Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 12, pp 2493–2504 | Cite as

Preimplantation Genetic Testing for Aneuploidy Improves Clinical, Gestational, and Neonatal Outcomes in Advanced Maternal Age Patients Without Compromising Cumulative Live-Birth Rate.

  • Laura Sacchi
  • Elena Albani
  • Amalia Cesana
  • Antonella Smeraldi
  • Valentina Parini
  • Marco Fabiani
  • Maurizio Poli
  • Antonio Capalbo
  • Paolo Emanuele Levi-SettiEmail author
Assisted Reproduction Technologies



To report the effects of blastocyst stage aneuploidy testing on clinical, gestational, and neonatal outcomes for patients of advanced maternal age undergoing IVF.


This is a single-center observational-cohort study with 2 years follow-up. The study includes a total of 2538 couples undergoing 2905 egg collections (control group), 308 (PGT-A), and 106 (drop-out group, consenting for PGT-A but withdrawing due to poor embryological outcome)


Compared with control group, PGT-A showed improved clinical outcomes (live-birth rate per transferred embryo, LBR 40.3% vs 11.0%) and reduced multiple pregnancy rate (MPR, 0% vs 11.1%) and pregnancy loss (PL, 3.6% vs 22.6%). Drop-out group showed the worst clinical outcomes suggesting that abandoning PGT-A due to poor response to ovarian stimulation is not a favorable option. Cytogenetic analysis of product of conceptions and CVS/amniocentesis showed higher aneuploid pregnancy rates for control group regardless of embryo transfer strategy (0%, 17.9%, and 19.9%, for PGT-A, control day 5 and day 3, respectively). Multivariate analysis showed no negative impact of PGT-A-related interventions on cumulative delivery rate (26.3%, 95% CI 21.5–31.6 vs 24.0%, 95% CI 22.5–25.6 for PGT-A and control, respectively) and on neonatal outcomes.


PGT-A improves clinical outcomes, particularly by reducing pregnancy loss and chromosomally abnormal pregnancy for patients of advanced maternal age, with no major impact on cumulative live-birth rate (CLBR) per egg retrieval.


Preimplantation genetic testing Advanced maternal age Clinical outcome Miscarriage Aneuploidy 


Supplementary material

10815_2019_1609_MOESM1_ESM.docx (51 kb)
ESM 1 (DOCX 51 kb)


  1. 1.
    Mastenbroek S, Repping S. Preimplantation genetic screening: back to the future. Hum Reprod. 2014:1846–50.CrossRefGoogle Scholar
  2. 2.
    Dahdouh EM, Balayla J, Garcia-Velasco JA. Comprehensive chromosome screening improves embryo selection: a meta-analysis. Fertil Steril. 2015;104:1503–12.CrossRefGoogle Scholar
  3. 3.
    Geraedts J, Sermon K. Preimplantation genetic screening 2.0: the theory. Mol Hum Reprod [Internet]. Oxford University Press; 2016;22:839–44. Available from:
  4. 4.
    Gleicher N, Orvieto R. Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review. J Ovarian Res. 2017:1–7.Google Scholar
  5. 5.
    Cox GF, Bürger J, Lip V, Mau UA, Sperling K, Wu B-L, et al. Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet. 2002;71:162–4.CrossRefGoogle Scholar
  6. 6.
    DeBaun MR, Niemitz EL, Feinberg AP. Association of in vitro fertilization with beckwith-wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003;72:156–60.CrossRefGoogle Scholar
  7. 7.
    Santos F, Hyslop L, Stojkovic P, Leary C, Murdoch A, Reik W, et al. Evaluation of epigenetic marks in human embryos derived from IVF and ICSI. Hum Reprod. 2010;25:2387–95.CrossRefGoogle Scholar
  8. 8.
    Martins WP, Nastri CO, Rienzi L, van der Poel SZ, Gracia C, Racowsky C. Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes. Ultrasound Obstet Gynecol. 2017:583–91.CrossRefGoogle Scholar
  9. 9.
    Tannus S, Cohen Y, Son WY, Shavit T, Dahan MH. Cumulative live-birth rate following elective single blastocyst transfer compared with double blastocyst transfer in women aged 40 years and over. Reprod BioMed Online. 2017;35:733–8.CrossRefGoogle Scholar
  10. 10.
    Styer AK, Wright DL, Wolkovich AM, Veiga C, Toth TL. Single-blastocyst transfer decreases twin gestation without affecting pregnancy outcome. Fertil Steril. 2008;89:1702–8.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    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.CrossRefGoogle Scholar
  13. 13.
    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.CrossRefGoogle Scholar
  14. 14.
    Somigliana E, Busnelli A, Paffoni A, Vigano P, Riccaboni A, Rubio C, et al. Cost-effectiveness of preimplantation genetic testing for aneuploidies. Fertil Steril. 2019;111:1169–76.CrossRefGoogle Scholar
  15. 15.
    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;97:870–5 Available from: Scholar
  16. 16.
    Scott RT Jr, Treff NR, Stevens J, Forman EJ, Hong KH, Katz-Jaffe MG, et al. Delivery of a chromosomally normal child from an oocyte with reciprocal aneuploid polar bodies. J Assist Reprod Genet. 2012;29:533–7 Available from: Scholar
  17. 17.
    Ubaldi FM, Cimadomo D, Capalbo A, Vaiarelli A, Buffo L, Trabucco E, et al. Preimplantation genetic diagnosis for aneuploidy testing in women older than 44 years: a multicenter experience. Fertil Steril. 2017;107.CrossRefGoogle Scholar
  18. 18.
    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.CrossRefGoogle Scholar
  19. 19.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280–91 Available from: Scholar
  20. 20.
    Bettio D, Capalbo A, Albani E, Rienzi L, Achille V, Venci A, et al. 45,X product of conception after preimplantation genetic diagnosis and euploid embryo transfer: evidence of a spontaneous conception confirmed by DNA fingerprinting. Reprod Biol Endocrinol. 2016;14.Google Scholar
  21. 21.
    Levi-Setti PE, Zerbetto I, Baggiani A, Zannoni E, Sacchi L, Smeraldi A, et al. An observational retrospective cohort trial on 4,828 IVF cycles evaluating different low prognosis patients following the Poseidon criteria. Front Endocrinol (Lausanne). 2019;10.Google Scholar
  22. 22.
    Levi-Setti PE, Menduni F, Smeraldi A, Patrizio P, Morenghi E, Albani E. Artificial shrinkage of blastocysts prior to vitrification improves pregnancy outcome: analysis of 1028 consecutive warming cycles. J Assist Reprod Genet [Internet]. Springer US; 2016;33:461–6. Available from: CrossRefGoogle Scholar
  23. 23.
    Tedeschi G, Albani E, Borroni EM, Parini V, Brucculeri AM, Maffioli E, et al. Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality. J Assist Reprod Genet. 2017;34:225–38.CrossRefGoogle Scholar
  24. 24.
    Cobo A, De Los Santos MJ, Castellò D, Gámiz P, Campos P, Remohí J. Outcomes of vitrified early cleavage-stage and blastocyst-stage embryos in a cryopreservation program: Evaluation of 3,150 warming cycles. Fertil Steril. 2012;98.CrossRefGoogle Scholar
  25. 25.
    Capalbo A, Treff NR, Cimadomo D, Tao X, Upham K, Ubaldi FM, et al. Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies. Eur J Hum Genet. 2015;23.CrossRefGoogle Scholar
  26. 26.
    Murugappan G, Shahine LK, Perfetto CO, Hickok LR, Lathi RB. Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. Hum Reprod. 2016.Google Scholar
  27. 27.
    Rienzi L, Capalbo A, Vajta G, Ubaldi FM. PGS for recurrent pregnancy loss: Still an open question. Hum Reprod. 2017:476–7.CrossRefGoogle Scholar
  28. 28.
    Levi Setti PE, Moioli M, Smeraldi A, Cesaratto E, Menduni F, Livio S, et al. Obstetric outcome and incidence of congenital anomalies in 2351 IVF/ICSI babies. J Assist Reprod Genet. 2016;33:711–7.CrossRefGoogle Scholar
  29. 29.
    Castillo CM, Horne G, Fitzgerald CT, Johnstone ED, Brison DR, Roberts SA. The impact of IVF on birthweight from 1991 to 2015: a cross-sectional study. Hum Reprod. 2019;34:920–31.CrossRefGoogle Scholar
  30. 30.
    Ubaldi FM, Capalbo A, Colamaria S, Ferrero S, Maggiulli R, Vajta G, et al. Reduction of multiple pregnancies in the advanced maternal age population after implementation of an elective single embryo transfer policy coupled with enhanced embryo selection: pre- and post-intervention study. Hum Reprod. 2015;30.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Laura Sacchi
    • 1
  • Elena Albani
    • 1
  • Amalia Cesana
    • 1
  • Antonella Smeraldi
    • 1
  • Valentina Parini
    • 1
  • Marco Fabiani
    • 2
  • Maurizio Poli
    • 2
  • Antonio Capalbo
    • 2
  • Paolo Emanuele Levi-Setti
    • 1
    Email author
  1. 1.Department of Gynecology, Division of Gynecology and Reproductive Medicine, Fertility CenterHumanitas Clinical and Research InstituteRozzanoItaly
  2. 2.Igenomix ItalyMarosticaItaly

Personalised recommendations