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Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 10, pp 1975–1987 | Cite as

The use of fluorescence in situ hybridization analysis on sperm: indications to perform and assisted reproduction technology outcomes

  • Zaida Sarrate
  • Joan BlancoEmail author
  • Fernando Marina-Rugero
  • Juan Manuel Moreno-García
  • Miguel Ruiz-Jorro
  • Rafael Lafuente-Varea
  • Fernando Graña-Zanón
  • Rocío Núñez-Calonge
  • Jorge Ten
  • Joaquín Rueda
Assisted Reproduction Technologies
  • 146 Downloads

Abstract

Purpose

To determine the consequences of an altered sperm fluorescence in situ hybridization (FISH) result for ART outcomes and the indications for a sperm FISH analysis.

Methods

Data from 439 infertile men were collected. Bivariate analyses were performed to determine the association of men’s age, seminal alterations, and sperm FISH indication, with the incidence of X, Y, 13, 18, and 21 sperm chromosomal abnormalities. A multivariate logistic regression analysis was performed to establish the most predictive variables for altered sperm FISH. Results from the IVF/ICSI cycles were collected for 248 out of 439 patients. Two distinct groups were established: 151 couples that used their own oocytes and 97 couples involved in egg donation programs. In both groups, ART outcomes were compared between normal and altered sperm FISH.

Results

Teratozoospermia and oligozoospermia were associated with sperm chromosome anomalies (p < 0.05). Indications for sperm FISH analysis with the highest predictability were teratozoospermia, male age, oligozoospermia, and implantation failure (AUC = 0.702). Embryo quality (p = 0.096), pregnancy rate (p = 0.054), and implantation rate (p = 0.089) were higher in own-oocytes couples with normal sperm FISH than in altered sperm FISH couples, although differences were not statistically significant. In donor-oocytes couples, in which high-quality embryos were transferred later than in own-oocytes couples (3.8 vs. 3.0 days), we did not identify differences in the ART outcome between normal and altered sperm FISH couples. In both groups, the possible interference of woman age was negligible.

Conclusions

Sperm FISH is indicated in middle-aged oligoteratozoospermic patients with implantation failures in previous IVF/ICSI cycles. Sperm chromosome anomalies have a moderate detrimental impact on embryo quality, implantation, and pregnancy rates.

Keywords

ART outcome Blastocyst transfer Male age Seminal parameters Sperm FISH indications 

Notes

Acknowledgments

The authors thank the Applied Statistics Service of the Universitat Autònoma de Barcelona for its support in the statistical treatment of the results. This manuscript has been proofread by Proof-Reading-Service.org.

Compliance with ethical standards

The Ethics Commission on Human and Animal Experimentation of the Universitat Autònoma de Barcelona approved the study.

References

  1. 1.
    Moosani N, Pattinson HA, Carter MD, Cox DM, Rademaker AW, Martin RH. Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization. Fertil Steril. 1995;64:811–7.CrossRefGoogle Scholar
  2. 2.
    Sarrate Z, Blanco J, Anton E, Egozcue S, Egozcue J, Vidal F. FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling. Asian J Androl. 2005;7:227–36.CrossRefGoogle Scholar
  3. 3.
    Sarrate Z, Vidal F, Blanco J. Role of sperm fluorescent in situ hybridization studies in infertile patients: indications, study approach, and clinical relevance. Fertil Steril. 2010;93:1892–902.CrossRefGoogle Scholar
  4. 4.
    Piomboni P, Stendardi A, Gambera L. Chromosomal aberrations and aneuploidies of spermatozoa. Adv Exp Med Biol. 2014;791:27–52.CrossRefGoogle Scholar
  5. 5.
    Chatziparasidou A, Christoforidis N, Samolada G, Nijs M. Sperm aneuploidy in infertile male patients: a systematic review of the literature. Andrologia. 2015;47:847–60.CrossRefGoogle Scholar
  6. 6.
    Ioannou D, Fortun J, Tempest HG. Meiotic nondisjunction and sperm aneuploidy in humans. Reproduction 2018;R15-R31. doi:  https://doi.org/10.1530/REP-18-0318.
  7. 7.
    Sarrate Z, Anton E. Fluorescence in situ hybridization (FISH) protocol in human sperm. J Vis Exp. 2009;31:1405.  https://doi.org/10.3791/1405.
  8. 8.
    Ramasamy R, Besada S, Lamb DJ. Fluorescent in situ hybridization of human sperm: diagnostics, indications, and therapeutic implications. Fertil Steril. 2014;102:1534–9.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Colombero LT, Hariprashad JJ, Tsai MC, Rosenwaks Z, Palermo GD. Incidence of sperm aneuploidy in relation to semen characteristics and assisted reproductive outcome. Fertil Steril. 1999;72:90–6.CrossRefGoogle Scholar
  10. 10.
    Calogero AE, De Palma A, Grazioso C, Barone N, Burrello N, Palermo I, et al. High sperm aneuploidy rate in unselected infertile patients and its relationship with intracytoplasmic sperm injection outcome. Hum Reprod. 2001;16:1433–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Burrello N, Vicari E, Shin P, Agarwal A, De Palma A, Grazioso C, et al. Lower sperm aneuploidy frequency is associated with high pregnancy rates in ICSI programmes. Hum Reprod. 2003;18:1371–6.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nagvenkar P, Zaveri K, Hinduja I. Comparison of the sperm aneuploidy rate in severe oligozoospermic and oligozoospermic men and its relation to intracytoplasmic sperm injection outcome. Fertil Steril. 2005;84:925–31.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Petit FM, Frydman N, Benkhalifa M, Le Du A, Aboura A, Fanchin R, et al. Could sperm aneuploidy rate determination be used as a predictive test before intracytoplasmic sperm injection? J Androl. 2005;26:235–41.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Mehdi M, Smatti B, Saad A, Guerin JF, Benchaib M. Analysis by fluorescence in situ hybridization (FISH) of the relationship between gonosomic aneuploidy and the results of assisted reproduction in men with severe oligozoospermia. Andrologia. 2006;38:137–41.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nicopoullos JD, Gilling-Smith C, Almeida PA, Homa S, Nice L, Tempest H, et al. The role of sperm aneuploidy as a predictor of the success of intracytoplasmic sperm injection? Hum Reprod. 2008;23:240–50.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Vialard F, Hammoud I, Molina-Gomes D, Wainer R, Bergere M, Albert M, et al. Gamete cytogenetic study in couples with implantation failure: aneuploidy rate is increased in both couple members. J Assist Reprod Genet. 2008;25:539–45.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Switzerland: WHO Press; 2010.Google Scholar
  18. 18.
    ASEBIR. (Asociación para el estudio de la Biología de la Reproducción). Cuadernos de Embriología Clínica. II. Criterios de valoración morfológicos de oocitos, embriones tempranos y blastocitos humanos. 3rd ed. Spain: ASEBIR; 2015.Google Scholar
  19. 19.
    Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: definition and management. Reprod Biomed Online. 2014;28:14–38.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod. 2006;21:2216–22.CrossRefGoogle Scholar
  21. 21.
    Royal College of Obstetricians and Gynaecologists. The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage (Green-Top Guideline no. 17). London: RCOG Press; 2011.Google Scholar
  22. 22.
    Blanco J, Egozcue J, Vidal F. Incidence of chromosome 21 disomy in human spermatozoa as determined by fluorescent in-situ hybridization. Hum Reprod. 1996;11:722–6.CrossRefGoogle Scholar
  23. 23.
    Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2000.CrossRefGoogle Scholar
  24. 24.
    Rives N, Saint Clair A, Mazurier S, Sibert L, Simeon N, Joly G, et al. Relationship between clinical phenotype, semen parameters and aneuploidy frequency in sperm nuclei of 50 infertile males. Hum Genet. 1999;105:266–72.CrossRefGoogle Scholar
  25. 25.
    Vegetti W, Van Assche E, Frias A, Verheyen G, Bianchi MM, Bonduelle M, et al. Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men. Hum Reprod. 2000;15:351–65.CrossRefGoogle Scholar
  26. 26.
    Calogero AE, De Palma A, Grazioso C, Barone N, Romeo R, Rappazzo G, et al. Aneuploidy rate in spermatozoa of selected men with abnormal semen parameters. Hum Reprod. 2001;16:1172–9.CrossRefGoogle Scholar
  27. 27.
    Martin RH, Rademaker AW, Greene C, Ko E, Hoang T, Barclay L, et al. A comparison of the frequency of sperm chromosome abnormalities in men with mild, moderate, and severe oligozoospermia. Biol Reprod. 2003;69:535–9.CrossRefGoogle Scholar
  28. 28.
    Faure AK, Aknin-Seifer I, Frérot G, Pelletier R, De Robertis C, Cans C, et al. Predictive factors for an increased risk of sperm aneuploidies in oligo-astheno-teratozoospermic males. Int J Androl. 2007;30:153–62.CrossRefGoogle Scholar
  29. 29.
    Durak Aras B, Aras I, Can C, Toprak C, Dikoglu E, Bademci G, et al. Exploring the relationship between the severity of oligozoospermia and the frequencies of sperm chromosome aneuploidies. Andrologia. 2012;44:416–22.CrossRefGoogle Scholar
  30. 30.
    Mokánszki A, Molnár Z, Ujfalusi A, Balogh E, Bazsáné ZK, Varga A, et al. Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients. Reprod Biomed Online. 2012;25:620–6.CrossRefGoogle Scholar
  31. 31.
    Miyamoto T, Hasuike S, Yogev L, Maduro MR, Ishikawa M, Westphal H, et al. Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet. 2003;362:1714–9.CrossRefGoogle Scholar
  32. 32.
    Sato H, Miyamoto T, Yogev L, Namiki M, Koh E, Hayashi H, et al. Polymorphic alleles of the human MEI1 gene are associated with human azoospermia by meiotic arrest. J Hum Genet. 2006;51:533–40.CrossRefGoogle Scholar
  33. 33.
    Akinloye O, Gromoll J, Callies C, Nieschlag E, Simoni M. Mutation analysis of the X-chromosome linked, testis-specific TAF7L gene in spermatogenic failure. Andrologia. 2007;39:190–5.CrossRefGoogle Scholar
  34. 34.
    Okutman O, Muller J, Baert Y, Serdarogullari M, Gultomruk M, Piton A, et al. Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family. Hum Mol Genet. 2015;24:5581–8.CrossRefGoogle Scholar
  35. 35.
    Yatsenko AN, Georgiadis AP, Röpke A, Berman AJ, Jaffe T, Olszewska M, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med. 2015;372:2097–107.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Gershoni M, Hauser R, Yogev L, Lehavi O, Azem F, Yavetz H, et al. A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes. Genet Med. 2017;19:998–1006.CrossRefGoogle Scholar
  37. 37.
    Zhang W, Song X, Ni F, Cheng J, Wu BL, Jiang H. Association analysis between HFM1 variations and idiopathic azoospermia or severe oligozoospermia in Chinese men. Sci China Life Sci. 2017;60:315–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wang XN, Li ZS, Ren Y, Jiang T, Wang YQ, Chen M, et al. The Wilms tumor gene, Wt1, is critical for mouse spermatogenesis via regulation of sertoli cell polarity and is associated with non-obstructive azoospermia in humans. PLoS Genet. 2013;9:e1003645.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Miyamoto T, Bando Y, Koh E, Tsujimura A, Miyagawa Y, Iijima M, et al. A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome. Andrology. 2016;4:75–81.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Li L, Sha YW, Su ZY, Mei LB, Ji ZY, Zhang Q, et al. A novel mutation in HAUS7 results in severe oligozoospermia in two brothers. Gene. 2018;639:106–10.CrossRefGoogle Scholar
  41. 41.
    Braun RE. Every sperm is sacred–or is it? Nat Genet. 1998;18:202–4.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hamer G, Novak I, Kouznetsova A, Höög C. Disruption of pairing and synapsis of chromosomes causes stage-specific apoptosis of male meiotic cells. Theriogenology. 2008;69:333–9.CrossRefGoogle Scholar
  43. 43.
    Burgoyne PS, Mahadevaiah SK, Turner JM. The consequences of asynapsis for mammalian meiosis. Nat Rev Genet. 2009;10:207–16.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Li XC, Barringer BC, Barbash DA. The pachytene checkpoint and its relationship to evolutionary patterns of polyploidization and hybrid sterility. Heredity (Edinb). 2009;102:24–30.CrossRefGoogle Scholar
  45. 45.
    Yan W. Male infertility caused by spermiogenic defects: lessons from gene knockouts. Mol Cell Endocrinol. 2009;306:24–32.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Gole LA, Wong PF, Ng PL, Wang XQ, Ng SC, Bongso A. Does sperm morphology play a significant role in increased sex chromosomal disomy? A comparison between patients with teratozoospermia and OAT by FISH. J Androl. 2001;22:759–63.PubMedGoogle Scholar
  47. 47.
    Härkönen K, Suominen J, Lähdetie J. Aneuploidy in spermatozoa of infertile men with teratozoospermia. Int J Androl. 2001;24:197–205.CrossRefGoogle Scholar
  48. 48.
    Templado C, Hoang T, Greene C, Rademaker A, Chernos J, Martin R. Aneuploid spermatozoa in infertile men: teratozoospermia. Mol Reprod Dev. 2002;61:200–4.CrossRefGoogle Scholar
  49. 49.
    Vicari E, de Palma A, Burrello N, Longo G, Grazioso C, Barone N, et al. Absolute polymorphic teratozoospermia in patients with oligo-asthenozoospermia is associated with an elevated sperm aneuploidy rate. J Androl. 2003;24:598–603.CrossRefGoogle Scholar
  50. 50.
    Machev N, Gosset P, Viville S. Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: teratozoospermia. Cytogenet Genome Res. 2005;111:352–7.CrossRefGoogle Scholar
  51. 51.
    Sun F, Ko E, Martin RH. Is there a relationship between sperm chromosome abnormalities and sperm morphology? Reprod Biol Endocrinol. 2006;4:1.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Strassburger D, Reichart M, Kaufman S, Kasterstein E, Komarovsky D, Bern O, et al. Morphology assessment and fluorescence in situ hybridization of the same spermatozoon using a computerized cell-scanning system. Hum Reprod. 2007;22:201–9.CrossRefGoogle Scholar
  53. 53.
    Mehdi M, Gmidène A, Brahem S, Guerin JF, Elghezal H, Saad A. Aneuploidy rate in spermatozoa of selected men with severe teratozoospermia. Andrologia. 2012;44:139–43.CrossRefGoogle Scholar
  54. 54.
    Ramasamy R, Scovell JM, Kovac JR, Cook PJ, Lamb DJ, Lipshultz LI. Fluorescence in situ hybridization detects increased sperm aneuploidy in men with recurrent pregnancy loss. Fertil Steril. 2015;103:906–9.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Fu G, Wei Y, Wang X, Yu L. Identification of candidate causal genes and their associated pathogenic mechanisms underlying teratozoospermia based on the spermatozoa transcript profiles. Andrologia. 2016;48:576–83.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Huang ZQ, Wang GX, Jiang XL, Tian EP, Yao WL, Zeng T. Systematic tracking of altered modules identifies disrupted pathways in teratozoospermia. Genet Mol Res 2016;15. doi  https://doi.org/10.4238/gmr.15027514.
  57. 57.
    Rubio C, Gil-Salom M, Simón C, Vidal F, Rodrigo L, Mínguez Y, et al. Incidence of sperm chromosomal abnormalities in a risk population: relationship with sperm quality and ICSI outcome. Hum Reprod. 2001;16:2084–92.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Li P, Hoshiai H. Detection of numerical chromosome abnormalities in human spermatozoa by three-color fluorescence in situ hybridization. J Obstet Gynaecol Res. 1998;24:385–92.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Aran B, Blanco J, Vidal F, Vendrell JM, Egozcue S, Barri PN, et al. Screening for abnormalities of chromosomes X, Y, and 18 and for diploidy in spermatozoa from infertile men participating in an in vitro fertilization-intracytoplasmic sperm injection program. Fertil Steril. 1999;72:696–701.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Hristova R, Ko E, Greene C, Rademaker A, Chernos J, Martin R. Chromosome abnormalities in sperm from infertile men with asthenoteratozoospermia. Biol Reprod. 2002;66:1781–3.CrossRefGoogle Scholar
  61. 61.
    Rives NM. Chromosome abnormalities in sperm from infertile men with normal somatic karyotypes: asthenozoospermia. Cytogenet Genome Res. 2005;111:358–62.CrossRefGoogle Scholar
  62. 62.
    Collodel G, Capitani S, Baccetti B, Pammolli A, Moretti E. Sperm aneuploidies and low progressive motility. Hum Reprod. 2007;22:1893–8.CrossRefGoogle Scholar
  63. 63.
    Pereira R, Sá R, Barros A, Sousa M. Major regulatory mechanisms involved in sperm motility. Asian J Androl. 2017;19:5–14.PubMedGoogle Scholar
  64. 64.
    Harris BS, Bishop KC, Kemeny HR, Walker JS, Rhee E, Kuller JA. Risk factors for birth defects. Obstet Gynecol Surv. 2017;72:123–35.CrossRefGoogle Scholar
  65. 65.
    Fonseka KG, Griffin DK. Is there a paternal age effect for aneuploidy? Cytogenet Genome Res. 2011;133:280–91.CrossRefGoogle Scholar
  66. 66.
    Sharma R, Agarwal A, Rohra VK, Assidi M, Abu-Elmagd M, Turki RF. Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring. Reprod Biol Endocrinol. 2015;13:35.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Eisenberg ML, Meldrum D. Effects of age on fertility and sexual function. Fertil Steril. 2017;107:301–4.CrossRefGoogle Scholar
  68. 68.
    Ioannou D, Tempest HG. Does genome organization matter in spermatozoa? A refined hypothesis to awaken the silent vessel. Syst Biol Reprod Med. 2018;2:1–17.Google Scholar
  69. 69.
    Braude P, Bolton V, Moore S. Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature. 1988;332:459–61.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Sánchez-Castro M, Jiménez-Macedo AR, Sandalinas M, Blanco J. Prognostic value of sperm fluorescence in situ hybridization analysis over PGD. Hum Reprod. 2009;24:1516–21.CrossRefGoogle Scholar
  71. 71.
    Rodrigo L, Peinado V, Mateu E, Remohí J, Pellicer A, Simón C, et al. Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos. Fertil Steril. 2010;94:1380–6.CrossRefGoogle Scholar
  72. 72.
    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.CrossRefGoogle Scholar
  73. 73.
    Rubio C, Rodrigo L, Mercader A, Mateu E, Buendía P, Pehlivan T, et al. Impact of chromosomal abnormalities on preimplantation embryo development. Prenat Diag. 2007;27:748–56.CrossRefGoogle Scholar
  74. 74.
    Capalbo A, Rienzi L, Cimadomo D, Maggiulli R, Elliott T, Wright G, et al. Correlation between standard blastocyst morphology, euploidy and implantation: an observational study in two centers involving 956 screened blastocysts. Hum Reprod. 2014;29:1173–81.CrossRefGoogle Scholar
  75. 75.
    Minasi MG, Colasante A, Riccio T, Ruberti A, Casciani V, Scarselli F, et al. Correlation between aneuploidy, standard morphology evaluation and morphokinetic development in 1730 biopsied blastocysts: a consecutive case series study. Hum Reprod. 2016;31:2245–54.CrossRefGoogle Scholar
  76. 76.
    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.CrossRefGoogle Scholar
  77. 77.
    Geraedts JPM. Chromosomal anomalies and recurrent miscarriage. Infertil Reprod Med Clin North Am. 1996;7:677–88.Google Scholar
  78. 78.
    Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med. 2015;5:a023119.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Carrell DT, Wilcox AL, Lowy L, Peterson CM, Jones KP, Erickson L, et al. Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstet Gynecol. 2003;101:1229–35.PubMedGoogle Scholar
  80. 80.
    Bernardini LM, Costa M, Bottazzi C, Gianaroli L, Magli MC, Venturini PL, et al. Sperm aneuploidy and recurrent pregnancy loss. Reprod Biomed Online. 2004;9:312–20.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Al-Hassan S, Hellani A, Al-Shahrani A, Al-Deery M, Jaroudi K, Coskun S. Sperm chromosomal abnormalities in patients with unexplained recurrent abortions. Arch Androl. 2005;51:69–76.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Neusser M, Rogenhofer N, Dürl S, Ochsenkühn R, Trottmann M, Jurinovic V, et al. Increased chromosome 16 disomy rates in human spermatozoa and recurrent spontaneous abortions. Fertil Steril. 2015;104:1130–7.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of Maternal Age on Oocyte and Embryo Competence. Front Endocrinol. 2018;9:327.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Zaida Sarrate
    • 1
  • Joan Blanco
    • 1
    Email author
  • Fernando Marina-Rugero
    • 2
  • Juan Manuel Moreno-García
    • 3
  • Miguel Ruiz-Jorro
    • 4
  • Rafael Lafuente-Varea
    • 5
  • Fernando Graña-Zanón
    • 6
  • Rocío Núñez-Calonge
    • 7
  • Jorge Ten
    • 8
  • Joaquín Rueda
    • 9
  1. 1.Genetics of Male Fertility Group, Unitat de Biologia Cel·lular, Facultat de BiociènciesUniversitat Autònoma de BarcelonaBellaterra (Cerdanyola del Vallès)Spain
  2. 2.Instituto CEFERBarcelonaSpain
  3. 3.UR Clínica VistahermosaAlicanteSpain
  4. 4.Crea Medicina de la ReproducciónValenciaSpain
  5. 5.CIRHBarcelonaSpain
  6. 6.CEFIVAOviedoSpain
  7. 7.Clínica TambreMadridSpain
  8. 8.Embryology UnitInstituto BernabéuAlicanteSpain
  9. 9.Departamento de Histología y Anatomía, Unidad de Genética, Cátedra de Biomedicina Reproductiva Clínica VistahermosaUniversidad Miguel HernándezSant Joan d’AlacantSpain

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