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

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 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 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 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)

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• Tiegs AW, Tao X, Landis J, Zhan Y, Franasiak JM, Seli E, Wells D, Fragouli E, Scott RT Jr. Sperm Mitochondrial DNA Copy Number Is Not a Predictor of Intracytoplasmic Sperm Injection (ICSI) Cycle Outcomes. Reprod Sci. 2020 Jun;27(6):1350-1356. doi: 10.1007/s43032-020-00163-0. Epub 2020 Jan 28.

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  PMID: 26277587 RESULT

• Sang Q, Li B, Kuang Y, Wang X, Zhang Z, Chen B, Wu L, Lyu Q, Fu Y, Yan Z, Mao X, Xu Y, Mu J, Li Q, Jin L, He L, Wang L. Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility. Am J Hum Genet. 2018 Apr 5;102(4):649-657. doi: 10.1016/j.ajhg.2018.02.015. Epub 2018 Mar 29.

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• Montag M, Koster 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. Reprod Biomed Online. 2012 May;24(5):521-6. doi: 10.1016/j.rbmo.2012.02.002. Epub 2012 Feb 10.

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• 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 Jun;35(6):1005-1010. doi: 10.1007/s10815-018-1124-6. Epub 2018 Feb 1.

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• Karabulut S, Aksunger O, Ata C, Sagiroglu Y, Keskin I. Artificial oocyte activation with calcium ionophore for frozen sperm cycles. Syst Biol Reprod Med. 2018 Oct;64(5):381-388. doi: 10.1080/19396368.2018.1452311. Epub 2018 Apr 5.

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• Kashir J, Nomikos M, Lai FA. Phospholipase C zeta and calcium oscillations at fertilisation: The evidence, applications, and further questions. Adv Biol Regul. 2018 Jan;67:148-162. doi: 10.1016/j.jbior.2017.10.012. Epub 2017 Oct 27.

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• Kashir J, Mistry BV, BuSaleh L, Abu-Dawas R, Nomikos M, Ajlan A, Abu-Dawud R, AlYacoub N, AlHassan S, Lai FA, Assiri AM, Coskun S. Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment. Andrology. 2020 Sep;8(5):1143-1159. doi: 10.1111/andr.12796. Epub 2020 May 20.

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• ESHRE Add-ons working group; Lundin K, Bentzen JG, Bozdag G, Ebner T, Harper J, Le Clef N, Moffett A, Norcross S, Polyzos NP, Rautakallio-Hokkanen S, Sfontouris I, Sermon K, Vermeulen N, Pinborg A. Good practice recommendations on add-ons in reproductive medicinedagger. Hum Reprod. 2023 Nov 2;38(11):2062-2104. doi: 10.1093/humrep/dead184.

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• 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.

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• Ebner T, Montag M; Oocyte Activation Study Group; Montag M, Van der Ven K, Van der Ven H, Ebner T, Shebl O, Oppelt P, Hirchenhain J, Krussel J, Maxrath B, Gnoth C, Friol K, Tigges J, Wunsch E, Luckhaus J, Beerkotte A, Weiss D, Grunwald K, Struller D, Etien C. Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study. Reprod Biomed Online. 2015 Apr;30(4):359-65. doi: 10.1016/j.rbmo.2014.11.012. Epub 2014 Dec 9.

  PMID: 25596904 RESULT

• Capalbo A, Ottolini CS, Griffin DK, Ubaldi FM, Handyside AH, Rienzi L. Artificial oocyte activation with calcium ionophore does not cause a widespread increase in chromosome segregation errors in the second meiotic division of the oocyte. Fertil Steril. 2016 Mar;105(3):807-814.e2. doi: 10.1016/j.fertnstert.2015.11.017. Epub 2015 Dec 1.

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• 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 Jan;13(4):324-329. doi: 10.22074/ijfs.2020.5750. Epub 2019 Nov 11.

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• Aydinuraz B, Dirican EK, Olgan S, Aksunger O, Erturk OK. Artificial oocyte activation after intracytoplasmic morphologically selected sperm injection: A prospective randomized sibling oocyte study. Hum Fertil (Camb). 2016 Dec;19(4):282-288. doi: 10.1080/14647273.2016.1240374. Epub 2016 Oct 13.

  PMID: 27734719 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 11, 2026

Record last verified: 2026-03