Comparison of Two Types of Calcium (Ca²⁺) Ionophore Treatments for Oocyte Activation in Cases of Suboptimal Fertilization Potential

NCT07570342 | Not Yet Recruiting DMC

• 1 other identifier: 2503-ABU-008-NH
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to investigate the effectiveness and safety of assisted oocyte activation (AOA) using Ca²⁺ ionophores in cases of total fertilization failure (TFF) due to oocyte activation deficiency (OAD). The study will be conducted in two phases: Phase I will compare the fertilization rates of oocytes exposed to two types of Ca²⁺ ionophore treatments- Ionomycin solution and commercially available CultActive-against a control group without calcium ionophore treatment. Phase II will assess whether an additional injection of CaCl2, prior to exposure to the chosen ionophore from Phase I, further improves fertilization outcomes. The goal is to identify the optimal AOA protocol for improving fertilization rates and to evaluate the safety and efficacy of this approach in relation to ploidy, with a focus on ensuring normal pre-implantation embryo development.

Conditions

ICSI; Male Infertility; PGT-A; Testicular Sperm Extraction in Azoospermic Patients

Keywords

ICSI; PGT-A; artificial oocyte activation; AOA; calcium ionophore; ionomycin; TESE; Immotile sperm; Failed fertilization

Outcome Measures

Primary Outcomes (2)

• Fertilization rates and abnormal fertilization.

  The primary endpoint is the proportion of metaphase II (MII) oocytes that achieve normal fertilisation (2 pronuclei; 2PN) following insemination or ICSI, compared across study groups. Additionally, the incidence of abnormal fertilisation (e.g., 0PN, 1PN, ≥3PN) will be evaluated. Fertilisation assessment will be performed at the standard time point of 16-20 hours post-insemination/ICSI.

  16-20 hours post-insemination/ICSI

• Oocyte Degeneration Rate

  The proportion of metaphase II (MII) oocytes that undergo degeneration following ICSI across the study groups. Degeneration will be assessed at the standard post-ICSI evaluation time point, and expressed as the percentage of injected oocytes exhibiting morphological signs of degeneration.

  24 hours post-ICSI

Secondary Outcomes (3)

• Usable Blastocyst Rate

  7 days post fertilization

• Blastocyst Quality at Time of Biopsy

  7 days post fertilization

• Blastocyst Ploidy on Day 5, 6, or 7

  From enrollment to the end of treatment at 4 week

Study Arms (3)

Group 1: Oocyte Activation (OA) CultActive

OTHER

Oocytes are cultured immediately after injection in a pre-calibrated OA-CultActive dish for 15 min in CO2 incubator, then injected oocytes are rinsed well in culture dish/ Embryoscope slide in GT-culture medium. Then transferred to the numbered droplet or well.

Other: Group 1: Oocyte Activation (OA) CultActive

Group 2: Oocyte Activation (OA) Ionomycin

OTHER

Oocytes are placed immediately after injection in a pre-calibrated OA-Ionomycin dish (dish 1) for 7 - 10 min in CO2 incubator, then they are rinsed well and placed in another culture dish (dish 2) for 25 min in CO2 incubator. Then MIIs are exposed again in OA-Ionomycin dish for 10 min, then they are rinsed well and placed into culture dish/ Embryoscope slide in GT-culture medium. Then transferred to the numbered droplet or well.

Other: Group 2: Oocyte Activation (OA) Ionomycin

Group 3: Control

OTHER

Oocytes are cultured as per routine practice after injection in culture dish/ Embryoscope slide in routine culture GT-culture medium.

Other: Group 3: Control

Interventions

Group 1: Oocyte Activation (OA) CultActive OTHER

Oocytes are cultured immediately after injection in a pre-calibrated OA-CultActive dish for 15 min in CO2 incubator, then injected oocytes are rinsed well in culture dish/ Embryoscope slide in GT-culture medium. Then transferred to the numbered droplet or well.

Group 1: Oocyte Activation (OA) CultActive

Group 2: Oocyte Activation (OA) Ionomycin OTHER

Oocytes are placed immediately after injection in a pre-calibrated OA-Ionomycin dish (dish 1) for 7 - 10 min in CO2 incubator, then they are rinsed well and placed in another culture dish (dish 2) for 25 min in CO2 incubator. Then MIIs are exposed again in OA-Ionomycin dish for 10 min, then they are rinsed well and placed into culture dish/ Embryoscope slide in GT-culture medium. Then transferred to the numbered droplet or well.

Group 2: Oocyte Activation (OA) Ionomycin

Group 3: Control OTHER

Oocytes are cultured as per routine practice after injection in culture dish/ Embryoscope slide in routine culture GT-culture medium.

Group 3: Control

Eligibility Criteria

• Age: 18 Years - 43 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients undergoing assisted reproductive technology cycles when ICSI is indicated.
• Patients with a minimum of 3 MII oocytes after denudation.
• Maternal age 18-43 years old.
• PGT-A cycles with only trophectoderm biopsies on day 5/6/7.
• BMI\<35.
• Fresh and frozen immotile ejaculated sperm.
• Fresh and frozen TESE sperm (motile and immotile).
• Globozoospermia.
• \. Couples undergoing ICSI due to poor fertilization history (≤30%), or previous fertilization failure.

You may not qualify if:

• PGT-M/SR cycles.
• Fresh and frozen motile ejaculated / FNA sperm.
• IVF inseminated oocytes.

Sponsors & Collaborators

• ART Fertility Clinics LLC: lead

Related Publications (24)

• 24. Yeste M, Jones C, Amdani SN, Patel S, Coward K. Oocyte activation deficiency: a role for an oocyte contribution? Hum Reprod Update 2016a Jan-Feb;22:23-47.

  RESULT

• 23. Ye Y, Li N, Yan X, Wu R, Zhou W, Cheng L, Li Y. Genetic analysis of embryo in a human case of spontaneous oocyte activation: a case report. Gynecol Endocrinol 2020;36:294-296.

  RESULT

• 22. Yang X, Shu L, Cai L, Sun X, Cui Y, Liu J. Homozygous missense mutation Arg207Cys in the WEE2 gene causes female infertility and fertilization failure. J Assist Reprod Genet 2019;36:965-971.

  RESULT

• 21. Tosti E, Me ne zo Y. Gamete activation: basic knowledge and clinical applications. Hum Reprod Update 2016;22:420-439.

  RESULT

• 20. Tiegs AW, Tao X, Landis J, Zhan Y, Franasiak JM, Seli E, Wells D, Fragouli E, Scott RT. Sperm mitochondrial DNA copy number is not a predictor of intracytoplasmic sperm injection (ICSI) cycle outcomes. Reprod Sci 2020;27:1350-1356.

  RESULT

• 19. Tesarik J, Rienzi L, Ubaldi F, Mendoza C, Greco E. Use of a modified intracytoplasmic sperm injection technique to overcome spermborne and oocyte-borne oocyte activation failures. Fertil Steril 2002;78:619-624.

  RESULT

• 18. Santella L, Dale B. Assisted yes, but where do we draw the line? Reprod Biomed Online 2015;31:476-478.

  RESULT

• 17. Sang Q, Li B, Kuang Y, Wang X, Zhang Z, Chen B, Wu L, Lyu Q, Fu Y, Yan Z et al. Homozygous mutations in WEE2 cause fertilization failure and female infertility. Am J Hum Genet 2018;102:649-657.

  RESULT

• 16. Montag M, Ko ̈ ster 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. Reproductive Biomed Online 2012;24:521-526.

  RESULT

• 15. Mateizel I, Verheyen G, Van de Velde H, Tournaye H, Belva F. Obstetric and neonatal outcome following ICSI with assisted oocyte activation by Ca2+ ionophore treatment. J Assist Reprod Genet 2018;35:1005-1010.

  RESULT

• 14. Karabulut S, Aks ̈ unger ̈ O, Ata C, Sag ıroglu Y, Keskin _I. I _. Artificial oocyte activation with Ca2+ ionophore for frozen sperm cycles. Syst Biol Reprod Med 2018;64:381-388.

  RESULT

• 13. Kashir J, Nomikos M, Lai FA. Phospholipase C zeta and Ca2+ oscillations at fertilisation: the evidence, applications, and further questions. Adv Biol Regul 2018;67:148-162.

  RESULT

• 12. Kashir J, Mistry BV, BuSaleh L, Abu-Dawas R, Nomikos M, Ajlan A, Abu-Dawud R, AlYacoub N, AlHassan S, Lai FA et al. Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment. Andrology 2020b;8:1143-1159.

  RESULT

• 11. Kashir J. Increasing associations between defects in phospholipase C zeta and conditions of male infertility: not just ICSI failure? J Assist Reprod Genet 2020;37:1273-1293.

  RESULT

• 10. Kamath et al. Oocyte activation for women following intracytoplasmic sperm injection (ICSI). Cochrane Database Syst Rev. 2021; 2021(6): CD014040. Published online 2021 Jun 19. doi: 10.1002/14651858.CD014040

  RESULT

• 9. Lundin K et al. Good practice recommendations on add-ons in reproductive medicine† ESHRE Add-ons working group Human Reproduction 2023; 38:2062-2104, https://doi.org/10.1093/humrep/dead184.

  RESULT

• 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 Feb 7;2022(2):hoac003. doi: 10.1093/hropen/hoac003. eCollection 2022.

  PMID: 35261925 RESULT

• 7. 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;17:662-668.

  RESULT

• 6. Ebner T, Montag M, Montag M, Van der Ven K, Van der Ven H, Ebner T, Shebl O, Oppelt P, Hirchenhain J, Krüssel J et al. Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study. Reprod BioMed Online 2015;30:359-365.

  RESULT

• 5. Capalbo A, Ottolini CS, Griffin DK, Ubaldi FM, Handyside AH, Rienzi L. Artificial oocyte activation with Ca2+ ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte. Fertil Steril 2016;105:807-814.e2.

  RESULT

• 4. Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA 2015;313:255-263.

  RESULT

• 3. Bonte D, Ferrer-Buitrago M, Dhaenens L, Popovic M, Thys V, De Croo I, De Gheselle S, Steyaert N, Boel A, Vanden Meerschaut F 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;112:266-274.

  RESULT

• 2. Bassiri F, Nasr-Esfahani MH, Forozanfar M, Tavalaee M. Relationship between sperm parameters with sperm function tests in infertile men with at least one failed cycle after intracytoplasmic sperm injection cycle. Int J Fertil Steril 2020;13:324-329.

  RESULT

• 1. Aksunger O, Erturk OK, Olgan S, Aydinuraz B, Dirican EK. Artificial oocyte activation after intracytoplasmic morphologically selected sperm injection: a prospective randomized sibling oocyte study. Human Fertility 2016;19:282-288.

  RESULT

MeSH Terms

Conditions

Infertility, Male

Interventions

Ionomycin

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Fatty Acids, Unsaturated; Fatty Acids; Lipids

Study Officials

• BARBARA LAWRENZ

  ART Fertility Clinics LLC

  STUDY DIRECTOR

Central Study Contacts

JONALYN EDADES, EMBA Healthcare Management

CONTACT

026528000; jonalyn.edades@artfertilityclinics.com

barbara lawrenz, PhD

CONTACT

026528000; barbara.lawrenz@artfertilityclinics.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Embryologist

Study Record Dates

• First Submitted: April 30, 2026
• First Posted: May 6, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-03