Child Follow-up in Women Treated With Conventional IVF or ICSI

Developmental Outcomes of Children Born Through Intracytoplasmic Sperm Injection (ICSI) Versus Conventional in Vitro Fertilization (IVF) in Couples With Non-male Factor Infertility

To compare the physical, mental and motor development of babies born from pregnancy using ICSI technique and and conventional IVF in non-male factor infertile couples. Based on our previous RCT (NCT03428919), the non-male factor couples were randomly assigned to IVF or ICSI, which leads to the similarity in characteristics of these two groups. Hence, the result of analyzing these offsprings would be preciously valuable.

Study Overview

• Status: Completed
• Conditions: Conventional IVF, ICSI
• Intervention / Treatment: Other: Physical development and General Health; Other: Developmental Red flags; Other: Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3

Detailed Description

Over the past two decades, intracytoplasmic sperm injection (ICSI) indications have been extended and routinely applied to all cases of assisted reproductive techniques: unexplained infertility, poor-quality oocytes, low oocyte yeild, advanced marternal age, prior failed fertilization with conventional insemination, after in-vitro maturation of oocytes and for cases of cryopreserved oocytes (Practice Committees of the American Society for Reproductive Medicine, 2020). In 2004, fertilization using ICSI accounted for nearly 60% of all aspirations globally. In the Middle East, the number of ICSI cycles increased rapidly from 2000 (47.6%) to 2007 (65.2%), and reached 97.8% in the Middle East in 2007 (Ishihara et al, 2015). Another survey recorded in Europe in 2011, out of a total of 437,510 cycles of fresh embryo transfer, 68% of cycles were performed using ICSI techniques. In male infertility cases, the rate of implementation of ICSI increased from 76.3% to 93.3%. In particular, in cases of non-male-factor infertility, the incidence of ICSI also increased from 15.4% to 66.9%. From 2008-2012, of 494 907 treatment cycles, 74.6% used ICSI. In which, ICSI accounts for 92.9% of the cycle of male infertility and 64.5% of the cycle of non-male-factor infertility (Boulet, 2015).

However, ICSI is an invasive technique that bypasses the natural barriers of fertilization. This has led to concern about an increase in the incidence of anomalies in ICSI-born babies as this technique is increasingly being used in all cases of contraception. In contrast, there are studies that have also compared IVF with ICSI and show that in the ICSI cycle, the incidence of multiple pregnancies and low birth weight infants is lower than that of IVF, although there is no difference in infant survival between the two groups (Boulet et al, 2015).

In addition to the short-term outcomes, the investigators also have to consider the long-term maternal and neonatal outcomes. There is still not much evidence comparing the effects of the above methods, if any, on the psychomotor development in children.

Therefore, the investigators decide to conduct a study to compare the physical, mental and motor development of babies born from pregnancy using ICSI technique and and conventional IVF in non-male factor infertile couples.

• Study Type: Observational
• Enrollment (Actual): 322

Contacts and Locations

Study Locations

• Vietnam
  • Tan Binh
    • Ho Chi Minh City, Tan Binh, Vietnam
      • Mỹ Đức Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Live babies born through intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF) in couples with non-male factor infertility (NCT03428919)

Description

Inclusion Criteria:

• Live babies born from ICSI Versus Conventional IVF in Non-male Factor Couples (NCT03428919)
• Parents agree to participate in the study.

Exclusion Criteria:

• Babies died after the perinatal period.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICSI technique; In ICSI group, insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. OCCs will be stripped by using hyaluronidase. Only matured oocytes will be inseminated.	Other: Physical development and General Health; Physical development and General health examination; Other: Developmental Red flags; Developmental Red flags Questionnaires; Other: 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.
Conventional IVF; In conventional IVF group, insemination will be performed by conventional IVF. Two hours after retrieval, collected OCCs will be inseminated for another 2 hours, at a concentration of 100,000 motile sperm/ml. Inseminated OCCs will be cultured overnight in culture medium.	Other: Physical development and General Health; Physical development and General health examination; Other: Developmental Red flags; Developmental Red flags Questionnaires; Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients having abnormal ASQ-3 scores in each aspect	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. Abnormal ASQ-3 score in an aspect = ASQ-3 score of 2 standard deviations below the mean of the aspect.	Up to 66 months after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 66 months after birth
Name of diseases that lead to hospital admission	Name of diseases that lead to hospital admission	Up to 66 months after birth
Weight	Weight on the examination date	Through study completion, an average of 1.5 months
Height	Height on the examination date	Through study completion, an average of 1.5 months
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 66 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 66 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 66 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 66 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: From 12 to < 18 month-old: Doesn't crawl; Can't stand when supported; Doesn't search for things that he/she sees the participants hide; Doesn't say single words ("baba", "mama"...); Doesn't learn gestures like waving or shaking head; Doesn't point to things; Loses skills he/she once had From 18 to < 24 month-old: Doesn't point to show things to others; Can't walk; Doesn't know what familiar things are for; Doesn't gain new words; Doesn't have at least 6 words; Doesn't notice or mind when a caregiver leaves or returns; Lose skills he once had From 24 to < 36 month-old: Doesn't use 2-word phrases; Doesn't know what to do with common things, like a brush, spoon; Doesn't copy actions and words; Doesn't follow simple instructions; Doesn't walk steadily; Loses skills he/she once had	From 2 to 5.5 years after birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of long-term illness and chronic conditions	The rate of long-term illness and chronic conditions	Up to 66 months after birth

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital
• Investigators: Principal Investigator: Nghia A Nguyen, MD, PhD, Mỹ Đức Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): October 1, 2021

Study Registration Dates

• First Submitted: April 27, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 04/2021/MĐ-HĐĐĐ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No