Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study

Ebner, Thomas; Oppelt, Peter; Wöber, Martina; Staples, P.; Mayer, RB; Sonnleitner, U.; Bulfon-Vogl, S.; Gruber, Irmhild; Haid, A.; Shebl, Omar

doi:10.1093/humrep/deu285

Cited by 58 publications

(62 citation statements)

References 45 publications

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“…Calcium ionophore is a lipid-soluble molecule that permits calcium transport across the cell membrane, transiently increasing cytoplasmic calcium levels, thereby enabling oocyte activation and fertilization. (Meerschaut et al, 2014) In this study we compared the use of calcium ionophore to non intervention in cases with Contrary to the previous findings, (Ebner et al, 2015) found that AOA with calcium ionophore failed to improve the fertilization rates. Nonetheless, they found that exposure to calcium ionophore improved the number of embryo progression to blastocyst stage in cases with previous embryo development problems.…”

Section: Discussion:-contrasting

confidence: 63%

Effect of oocyte activation with calcium ionophore on ICSI outcomes in patients with previous fertilization failure

Hebisha

Aboelazm

Adel

et al. 2016

Fertility and Sterility

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Background: Chemical activation is the most frequently used method for artificial oocyte activation (AOA), results in high fertilization rate. Objective: To evaluate the efficiency of oocyte activation with calcium ionophore on fertilization and pregnancy outcomes after intracytoplasmic sperm injection (ICSI) in patients with previous fertilization failure. Design: prospective controlled study Materials and methods: One hundred and eight patients with history of previous fertilization failure undergoing IVF/ICSI treatment with long agonist protocol were randomly divided into two groups: group A (n=54) and group B (n=54) ; a total of 756 metaphase II (MII) oocytes were retrieved . In the oocytes of group A(n=350 oocyte), routine ICSI was applied; while in oocytes in group B (n=406 oocyte) immediately after ICSI, were entered in culture medium supplemented with 5 µΜ calcium ionophore (A23187) for 10 minutes and then washed at least five times with MOPS solution. Main outcome measures: In both groups, the fertilization was evaluated after 16-18 hours. Results: The number of fertilized oocytes and embryos obtained were significantly different between two groups (p=<0.001*). Fertilization rate was significantly higher in group B -where calcium ionophore was applied-compared to group A(control group) (32.2% vs. 9.1%, respectively ,p=0.01*); and Cleavage rate also was significantly higher in group B compared to group A (27.4% vs 12.5% respectively, p=0.028*). Implantation rate was significantly higher in group B than in group A (18.32% vs. 3.12 % respectively, p=0.035*) Pregnancy rate also was significantly higher in group B than in group A (22.2% vs. 1.85% respectively, p=0.042*). Conclusion: Chemical oocyte activation with calcium ionophore resulted in a significant improvement in fertilization, cleavage, implantation and pregnancy rates after ICSI in infertile patients with previous fertilization failure.

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Section: Discussion:-contrasting

confidence: 63%

Effect of oocyte activation with calcium ionophore on ICSI outcomes in patients with previous fertilization failure

Hebisha

Aboelazm

Adel

et al. 2016

Fertility and Sterility

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“…The finding that one blastocyst arose from an oocyte stimulated with Ca 2+ -induced activation from a PCOS patient, which led to a term infant female, raises the additional possible benefit of Ca 2+ ionophore on preimplantation embryogenesis. Although beyond the scope of this report, Ca 2+ ionophore has been shown to improve embryo development and pregnancy outcome in patients with a history of previous impaired embryo development [17]. Therefore, it is also possible that successful pregnancies after ICSI supplemented with artificial activation of oocytes matured in vitro [33] might be the result of enhanced embryo competence from both improved fertilization and preimplantation embryogenesis [10,15,17].…”

Section: Discussionmentioning

confidence: 91%

“…Calcium-dependent oocyte activation is a critical step in oocyte fertilization and preimplantation embryo development [8,14,17]. As a crucial sperm protein governing Ca 2+ -dependent oocyte activation, PLC-ζ released into the oocyte during sperm-oocyte membrane fusion [2] acts on phosphatidylinositol 4,5-biphosphate (PIP 2 ) [18] to induce its hydrolysis forming the second messengers inositol 1,4,5 triphosphate (IP 3 ) and diacylglycerol (DAG) [18].…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent IP 3 binding to its own receptor on the endoplasmic reticulum (ER) [19] opens Ca 2+ channels, which release Ca 2+ from the ER into the cytoplasm of the oocyte [19]. The resulting Ca 2+ oscillations within the oocyte [18,19] disseminate from the cortical region throughout the ooplasm [20,21] at 10-to 20-min intervals [22], triggering oocyte activation [23] to initiate oocyte fertilization and preimplantation embryogenesis [8,14,17].…”

Section: Discussionmentioning

confidence: 99%

“…Data regarding Ca 2+ ionophore use with ICSI and its relationship to human oocyte competence, embryo development, and neurodevelopmental outcomes in children appear reassuring [17,37,38], but immature oocytes or mature oocytes failing to fertilize may harbor inherent defects that potentially harm the embryo [39]. Also relevant is the potential impact of Ca 2+ ionophore use with ICSI on the rates of miscarriage, genetic abnormalities, and minor as well as major congenital malformations [15,40].…”

Section: Discussionmentioning

confidence: 99%

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Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

Chithiwala

Lee

Hill

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca 2+ ) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro. Methods An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC-ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca 2+ release. A second IVF cycle was performed using Ca 2+ ionophore with ICSI to enhance Ca 2+ -induced oocyte activation of oocytes matured in vitro.Results Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca 2+ release. Nevertheless, with this sperm and supplementation of Ca 2+ ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth. Conclusions Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca 2+ -dependent oocyte activation during ICSI. Under this condition, use of Ca 2+ ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca 2+ -dependent mechanisms governing fertilization and preimplantation embryogenesis.

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Oocyte Treatment and Preparation for Microinjection

Ebner¹

2019

In Vitro Fertilization

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Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study

Abstract: No funding received. T.E. reports fees from Gynemed, outside the submitted work. All co-authors have no interest to declare.

Cited by 58 publications

References 45 publications

Effect of oocyte activation with calcium ionophore on ICSI outcomes in patients with previous fertilization failure

Effect of oocyte activation with calcium ionophore on ICSI outcomes in patients with previous fertilization failure

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

Oocyte Treatment and Preparation for Microinjection

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