Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 10, pp 2047–2055 | Cite as

Male factor infertility impacts the rate of mosaic blastocysts in cycles of preimplantation genetic testing for aneuploidy

  • Nicoletta Tarozzi
  • Marco Nadalini
  • Cristina Lagalla
  • Giovanni CoticchioEmail author
  • Carlotta Zacà
  • Andrea Borini
Assisted Reproduction Technologies
  • 172 Downloads

Abstract

Purpose

In this study, we tested the hypothesis that, in PGT-A cycles, decreased semen quality is associated with increased rates of mosaic blastocysts.

Methods

In a retrospective analysis, three hundred and forty PGT-A cycles are divided into study groups according to semen quality. Cycles were initially divided into two groups, discerning couples with absence of male factor of infertility (non-male factor: NMF; N = 146 cycles) from couples with a male factor of infertility (MF; N = 173 cycles). Couples with severe male factor (SMF) infertility (n = 22) were assessed separately. Embryos were cultured to the blastocyst stage and chromosomally assessed by array comparative genomic hybridization (aCGH). The study did not involve specific interventions.

Results

The reproductive outcome of MF and NMF groups did not indicate statistically significant differences. However, while no differences were found between MF and NMF groups in terms of euploid or aneuploid blastocysts rates, a significantly higher rate of mosaic blastocysts was observed in the MF group (3.6% vs. 0.5%, respectively; P = 0.03). A similar pattern of results was observed in the SMF group when compared with those of the other PGT-A cycles taken together (no SMF). In particular, a significantly higher rate of mosaic blastocysts was observed in the SMF group (7.7% and 1.8%, respectively; P = 0.008).

Conclusions

The study outcome strongly suggests that compromised semen quality is associated with increased rates of mosaic blastocysts analysed in PGT-A cycles. Sperm assessment appears therefore as an important factor in the determination of embryo development and for a more precise prognostic assessment of PGT-A cases.

Keywords

Aneuploidy Mosaicism Blastocyst Semen Infertility 

Notes

Supplementary material

10815_2019_1584_MOESM1_ESM.docx (32 kb)
ESM 1 (DOCX 31 kb)

References

  1. 1.
    Griffin DK, Ogur C. Chromosomal analysis in IVF: just how useful is it? Reproduction. 2018;156:F29–50.PubMedPubMedCentralGoogle Scholar
  2. 2.
    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.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280–91.PubMedPubMedCentralGoogle Scholar
  4. 4.
    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;23:706–22.PubMedPubMedCentralGoogle Scholar
  5. 5.
    McCoy RC. Mosaicism in preimplantation human embryos: when chromosomal abnormalities are the norm. Trends Genet. 2017;33:448–63.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Munné S, Wells D. Detection of mosaicism at blastocyst stage with the use of high-resolution next-generation sequencing. Fertil Steril. 2017;107:1085–91.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Munné S. Origins of mosaicism and criteria for the transfer of mosaic embryos. Reprod BioMed Online. 2018;36:369–70.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Sekhon L, Feuerstein J, Nazem TG, Briton-Jones C, Lee JA, Grunfeld L, et al. The incidence of mosaicism is not associated with advanced maternal age or diminished ovarian reserve. Fertil Steril [Internet. 2017;108(3):e217.Google Scholar
  9. 9.
    Tarozzi N, Nadalini M, Bizzaro D, Serrao L, Fava L, Scaravelli G, et al. Sperm-hyaluronan-binding assay: clinical value in conventional IVF under Italian law. Reprod BioMed Online. 2009;19(Suppl 3):35–43.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Borini A, Bonu MA, Coticchio G, Bianchi V, Cattoli M, Flamigni C. Pregnancies and births after oocyte cryopreservation. Fertil Steril. 2004;82:601–5.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Borini A, Bafaro MG, Bianchi L, Violini F, Bonu MA, Flamigni C. Oocyte donation programme: results obtained with intracytoplasmic sperm injection in cases of severe male factor infertility or previous failed fertilisation. Hum Reprod. 1996;11:548–50.PubMedPubMedCentralGoogle Scholar
  12. 12.
    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;34:137–46.PubMedPubMedCentralGoogle Scholar
  13. 13.
    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.PubMedPubMedCentralGoogle Scholar
  14. 14.
    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;136:805–19.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Cobo A, Bellver J, Domingo J, Pérez S, Crespo J, Pellicer A, et al. New options in assisted reproduction technology: the Cryotop method of oocyte vitrification. Reprod BioMed Online. 2008;17:68–72.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Zacà C, Bazzocchi A, Pennetta F, Bonu MA, Coticchio G, Borini A. Cumulative live birth rate in freeze-all cycles is comparable to that of a conventional embryo transfer policy at the cleavage stage but superior at the blastocyst stage. Fertil Steril. 2018;110:703–9.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Webster A, Schuh M. Mechanisms of aneuploidy in human eggs. Trends Cell Biol. 2017;27:55–68.PubMedPubMedCentralGoogle Scholar
  18. 18.
    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.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Mantikou E, Wong KM, Repping S, Mastenbroek S. Molecular origin of mitotic aneuploidies in preimplantation embryos. Biochim Biophys Acta. 2012;1822:1921–30.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Bean CJ, Hunt PA, Millie EA, Hassold TJ. Analysis of a malsegregating mouse Y chromosome: evidence that the earliest cleavage divisions of the mammalian embryo are non-disjunction-prone. Hum Mol Genet. 2001;10:963–72.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Coonen E, Derhaag JG, Dumoulin JC, van WLC, Bras M, Janssen M, et al. Anaphase lagging mainly explains chromosomal mosaicism in human preimplantation embryos. Hum Reprod. 2004;19:316–24.PubMedPubMedCentralGoogle Scholar
  22. 22.
    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.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Katz-Jaffe MG, Trounson AO, Cram DS. Chromosome 21 mosaic human preimplantation embryos predominantly arise from diploid conceptions. Fertil Steril. 2005;84:634–43.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Baart EB, Martini E, Eijkemans MJ, Van OD, Beckers NG, Verhoeff A, et al. Milder ovarian stimulation for in-vitro fertilisation reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22:980–8.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Munne S, Magli C, Adler A, Wright G, de BK, Mortimer D, et al. Treatment-related chromosome abnormalities in human embryos. Hum Reprod. 1997;12:780–4.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Verpoest W, Fauser BC, Papanikolaou E, Staessen C, Van LL, Donoso P, et al. Chromosomal aneuploidy in embryos conceived with unstimulated cycle IVF. Hum Reprod. 2008;23:2369–71.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Bean CJ, Hassold TJ, Judis L, Hunt PA. Fertilisation in vitro increases non-disjunction during early cleavage divisions in a mouse model system. Hum Reprod. 2002;17:2362–7.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Baumann C, Viveiros MM, De LFR. Loss of maternal ATRX results in centromere instability and aneuploidy in the mammalian oocyte and pre-implantation embryo. PLoS Genet. 2010;6:e1001137.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Liu L, Blasco MA, Keefe DL. Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO Rep. 2002;3:230–4.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Wells D, Bermudez MG, Steuerwald N, Thornhill AR, Walker DL, Malter H, et al. Expression of genes regulating chromosome segregation, the cell cycle and apoptosis during human preimplantation development. Hum Reprod. 2005;20:1339–48.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Zheng P, Dean J. Role of Filia, a maternal effect gene, in maintaining euploidy during cleavage-stage mouse embryogenesis. Proc Natl Acad Sci U S A. 2009;106:7473–8.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Brooker AS, Berkowitz KM. The roles of cohesins in mitosis, meiosis, and human health and disease. Methods Mol Biol. 2014;1170:229–66.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Lister LM, Kouznetsova A, Hyslop LA, Kalleas D, Pace SL, Barel JC, et al. Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. Curr Biol. 2010;20:1511–21.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Tsutsumi M, Fujiwara R, Nishizawa H, Ito M, Kogo H, Inagaki H, et al. Age-related decrease of meiotic cohesins in human oocytes. PLoS One. 2014;9:e96710.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Munne S. Chromosome abnormalities in human embryos. Hum Reprod Update [Internet. 1998;4(6):842–55.  https://doi.org/10.1093/humupd/4.6.842.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Munné S, Cohen J, Sable D. Preimplantation genetic diagnosis for advanced maternal age and other indications. Fertil Steril. 2002;78:234–6.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Palermo G, Munné S, Cohen J. The human zygote inherits its mitotic potential from the male gamete. Hum Reprod. 1994;9:1220–5.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Sathananthan AH, Kola I, Osborne J, Trounson A, Ng SC, Bongso A, et al. Centrioles in the beginning of human development. Proc Natl Acad Sci U S A. 1991;88:4806–10.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Terada Y, Nakamura S, Morita J, Tachibana M, Morito Y, Ito K, et al. Use of mammalian eggs for assessment of human sperm function: molecular and cellular analyses of fertilisation by intracytoplasmic sperm injection. Am J Reprod Immunol. 2004;51:290–3.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Yoshimoto-Kakoi T, Terada Y, Tachibana M, Murakami T, Yaegashi N, Okamura K. Assessing centrosomal function of infertile males using heterologous ICSI. Syst Biol Reprod Med. 2008;54:135–42.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Silber S, Escudero T, Lenahan K, Abdelhadi I, Kilani Z, Munné S. Chromosomal abnormalities in embryos derived from testicular sperm extraction. Fertil Steril. 2003;79:30–8.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Magli MC, Gianaroli L, Ferraretti AP, Gordts S, Fredericks V, Crippa A. Paternal contribution to aneuploidy in preimplantation embryos. Reprod BioMed Online. 2009;18:536–42.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Borges E Jr, Zanetti BF, Setti AS, Braga DPAF, Provenza RR, Iaconelli A Jr. Sperm DNA fragmentation is correlated with poor embryo development, lower implantation rate, and higher miscarriage rate in reproductive cycles of non-male factor infertility. Fertil Steril. 2019;112:483–90.  https://doi.org/10.1016/j.fertnstert.2019.04.029.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    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.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Mazzilli R, Cimadomo D, Vaiarelli A, Capalbo A, Dovere L, Alviggi E, et al. Effect of the male factor on the clinical outcome of intracytoplasmic sperm injection combined with preimplantation aneuploidy testing: observational longitudinal cohort study of 1,219 consecutive cycles. Fertil Steril. 2017;108:961–72.e3.PubMedPubMedCentralGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.9.Baby - Family and Fertility CenterBolognaItaly

Personalised recommendations