Health of Children Born From ICSI With AOA (AOA-BABIES)

April 10, 2025 updated by: Mỹ Đức Hospital

Physical, Mental, and Motor Development of Children Born From Intracytoplasmic Sperm Injection With Assisted Oocyte Activation With Calcium Ionophore

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.

Study Overview

Status

Completed

Conditions

Detailed Description

Intracytoplasmic sperm injection (ICSI) is the most widely utilized assisted reproductive technique (ART) worldwide. Fertilization rates obtained after ICSI treatment are reported between 70 and 80%, representing the most efficient ART; however, complete post-ICSI fertilization failure still occurs in 3-5% of cases.

The leading cause of failed fertilization is failure to achieve oocyte activation, a crucial stage in the initiation of embryo development during fertilization. Assisted oocyte activation (AOA) using a calcium ionophore has been used for over a decade following ICSI fertilization failure. AOA is not considered a routine practice of ART yet, which is only suitable for patients with proper indications, including (i) total fertilization failure or low fertilization rate (<30%) in the previous IVF; (ii) severe male factor infertility; (iii) patients with a history of embryo arrest or poor embryo quality in previous IVF cycle.

Regarding technique, the artificial rise of induced calcium rises cannot precisely mimic the physiologically sperm-induced calcium oscillations. Little is known yet about the possible adverse effects of ionophores on post-implantation embryo development. Numerous studies have been conducted to compare the development of children born from ICSI - AOA versus non-AOA. Thus, the investigators performed this study to investigate the physical, mental, and motor development of children born following ICSI - AOA using the Developmental Red Flags and Ages & Stages Third Edition (ASQ-3) Questionnaires.

Study Type

Observational

Enrollment (Actual)

63

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Vietnam
      • Ho Chi Minh City, Vietnam, 70000
        • Mỹ Đức Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 1 year (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-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)

Description

Inclusion Criteria:

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)

Exclusion Criteria:

Embryos with PGT. Oocyte donation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
ICSI + AOA
Children born after ICSI + AOA
Control
Children born after ICSI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of abnormal ASQ-3 score
Time Frame: 12 months after birth

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Score of Communication
Time Frame: 12 months after birth
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.
12 months after birth
Score of Gross motor
Time Frame: 12 months after birth
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.
12 months after birth
Score of Fine motor
Time Frame: 12 months after birth
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.
12 months after birth
Score of Problem-solving skill
Time Frame: 12 months after birth
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.
12 months after birth
Score of Personal-Social
Time Frame: 12 months after birth
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. Total score will be used: minimum = 0 and maximum = 60. Each aspect in each stage has an alternative threshold.
12 months after birth
The rate of children who have at least one red flag sign(s):
Time Frame: 12 months after birth

For children at 12 months: they

  • No response when being called by their name
  • Does not understand "no"
  • Can not stand even when being supported
  • Apathy or non-observance of the caregiver
  • Does not look at the point where the caregiver points
12 months after birth
Duration of breastfeeding
Time Frame: 12 months after birth
Duration of breastfeeding
12 months after birth
Infant age at which weaning starts
Time Frame: 12 months after birth
Infant age at which weaning starts
12 months after birth
Name of diseases that lead to hospital admission
Time Frame: 12 months after birth
Name of diseases that lead to hospital admission
12 months after birth
Number of hospital admission
Time Frame: 12 months after birth
Number of hospital admission
12 months after birth
Weight
Time Frame: 12 months after birth
Weight on the examination date
12 months after birth
Height
Time Frame: 12 months after birth
Height on the examination date
12 months after birth

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gestational age at delivery
Time Frame: At birth
Gestational age at delivery
At birth
Rate of congenital anomalies
Time Frame: At birth
Any congenital anomalies detected in baby born
At birth
Mode of delivery
Time Frame: At birth
Vaginal birth or C-section
At birth
Birth weight
Time Frame: At birth
Weight of baby born
At birth
Length circumference
Time Frame: At birth
Length circumference after birth
At birth
Head circumference
Time Frame: At birth
Head circumference after birth
At birth
Rate of Periventricular haemorrhage
Time Frame: Up to 28 days after birth
Periventricular haemorrhage II B or worse, will be diagnosed by repeated neonatal cranial ultrasound by the neonatologist according to the guidelines on neuro-imaging described by de Vries et al.
Up to 28 days after birth
Rate of Necrotizing enterocolitis
Time Frame: Up to 28 days after birth
Necrotizing enterocolitis (NEC) will be diagnosed according to Bell.
Up to 28 days after birth
Rate of Proven sepsis
Time Frame: Up to 28 days after birth
Proven sepsis, will be diagnosed on the combination of clinical signs and positive blood cultures.
Up to 28 days after birth
Rate of Composite of poor perinatal outcomes
Time Frame: Up to 28 days after birth
Composite of poor perinatal outcomes, defined as intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.
Up to 28 days after birth
Length of neonatal intensive care unit (NICU) admission
Time Frame: Up to 28 days after birth
Number of admission days to NICU
Up to 28 days after birth
Rate of Respiratory distress syndrome
Time Frame: Up to 28 days after birth
Respiratory distress syndrome (RDS), diagnosed as the presence of tachypnoea >60/minute, sternal recession and expiratory grunting, need for supplemental oxygen, and a radiological picture of diffuse reticulogranular shadowing with an air bronchogram
Up to 28 days after birth
Rate of long-term illness and chronic conditions
Time Frame: Up to 28 days after birth
Any long-term illness and chronic condition appears in a child.
Up to 28 days after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mỹ Đức Hospital

Investigators

  • Principal Investigator: Lan Vuong Ngoc, PhD, Mỹ Đức Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2022

Primary Completion (Actual)

March 30, 2023

Study Completion (Actual)

March 30, 2023

Study Registration Dates

First Submitted

October 10, 2022

First Submitted That Met QC Criteria

October 10, 2022

First Posted (Actual)

October 13, 2022

Study Record Updates

Last Update Posted (Actual)

April 15, 2025

Last Update Submitted That Met QC Criteria

April 10, 2025

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10/22/DD-BVMD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe