Calcifer: Efficacy of Oocyte Activation With Two Types of Ca2+ Ionophore: a Prospective Randomized Study.

Sponsor

Instituto Valenciano de Infertilidad, IVI VALENCIA (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06106412

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a prospective ranzomized analysis including 372 human oocytes from 44 women. Half of the oocytes from the same patient will be randomly allocated to induce oocyte activation using two protocols: in protocol nº 1 we will use ionomycin (prepared solution), protocol nª2 A23187 (GM508 CultActive Gynemed) will be applied. Non treated oocytes will serve as control. Oocyte fertilization rates, embryo development and embryo quality will be analyzed. Obstetrics variables of offspring will be also followed and compared.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female	Drug: Activation Product Drug: Activation Product	N/A

Detailed Description

Background: Oocyte non-activation (OAD) is the main cause of fertilization failure in intracytoplasmic sperm injection (ICSI) cycles. Oocyte activation involves a series of consecutive events that take place in the oocyte during fertilization, triggered by the action of sperm-specific phospholipase C zeta (PLCz) that causes an increase in the amount of free Ca2+. This increase, as well as its transient elevations in space and time, is species-specific. Defects in this pattern of Ca2+ release and oscillation are attributed to most cases of OAD. Several strategies have been described and applied to achieve artificial oocyte activation (AOA), which use mechanical, electrical, or chemical stimuli, among which the use of calcium ionophores such as ionomycin and A23187 (calcimycin) predominates. Documented fertilization and pregnancy rates appear to be improved in patients with previous low fertilization rates or total fertilization failures after using ICSI-AOA compared to conventional ICSI. However, the lack of well-designed studies, the heterogeneity of the population undergoing AOA, and the scarcity of results comparing different AOA protocols make it difficult to assess the clinical efficacy and safety of the technique.

Study question: In patients with prior fertilization failure or low fertilization rates (30% or less), does AOA improve reproductive outcomes compared to conventional ICSI in patients with prior fertilization failure? and if it does, which protocol is more efficient?

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective ranzomized analysisProspective ranzomized analysis

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Oocyte Activation With Two Types of Ca2+ Ionophore: a Prospective Randomized Study.

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GROUP 1 IONOMYCIN SIGMA The oocytes obtained from the patients allocated to this group will be subdivided again in two groups Group 1a: Oocytes treated with SIGMA ionomycin (treatment). Group 1b: Oocytes that will not be treated with any activator (Control).	Drug: Activation Product Oocytes will be activated with Ionomycin SIGMA Other Names: Ionomycin SIGMA
Active Comparator: GROUP 2 A23187 The oocytes obtained from the patients allocated to this group will be subdivided again in two groups Group 2a: Oocytes treated with A23187 (treatment). Group 2b: Oocytes that will not be treated with any activator (Control).	Drug: Activation Product Oocytes will be activated with A23187 Other Names: A23187

Arm

Intervention/Treatment

Experimental: GROUP 1 IONOMYCIN SIGMA

The oocytes obtained from the patients allocated to this group will be subdivided again in two groups Group 1a: Oocytes treated with SIGMA ionomycin (treatment). Group 1b: Oocytes that will not be treated with any activator (Control).

Drug: Activation Product

Oocytes will be activated with Ionomycin SIGMA

Other Names:

Ionomycin SIGMA

Active Comparator: GROUP 2 A23187

The oocytes obtained from the patients allocated to this group will be subdivided again in two groups Group 2a: Oocytes treated with A23187 (treatment). Group 2b: Oocytes that will not be treated with any activator (Control).

Drug: Activation Product

Oocytes will be activated with A23187

Other Names:

A23187

Outcome Measures

Primary Outcome Measures

Improvement in the percetage of usable blastocyst per injeected oocyte [1 YEAR]
To evaluate which AOA protocol with the use of two calcium (Ca2+) ionophores, ionomycin and A23187 (calcimycin), is better (improvement from 15% to 25%)

Secondary Outcome Measures

Sequencing unfertilized oocytes and arrested embryos using RNAseq [1 year]
To sequence oocytes and embryos
Quantification of PLCZ in sperm cells by flow [1 year]
To quantify PLCZ in sperm

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Own oocyte patients who have had previous fertilization failure in previous cycles.
Own oocyte patients with fertilization rate in previous cycles less than or equal to 30% of the microinjected oocytes.