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Ultrastructural and cytogenetic analyses of mature human oocyte dysmorphisms with respect to clinical outcomes

  • Gamete Biology
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Abstract

Purpose

The study aimed to describe the ultrastructure of two human mature oocyte intracytoplasmic dysmorphisms, the bull-eye inclusion and the granular vacuole, with evaluation of clinical outcomes after intracytoplasmic sperm injection (ICSI) treatment.

Methods

We retrospectively evaluated 4099 consecutive ICSI cycles during the period 2003–2013. Three groups were compared: controls, those with a bulls-eye inclusion, and those with granular vacuoles. Oocyte dysmorphisms were evaluated by transmission electron microscopy and in situ fluorescence hybridization (FISH). Detailed data on demographic and stimulation characteristics, as well as on embryological, clinical, and newborn outcomes, are fully presented.

Results

The bull-eye inclusion is a prominent smooth round structure containing trapped vesicles, being surrounded by lipid droplets. The presence of this dysmorphism in the oocyte cohort had no clinical impact except when transferred embryos were exclusively derived from dysmorphism oocytes. The granular vacuole is delimited by a discontinuous double membrane and contains lipid droplets and vesicles. As FISH analysis revealed the presence of chromosomes, they probably represent pyknotic nuclei. The presence of this dysmorphism in the oocyte cohort had no clinical impact except when at least one transferred embryo was derived from dimorphic oocytes.

Conclusions

Poor clinical outcomes were observed with transfer of embryos derived from dysmorphism oocytes, although without causing gestation or newborn problems. The bull-eye inclusion and granular vacuoles may thus be new prognostic factors for clinical outcomes.

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References

  1. Van Blerkom J. Occurrence and developmental consequences of aberrant cellular organization in meiotically mature human oocytes after exogenous ovarian hyperstimulation. J Elect Microsc Techn. 1990;16:324–46.

    Article  Google Scholar 

  2. Van Blerkom J, Henry G. Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation. Hum Reprod. 1992;7:379–90.

    PubMed  Google Scholar 

  3. Magli NC, Jones GM, Lundi K, Van den Abbeel E, The ESHRE Special Interest Group on Embryology. Atlas of human embryology: from oocytes to preimplantation embryos. Hum Reprod. 2012;27 Suppl 1:1–91.

    Article  Google Scholar 

  4. Sundström P, Nilsson BO. Meiotic and cytoplasmic maturation of oocytes collected in stimulated cycles is asynchronous. Hum Reprod. 1988;3:613–9.

    PubMed  Google Scholar 

  5. Ebner T, Moser M, Sommergruber M, Tews G. Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development. Hum Reprod Update. 2003;9:251–62.

    Article  CAS  PubMed  Google Scholar 

  6. Ebner T, Moser M, Tews G. Is oocyte morphology prognostic of embryo developmental potential after ICSI? Reprod BioMed Online. 2006;12:507–12.

    Article  PubMed  Google Scholar 

  7. Rienzi L, Vajta G, Ubaldi F. Predictive value of oocyte morphology in human IVF: a systematic review of the literature. Hum Reprod Update. 2011;17:34–45.

    Article  PubMed  Google Scholar 

  8. Keef D, Kumar M, Kalmbach K. Oocyte competency is the key to embryo potential. Fertil Steril. 2015;103:317–22.

    Article  Google Scholar 

  9. Ebner T, Balaban B, Moser M, Shebl O, Urman B, Ata B, et al. Automatic user-independent zona pellucida imaging at the oocyte stage allows for the prediction of preimplantation development. Fertil Steril. 2010;94:913–20.

    Article  PubMed  Google Scholar 

  10. Shi W, Xu B, Wu L-M, Jin R-T, Luan H-B, Luo L-H, et al. Oocytes with a dark zona pellucida demonstrate lower fertilization, implantation and clinical pregnancy rates in IVF/ICSI cycles. PLoS One. 2014;9:e89409. doi:10.1371/journal.pone.0089409.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sauerbrun-Cutler M-T, Vega M, Breborowicz A, Gonzales E, Stein D, Lederman M, et al. Oocyte zona pellucida dysmorphology is associated with diminished in-vitro fertilization success. J Ovarian Res. 2015;8:5. doi:10.1186/s13048-014-0111-5.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sousa M, Teixeira da Silva J, Silva J, Cunha M, Viana P, Oliveira E, et al. Embryological, clinical and ultrastructural study of human oocytes presenting indented zona pellucida. Zygote. 2015;23:145–57.

    Article  CAS  PubMed  Google Scholar 

  13. Ebner T, Moser M, Yaman C, Feichtinger O, Hartl J, Tews G. Elective transfer of embryos selected on the basis of first polar body morphology is associated with increased rates of implantation and pregnancy. Fertil Steril. 1999;72:599–603.

    Article  CAS  PubMed  Google Scholar 

  14. Ebner T, Yaman C, Moser M, Sommergruber M, Feichtinger O, Tews G. Prognostic value of first polar body morphology on fertilization rate and embryo quality in intracytoplasmic sperm injection. Hum Reprod. 2000;15:427–30.

    Article  CAS  PubMed  Google Scholar 

  15. Cupisti S, Conn CM, Fragouli E, Whalley K, Mills JS, Faed MJW, et al. Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms. Prenat Diagn. 2003;23:663–8.

    Article  CAS  PubMed  Google Scholar 

  16. Geraedts J, Montag M, Magli MC, Repping S, Handyside A, Staessen C, et al. Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results. Hum Reprod. 2011;26:3173–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schmutzler AG, Acar-Perk B, Weimer J, Salmassi A, Sievers K, Tobler M, et al. Oocyte morphology on day 0 correlates with aneuploidy as detected by polar body biopsy and FISH. Arch Gynecol Obstet. 2014;289:445–50.

    Article  PubMed  Google Scholar 

  18. Zhou W, Fu L, Sha W, Chu D, Li Y. Relationship of polar bodies morphology to embryo quality and pregnancy outcome. Zygote. 2015. doi:10.1017/S0967199415000325.

    PubMed Central  Google Scholar 

  19. Rienzi L, Ubaldi F, Martinez F, Iacobelli M, Minasi MG, Ferrero S, et al. Relationship between meiotic spindle location with regard to the polar body position and oocyte developmental potential after ICSI. Hum Reprod. 2003;18:1289–93.

    Article  CAS  PubMed  Google Scholar 

  20. Petersen CG, Oliveira JBA, Mauri AL, Massaro FC, Baruffi RLR, Pontes A, et al. Relationship between visualization of meiotic spindle in human oocytes and ICSI outcomes: a meta-analysis. Reprod BioMed Online. 2009;18:235–43.

    Article  CAS  PubMed  Google Scholar 

  21. Korkmaz C, Tekin YB, Sakinci M, Ercan CM. Effects of maternal ageing on ICSI outcomes and embryo development in relation to oocytes morphological characteristics of birefringent structures. Zygote. 2015;23:550–5.

    Article  PubMed  Google Scholar 

  22. Ménézo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote. 2010;18:357–65.

    Article  PubMed  Google Scholar 

  23. Ebner T, Moser M, Yaman C, Sommergruber M, Hartl J, Jesacher K, et al. Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI. Hum Reprod. 2002;17:1317–20.

    Article  CAS  PubMed  Google Scholar 

  24. Ebner T, Moser M, Sommergruber M, Puchner M, Wiesinger R, Tews G. Developmental competence of oocytes showing increased cytoplasmic viscosity. Hum Reprod. 2003;18:1294–8.

    Article  CAS  PubMed  Google Scholar 

  25. Ebner T, Shebl O, Moser M, Sommergruber M, Tews G. Developmental fate of ovoid oocytes. Hum Reprod. 2008;23:62–6.

    Article  CAS  PubMed  Google Scholar 

  26. Machtinger R, Politch JA, Hornstein MD, Ginsburg ES, Racowsky C. A giant oocyte in a cohort of retrieved oocytes: does it have any effect on the in vitro fertilization cycle outcome? Fertil Steril. 2011;95:573–6.

    Article  PubMed  Google Scholar 

  27. Sousa M, Barros A, Silva J, Tesarik J. Developmental changes in calcium contents of ultrastructurally distinct subcellular compartments of preimplantation embryos. Mol Hum Reprod. 1997;3:83–90.

    Article  CAS  PubMed  Google Scholar 

  28. Wilding M, Dale B, Marino M, di Matteo, Alviggi C, Pisaturo ML, et al. Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Hum Reprod. 2001;16:909–17.

    Article  CAS  PubMed  Google Scholar 

  29. Wells D, Bermúdez MG, Steuerwald N, Malter HE, Thornhill AR, Cohen J. Association of abnormal morphology and altered gene expression in human preimplantation embryos. Fertil Steril. 2005;84:343–55.

    Article  CAS  PubMed  Google Scholar 

  30. Gasca S, Pellestor F, Assou S, Loup V, Anahory T, Dechaud H, et al. Identifying new human oocyte marker genes: a microarray approach. Reprod BioMed Online. 2007;14:175–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Grøndahl ML, Andersen CY, Bogstad J, Nielsen FC, Meinertz H, Borup R. Gene expression profiles of single human mature oocytes in relation to age. Hum Reprod. 2010;25:957–68.

    Article  PubMed  Google Scholar 

  32. Kakourou G, Jaroudi S, Tulay P, Heath C, Serhal P, Haper JC, et al. Investigation of gene expression profiles before and after embryonic genome activation and assessment of functional pathways at the human metaphase II oocyte and blastocyst stage. Fertil Steril. 2013;99:803–14.

    Article  CAS  PubMed  Google Scholar 

  33. Alikani M, Palermo G, Adler A, Bertoli M, Blake M, Cohen J. Intracytoplasmic sperm injection in dysmorphic human oocytes. Zygote. 1995;3:283–8.

    Article  CAS  PubMed  Google Scholar 

  34. De Sutter P, Dozortsev D, Qian C, Dhont M. Oocyte morphology does not correlate with fertilization rate and embryo quality after intracytoplasmic sperm injection. Hum Reprod. 1996;11:595–7.

    Article  PubMed  Google Scholar 

  35. Sherhal PF, Ranieri DM, Kinis A, Marchant S, Davies M, Khadum IM. Oocyte morphology predicts outcome of intracytoplasmic sperm injection. Hum Reprod. 1997;12:1267–70.

    Article  Google Scholar 

  36. Xia P. Intracytoplasmic sperm injection: correlation of oocyte grade based on polar body, perivitelline space and cytoplasmic inclusions with fertilization and embryo quality. Hum Reprod. 1997;12:1750–5.

    Article  CAS  PubMed  Google Scholar 

  37. Balaban B, Urman B, Sertac A, Alatas C, Aksoy S, Mercan R. Oocyte morphology does not affect fertilization rate, embryo quality and implantation rate after intracytoplasmic sperm injection. Hum Reprod. 1998;13:3431–3.

    Article  CAS  PubMed  Google Scholar 

  38. Loutradis D, Drakakis P, Kallianidis K, Milingos S, Dendrinos S, Michalas S. Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril. 1999;72:240–4.

    Article  CAS  PubMed  Google Scholar 

  39. Chamayou S, Ragolia C, Alecci C, Storaci G, Maglia E, Russo E, et al. Meiotic spindle presence and oocyte morphology do not predict clinical ICSI outcomes: a study of 967 transferred embryos. Reprod Biomed Online. 2006;13:661–7.

    Article  CAS  PubMed  Google Scholar 

  40. Yakin K, Balaban B, Isiklar A, Urman B. Oocyte dysmophism is not associated with aneuploidy in the developing embryo. Fertil Steril. 2007;88:811–6.

    Article  PubMed  Google Scholar 

  41. Figueira RCS, Braga DPAF, Semião-Francisco L, Madaschi C, Iaconelli Jr A, Borges Jr E. Metaphase II human oocyte morphology: contributing factors and effects on fertilization potential and embryo developmental ability in ICSI cycles. Fertil Steril. 2010;94:1115–7.

    Article  Google Scholar 

  42. Braga DPAF, Setti AS, Figueira RCS, Machado RB, Iaconelli Jr A, Borges Jr E. Influence of oocyte dysmorphisms on blastocyst formation and quality. Fertil Steril. 2013;100:748–54.

    Article  PubMed  Google Scholar 

  43. Ashrafi M, Karimian L, Eftekhari-Yazdi P, Hasani F, Arabipoor A, Bahmanabadi A, et al. Effect of oocyte dysmorphisms on intracytoplasmic sperm injection cycle outcomes in normal ovarian responders. J Obstet Gynaecol Res. 2015;41:1912–20.

    Article  CAS  PubMed  Google Scholar 

  44. Yu EJ, Ahn H, Lee JM, Jee BC, Kim SH. Fertilization and embryo quality of mature oocytes with specific morphological abnormalities. Clin Exp Reprod Med. 2015;42:156–62.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Otsuki J, Nagai Y, Chiba K. Lipofuscin bodies in human oocytes as an indicator of oocyte quality. J Assist Reprod Genet. 2007;24:263–70.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Kahraman S, Yakin K, Dönmez E, Samli H, Bahçe M, Cengiz G, et al. Relationship between granular cytoplasm of oocytes and pregnancy outcome following intracytoplasmic sperm injection. Hum Reprod. 2000;15:2390–3.

    Article  CAS  PubMed  Google Scholar 

  47. Ebner T, Sommergruber M, Moser M, Shebl O, Schreier-Lechner E, Tews G. Basal level of anti-Mullerian hormone is associated with oocyte quality in stimulated cycles. Hum Reprod. 2006;21:2022–6.

    Article  CAS  PubMed  Google Scholar 

  48. Ebner T, Moser M, Sommergruber M, Gaiswinkler U, Shebl O, Jesacher K, et al. Occurrence and developmental consequences of vacuoles throughout preimplantation development. Fertil Steril. 2005;83:1635–40.

    Article  PubMed  Google Scholar 

  49. Bianchi V, Macchiarelli G, Borini A, Lappi M, Cecconi S, Miglietta S, et al. Fine morphological assessment of quality of human mature oocytes after slow freezing or vitrification with a closed device: a comparative analysis. Reprod Biol Endocrinol. 2014;12:110. doi:10.1186/1477-7827-12-110.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Palmerini MG, Antinori M, Maione M, Cerusico F, Versaci C, Nottola SA, et al. Ultrastructure of immature and mature human oocytes after cryotop vitrification. J Reprod Dev. 2014;60:411–20.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Bianchi S, Macchiarelli G, Micara G, Linari A, Boninsegna C, Aragona C, et al. Ultrastructural markers of quality are impaired in human metaphase II aged oocytes: a comparison between reproductive and in vitro aging. J Assist Reprod Genet. 2015;32:1343–58.

    Article  CAS  PubMed  Google Scholar 

  52. Fancsovits P, Murber A, Gilán ZT, Rigó Jr J, Urbancsek J. Human oocytes containing large cytoplasmic vacuoles can result in pregnancy and viable offspring. Reprod BioMed Online. 2011;23:513–6.

    Article  PubMed  Google Scholar 

  53. Otsuki J, Okada A, Morimoto K, Nagai Y, Kubo H. The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes. Hum Reprod. 2004;19:1591–7.

    Article  CAS  PubMed  Google Scholar 

  54. Ebner T, Moser M, Shebl O, Sommerguber M, Tews G. Prognosis of oocytes showing aggregation of smooth endoplasmic reticulum. Reprod BioMed Online. 2008;16:113–8.

    Article  PubMed  Google Scholar 

  55. Akarsu C, Çağlar G, Vicdan K, Sözen E, Biberoğlu K. Smooth endoplasmic reticulum aggregations in all retrieved oocytes causing recurrent multiple anomalies: case report. Fertil Steril. 2009;92(1496):e1–3.

    PubMed  Google Scholar 

  56. Sá R, Cunha M, Silva J, Luís A, Oliveira C, Teixeira da Silva J, et al. Ultrastructure of tubular smooth endoplasmic reticulum aggregates in human metaphase II oocytes and clinical implications. Fertil Steril. 2011;96:143–9.

    Article  PubMed  Google Scholar 

  57. Mateizel I, Van Landuyt L, Tournaye H, Verheyen G. Deliveries of normal healthy babies from embryos originating from oocytes showing the presence of smooth endoplasmic reticulum aggregates. Hum Reprod. 2013;28:2111–7.

    Article  CAS  PubMed  Google Scholar 

  58. Hattori H, Nakamura Y, Nakajo Y, Araki Y, Kyono K. Deliveries of babies with normal health derived from oocytes with smooth endoplasmic reticulum clusters. J Assist Reprod Genet. 2014;31:1461–7.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Shaw-Jackson C, Van Beirs N, Thomas A-L, Rozenberg S, Autin C. Can healthy babies originate from oocytes with smooth endoplasmic reticulum aggregates? A systematic mini-review. Hum Reprod. 2014;29:1380–6.

    Article  PubMed  Google Scholar 

  60. Restelli L, Noci SD, Mangiarini A, Ferrari S, Somigliana E, Paffoni A. The impact of Alpha/ESHRE consensus regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in vitro fertilization outcome. J Assist Reprod Genet. 2015;32:1629–35.

    Article  PubMed  Google Scholar 

  61. Van Beirs N, Shaw-Jackson C, Rozenberg S, Autin C. Policy of IVF centres towards oocytes affected by smooth endoplasmic reticulum aggregates: a multicentric survey study. J Assist Reprod Genet. 2015;32:945–50.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rooney DE, Czepulkowski BH. Human chromosome preparation. Essential techniques. UK: John Wiley & Sons Ltd; 1997 (Series Editor: B Rickwood).

    Google Scholar 

  63. Huirne JA, Homburg R, Lambalk CB. Are GnRH antagonists comparable to agonists for use in IVF? Hum Reprod. 2007;22:2805–13.

    Article  CAS  PubMed  Google Scholar 

  64. Pinto F, Oliveira C, Cardoso MF, Teixeira da Silva J, Silva J, Sousa M, et al. Impact of GnRH ovarian stimulation protocols on intracytoplasmic sperm injection outcomes. Reprod Biol Endocrinol. 2009;7:5. doi:10.1186/1477-7827-7-5.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Tesarik J, Sousa M. Key elements of a highly efficient intracytoplasmic sperm injection technique: Ca2+ fluxes and oocyte cytoplasmic dislocation. Fertil Steril. 1995;64:770–6.

    Article  CAS  PubMed  Google Scholar 

  66. Vandervorst M, Liebaers I, Sermon K, Staessen C, De Vos A, Van de Velde H, et al. Successful preimplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes. Hum Reprod. 1998;13:3169–76.

    Article  CAS  PubMed  Google Scholar 

  67. Gardner DK, Lane ML, Stevens J, Schlenker T, Schollcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8.

    Article  CAS  PubMed  Google Scholar 

  68. Radesic B, Tremellen K. Oocyte maturation employing a GnRH agonist in combination with low-dose hCG luteal rescue minimizes the severity of ovarian hyperstimulation syndrome while maintaining excellent pregnancy rates. Hum Reprod. 2011;26:3437–42.

    Article  CAS  PubMed  Google Scholar 

  69. Sousa M, Tesarik J. Ultrastructural analysis of fertilization failure after intracytoplasmic sperm injection. Hum Reprod. 1994;9:2374–80.

    CAS  PubMed  Google Scholar 

  70. El Shafie M, Sousa M, Windt M-L, Kruger TF. An atlas of the ultrastructure of human oocytes. A guide for assisted reproduction. NY, USA: The Parthenon Publishing Group; 2000.

    Google Scholar 

  71. Coonen E, Dumoulin JCM, Ramaekers FCS, Hopman AHN. Optimal preparation of preimplantation embryo interphase nuclei for analysis by fluorescence in-situ hybridization. Hum Reprod. 1994;9:533–7.

    CAS  PubMed  Google Scholar 

  72. Harper JC, Coonen E, Ramaekers FCS, Delhanty JDA, Handyside AH, Wilston RML, et al. Identification of the sex of human preimplantation embryos in two hours using an improved spreading method and fluorescent in-situ hybridization (FISH) using directly labelled probes. Hum Reprod. 1994;9:721–4.

    CAS  PubMed  Google Scholar 

  73. Alves C, Sousa M, Silva J, Barros A. Preimplantation genetic diagnosis using FISH for carriers of Robertsonian translocations: the Portuguese experience. Prenat Diagn. 2002;22:1153–62.

    Article  PubMed  Google Scholar 

  74. Turnpenny P, Ellard S. Emery’s elements of medical genetics. Philadelphia, USA: Elsevier, Churchill Livingstone; 2012.

    Google Scholar 

  75. Forabosco A, Percesepe A, Santucci S. Incidence of non-age-dependent chromosomal abnormalities: a population-based study on 88965 amniocenteses. Eur J Hum Genet. 2009;17:897–903.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Papanikolaou EG, Vernaeve V, Kolibianakis E, Van Assche E, Bonduelle M, Liebaers I, et al. Is chromosome analysis mandatory in the initial investigation of normovulatory women seeking infertility treatment? Hum Reprod. 2005;20:2899–903.

    Article  CAS  PubMed  Google Scholar 

  77. Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005;106:1039–45.

    Article  PubMed  Google Scholar 

  78. Ravel C, Berthaut I, Bresson JL, Siffroi JP, et al. Prevalence of chromosomal abnormalities in phenotypically normal and fertile adult males: large-scale survey of over 10000 sperm donor karyotypes. Hum Reprod. 2006;21:1484–89.

    Article  CAS  PubMed  Google Scholar 

  79. Clementini E, Palka C, Iezzi L, Stuppia L, Guanciali-Franchi P, Tiboni GM. Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques. Hum Reprod. 2005;20:437–42.

    Article  CAS  PubMed  Google Scholar 

  80. Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C. Male infertility: role of genetic background. Reprod BioMed Online. 2007;14:734–45.

    Article  CAS  PubMed  Google Scholar 

  81. Gekas J, Thepot F, Turleau C, Siffroi JP, Dadoune JP, Wasels R, et al. Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men. Hum Reprod. 2001;16:82–90.

    Article  CAS  PubMed  Google Scholar 

  82. Schreurs A, Legius E, Meuleman C, Fryns J-P, D’Hooghe TM. Increased frequency of chromosomal abnormalities in female partners of couples undergoing in vitro fertilization or intracytoplasmic sperm injection. Fertile Steril. 2000;74:94–6.

    Article  CAS  Google Scholar 

  83. De Sutter P, Stadhoufers R, Dutré M, Gerris J, Dhont M. Prevalence of chromosomal abnormalities and timing of karyotype analysis in patients with recurrent implantation failure (RIF) following assisted reproduction. FVV ObGyn. 2012;4:59–65.

    Google Scholar 

  84. Sousa M, Barros A, Tesarik J. Developmental changes in calcium dynamics, protein kinase C distributions and endoplasmic reticulum organization in human preimplantation embryos. Mol Hum Reprod. 1996;2:967–77.

    Article  CAS  PubMed  Google Scholar 

  85. Norppa H, Falck GC-M. What do human micronuclei contain? Mutagenesis. 2003;18:221–33.

    Article  CAS  PubMed  Google Scholar 

  86. Shimizu N. Molecular mechanisms of the origin of micronuclei from extrachromosomal elements. Mutagenesis. 2011;26:119–23.

    Article  CAS  PubMed  Google Scholar 

  87. Mantikou E, Wong KM, Repping S, Masteenbroek S. Molecular origin of mitotic aneuploidies in preimplantation embryos. Biochem Biophy Acta. 1822;2012:1921–30.

    Google Scholar 

  88. Nottola SA, Macchiarelli G, Familiari G. Fine structural markers of human oocyte quality in assisted reproduction. Austin J Reprod Med Infertil. 2014;1:5.

    Google Scholar 

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Acknowledgments

The authors would like to that the following persons: for oocyte retrieval to Jorge Beires, MD, PhD, Specialist in Gynecology and Obstetrics, from the Department of Gynecology and Obstetrics, Director of the Unit of Gynecology and Reproductive Medicine, Hospital of S. John, E.P.E., Porto, Portugal and José Manuel Teixeira da Silva, MD, Specialist in Gynecology and Obstetrics; for anesthesiology to José Correia, MD, Anesthetist (Department of Anesthesiology, Hospital of S. John, E.P.E., Porto, Portugal); for IVF laboratorial work assistance to Paulo Viana, MSc., Biologist, Clinical Embryologist and Nuno Barros MSc., Microbiologist (CGR-ABarros); for spermiology laboratorial work to Ana Gonçalves, MSc., Biochemist and Cláudia Osório MSc., Biologist (CGR-ABarros); for technical support on FISH analysis to Ana Raquel Azevedo, Ph.D. (ICBAS-UP); and for transmission electron microscopy technical support to Célia Soares, M.D. and Ângela Alves, BSc., Technical assistant for teaching and research (ICBAS-UP).

We also would like to thank all colleagues from the many other research articles, reviews, book chapters, and books that we did not cite in this manuscript but whose lecture was fundamental to the writing of the present manuscript.

Funding

UMIB is funded by National Funds through FCT-Foundation for Science and Technology, under the Pest-OE/SAU/UI0215/2014.

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Correspondence to Mário Sousa.

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The authors declare that they have followed all the rules of ethical conduct regarding originality, data processing and analysis, duplicate publication, and patient treatments.

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The authors declare that they have no competing interests.

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Informed consent was obtained from all individual participants included in the study.

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Capsule Poor clinical outcomes were observed with mixed or pure transfer of embryos derived from oocytes containing bull-eye inclusions or granular-vacuoles. These dimorphisms may be new prognostic factors for clinical outcomes.

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Sousa, M., Cunha, M., Silva, J. et al. Ultrastructural and cytogenetic analyses of mature human oocyte dysmorphisms with respect to clinical outcomes. J Assist Reprod Genet 33, 1041–1057 (2016). https://doi.org/10.1007/s10815-016-0739-8

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