NCT05578118

Brief Summary

The investigators follow up on the development of children born from ICSI-AOA using the Developmental Red Flags and Ages \& Stages Third Edition (ASQ-3) Questionnaires to give strong evidence about the safety of AOA in assisted reproductive technology.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Oct 2022

Shorter than P25 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 10, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 13, 2022

Completed
10 days until next milestone

Study Start

First participant enrolled

October 23, 2022

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2023

Completed
Last Updated

April 15, 2025

Status Verified

August 1, 2023

Enrollment Period

5 months

First QC Date

October 10, 2022

Last Update Submit

April 10, 2025

Conditions

InfertilityIntracytoplasmic Sperm Injection

Keywords

ICSITotal fertilization failureAOAASQ-3Health of children

Outcome Measures

Primary Outcomes (1)

  • The percentage of abnormal ASQ-3 score

    ASQ-3 (Ages and Stages Questionaires®) has 5 aspects: Communication, Gross Motor, Fine Motor, Problem-solving, and Personal-Social Each element has 6 questions. If the answer is Yes, score = 10, Sometimes = 5, and Not yet = 0. ASQ-3 average = average score of 5 aspects.

    12 months after birth

Secondary Outcomes (12)

  • Score of Communication

    12 months after birth

  • Score of Gross motor

    12 months after birth

  • Score of Fine motor

    12 months after birth

  • Score of Problem-solving skill

    12 months after birth

  • Score of Personal-Social

    12 months after birth

  • +7 more secondary outcomes

Other Outcomes (13)

  • Gestational age at delivery

    At birth

  • Mode of delivery

    At birth

  • Birth weight

    At birth

  • +10 more other outcomes

Study Arms (2)

ICSI + AOA

Children born after ICSI + AOA

Control

Children born after ICSI

Eligibility Criteria

Age12 Months - 12 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

In the ICSI+AOA group, indications of AOA are: * Previous failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\<35%) or poor embryo result (number of embryos/pick-up oocytes\<35%, \<3 embryos, no good-quality embryo) * Using sperm after retrieval technique, cryptozoospermia In the Control group, the indications of AOA for the next IVF cycle (if patients continue the next IVF cycle) are: * Currently failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\<35%) or poor embryo result (number of embryos/pick-up oocytes\<35%, \<3 embryos, no good-quality embryo)

You may qualify if:

  • All single, live babies born following ICSI with AOA and ICSI without AOA from 08/2020 to 04/2021.
  • Parents consent to participate in the study. Group ICSI+AOA: Embryos from ICSI with AOA with calcium ionophore
  • In the ICSI+AOA group, indications of AOA are:
  • Previous failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\<35%) or poor embryo result (number of embryos/pick-up oocytes\<35%, \<3 embryos, no good-quality embryo)
  • Using sperm after retrieval technique, cryptozoospermia Group Control: Embryos from ICSI without AOA.
  • In the Control group, the indications of AOA for the next IVF cycle (if patients continue the next IVF cycle) are:
  • Currently failed IVF treatment with no fertilization or poor fertilization rate (fertilized oocytes/pick-up oocytes\<35%) or poor embryo result (number of embryos/pick-up oocytes\<35%, \<3 embryos, no good-quality embryo)

You may not qualify if:

  • Embryos with PGT. Oocyte donation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mỹ Đức Hospital

Ho Chi Minh City, 70000, Vietnam

Location

Related Publications (23)

  • Alberio R, Zakhartchenko V, Motlik J, Wolf E. Mammalian oocyte activation: lessons from the sperm and implications for nuclear transfer. Int J Dev Biol. 2001 Oct;45(7):797-809.

    PMID: 11732839RESULT

  • Bos-Mikich A, Whittingham DG, Jones KT. Meiotic and mitotic Ca2+ oscillations affect cell composition in resulting blastocysts. Dev Biol. 1997 Feb 1;182(1):172-9. doi: 10.1006/dbio.1996.8468.

    PMID: 9073459RESULT

  • 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.

    PMID: 26658129RESULT

  • D'haeseleer E, Vanden Meerschaut F, Bettens K, Luyten A, Gysels H, Thienpont Y, De Witte G, Heindryckx B, Oostra A, Roeyers H, Sutter PD, van Lierde K. Language development of children born following intracytoplasmic sperm injection (ICSI) combined with assisted oocyte activation (AOA). Int J Lang Commun Disord. 2014 Nov;49(6):702-9. doi: 10.1111/1460-6984.12100. Epub 2014 May 26.

    PMID: 24861451RESULT

  • Ducibella T, Huneau D, Angelichio E, Xu Z, Schultz RM, Kopf GS, Fissore R, Madoux S, Ozil JP. Egg-to-embryo transition is driven by differential responses to Ca(2+) oscillation number. Dev Biol. 2002 Oct 15;250(2):280-91.

    PMID: 12376103RESULT

  • Ebner T, Oppelt P, Wober M, Staples P, Mayer RB, Sonnleitner U, Bulfon-Vogl S, Gruber I, Haid AE, Shebl O. Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study. Hum Reprod. 2015 Jan;30(1):97-102. doi: 10.1093/humrep/deu285. Epub 2014 Nov 5.

    PMID: 25376461RESULT

  • Fawzy M, Emad M, Mahran A, Sabry M, Fetih AN, Abdelghafar H, Rasheed S. Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves clinical and embryological outcomes compared with ICSI alone: results of a randomized clinical trial. Hum Reprod. 2018 Sep 1;33(9):1636-1644. doi: 10.1093/humrep/dey258.

    PMID: 30099496RESULT

  • Heytens E, Soleimani R, Lierman S, De Meester S, Gerris J, Dhont M, Van der Elst J, De Sutter P. Effect of ionomycin on oocyte activation and embryo development in mouse. Reprod Biomed Online. 2008 Dec;17(6):764-71. doi: 10.1016/s1472-6483(10)60403-8.

    PMID: 19079959RESULT

  • Hirata, K., Nakamura, Y., Hattori, H., Kuchiki, M., Sakamoto, E., & Kyono, K. (2013). Follow-up child growth regarding new technologies: Testicular sperm extraction (TESE), in vitro maturation (IVM), and assisted oocyte activation (AOA). Fertility and Sterility, 100(3), S470. https://doi.org/10.1016/j.fertnstert.2013.07.445

    RESULT

  • Kashir J, Nomikos M, Lai FA, Swann K. Sperm-induced Ca2+ release during egg activation in mammals. Biochem Biophys Res Commun. 2014 Aug 1;450(3):1204-11. doi: 10.1016/j.bbrc.2014.04.078. Epub 2014 Apr 21.

    PMID: 24769204RESULT

  • Kim BY, Yoon SY, Cha SK, Kwak KH, Fissore RA, Parys JB, Yoon TK, Lee DR. Alterations in calcium oscillatory activity in vitrified mouse eggs impact on egg quality and subsequent embryonic development. Pflugers Arch. 2011 May;461(5):515-26. doi: 10.1007/s00424-011-0955-0. Epub 2011 Mar 23.

    PMID: 21431324RESULT

  • Koo OJ, Jang G, Kwon DK, Kang JT, Kwon OS, Park HJ, Kang SK, Lee BC. Electrical activation induces reactive oxygen species in porcine embryos. Theriogenology. 2008 Oct 15;70(7):1111-8. doi: 10.1016/j.theriogenology.2008.06.031.

    PMID: 18675447RESULT

  • Miller N, Biron-Shental T, Sukenik-Halevy R, Klement AH, Sharony R, Berkovitz A. Oocyte activation by calcium ionophore and congenital birth defects: a retrospective cohort study. Fertil Steril. 2016 Sep 1;106(3):590-596.e2. doi: 10.1016/j.fertnstert.2016.04.025. Epub 2016 Apr 30.

    PMID: 27143515RESULT

  • Ozil JP, Huneau D. Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development. Development. 2001 Mar;128(6):917-28. doi: 10.1242/dev.128.6.917.

    PMID: 11222146RESULT

  • Ozil JP, Banrezes B, Toth S, Pan H, Schultz RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol. 2006 Dec 15;300(2):534-44. doi: 10.1016/j.ydbio.2006.08.041. Epub 2006 Aug 25.

    PMID: 16996050RESULT

  • Swann K, Ozil JP. Dynamics of the calcium signal that triggers mammalian egg activation. Int Rev Cytol. 1994;152:183-222. doi: 10.1016/s0074-7696(08)62557-7. No abstract available.

    PMID: 8206704RESULT

  • Eftekhar M, Janati S, Rahsepar M, Aflatoonian A. Effect of oocyte activation with calcium ionophore on ICSI outcomes in teratospermia: A randomized clinical trial. Iran J Reprod Med. 2013 Nov;11(11):875-82.

    PMID: 24639711RESULT

  • Tesarik J, Sousa M. Key elements of a highly efficient intracytoplasmic sperm injection technique: Ca2+ fluxes and oocyte cytoplasmic dislocation. Fertil Steril. 1995 Oct;64(4):770-6. doi: 10.1016/s0015-0282(16)57853-4.

    PMID: 7672149RESULT

  • Vanden Meerschaut F, Leybaert L, Nikiforaki D, Qian C, Heindryckx B, De Sutter P. Diagnostic and prognostic value of calcium oscillatory pattern analysis for patients with ICSI fertilization failure. Hum Reprod. 2013 Jan;28(1):87-98. doi: 10.1093/humrep/des368. Epub 2012 Oct 18.

    PMID: 23081875RESULT

  • Vanden Meerschaut F, Nikiforaki D, De Roo C, Lierman S, Qian C, Schmitt-John T, De Sutter P, Heindryckx B. Comparison of pre- and post-implantation development following the application of three artificial activating stimuli in a mouse model with round-headed sperm cells deficient for oocyte activation. Hum Reprod. 2013 May;28(5):1190-8. doi: 10.1093/humrep/det038. Epub 2013 Mar 12.

    PMID: 23482335RESULT

  • Vanden Meerschaut F, Nikiforaki D, Heindryckx B, De Sutter P. Assisted oocyte activation following ICSI fertilization failure. Reprod Biomed Online. 2014 May;28(5):560-71. doi: 10.1016/j.rbmo.2014.01.008. Epub 2014 Jan 31.

    PMID: 24656559RESULT

  • WHO child growth standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. (n.d.). Retrieved June 10, 2022, from https://www.who.int/publications-detail-redirect/924154693X

    RESULT

  • Yoshida S, Plant S. Mechanism of release of Ca2+ from intracellular stores in response to ionomycin in oocytes of the frog Xenopus laevis. J Physiol. 1992 Dec;458:307-18. doi: 10.1113/jphysiol.1992.sp019419.

    PMID: 1302268RESULT

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Study Officials

  • Lan Vuong Ngoc, PhD

    Mỹ Đức Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 10, 2022

First Posted

October 13, 2022

Study Start

October 23, 2022

Primary Completion

March 30, 2023

Study Completion

March 30, 2023

Last Updated

April 15, 2025

Record last verified: 2023-08

Locations

VN(1)