Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 1, pp 165–172 | Cite as

Rates of live birth after mosaic embryo transfer compared with euploid embryo transfer

  • Lei Zhang
  • Daimin Wei
  • Yueting Zhu
  • Yuan Gao
  • Junhao YanEmail author
  • Zi-Jiang Chen
Assisted Reproduction Technologies
  • 255 Downloads

Abstract

Purpose

Mosaicism is a prevalent characteristic of human preimplantation embryos. This retrospective cohort study aimed to investigate pregnancy outcomes after transfer of mosaic or euploid embryos.

Methods

The embryos, which had been transferred as “euploidy,” were processed using array-based comparative genomic hybridization (aCGH). The original aCGH charts of the transferred embryos were reanalyzed. Mosaic and control euploid embryos were defined according to log2 ratio calls.

Results

Overall, 102 embryos were determined to be mosaic, of which 101 were estimated to harbor no more than 50% aneuploid mosaicism. Additionally, 268 euploid embryos were matched as controls. The rates of live birth (46.6% vs. 59.1%, odds ratio (OR) 0.60, 95% confidence interval (CI) 0.38–0.95), and biochemical pregnancy (65.7% vs. 76.1%, OR 0.60, 95% CI 0.37–0.99) per transfer cycle were significantly lower after mosaic embryo transfer than after euploid embryo transfer. The rates of clinical pregnancy and pregnancy loss and the risks of obstetric outcomes did not differ significantly between the two groups.

Conclusions

Compared with euploid embryo transfer, mosaic embryo transfer is associated with a lower rate of live birth, which is mainly attributed to a decreased rate of conception. However, as mosaic embryo transfer yielded a live birth rate of 46.6%, patients without euploid embryos could be counseled regarding this alternative option.

Keywords

Embryo transfer Mosaic embryo Live birth Obstetric outcome Mosaicism 

Notes

Acknowledgements

The authors expressed thanks to Wenjie Jiang, Hongqiang Xie, Hongchang Li, and Ping Li from Reproductive Hospital Affiliated to Shandong University for performing PGT procedures and following up.

Funding information

This study was funded by the National Key Research and Development Program of China (grant number 2016YFC1000202), National Natural Science Foundation of China (grant number 81671522), and Innovative Foundation of Reproductive Hospital Affiliated to Shandong University (grant number 20171114).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10815_2018_1322_MOESM1_ESM.docx (38 kb)
ESM 1 (DOCX 37 kb)
10815_2018_1322_MOESM2_ESM.docx (16 kb)
ESM 2 (DOCX 16 kb)

References

  1. 1.
    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(4):571–81.  https://doi.org/10.1093/humupd/dmu016.CrossRefGoogle Scholar
  2. 2.
    Delhanty JD, Griffin DK, Handyside AH, Harper J, Atkinson GH, Pieters MH, et al. Detection of aneuploidy and chromosomal mosaicism in human embryos during preimplantation sex determination by fluorescent in situ hybridisation (FISH). Hum Mol Genet. 1993;2(8):1183–5.CrossRefGoogle Scholar
  3. 3.
    Munne S, Weier HU, Grifo J, Cohen J. Chromosome mosaicism in human embryos. Biol Reprod. 1994;51(3):373–9.CrossRefGoogle Scholar
  4. 4.
    McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet. 2017;33(7):448–63.  https://doi.org/10.1016/j.tig.2017.04.001.CrossRefGoogle Scholar
  5. 5.
    Delhanty JD, Harper JC, Ao A, Handyside AH, Winston RM. Multicolour FISH detects frequent chromosomal mosaicism and chaotic division in normal preimplantation embryos from fertile patients. Hum Genet. 1997;99(6):755–60.CrossRefGoogle Scholar
  6. 6.
    Evsikov S, Verlinsky Y. Mosaicism in the inner cell mass of human blastocysts. Hum Reprod. 1998;13(11):3151–5.CrossRefGoogle Scholar
  7. 7.
    Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15(8):1781–6.CrossRefGoogle Scholar
  8. 8.
    Capalbo A, Wright G, Elliott T, Ubaldi FM, Rienzi L, Nagy ZP. FISH reanalysis of inner cell mass and trophectoderm samples of previously array-CGH screened blastocysts shows high accuracy of diagnosis and no major diagnostic impact of mosaicism at the blastocyst stage. Hum Reprod. 2013;28(8):2298–307.  https://doi.org/10.1093/humrep/det245.CrossRefGoogle Scholar
  9. 9.
    Bielanska M, Tan SL, Ao A. High rate of mixoploidy among human blastocysts cultured in vitro. Fertil Steril. 2002;78(6):1248–53.CrossRefGoogle Scholar
  10. 10.
    Vorsanova SG, Kolotii AD, Iourov IY, Monakhov VV, Kirillova EA, Soloviev IV, et al. Evidence for high frequency of chromosomal mosaicism in spontaneous abortions revealed by interphase FISH analysis. J Histochem Cytochem. 2005;53(3):375–80.  https://doi.org/10.1369/jhc.4A6424.2005.CrossRefGoogle Scholar
  11. 11.
    Forsberg LA, Gisselsson D, Dumanski JP. Mosaicism in health and disease—clones picking up speed. Nat Rev Genet. 2017;18(2):128–42.  https://doi.org/10.1038/nrg.2016.145.CrossRefGoogle Scholar
  12. 12.
    Simon C. Introduction: to transfer or not transfera mosaic embryo, that is the question. Fertil Steril. 2017;107(5):1083–4.  https://doi.org/10.1016/j.fertnstert.2017.03.025.CrossRefGoogle Scholar
  13. 13.
    Maxwell SM, Colls P, Hodes-Wertz B, DH MC, McCaffrey C, Wells D, et al. Why do euploid embryos miscarry? A case-control study comparing the rate of aneuploidy within presumed euploid embryos that resulted in miscarriage or live birth using next-generation sequencing. Fertil Steril. 2016;106(6):1414–9.  https://doi.org/10.1016/j.fertnstert.2016.08.017.CrossRefGoogle Scholar
  14. 14.
    Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, et al. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011;95(3):953–8.  https://doi.org/10.1016/j.fertnstert.2010.09.010.CrossRefGoogle Scholar
  15. 15.
    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(1):24.  https://doi.org/10.1186/1755-8166-5-24.CrossRefGoogle Scholar
  16. 16.
    Sermon K, Capalbo A, Cohen J, Coonen E, De Rycke M, De Vos A, et al. The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. Mol Hum Reprod. 2016;22(8):845–57.  https://doi.org/10.1093/molehr/gaw034.CrossRefGoogle Scholar
  17. 17.
    Fiorentino F, Spizzichino L, Bono S, Biricik A, Kokkali G, Rienzi L, et al. PGD for reciprocal and Robertsonian translocations using array comparative genomic hybridization. Hum Reprod. 2011;26(7):1925–35.  https://doi.org/10.1093/humrep/der082.CrossRefGoogle Scholar
  18. 18.
    Alfarawati S, Fragouli E, Colls P, Wells D. First births after preimplantation genetic diagnosis of structural chromosome abnormalities using comparative genomic hybridization and microarray analysis. Hum Reprod. 2011;26(6):1560–74.  https://doi.org/10.1093/humrep/der068.CrossRefGoogle Scholar
  19. 19.
    Franasiak JM, Scott RT Jr. Embryonic aneuploidy: overcoming molecular genetics challenges improves outcomes and changes practice patterns. Trends Mol Med. 2014;20(9):499–508.  https://doi.org/10.1016/j.molmed.2014.06.006.CrossRefGoogle Scholar
  20. 20.
    Colls P, Escudero T, Fischer J, Cekleniak NA, Ben-Ozer S, Meyer B, et al. Validation of array comparative genome hybridization for diagnosis of translocations in preimplantation human embryos. Reprod BioMed Online. 2012;24(6):621–9.  https://doi.org/10.1016/j.rbmo.2012.02.006.CrossRefGoogle Scholar
  21. 21.
    Greco E, Minasi MG, Fiorentino F. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med. 2015;373(21):2089–90.  https://doi.org/10.1056/NEJMc1500421.CrossRefGoogle Scholar
  22. 22.
    Fragouli E, Alfarawati S, Spath K, Babariya D, Tarozzi N, Borini A, et al. Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid-aneuploid blastocysts. Hum Genet. 2017;136(7):805–19.  https://doi.org/10.1007/s00439-017-1797-4.CrossRefGoogle Scholar
  23. 23.
    Munne S, Blazek J, Large M, Martinez-Ortiz PA, Nisson H, Liu E, et al. Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing. Fertil Steril. 2017;108(1):62–71.e8.  https://doi.org/10.1016/j.fertnstert.2017.05.002.CrossRefGoogle Scholar
  24. 24.
    Spinella F, Fiorentino F, Biricik A, Bono S, Ruberti A, Cotroneo E, et al. Extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments. Fertil Steril. 2018;109(1):77–83.  https://doi.org/10.1016/j.fertnstert.2017.09.025.CrossRefGoogle Scholar
  25. 25.
    Zhang Q, Li G, Zhang L, Sun X, Zhang D, Lu J et al. Maternal common variant rs2305957 spanning PLK4 is associated with blastocyst formation and early recurrent miscarriage. Fertil Steril 2017;107(4):1034–40 e5. doi: https://doi.org/10.1016/j.fertnstert.2017.01.006, 1040.e5.
  26. 26.
    Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155–8.  https://doi.org/10.1016/s0015-0282(00)00518-5.CrossRefGoogle Scholar
  27. 27.
    Lledo B, Morales R, Ortiz JA, Blanca H, Ten J, Llacer J, et al. Implantation potential of mosaic embryos. Syst Biol Reprod Med. 2017;63(3):206–8.  https://doi.org/10.1080/19396368.2017.1296045.CrossRefGoogle Scholar
  28. 28.
    Garrisi G, Walmsley RH, Bauckman K, Mendola RJ, Colls P, Munne S. Discordance among serial biopsies of mosaic embryos. Fertil Steril. 2016;106((3):e151.  https://doi.org/10.1016/j.fertnstert.2016.07.447.CrossRefGoogle Scholar
  29. 29.
    Durrbaum M, Kuznetsova AY, Passerini V, Stingele S, Stoehr G, Storchova Z. Unique features of the transcriptional response to model aneuploidy in human cells. BMC Genomics. 2014;15:139.  https://doi.org/10.1186/1471-2164-15-139.CrossRefGoogle Scholar
  30. 30.
    Williams BR, Prabhu VR, Hunter KE, Glazier CM, Whittaker CA, Housman DE, et al. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells. Science. 2008;322(5902):703–9.  https://doi.org/10.1126/science.1160058.CrossRefGoogle Scholar
  31. 31.
    Lavon N, Narwani K, Golan-Lev T, Buehler N, Hill D, Benvenisty N. Derivation of euploid human embryonic stem cells from aneuploid embryos. Stem Cells. 2008;26(7):1874–82.  https://doi.org/10.1634/stemcells.2008-0156.CrossRefGoogle Scholar
  32. 32.
    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.  https://doi.org/10.1038/ncomms11165.CrossRefGoogle Scholar
  33. 33.
    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.CrossRefGoogle Scholar
  34. 34.
    Marin D, Scott RT Jr, Treff NR. Preimplantation embryonic mosaicism: origin, consequences and the reliability of comprehensive chromosome screening. Curr Opin Obstet Gynecol. 2017;29(3):168–74.  https://doi.org/10.1097/GCO.0000000000000358.CrossRefGoogle Scholar
  35. 35.
    Popovic M, Dheedene A, Christodoulou C, Taelman J, Dhaenens L, Van Nieuwerburgh F, et al. Chromosomal mosaicism in human blastocysts: the ultimate challenge of preimplantation genetic testing? Hum Reprod. 2018;33(7):1342–54.  https://doi.org/10.1093/humrep/dey106.CrossRefGoogle Scholar
  36. 36.
    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(1):33.  https://doi.org/10.1186/s12958-017-0251-8.CrossRefGoogle Scholar
  37. 37.
    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.Google Scholar
  38. 38.
    Segawa T, Kuroda T, Kato K, Kuroda M, Omi K, Miyauchi O, et al. Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study. Reprod BioMed Online. 2017;34(2):203–10.  https://doi.org/10.1016/j.rbmo.2016.11.005.CrossRefGoogle Scholar
  39. 39.
    Malvestiti F, Agrati C, Grimi B, Pompilii E, Izzi C, Martinoni L, et al. Interpreting mosaicism in chorionic villi: results of a monocentric series of 1001 mosaics in chorionic villi with follow-up amniocentesis. Prenat Diagn. 2015;35(11):1117–27.  https://doi.org/10.1002/pd.4656.CrossRefGoogle Scholar
  40. 40.
    Munne S, Grifo J, Wells D. Mosaicism: “survival of the fittest” versus “no embryo left behind”. Fertil Steril. 2016;105(5):1146–9.  https://doi.org/10.1016/j.fertnstert.2016.01.016.CrossRefGoogle Scholar
  41. 41.
    Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, et al. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014;101(5):1375–82.  https://doi.org/10.1016/j.fertnstert.2014.01.051.CrossRefGoogle Scholar
  42. 42.
    Yang Z, Lin J, Zhang J, Fong WI, Li P, Zhao R, et al. Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study. BMC Med Genet. 2015;8:30.  https://doi.org/10.1186/s12920-015-0110-4.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lei Zhang
    • 1
    • 2
    • 3
    • 4
  • Daimin Wei
    • 1
    • 2
    • 3
    • 4
  • Yueting Zhu
    • 1
    • 2
    • 3
    • 4
  • Yuan Gao
    • 1
    • 2
    • 3
    • 4
  • Junhao Yan
    • 1
    • 2
    • 3
    • 4
    Email author
  • Zi-Jiang Chen
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
  1. 1.Center for Reproductive MedicineShandong Provincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.National Research Center for Assisted Reproductive Technology and Reproductive GeneticsJinanChina
  3. 3.The Key Laboratory of Reproductive Endocrinology (Shandong University)Ministry of EducationJinanChina
  4. 4.Shandong Provincial Key Laboratory of Reproductive MedicineJinanChina
  5. 5.Center for Reproductive Medicine, Ren Ji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  6. 6.Shanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghaiChina

Personalised recommendations