Artificial Egg Activation Using Calcium Ionophore

Abstract

Artificial oocyte activation, most commonly using calcium ionophore, is a treatment add-on utilized to avoid recurrence of abnormally low or total failed fertilization following in vitro fertilization/intracytoplasmic sperm injection. It aims to modify defective physiological processes, specifically calcium-mediated cell signaling that are critical to events required for fertilization. Routine application of artificial oocyte activation is neither required nor recommended; however, it represents an invaluable intervention for a subgroup of patients affected by sperm-related oocyte activation deficiency.

Keywords

artificial oocyte activation - calcium ionophore - failed fertilization - add-on - ART adjuvant

Publication History

Article published online:
10 March 2022

• References

• 1 Chang MC. Fertilizing capacity of spermatozoa deposited into the fallopian tubes. Nature 1951; 168 (4277): 697-698
• 2 Austin CR. Observations on the penetration of the sperm in the mammalian egg. Aust J Sci Res, B 1951; 4 (04) 581-596
• 3 Austin CR. The capacitation of the mammalian sperm. Nature 1952; 170 (4321): 326
• 4 Castillo J, Jodar M, Oliva R. The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Hum Reprod Update 2018; 24 (05) 535-555
• 5 Swann K, Saunders CM, Rogers NT, Lai FA. PLCzeta(zeta): a sperm protein that triggers Ca2+ oscillations and egg activation in mammals. Semin Cell Dev Biol 2006; 17 (02) 264-273
• 6 Marangos P, FitzHarris G, Carroll J. Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei. Development 2003; 130 (07) 1461-1472
• 7 Gat I, Orvieto R. “This is where it all started” - the pivotal role of PLCζ within the sophisticated process of mammalian reproduction: a systemic review. Basic Clin Androl 2017; 27: 9
• 8 Saunders CM, Larman MG, Parrington J. et al. PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development. Development 2002; 129 (15) 3533-3544
• 9 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) 2513-2522
• 10 Young C, Grasa P, Coward K, Davis LC, Parrington J. Phospholipase C zeta undergoes dynamic changes in its pattern of localization in sperm during capacitation and the acrosome reaction. Fertil Steril 2009; 91 (5, Suppl): 2230-2242
• 11 Saleh A, Kashir J, Thanassoulas A, Safieh-Garabedian B, Lai FA, Nomikos M. Essential role of sperm-specific PLC-zeta in egg activation and male factor infertility: an update. Front Cell Dev Biol 2020; 8: 28
• 12 Rebecchi MJ, Pentyala SN. Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev 2000; 80 (04) 1291-1335
• 13 Yeste M, Jones C, Amdani SN. et al. Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCζ) in human sperm?. Sci Rep 2016; 6: 27543
• 14 Nomikos M, Blayney LM, Larman MG. et al. Role of phospholipase C-zeta domains in Ca2+-dependent phosphatidylinositol 4,5-bisphosphate hydrolysis and cytoplasmic Ca2+ oscillations. J Biol Chem 2005; 280 (35) 31011-31018
• 15 Georgadaki K, Khoury N, Spandidos DA, Zoumpourlis V. The molecular basis of fertilization. (Review) Int J Mol Med 2016; 38 (04) 979-986
• 16 Kashir J, Jones C, Coward K. Calcium oscillations, oocyte activation, and phospholipase C zeta. Adv Exp Med Biol 2012; 740: 1095-1121
• 17 Mehlmann LM, Mikoshiba K, Kline D. Redistribution and increase in cortical inositol 1,4,5-trisphosphate receptors after meiotic maturation of the mouse oocyte. Dev Biol 1996; 180 (02) 489-498
• 18 Malcuit C, Knott JG, He C. et al. Fertilization and inositol 1,4,5-trisphosphate (IP3)-induced calcium release in type-1 inositol 1,4,5-trisphosphate receptor down-regulated bovine eggs. Biol Reprod 2005; 73 (01) 2-13
• 19 Kline D, Kline JT. Repetitive calcium transients and the role of calcium in exocytosis and cell cycle activation in the mouse egg. Dev Biol 1992; 149 (01) 80-89
• 20 Fissore RA, Dobrinsky JR, Balise JJ, Duby RT, Robl JM. Patterns of intracellular Ca2+ concentrations in fertilized bovine eggs. Biol Reprod 1992; 47 (06) 960-969
• 21 Miyazaki S, Ito M. Calcium signals for egg activation in mammals. J Pharmacol Sci 2006; 100 (05) 545-552
• 22 Sfontouris IA, Nastri CO, Lima ML, Tahmasbpourmarzouni E, Raine-Fenning N, Martins WP. Artificial oocyte activation to improve reproductive outcomes in women with previous fertilization failure: a systematic review and meta-analysis of RCTs. Hum Reprod 2015; 30 (08) 1831-1841
• 23 Whitaker M. Calcium at fertilization and in early development. Physiol Rev 2006; 86 (01) 25-88
• 24 Yoon SY, Jellerette T, Salicioni AM. 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) 3671-3681
• 25 Heytens E, Parrington J, Coward K. et al. Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men. Hum Reprod 2009; 24 (10) 2417-2428
• 26 Amdani SN, Jones C, Coward K. Phospholipase C zeta (PLCζ): oocyte activation and clinical links to male factor infertility. Adv Biol Regul 2013; 53 (03) 292-308
• 27 Aghajanpour S, Ghaedi K, Salamian A. et al. Quantitative expression of phospholipase C zeta, as an index to assess fertilization potential of a semen sample. Hum Reprod 2011; 26 (11) 2950-2956
• 28 Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011; 26 (06) 1270-1283
• 29 ESHRE Special Interest Group of Embryology, Alpha Scientists in Reproductive Medicine. The Vienna consensus: report of an expert meeting on the development of art laboratory performance indicators. Hum Reprod Open 2017; 2017 (02) hox011
• 30 Nicopoullos JD, Whitney E, Wells V, Batha S, Faris R, Abdalla H. Case reports to suggest an algorithm for management of total fertilisation failure prior to use of donor gametes. J Assist Reprod Genet 2015; 32 (11) 1679-1684
• 31 Cheung S, Xie P, Parrella A, Keating D, Rosenwaks Z, Palermo GD. Identification and treatment of men with phospholipase Cζ-defective spermatozoa. Fertil Steril 2020; 114 (03) 535-544
• 32 Swain JE, Pool TB. ART failure: oocyte contributions to unsuccessful fertilization. Hum Reprod Update 2008; 14 (05) 431-446
• 33 Vanden Meerschaut F, Nikiforaki D, De Gheselle S. et al. Assisted oocyte activation is not beneficial for all patients with a suspected oocyte-related activation deficiency. Hum Reprod 2012; 27 (07) 1977-1984
• 34 Aarabi M, Balakier H, Bashar S. et al. Sperm content of postacrosomal WW binding protein is related to fertilization outcomes in patients undergoing assisted reproductive technology. Fertil Steril 2014; 102 (02) 440-447
• 35 Escoffier J, Lee HC, Yassine S. et al. Homozygous mutation of PLCZ1 leads to defective human oocyte activation and infertility that is not rescued by the WW-binding protein PAWP. Hum Mol Genet 2016; 25 (05) 878-891
• 36 Freour T, Barragan M, Torra-Massana M, Ferrer-Vaquer A, Vassena R. Is there an association between PAWP/WBP2NL sequence, expression, and distribution in sperm cells and fertilization failures in ICSI cycles?. Mol Reprod Dev 2018; 85 (02) 163-170
• 37 Azad N, Nazarian H, Nazari L. et al. Evaluation of PAWP and PLC? Expression in infertile men with previous ICSI fertilization failure. Urol J 2018; 15 (03) 116-121
• 38 Kamali-Dolat Abadi M, Tavalaee M, Shahverdi A, Nasr-Esfahani MH. Evaluation of PLCζ and PAWP expression in globozoospermic individuals. Cell J 2016; 18 (03) 438-445
• 39 Ebner T, Köster M, Shebl O. 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 (06) 1432-1437
• 40 Anifandis G, Michopoulos A, Daponte A. et al. Artificial oocyte activation: physiological, pathophysiological and ethical aspects. Syst Biol Reprod Med 2019; 65 (01) 3-11
• 41 Mahowald AP, Goralski TJ, Caulton JH. In vitro activation of Drosophila eggs. Dev Biol 1983; 98 (02) 437-445
• 42 Bradshaw J, Jung T, Fulka Jr J, Moor RM. UV irradiation of chromosomal DNA and its effect upon MPF and meiosis in mammalian oocytes. Mol Reprod Dev 1995; 41 (04) 503-512
• 43 Kimura Y, Yanagimachi R. Intracytoplasmic sperm injection in the mouse. Biol Reprod 1995; 52 (04) 709-720
• 44 Yanagida K, Katayose H, Yazawa H, Kimura Y, Konnai K, Sato A. The usefulness of a piezo-micromanipulator in intracytoplasmic sperm injection in humans. Hum Reprod 1999; 14 (02) 448-453
• 45 Egashira A, Murakami M, Haigo K, Horiuchi T, Kuramoto T. A successful pregnancy and live birth after intracytoplasmic sperm injection with globozoospermic sperm and electrical oocyte activation. Fertil Steril 2009; 92 (06) 2037.e5-2037.e9
• 46 Yanagida K, Morozumi K, Katayose H, Hayashi S, Sato A. Successful pregnancy after ICSI with strontium oocyte activation in low rates of fertilization. Reprod Biomed Online 2006; 13 (06) 801-806
• 47 Kim JW, Choi JL, Yang SH, Yoon SH, Jung JH, Lim JH. Live birth after SrCl(2) oocyte activation in previous repeated failed or low fertilization rates after ICSI of frozen-thawed testicular spermatozoa: case report. J Assist Reprod Genet 2012; 29 (12) 1393-1396
• 48 Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 1998; 394 (6691): 369-374
• 49 Kyono K, Kumagai S, Nishinaka C. et al. Birth and follow-up of babies born following ICSI using SrCl2 oocyte activation. Reprod Biomed Online 2008; 17 (01) 53-58
• 50 Kim JW, Kim SD, Yang SH, Yoon SH, Jung JH, Lim JH. Successful pregnancy after SrCl2 oocyte activation in couples with repeated low fertilization rates following calcium ionophore treatment. Syst Biol Reprod Med 2014; 60 (03) 177-182
• 51 Fawzy M, Emad M, Mahran A. et al. Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves clinical and embryological outcomes compared with ICSI alone: results of a randomized clinical trial. Hum Reprod 2018; 33 (09) 1636-1644
• 52 Norozi-Hafshejani M, Tavalaee M, Azadi L, Bahadorani M, Nasr-Esfahani MH. Effects of assisted oocyte activation with calcium- ionophore and strontium chloride on in vitro ICSI outcomes. Iran J Basic Med Sci 2018; 21 (11) 1109-1117
• 53 Murugesu S, Saso S, Jones BP. et al. Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? A meta-analysis. Fertil Steril 2017; 108 (03) 468-482.e3
• 54 Yanagida K, Fujikura Y, Katayose H. The present status of artificial oocyte activation in assisted reproductive technology. Reprod Med Biol 2008; 7 (03) 133-142
• 55 Swann K, Yu Y. The dynamics of calcium oscillations that activate mammalian eggs. Int J Dev Biol 2008; 52 (5-6): 585-594
• 56 Nikiforaki D, Vanden Meerschaut F, de Roo C. et al. Effect of two assisted oocyte activation protocols used to overcome fertilization failure on the activation potential and calcium releasing pattern. Fertil Steril 2016; 105 (03) 798-806.e2
• 57 Tesarik J, Sousa M, Testart J. Human oocyte activation after intracytoplasmic sperm injection. Hum Reprod 1994; 9 (03) 511-518
• 58 Hoshi K, Yanagida K, Yazawa H, Katayose H, Sato A. Intracytoplasmic sperm injection using immobilized or motile human spermatozoon. Fertil Steril 1995; 63 (06) 1241-1245
• 59 Sallam HN, Sallam NH. Religious aspects of assisted reproduction. Facts Views Vis ObGyn 2016; 8 (01) 33-48
• 60 Bonte D, Ferrer-Buitrago M, Dhaenens L. et al. Assisted oocyte activation significantly increases fertilization and pregnancy outcome in patients with low and total failed fertilization after intracytoplasmic sperm injection: a 17-year retrospective study. Fertil Steril 2019; 112 (02) 266-274
• 61 Karabulut S, Aksünger Ö, Ata C, Sağıroglu Y, Keskin İ. Artificial oocyte activation with calcium ionophore for frozen sperm cycles. Syst Biol Reprod Med 2018; 64 (05) 381-388
• 62 Kashir J, Heynen A, Jones C. et al. Effects of cryopreservation and density-gradient washing on phospholipase C zeta concentrations in human spermatozoa. Reprod Biomed Online 2011; 23 (02) 263-267
• 63 Lv M, Zhang D, He X. et al. Artificial oocyte activation to improve reproductive outcomes in couples with various causes of infertility: a retrospective cohort study. Reprod Biomed Online 2020; 40 (04) 501-509
• 64 Li J, Zheng X, Lian Y. et al. Artificial oocyte activation improves cycles with prospects of ICSI fertilization failure: a sibling oocyte control study. Reprod Biomed Online 2019; 39 (02) 199-204
• 65 Meng X, Melo P, Jones C. et al. Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management. Fertil Steril 2020; 114 (01) 163-174
• 66 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 (01) 87-98
• 67 Kashir J, Konstantinidis M, Jones C. et al. A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility. Hum Reprod 2012; 27 (01) 222-231
• 68 Torra-Massana M, Cornet-Bartolomé D, Barragán M. et al. Novel phospholipase C zeta 1 mutations associated with fertilization failures after ICSI. Hum Reprod 2019; 34 (08) 1494-1504
• 69 Yuan P, Yang C, Ren Y. et al. A novel homozygous mutation of phospholipase C zeta leading to defective human oocyte activation and fertilization failure. Hum Reprod 2020; 35 (04) 977-985
• 70 Yuan P, Zheng L, Liang H. et al. Novel mutations in the PLCZ1 gene associated with human low or failed fertilization. Mol Genet Genomic Med 2020; 8 (10) e1470
• 71 Wang F, Zhang J, Kong S. et al. A homozygous nonsense mutation of PLCZ1 cause male infertility with oocyte activation deficiency. J Assist Reprod Genet 2020; 37 (04) 821-828
• 72 Yan Z, Fan Y, Wang F. et al. Novel mutations in PLCZ1 cause male infertility due to fertilization failure or poor fertilization. Hum Reprod 2020; 35 (02) 472-481
• 73 Mu J, Zhang Z, Wu L. et al. The identification of novel mutations in PLCZ1 responsible for human fertilization failure and a therapeutic intervention by artificial oocyte activation. Mol Hum Reprod 2020; 26 (02) 80-87
• 74 Dai J, Zhang T, Guo J. et al. Homozygous pathogenic variants in ACTL9 cause fertilization failure and male infertility in humans and mice. Am J Hum Genet 2021; 108 (03) 469-481
• 75 Long R, Wang M, Yang QY, Hu SQ, Zhu LX, Jin L. Risk of birth defects in children conceived by artificial oocyte activation and intracytoplasmic sperm injection: a meta-analysis. Reprod Biol Endocrinol 2020; 18 (01) 123
• 76 Deemeh MR, Tavalaee M, Nasr-Esfahani MH. Health of children born through artificial oocyte activation: a pilot study. Reprod Sci 2015; 22 (03) 322-328
• 77 Mani S, Mainigi M. Embryo culture conditions and the epigenome. Semin Reprod Med 2018; 36 (3–04): 211-220
• 78 Kelley RL, Gardner DK. Individual culture and atmospheric oxygen during culture affect mouse preimplantation embryo metabolism and post-implantation development. Reprod Biomed Online 2019; 39 (01) 3-18
• 79 Chronopoulou E, Harper JC. IVF culture media: past, present and future. Hum Reprod Update 2015; 21 (01) 39-55
• 80 Gatimel N, Moreau J, Parinaud J, Léandri RD. Need for choosing the ideal pH value for IVF culture media. J Assist Reprod Genet 2020; 37 (05) 1019-1028
• 81 Vanden Meerschaut F, D'Haeseleer E, Gysels H. et al. Neonatal and neurodevelopmental outcome of children aged 3-10 years born following assisted oocyte activation. Reprod Biomed Online 2014; 28 (01) 54-63
• 82 D'haeseleer E, Vanden Meerschaut F, Bettens K. et al. Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA). Int J Lang Commun Disord 2014; 49 (06) 702-709
• 83 Miller N, Biron-Shental T, Sukenik-Halevy R, Klement AH, Sharony R, Berkovitz A. Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril 2016; 106 (03) 590-596.e2