Effect of Calcium Ionophore (A23187) on Embryo Development and Its Safety in PGT Cycles

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Jan 23

PMID 36686427

Authors

Junya Zhang

Guidong Yao

Tongwei Zhang

Jingyi Hu

Guang Yang

Jiahuan He

Qina He

Huiying Fan

Yucheng Bai

Yingpu Sun

Affiliations

Soon will be listed here.

Abstract

Background: Intracytoplasmic sperm injection (ICSI) has tremendous advantages for resolving the problem of male infertility. However, ICSI fertilization can fail in some patients because of various reasons, primarily because of the failure of oocyte activation. Oocytes have been activated using calcium ionophore (A23187) in previous clinical cases of ICSI fertilization failure. However, studies on the efficiency of calcium ionophore (A23187) activation, its effects on the developmental potential of embryos, and its effects on pregnancy outcomes after embryo transfer are relatively limited.

Methods: In this study, we investigated the safety and long-term efficacy of calcium ionophore (A23187) by analyzing its effects on fertilization, embryonic development, aneuploidy, and pregnancy outcomes in patients undergoing preimplantation genetic testing (PGT) cycles.

Results: Comparative analyses of the activation followed by PGT (A-PGT) and PGT groups revealed no significant differences between the oocyte cleavage rate and high-quality embryo rate (98.19% vs. 98.63% and 63.13% vs. 68.39%, respectively, > 0.05). Although the blastocyst formation rate was significantly lower in the A-PGT group than that in the PGT group (52.22% vs. 59.90%, < 0.05), no significant difference was observed in the blastocyst aneuploidy rates of the two groups (24.49% vs. 24.55%, > 0.05). Furthermore, no significant differences were observed between the two groups in terms of the live birth rate (43.75% vs. 52.99%), week of delivery, and birth weight of the infants after transfer of euploid blastocysts ( > 0.05). Furthermore, the 2PN rate, oocyte cleavage rate, blastocyst formation rate, and live birth rate were found to be significantly lower in the A-ICSI group than those in the ICSI group ( < 0.01), but there was no significant difference between the two groups in the week of delivery and birth weight of live births ( > 0.05).

Discussion: These results suggest that the use of calcium ionophore (A23187) activation as an option in cases of ICSI fertilization failure does not affect the ploidy of developing blastocysts and has no significant effects on the week of delivery or birth weight after transfer. Thus, we provide a scientific basis for the clinical safety of oocyte activation using calcium ionophore (A23187).

Citing Articles

Exploring key embryonic developmental morphokinetic parameters that affect clinical outcomes during the PGT cycle using time-lapse monitoring systems.

Jiang R, Yang G, Wang H, Fang J, Hu J, Zhang T BMC Pregnancy Childbirth. 2024; 24(1):870.

PMID: 39732641 PMC: 11681760. DOI: 10.1186/s12884-024-07080-z.

Assessing the impact of calcium ionophore on pregnancy outcomes in artificial oocyte activation cycles: a 10-year update of systematic review and meta-analysis.

Zhang J, Sui Y, Xiao M, Sun X, Fu J J Assist Reprod Genet. 2024; 42(1):165-183.

PMID: 39557784 PMC: 11806169. DOI: 10.1007/s10815-024-03319-y.

Human oocyte zona pellucida abnormalities: evaluation of clinical impact for different zona pellucida abnormalities and role of using assisted hatching.

Wang H, Yang G, Jiang R, Zhai J, Jin H, Song W J Assist Reprod Genet. 2024; 42(1):303-317.

PMID: 39520601 PMC: 11806172. DOI: 10.1007/s10815-024-03306-3.

References

Niu W, Wang L, Xu J, Li Y, Shi H, Li G . Improved clinical outcomes of preimplantation genetic testing for aneuploidy using MALBAC-NGS compared with MDA-SNP array. BMC Pregnancy Childbirth. 2020; 20(1):388. PMC: 7333433. DOI: 10.1186/s12884-020-03082-9. View

Lehmann P, Velez M, Saumet J, Lapensee L, Jamal W, Bissonnette F . Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF. J Assist Reprod Genet. 2014; 31(4):493-8. PMC: 3969465. DOI: 10.1007/s10815-014-0193-4. View

Mu J, Zhang Z, Wu L, Fu J, Chen B, Yan Z . 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(2):80-87. DOI: 10.1093/molehr/gaaa003. View

Miao Y, Stein P, Jefferson W, Padilla-Banks E, Williams C . Calcium influx-mediated signaling is required for complete mouse egg activation. Proc Natl Acad Sci U S A. 2012; 109(11):4169-74. PMC: 3306664. DOI: 10.1073/pnas.1112333109. View

Kashir J, Nomikos M, Lai F . Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions. Adv Biol Regul. 2017; 67:148-162. DOI: 10.1016/j.jbior.2017.10.012. View

Aydinuraz B, Dirican E, Olgan S, Aksunger O, Erturk O . Artificial oocyte activation after intracytoplasmic morphologically selected sperm injection: A prospective randomized sibling oocyte study. Hum Fertil (Camb). 2016; 19(4):282-288. DOI: 10.1080/14647273.2016.1240374. View

Yeste M, Jones C, Amdani S, Patel S, Coward K . Oocyte activation deficiency: a role for an oocyte contribution?. Hum Reprod Update. 2015; 22(1):23-47. DOI: 10.1093/humupd/dmv040. View

Gardner D, Lane M, Stevens J, Schlenker T, Schoolcraft W . Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000; 73(6):1155-8. DOI: 10.1016/s0015-0282(00)00518-5. View

Sunderam S, Boulet S, Kawwass J, Kissin D . Comparing fertilization rates from intracytoplasmic sperm injection to conventional in vitro fertilization among women of advanced age with non-male factor infertility: a meta-analysis. Fertil Steril. 2020; 113(2):354-363.e1. PMC: 10983030. DOI: 10.1016/j.fertnstert.2019.09.035. View

10.

Xu Z, Yao G, Niu W, Fan H, Ma X, Shi S . Calcium Ionophore (A23187) Rescues the Activation of Unfertilized Oocytes After Intracytoplasmic Sperm Injection and Chromosome Analysis of Blastocyst After Activation. Front Endocrinol (Lausanne). 2021; 12:692082. PMC: 8320372. DOI: 10.3389/fendo.2021.692082. View

11.

Yanagida K, Katayose H, Hirata S, Yazawa H, Hayashi S, Sato A . Influence of sperm immobilization on onset of Ca(2+) oscillations after ICSI. Hum Reprod. 2001; 16(1):148-152. DOI: 10.1093/humrep/16.1.148. View

12.

Santella L, Dale B . Assisted yes, but where do we draw the line?. Reprod Biomed Online. 2015; 31(4):476-8. DOI: 10.1016/j.rbmo.2015.06.013. View

13.

Miller N, Biron-Shental T, Sukenik-Halevy R, Klement A, Sharony R, Berkovitz A . Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril. 2016; 106(3):590-596.e2. DOI: 10.1016/j.fertnstert.2016.04.025. View

14.

Ebner T, Sommergruber M, Moser M, Shebl O, Schreier-Lechner E, Tews G . Basal level of anti-Müllerian hormone is associated with oocyte quality in stimulated cycles. Hum Reprod. 2006; 21(8):2022-6. DOI: 10.1093/humrep/del127. View

15.

Ebner T, Koster M, Shebl O, Moser M, van der Ven H, Tews G . 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. DOI: 10.1016/j.fertnstert.2012.07.1134. View

16.

Ferrer-Buitrago M, Dhaenens L, Lu Y, Bonte D, Vanden Meerschaut F, De Sutter P . Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI. Hum Reprod. 2018; 33(3):416-425. DOI: 10.1093/humrep/dex376. View

17.

Murugesu S, Saso S, Jones B, Bracewell-Milnes T, Athanasiou T, Mania A . Does the use of calcium ionophore during artificial oocyte activation demonstrate an effect on pregnancy rate? A meta-analysis. Fertil Steril. 2017; 108(3):468-482.e3. DOI: 10.1016/j.fertnstert.2017.06.029. View

18.

Mateizel I, Verheyen G, Van de Velde H, Tournaye H, Belva F . Obstetric and neonatal outcome following ICSI with assisted oocyte activation by calcium ionophore treatment. J Assist Reprod Genet. 2018; 35(6):1005-1010. PMC: 6030021. DOI: 10.1007/s10815-018-1124-6. View

19.

Kashir J, Ganesh D, Jones C, Coward K . Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application. Hum Reprod Open. 2022; 2022(2):hoac003. PMC: 8894871. DOI: 10.1093/hropen/hoac003. View

20.

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(6):2037.e5-9. DOI: 10.1016/j.fertnstert.2009.08.013. View