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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infertility, Intracytoplasmic Sperm Injection

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ICSI + AOA<br>Children born after ICSI + AOA | |
| Control<br>Children born after ICSI | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score of Communication | 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 | 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 | 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 | 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 | 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): | 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 | Duration of breastfeeding | 12 months after birth | 
| Infant age at which weaning starts | Infant age at which weaning starts | 12 months after birth | 
| Name of diseases that lead to hospital admission | Name of diseases that lead to hospital admission | 12 months after birth | 
| Number of hospital admission | Number of hospital admission | 12 months after birth | 
| Weight | Weight on the examination date | 12 months after birth | 
| Height | Height on the examination date | 12 months after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ICSI, Total fertilization failure, AOA, ASQ-3, Health of children