Health of IVF Versus IVM Children (FM-BABIES)

Study Overview
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Brief Summary
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The investigators conduct a follow up of our randomized controlled trial (RCT) to investigate the development of children born from In-vitro fertilization (IVF) and In-vitro maturation (IVM), in order to give strong evidence about the safety of IVM in women with high antral follicle count or especially polycystic ovary syndrome (PCOS).

Detailed Description
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Since the birth of the first baby born from in-vitro maturation (IVM) in 1991, this technique has been considered an alternative solution for treating infertility beside conventional controlled ovarian stimulation for in-vitro fertilization (IVF). Since then, there are already more than 5000 children born from IVM, and that number is on the trend of increasing. Regarding technique, immature oocytes (germinal vesicle - GV) were aspirated from secondary follicles sized from 2-10mm, under follicle-stimulating hormone (FSH) priming or no ovarian stimulation at all. Afterward, the maturation process was undertaken in an artificial medium, out of a living body. This technique, by reducing the usage of external hormones, is highly effective in minimizing the risk of ovarian hyperstimulation syndrome (OHSS) in women with high antral follicle count, especially polycystic ovarian syndrome, with a rate of OHSS recorded as low as 0 percent. Alongside that, the pregnancy rate, as well as the live birth rate of IVM, when proceeded well, is not lower than conventional IVF. Until now, there is only one randomized controlled trial comparing these two techniques directly. Due to differences in the process of culturing between IVM and IVF, primarily the maturation is undertaken in an artificial medium, the health of children born from IVM received many interests. Numerous studies have been conducted to compare the development of children born from IVM and IVF. Neonatal outcomes of children born from IVM and IVF are considerably comparable. And the development of children born from these two techniques is not significantly different. All the information, as mentioned above, was not from randomized controlled trials but retrospective or prospective cohort studies. Thus, we conduct a follow up of our RCT to investigate the development of children born from IVM and IVM, to give strong evidence about the safety of IVM in women with high antral follicle count or especially PCOS.

Official Title
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Follow-up of Children Born From In-vitro Maturation Versus In-vitro Fertilization: Follow-up of a Randomized Controlled Trial

Conditions
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IVF, Infertility, IVM

Intervention / Treatment
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* Diagnostic Test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3
* Other: Physical development and General Health
* Diagnostic Test: Developmental Red flags


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All live babies born following the In-vitro Maturation and In-vitro fertilization from our FM study. Parents agree to participate in the study. Exclusion Criteria: Babies died under or at 24 months

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IVF children<br>Children born from in-vitro fertilization | Diagnostic Test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3<br>* Ages & Stages Questionnaires®, Third Edition (ASQ®-3) is a developmental screening tool designed for use by early educators and health care professionals. It relies on parents as experts, is easy-to-use, family-friendly and creates the snapshot needed to catch delays and celebrate milestones.<br>Other: Physical development and General Health<br>* Physical development and General health examination<br>Diagnostic Test: Developmental Red flags<br>* Developmental Red flags Questionnaires<br>|
| IVM children<br>Children born from in-vitro maturation | Diagnostic Test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3<br>* Ages & Stages Questionnaires®, Third Edition (ASQ®-3) is a developmental screening tool designed for use by early educators and health care professionals. It relies on parents as experts, is easy-to-use, family-friendly and creates the snapshot needed to catch delays and celebrate milestones.<br>Other: Physical development and General Health<br>* Physical development and General health examination<br>Diagnostic Test: Developmental Red flags<br>* Developmental Red flags Questionnaires<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The average total ASQ-3 score | ASQ-3 (Ages and Stages Questionaires®) has 5 aspects: Communication, Gross motor, Fine motor, Problem solving and Personal-Social Each aspect has 6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0. ASQ-3 average = average score of 5 aspects. | Up to 24 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 aspects in each stages has alternative threshold | Up to 24 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 aspects in each stages has alternative threshold | Up to 24 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 aspects in each stages has alternative threshold | Up to 24 months after birth | 
| Score of Problem solving | 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 aspects in each stages has alternative threshold | Up to 24 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 aspects in each stages has alternative threshold | Up to 24 months after birth | 
| The rate of children who have at least one red flag sign | He or she has at least one red flag sign by age For children at 6 months: he or she Do not know to flip before 3 months Still holding hands constantly at 3 months Do not pay attention to the stimulation from the environment Poor head control No access to objects/ toys before 5 months No laughter For children at 12 months: he or she No babbling before 6 months Unable to sit down in a W-style at 7 months Unable to identify audio source before 10 months Still holding things in your mouth often for 12 months For children at 24 months: he or she Do not speak consonants before 15 months Do not know imitate before 16 months Do not know to point fingers to attract attention about objects that he or she cares about Show right-handedness before 18 months Unable to ascend and descend stairs at 24 months Repeat the machinery of others' words Not reached the single 50 marks yet by 24 months | From 6 months to 24 months after birth | 
| Duration of breast-feeding | Duration of breast-feeding | Up to 24 months after birth | 
| Infant age at which weaning starts | Infant age at which weaning starts | Up to 24 months after birth | 
| Name of diseases that lead to hospital admission | Name of diseases that lead to hospital admission | Up to 24 months after birth | 
| Number of hospital admission | Number of hospital admission | Up to 24 months after birth | 
| Weight | Weight on the examination date | Up to 24 months after birth | 
| Height | Height on the examination date | Up to 24 months after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Health of children, IVF, IVM, ASQ-3