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

  • Assisted Reproduction Technologies
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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.

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References

  1. Griffin DK, Ogur C. Chromosomal analysis in IVF: just how useful is it? Reproduction. 2018;156:F29–50.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  3. Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280–91.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  7. Munné S. Origins of mosaicism and criteria for the transfer of mosaic embryos. Reprod BioMed Online. 2018;36:369–70.

    PubMed  Google Scholar 

  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. 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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  17. Webster A, Schuh M. Mechanisms of aneuploidy in human eggs. Trends Cell Biol. 2017;27:55–68.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  19. Mantikou E, Wong KM, Repping S, Mastenbroek S. Molecular origin of mitotic aneuploidies in preimplantation embryos. Biochim Biophys Acta. 2012;1822:1921–30.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Brooker AS, Berkowitz KM. The roles of cohesins in mitosis, meiosis, and human health and disease. Methods Mol Biol. 2014;1170:229–66.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  36. Munné S, Cohen J, Sable D. Preimplantation genetic diagnosis for advanced maternal age and other indications. Fertil Steril. 2002;78:234–6.

    PubMed  Google Scholar 

  37. Palermo G, Munné S, Cohen J. The human zygote inherits its mitotic potential from the male gamete. Hum Reprod. 1994;9:1220–5.

    CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. 9.Baby - Family and Fertility Center, Via Dante 15, 40125, Bologna, Italy

    Nicoletta Tarozzi, Marco Nadalini, Cristina Lagalla, Giovanni Coticchio, Carlotta Zacà & Andrea Borini

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  1. Nicoletta Tarozzi
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  2. Marco Nadalini
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  3. Cristina Lagalla
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  4. Giovanni Coticchio
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  5. Carlotta Zacà
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  6. Andrea Borini
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Correspondence to Giovanni Coticchio.

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Tarozzi, N., Nadalini, M., Lagalla, C. et al. Male factor infertility impacts the rate of mosaic blastocysts in cycles of preimplantation genetic testing for aneuploidy. J Assist Reprod Genet 36, 2047–2055 (2019). https://doi.org/10.1007/s10815-019-01584-w

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  • DOI: https://doi.org/10.1007/s10815-019-01584-w

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