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The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
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Obstetrics and Gynegology2020№11
Cytoplasmic fragmentation of human preimplantation...

Cytoplasmic fragmentation of human preimplantation embryos

DOI
https://dx.doi.org/10.18565/aig.2020.11.61-70

Kirienko K.V., Apryshko V.P., Yakovenko S.A.

1) AltraVita Clinic of Human Reproduction, “IVF CENTER” LLC, Moscow, Russia; 2) Faculty of Physics, M.V. Lomonosov Moscow State University, Moscow, Russia
This investigation has attempted to generalize and systematize knowledge about the cytoplasmic embryo fragmentation phenomenon, to reveal the causes and mechanisms of its occurrence, and to describe its impact on embryo viability and clinical outcomes of IVF programs. Since human embryo fragmentation is most common during the embryological stage of IVF programs, the phenomenon itself has not been studied sufficiently. Rare attempts to investigate this phenomenon have narrowly focused on the association of the fragmentation with apoptosis. The reasons for this limited knowledge were ethical obstacles and practical difficulties associated with the use of human eggs and embryos for experiments. The lack of a suitable model among animal embryos and the relatively low occurrence and significance of fragmentation in experimental embryology (in mouse embryos) also contributed to the exclusion of the fragmentation phenomenon as a worthy object of investigation. The review included the data obtained over a fairly extensive period and an attempt was undertaken to comprehensively cover the topic of embryo fragmentation. Conclusion. Despite the fact that the effect of a low fragmentation fraction (<10%) on the effectiveness of ART programs is insignificant, a significant fragmentation fraction (> 25-30%) reduces embryo viability. The results of studies investigating the microsurgical removal of cytoplasmic fragments and its positive impact on the viability of embryos and the clinical outcomes of IVF programs are controversial and require further confirmation.

Keywords

embryo fragmentation
in vitro fertilization
developmental anomaly
embryo viability
Full text (in Russian)

References

  1. Edwards R.G., Steptoe P.C., Purdy J.M. Fertilization and cleavage in vitro of preovulatory human oocytes. Nature. 1970; 227(5265): 1307-9. https://dx.doi.org/10.1038/2271307a0.
  2. Hertig A.T., Rock J., Adams E.C., Menkin M.C. On the preimplantation stages of the human ovum: a description of four normal and four abnormal specimens ranging from the second to the fifth day of development. Contrib. Embryol. 1954; 35: 199-220.
  3. Ortiz M.E., Croxatto H.B. Observations on the transport, aging, and development of ova in the human genital tract. In: Talwar G.P., ed. Recent advances in reproduction and regulation of fertility. New York: Elsevier/North-Holland Biomedical Press; 1979: 307-17.
  4. Buster J.E., Bustillo M., Rodi I.A., Cohen S.W., Hamilton M., Simon J.A. et al. Biologic and morphologic development of donated human ova recovered by nonsurgical uterine lavage. Am. J. Obstet. Gynecol. 1985; 153(2): 211-7. https://dx.doi.org/10.1016/0002-9378(85)90116-4.
  5. Alikani M. Cytoplasmic fragmentation in human embryos in vitro: implications and the relevance of fragment removal. In: Gardner D., Weissman A., Howles C., Shoham Z., eds. Textbook of assisted reproductive techniques, laboratory and clinical perspectives. London: Martin Dunitz; 2001: 169-82.
  6. Puissant F., Van Rysselberge M., Barlow P., Deweze J., Leroy F. Embryo scoring as a prognostic tool in IVF treatment. Hum. Reprod. 1987; 2(8): 705-8. https://dx.doi.org/10.1093/oxfordjournals.humrep.a136618.
  7. Antczak M., Van Blerkom J. Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains. Hum. Reprod. 1999; 14(2): 429-47. https://dx.doi.org/10.1093/humrep/14.2.429.
  8. Dale B., Tosti E., Iaccarino M. Is the plasma membrane of the human oocyte reorganised fol-lowing fertilisation and early cleavage? Zygote. 1995; 3(1): 31-6. https://dx.doi.org/10.1017/S0967199400002355.
  9. Van Blerkom J., Davis P., Alexander S. A microscopic and biochemical study of fragmentation phenotypes in stage-appropriate human embryos. Hum. Reprod. 2001; 16(4): 719-29. https://dx.doi.org/10.1093/humrep/16.4.719.
  10. Halvaei I., Khalili M.A., Esfandiari N., Safari S., Talebi A.R., Miglietta S., Nottola S.A. Ultrastructure of cytoplasmic fragments in human cleavage stage embryos. J. Assist. Reprod. Genet. 2016; 33(12): 1677-84. https://dx.doi.org/10.1007/s10815-016-0806-1.
  11. Johansson M., Hardarson T., Lundin K. There is a cutoff limit in diameter between a blastomere and a small anucleate fragment. J. Assist. Reprod. Genet. 2003; 20(8): 309-13. https://dx.doi.org/10.1023/A:1024805407058.
  12. Motta P.M., Nottola S.A., Makabe S., Heyn R. Mitochondrial morphology in human fetal and adult female germ cells. Hum. Reprod. 2000; 15(Suppl. 2): 129-47. https://dx.doi.org/10.1093/humrep/15.suppl_2.129.
  13. Chi H.J., Koo J.J., Choi S.Y., Jeong H.J., Roh S.I. Fragmentation of embryos is associated with both necrosis and apoptosis. Fertil. Steril. 2011; 96(1): 187-92. https://dx.doi.org/10.1016/j.fertnstert.2011.04.020.
  14. Hardarson T., Lofman C., Coull G., Sjogren A., Hamberger L., Edwards R.G. Internalization of cellular fragments in a human embryo: time-lapse recordings. Reprod. Biomed. Online. 2002; 5(1): 36-8. https://dx.doi.org/10.1016/s1472-6483(10)61594-5.
  15. Alikani M. Epithelial cadherin distribution in abnormal human preimplantation embryos. Hum. Reprod. 2005; 20(12): 3369-75. https://dx.doi.org/10.1093/humrep/dei242.
  16. Van Blerkom J., Antczak M., Schrader R. The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristic cs. Hum. Reprod. 1997; 12(5): 1047-55. https://dx.doi.org/10.1093/humrep/12.5.1047.
  17. Pickering S.J., Braude P.R., Johnson M.H., Cant A., Currie J. Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte. Fertil. Steril. 1990; 54(1): 102-8. https://dx.doi.org/10.1016/s0015-0282(16)53644-9.
  18. Pellestor F., Dufour M.C., Arnal F., Humeau C. Direct assessment of the rate of chromosomal abnormalities in grade IV human embryos produced by in-vitro fertilization procedure. Hum. Reprod. 1994; 9(2): 293-302. https://dx.doi.org/10.1093/oxfordjournals.humrep.a138497.
  19. Jurisicova A., Varmuza S., Caspar R.F. Programmed cell death and human embryo fragmentation. Mol. Hum. Reprod. 1996; 2(2): 93-8. https://dx.doi.org/10.1093/molehr/2.2.93.
  20. Yang H.W., Hwang K.J., Kwon H.C., Kim H.S., Choi K.W., Oh K.S. Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos. Hum. Reprod. 1998; 13(4): 998-1002. https://dx.doi.org/10.1093/humrep/13.4.998.
  21. Monks N.J., Turner K., Hooper M.A.K., Kumar A., Verma S., Lenton E.A. Development of embryos from natural cycle in vitro fertilization: impact of medium type and female infertility factors. Hum. Reprod. 1993; 8(2): 266-71. https://dx.doi.org/10.1093/oxfordjournals.humrep.a138035.
  22. Squirrell J.M., Lane M., Bavister B.D. Altering intracellular pH disrupts development and cellu-lar organization in preimplantation hamster embryos. Biol. Reprod. 2002; 64(6): 1845-54. https://dx.doi.org/10.1095/biolreprod64.6.1845.
  23. Begg D.A., Rebhun L.I. PH regulates the polymerization of actin in the sea urchin egg cortex. J. Cell Biol. 1979; 83(1): 241-8. https://dx.doi.org/10.1083/jcb.83.1.241.
  24. Pellestor F. Frequency and distribution of aneuploidy in human female gametes. Hum. Genet. 1991; 86(3): 283-8. https://dx.doi.org/10.1007/BF00202410.
  25. Munne S., Alikani M., Tomkin G., Grifo J., Cohen J. Embryo morphology, developmental rates and maternal age are correlated with chromosome abnormalities. Fertil. Steril. 1995; 64(2): 382-91. https://dx.doi.org/10.1016/S0015-0282(16)57739-5.
  26. Munne S., Sandalinas M., Cohen J. Chromosome abnormalities in human embryos. In: Gardner D., Weissman A., Howles C., Shoham Z., eds. Textbook of assisted reproductive techniques, laboratory and clinical perspectives. London, United Kingdom: Martin Dunitz; 2001: 297-318.
  27. Wyllie A.H., Kerr J.F.R., Currie A.R. Cell death: the significance of apoptosis. Int. Rev. Cytol. 1980; 68: 251-306. https://dx.doi.org/10.1016/s0074-7696(08)62312-8.
  28. Wlodkowic D., Skommer J., Darzynkiewicz Z. Flow cytometry-based apoptosis detection. Methods Mol. Biol. 2009; 559: 19-32. https://dx.doi.org/10.1007/978-1-60327-017-5_2.
  29. Enders A.C., Lantz K.C., Schlafke S. Differentiation of the inner cell mass of the baboon blastocyst. Anat. Rec. 1990; 226(2): 237-48. https://dx.doi.org/10.1002/ar.1092260213.
  30. Martin S.J., Reutelingsperger C.P.M., McGahon A.J., Rader J.A., van Schie R.C.A.A., LaFace D.M., Green D.R. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 1995; 182(5): 1545-56. https://dx.doi.org/10.1084/jem.182.5.1545.
  31. Levy R., Benchaib M., Cordonier H., Couchier C., Guerin J.F. Annexin V labelling and terminal transferase-mediated DNA end labelling (TUNEL) assay in human arrested embryos. Mol. Hum. Reprod. 1998; 4(8): 775-83. https://dx.doi.org/10.1093/molehr/4.8.775.
  32. Majno G., Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am. J. Pathol. 1995; 146(1): 3-15.
  33. Van Blerkom J., Davis P., Alexander S. Differential mitochondrial distribution in human pronuclear embryos leads to disproportionate inheritance between blastomeres: relationship to microtubular organization, ATP content and competence. Hum. Reprod. 2000; 15(12): 2621-33. https://dx.doi.org/10.1093/humrep/15.12.2621.
  34. Halvaei I., Khalili M.A., Razi M.H., Nottola S.A. The effect of immature oocytes quantity on the rates of oocytes maturity and morphology, fertilization, and embryo development in ICSI cycles. J. Assist. Reprod. Genet. 2012; 29(8): 803-10. https://dx.doi.org/10.1007/s10815-012-9799-6.
  35. Rankin T., Talbot P., Lee E., Dean J. Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss. Development. 1999; 126(17): 3847-55.
  36. Sathananthan A. Ultrastructure of the human egg. Hum. Cell. 1997; 10(1): 21-38.
  37. Farhi J., Nahum H., Weissman A., Zahalka N., Glezerman M., Levran D. Coarse granulation in the perivitelline space and IVF-ICSI outcome. J. Assist. Reprod. Genet. 2002; 19(12): 545-9. https://dx.doi.org/10.1023/A:1021243530358.
  38. Hoover L., Baker A., Check J., Lurie D., O’Shaughnessy A. Evaluation of a new embryo-grading system to predict pregnancy rates following in vitro fertilization. Gynecol. Obstet. Invest. 1995; 40(3): 151-7. https://dx.doi.org/10.1159/000292326.
  39. Morgan K., Wiemer K., Steuerwald N., Hoffman D., Maxson W., Godke R. Use of videocinematography to assess morphological qualities of conventionally cultured and cocultured embryos. Hum. Reprod. 1995; 10(9): 2371-6. https://dx.doi.org/10.1093/oxfordjournals.humrep.a136301.
  40. Alikani M., Cohen J., Tomkin G., Garrisi G.J., Mack C., Scott R.T. Human embryo fragmentation in vitro and its implications for pregnancy and implantation. Fertil. Steril. 1999; 71(5): 836-42. https://dx.doi.org/10.1016/s0015-0282(99)00092-8.
  41. Mio Y., Maeda K. Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. Am. J. Obstet. Gynecol. 2008; 199(6): 660. e1-5. https://dx.doi.org/10.1016/j.ajog.2008.07.023.
  42. Hardarson T., Hanson C., Sjogren A., Lundin K. Human embryos with unevenly sized blasto-meres have lower pregnancy and implantation rates: indications for aneuploidy and multi-nucleation. Hum. Reprod. 2001; 16(2): 313-8. https://dx.doi.org/10.1093/humrep/16.2.313.
  43. Munne S., Alikani M., Grifo J., Cohen J. Monospermic polyploidy and atypical embryo morphology. Hum. Reprod. 1994; 9(3): 506-10. https://dx.doi.org/10.1093/oxfordjournals.humrep.a138536.
  44. Balakier H., Cadesky K. The frequency and developmental capability of human embryos containing multinucleated blastomeres. Hum. Reprod. 1997; 12(4): 800-4. https://dx.doi.org/10.1093/humrep/12.4.800.
  45. Kligman I., Benadiva C., Alikani M., Munne S. The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities. Hum. Reprod. 1996; 11(7): 1492-8. https://dx.doi.org/10.1093/oxfordjournals.humrep.a019424.
  46. Staessen C., Van Steirteghem A. The genetic constitution of multinuclear blastomeres and their derivative daughter blastomeres. Hum. Reprod. 1998; 13(6): 1625-31. https://dx.doi.org/10.1093/humrep/13.6.1625.
  47. Yin H., Jiang H., He R., Wang C., Zhu J., Luan K. The effects of fertilization mode, embryo morphology at day 3, and female age on blastocyst formation and the clinical outcomes. Syst. Biol. Reprod. Med. 2015; 61(1): 50-6. https://dx.doi.org/10.3109/19396368.2014.967368.
  48. Rhenman A., Berglund L., Brodin T., Olovsson M., Milton K., Hadziosmanovic N. et al. Which set of embryo variables is most predictive for live birth?A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos. Hum. Reprod. 2015; 30(1): 28-36. https://dx.doi.org/10.1093/humrep/deu295.
  49. Ziebe S., Petersen K., Lindenberg S., Andersen A.G., Gabrielsen A., Andersen A.N. Embryo morphology or cleavage stage: How to select the best embryos for transfer after in vitro fertilization. Hum. Reprod. 1997; 12(7): 1545-9. https://dx.doi.org/10.1093/humrep/12.7.1545.
  50. Racowsky C., Stern J.E., Gibbons W.E., Behr B., Pomeroy K.O., Biggers J.D. National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: Associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate. Fertil. Steril. 2011; 95(6): 1985-9. https://dx.doi.org/10.1016/j.fertnstert.2011.02.009.
  51. Tan J.H., Chen J.J., Lim L.J., Wong P.S. The impact of in vitro human embryo fragmentation on blastocyst development and ploidy using Next-Generation Sequencing (NGS). Reprod. Biomed. Online. 2019; 38(Suppl. 1): e23. https://dx.doi.org/10.1016/j.rbmo.2019.03.039.
  52. ALPHA Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: Proceedings of an expert meeting. Hum. Reprod. 2011; 26(6): 1270-83. https://dx.doi.org/10.1093/humrep/der037.
  53. Hardy K., Stark J., Winston R.M.L. Maintenance of the inner cell mass in human blastocysts from fragmented embryos. Biol. Reprod. 2003; 68(4): 1165-9. https://dx.doi.org/10.1095/biolreprod.102.010090.
  54. Magli M.C., Gianaroli L., Ferraretti A.P., Lappi M., Ruberti A., Farfalli V. Embryo morphology and development are dependent on the chromosomal complement. Fertil. Steril. 2007; 87(3): 534-41. https://dx.doi.org/10.1016/j.fertnstert.2006.07.1512.
  55. Halvaei I., Khalili M.A., Safari S., Esfandiari N. Ongoing pregnancies following cosmetic micromanipulation of preimplantation embryos in patients with implantation failure. Case Rep. Med. 2015; 2015: 734793. https://dx.doi.org/10.1155/2015/734793.
  56. Alikani M. The origins and consequences of fragmentation in mammalian eggs and embryos. In: Elder K., Cohen J., eds. Human preimplantation embryo selection. London: Informa Healthcare; 2007: 51-78.
  57. Racowsky C., Ohno-Machado L., Kim J., Biggers J.D. Is there an advantage in scoring early embryos on more than one day? Hum. Reprod. 2009; 24(9): 2104-13. https://dx.doi.org/10.1093/humrep/dep198.
  58. Alikani M., Calderon G., Tomkin G., Garrisi J., Kokot M., Cohen J. Cleavage anomalies in early human embryos and survival after prolonged culture in vitro. Hum. Reprod. 2000; 15(12): 2634-43. https://dx.doi.org/10.1093/humrep/15.12.2634.
  59. Eftekhari-Yazdi P., Valojerdi M.R., Ashtiani S.K., Eslaminejad M.B., Karimian L. Effect of fragment removal on blastocyst formation and quality of human embryos. Reprod. Biomed. Online. 2006; 13(6): 823-32. https://dx.doi.org/10.1016/s1472-6483(10)61031-0.
  60. Keltz M.D., Skorupski J.C., Bradley K., Stein D. Predictors of embryo fragmentation and outcome after fragment removal in in vitro fertilization. Fertil. Steril. 2006; 86(2): 321-4. https://dx.doi.org/10.1016/j.fertnstert.2006.01.048.
  61. Sözen E., Vicdan K., Akarsu C., Tuncay G., Buluc B., Colak M. A prospective, randomized, controlled study of fragment removal in women who have moderate fragmentated embryos. Hum. Reprod. 2012; 2(Suppl. 2): ii56-7.

Received 30.06.2020

Accepted 23.10.2020

About the Authors

Konstantin V. Kirienko, PhD, leading embryologist of AltraVita IVF clinic. Tel.: +7(967)167-79-23. E-mail: kkiriyenko@rambler.ru. ORCID: 0000-0001-8713-6231.
4A, Nagornaya str., 117186, Moscow, Russia.
Valentina P. Apryshko, PhD, Head of Embryology department of AltraVita IVF clinic. Tel.: +7(910)409-28-13. E-mail: supermycolog@mail.ru.
4A, Nagornaya str., 117186, Moscow, Russia.
Sergey A. Yakovenko, PhD, G.M. of AltraVita IVF clinic; researcher of Lomonosov Moscow state University, Faculty of Physics, Biophisics Department.
Tel.: +7(903)790-90-18. E-mail: altravita@mail.ru. 4A, Nagornaya str., 117186, Moscow, Russia; 1/2 Leninskie gori, 119991, Moscow, Russia.

For citation: Kirienko K.V., Apryshko V.P., Yakovenko S.A. Cytoplasmic fragmentation of human preimplantation embryos.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 11: 61-70 (in Russian).
https://dx.doi.org/10.18565/aig.2020.11.61-70

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