Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Effect of Artificial Oocyte Activation on Intra-Cytoplasmic Sperm Injection Outcomes in Patients with Lower Percentage of Sperm Containing Phospholipase Cζ: A Randomized Clinical Trial

Authors
1 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Reproductive Biology, School of Medicine, Semnan University of Medical Sciences, Semnan
3 Department of Obstetrics and Gynecology, Preventative Gynecology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Background: Artificial oocyte activation (AOA) is a specialized method in assisted reproductive technique (ART). According to increasing concern about using AOA, it is necessary to evaluate sperm-borne oocyte activating factors (SOAFs) including phospholipase C zeta (PLCζ). In this study, PLCζ before AOA was evaluated first and then the impact of AOA on pre-implantation embryo development was investigated. Methods: This prospective clinical trial enrolled couples subjected to ICSI. By evaluating PLCζ, semen samples were categorized into two groups; I (Control) and II (PLCζ deficient). Retrieved oocytes from partners were put into three categories: control group (Injected with sperm from group I, n=113), group without AOA (Injected with sperm from group II and no exposure to AOA, n=106), and group AOA (Injected with sperm from group II and exposure to AOA, n=114). Finally, fertilization results were compared via Kruskal-Wallis followed by Dunn’s multiple comparison test. The p<0.05 was considered statistically significant. Results: Fertilization rate was significantly lower in the group without AOA compared to control group (41.9±6.3 vs. 78.1±4.7, p<0.001). AOA improved fertilization rate in group AOA compared to the group without AOA (69.5±3.9 vs. 41.9±6.3, p<0.01); however, cleavage (91.7±2.8, 90.9±4.6, and 95.2±3.4, respectively) and embryo quality (2.5±0.1, 2.3±0.2, and 2.4±0.2, respectively) scores were not substantially different between groups of control, with and without AOA. Conclusion: We showed that PLCζ can be considered as a good biomarker in evaluation of oocyte activation capability. Further studies are required to establish the best use of PLCζ as a biomarker in clinics.
Keywords

  1. Tosti E, Menezo Y. Gamete activation: basic knowledge and clinical applications. Hum Reprod Update. 2016;22(4):420-39.
  2. Amdani SN, Yeste M, Jones C, Coward K. Sperm factors and oocyte activation: current controversies and considerations. Biol Reprod. 2015;93(2):50.
  3. Vadnais ML, Gerton GL. From PAWP to "Pop": opening up new pathways to fatherhood. Asian J Androl. 2015;17(3):443-4.
  4. Swann K, Lai FA. PLCzeta and the initiation of Ca(2+) oscillations in fertilizing mammalian eggs. Cell Calcium. 2013;53(1):55-62.
  5. Ramadan WM, Kashir J, Jones C, Coward K. Oocyte activation and phospholipase C zeta (PLCzeta): diagnostic and therapeutic implications for assisted reproductive technology. Cell Commun Signal. 2012;10(1):12.
  6. Yoon SY, Jellerette T, Salicioni AM, Lee HC, Yoo MS, Coward K, et al. Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development. J Clin Invest. 2008;118(11):3671-81.
  7. Heytens E, Parrington J, Coward K, Young C, Lambrecht S, Yoon SY, et al. Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men. Hum Reprod. 2009;24(10):2417-28.
  8. Kashir J, Jones C, Mounce G, Ramadan WM, Lemmon B, Heindryckx B, et al. Variance in total levels of phospholipase C zeta (PLC-zeta) in human sperm may limit the applicability of quantitative immunofluorescent analysis as a diagnostic indicator of oocyte activation capability. Fertil Steril. 2013;99(1):107-17.
  9. Nomikos M, Yu Y, Elgmati K, Theodoridou M, Campbell K, Vassilakopoulou V, et al. Phospholipase Cζ rescues failed oocyte activation in a prototype of male factor infertility. Fertil Steril. 2013;99(1):76-85.
  10. Vanden Meerschaut F, Nikiforaki D, Heindryckx B, De Sutter P. Assisted oocyte activation following ICSI fertilization failure. Reprod Biomed Online. 2014;28(5):560-71.
  11. Vanden Meerschaut F, Leybaert L, Nikiforaki D, Qian C, Heindryckx B, De Sutter P. Diagnostic and prognostic value of calcium oscillatory pattern analysis for patients with ICSI fertilization failure. Hum Reprod. 2013;28(1):87-98.
  12. Vanden Meerschaut F, Nikiforaki D, De Gheselle S, Dullaerts V, Van den Abbeel E, Gerris J, et al. Assisted oocyte activation is not beneficial for all patients with a suspected oocyte-related activation deficiency. Hum Reprod. 2012;27(7):1977-84.
  13. Vanden Meerschaut F, D’Haeseleer E, Gysels H, Thienpont Y, Dewitte G, Heindryckx B, et al. Neonatal and neurodevelopmental outcome of children aged 3-5 years born following assisted oocyte activation. Reprod Biomed Online. 28(1):54-63.
  14. Santella L, Dale B. Assisted yes, but where do we draw the line? Reprod Biomed Online. 2015;31(4):476-8.
  15. Nasr-Esfahani MH, Deemeh MR, Tavalaee M. Artificial oocyte activation and intracytoplasmic sperm injection. Fertil Steril. 2010;94(2):520-6.
  16. Amdani SN, Jones C, Coward K. Phospholipase C zeta (PL Cζ): oocyte activation and clinical links to male factor infertility. Adv Biol Regul. 2013;53(3):292-308.
  17. van Blerkom J, Cohen J, Johnson M. A plea for caution and more research in the 'experimental' use of ionophores in ICSI. Reprod Biomed Online. 2015;30(4):323-4.
  18. Kashir J, Heindryckx B, Jones C, De Sutter P, Parrington J, Coward K. Oocyte activation, phospholipase C zeta and human infertility. Hum Reprod Update. 2010;16(6):690-703.
  19. Yelumalai S, Yeste M, Jones C, Amdani SN, Kashir J, Mounce G, et al. Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection. Fertil Steril. 2015;104(3):561-8.4.
  20. Tavalaee M, Kiani-Esfahani A, Nasr-Esfahani MH. Relationship between potential sperm factors involved in oocyte activation and sperm DNA fragmentation with intra-cytoplasmic sperm injection clinical outcomes. Cell J. 2017;18(4):588-96.
  21. Azad N, Nazarian H, Nazari L, Ghaffari Novin M, Piryaei A, Heidari MH, et al. Evaluation of PAWP and PLC? expression in infertile men with previous ICSI fertilization failure. Urol J. 2018;15(3):116-21.
  22. World Health Organisation. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization Press; 2010. 307 p.
  23. Kruger TF, Menkveld R, Stander FS, Lombard CJ, Van der Merwe JP, van Zyl JA, et al. Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril. 1986;46(6):1118-23.
  24. Grasa P, Coward K, Young C, Parrington J. The pattern of localization of the putative oocyte activation factor, phospholipase Czeta, in uncapacitated, capacitated, and ionophore-treated human spermatozoa. Hum Reprod. 2008;23(11):2513-22.
  25. Montag M, Koster M, van der Ven K, Bohlen U, van der Ven H. The benefit of artificial oocyte activation is dependent on the fertilization rate in a previous treatment cycle. Reprod Biomed Online. 2012;24(5):521-6.
  26. Nasr-Esfahani MH, Salehi M, Razavi S, Mardani M, Bahramian H, Steger K, et al. Effect of protamine-2 deficiency on ICSI outcome. Reprod Biomed Online. 2004;9(6):652-8.
  27. Sheikhi A, Jalali M, Gholamian M, Jafarzadeh A, Jannati S, Mousavifar N. Elimination of apoptotic spermatozoa by magnetic-activated cell sorting improves the fertilization rate of couples treated with ICSI procedure. Andrology. 2013;1(6):845-9.
  28. Saunders CM, Larman MG, Parrington J, Cox LJ, Royse J, Blayney LM, et al. PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development. 2002;129(15):3533-44.
  29. Ozil JP, Banrezes B, Toth S, Pan H, Schultz RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006;300(2):534-44.
  30. Ferrer-Vaquer A, Barragan M, Freour T, Vernaeve V, Vassena R. PLCζ sequence, protein levels, and distribution in human sperm do not correlate with semen characteristics and fertilization rates after ICSI. J Assist Reprod Genet. 2016;33(6):747-56.
  31. Heindryckx B, De Gheselle S, Gerris J, Dhont M, De Sutter P. Efficiency of assisted oocyte activation as a solution for failed intracytoplasmic sperm injection. Reprod Biomed Online. 2008;17(5):662-8.
  32. Tavalaee M, Nasr-Esfahani MH. Expression profile of PLCζ, PAWP, and TR-KIT in association with fertilization potential, embryo development, and pregnancy outcomes in globozoospermic candidates for intra-cytoplasmic sperm injection and artificial oocyte activation. Andrology. 2016;4(5):850-6.
  33. Taylor SL, Yoon SY, Morshedi MS, Lacey DR, Jellerette T, Fissore RA, et al. Complete globozoospermia associated with PLCzeta deficiency treated with calcium ionophore and ICSI results in pregnancy. Reprod Biomed Online. 2010;20(4):559-64.
  34. Eftekhar M, Janati S, Rahsepar M, Aflatoonian A. Effect of oocyte activation with calcium ionophore on ICSI outcomes in teratospermia: a randomized clinical trial. Iran J Reprod Med. 2013;11(11):875-82.
  35. Nasr-Esfahani MH, Razavi S, Javdan Z, Tavalaee M. Artificial oocyte activation in severe teratozoospermia undergoing intracytoplasmic sperm injection. Fertil Steril. 2008;90(6):2231-7.
  36. Ebner T, Koster M, Shebl O, Moser M, Van der Ven H, Tews G, et al. Application of a ready-to-use calcium ionophore increases rates of fertilization and pregnancy in severe male factor infertility. Fertil Steril. 2012;98(6):1432-7.
  37. Chithiwala ZH, Lee HC, Hill DL, Jellerette-Nolan T, Fissore R, Grow D, et al. Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report. J Assisted Reprod Genet. 2015;32(9):1415-9.
  38. Heytens E, Schmitt-John T, Moser JM, Jensen NM, Soleimani R, Young C, et al. Reduced fertilization after ICSI and abnormal phospholipase C zeta presence in spermatozoa from the wobbler mouse. Reprod Biomed Online. 2010;21(6):742-9.
  39. Vanden Meerschaut F, Nikiforaki D, De Roo C, Lierman S, Qian C, Schmitt-John T, et al. Comparison of pre- and post-implantation development following the application of three artificial activating stimuli in a mouse model with round-headed sperm cells deficient for oocyte activation. Hum Reprod. 2013;28(5):1190-8.
  40. Ozil JP, Huneau D. Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development. Development. 2001;128(6):917-28.