Development of IVF/ICSI Children Born From Different Endometrial Preparation Protocols (MONARTBABIES)

Development of IVF/ICSI Children Born From Frozen Embryo Transfer Cycles With Different Endometrial Preparation Protocols: Follow-up of a Randomized Controlled Trial

The efficacy and safety of endometrial preparation regimens remain controversial. In the most recent meta-analysis, using natural and modified natural cycle protocol to prepare the endometrium in frozen embryo transfer resulted in higher live birth rates. In addition, the natural cycle reduces the risk of gestational hypertension, postpartum haemorrhage, and extremely preterm delivery compared with regimens using exogenous hormones.

Because there are many physiological and endocrinal differences in the frozen embryo transfer cycle with different endometrial preparation protocols, the development of children born from these regimens has received much attention. For example, there is a complete absence of the corpus luteum during the cycle of exogenous hormone administration. Or in the modified natural cycle, the pharmacokinetics is not entirely the same as the natural physiology when using an additional ovulatory injection with hCG. To date, there have been no longitudinal follow-up studies that evaluated and compared the long-term development of IVF/ICSI children born from frozen embryo transfer with different endometrial preparation protocols.

Thus, the investigators conduct a follow-up of our RCT to investigate the IVF/ICSI children born from frozen embryo transfer with different endometrial preparation protocols to give strong evidence about the safety of the three most common endometrial preparation protocols in women undergoing frozen embryo transfer.

Study Overview

• Status: Recruiting
• Conditions: Child Development; Endometrial Preparation
• Intervention / Treatment: Other: Physical development and General Health; Diagnostic test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3; Diagnostic test: Developmental Red flags

Detailed Description

Developing further from a previous randomized controlled clinical trial (MONART study - NCT04804020), the investigators decided to assess the physical, mental, and motor development of children up to 24 months after birth, with the aim of providing additional information on the safety of these regimens on the long-term health of the IVF/ICSI children.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Hieu LT Hoang; Phone Number: (+84) 969 166 318; Email: bshieu.hlt@gmail.com
• Study Contact Backup: Name: Vu NA Ho; Phone Number: (+84) 935 843 336; Email: bsvu.hna@myduchospital.vn

Study Locations

• Vietnam
  • Ho Chi Minh City, Vietnam, 70000
    • Recruiting
    • My Duc Hospital
    • Contact: Hieu LT Hoang, MD; Phone Number: (+84) 969 166 318; Email: bshieu.hlt@myduchospital.vn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 1 year (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Live IVF/ICSI babies born from frozen embryo transfer following the natural cycle, modified natural cycle, and artificial cycle from MONART study (NCT04804020)

Description

Inclusion Criteria:

• All live IVF/ICSI babies born from frozen embryo transfer following the natural cycle, modified natural cycle, and artificial cycle from MONART study
• Parents agree to participate in the study.

Exclusion Criteria:

• Babies died under or at 24 months

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Natural cycle children; Children born from frozen embryo transfer with natural cycle protocol	Other: Physical development and General Health; Physical development and General health examination; Diagnostic test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3; 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.; Diagnostic test: Developmental Red flags; Developmental Red flags Questionnaires
Modified natural cycle children; Children born from frozen embryo transfer with modified natural cycle protocol	Other: Physical development and General Health; Physical development and General health examination; Diagnostic test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3; 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.; Diagnostic test: Developmental Red flags; Developmental Red flags Questionnaires
Artificial cycle children; Children born from frozen embryo transfer with artificial cycle protocol	Other: Physical development and General Health; Physical development and General health examination; Diagnostic test: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3; 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.; Diagnostic test: Developmental Red flags; Developmental Red flags Questionnaires

What is the study measuring?

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 Lack of turning toward voices. Does not pass object from one hand to another. No smiling, laughing, or expression. For children at 12 months: he or she Child does not respond to name. Does not understand "no". Does not stand or bear weight on legs when supported. Indifferent or resistant attachment to caregiver. Does not look where caregiver points. For children at 18 months: he or she has Not using at least 6 words. Inability to walk independently. Absence of proto-imperative pointing (point to show interest) or showing gesture.	From 6 months to 24 months after birth

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital
• Investigators: Study Chair: Lan N Vuong, University of Medicine and Pharmacy at Ho Chi Minh City

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 14, 2022
• First Submitted That Met QC Criteria: August 14, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Child development; IVF/ICSI; Endometrial preparation; Natural cycle; Modified natural cycle; Artificial cycle
• Additional Relevant MeSH Terms: Public Health; Environment and Public Health; Population Characteristics; Demography; Epidemiologic Measurements; Health Status
• Other Study ID Numbers: 09/22/DD-BVMD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No