 193–203 (2024). https://doi.org/10.1007/s10815-023-02976-9

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