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OpenTrials
Completed

NCT Number: NCT04099784

Health of Frozen Transferred Versus Fresh Transferred Children

In order to give strong recommendation on the efficacy and safety of fresh versus frozen embryo transfer, we conduct this study in order to investigate the physical and mental development of children from fresh versus frozen embryo transfer. Based on our Freeze-only study (Vuong et al., 2018), the women without polycystic ovary syndrome undergoing the first or second IVF were randomly assigned to receive either fresh or frozen embryos on day 3 after oocyte retrieval, which leads to the similarity in characteristics of these two groups. Hence, the result from analysing these offsprings would be preciously valuable.

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Key information

Age range

1 month–66 month

Sex eligibility

All sexes

Study type

Observational

Primary location

Mỹ Đức Hospital

Ho Chi Minh City, Tan Binh, Vietnam

About this study

Since the first live birth after the transfer of a frozen-thawed embryo reported in 1984, cryopreservation has been considered as an enormous revolution in assisted reproductive technology (ART). It is observed that the trend of ART cycles using frozen embryo transfer is on the increase, which leads to a great deal number of children born from frozen embryos. This is the commencement of 2 embryo transfer strategies, the first one is transferring the fresh embryos, the other is freezing all the embryos and transfer them in the next cycle.

Comparing these two strategies, up till now, there are 4 published randomized control trials (RCTs) indicating different methods for certain groups of patients (Chen et al., 2016; Shi et al., 2018; Vuong et al., 2018; Wei et al., 2019). Regarding the efficacy, the freeze-all strategy outweighs the fresh embryo transfer in women with polycystic ovary syndrome (PCOS). While that efficacy gets a controversy in non-PCOS or ovulatory patients; two groups of authors indicated that these 2 strategies are equally effective, while the other group claims that the better result goes to cycles with frozen embryos. In term of safety, the rate of ovarian hyperstimulation syndrome (OHSS) is the equivalent or lower in the freeze-all group, which implies the important role of embryo-freezing in avoiding maternal risk. The question that whether freezing the embryos exerts effect on offspring is not thoroughly understood. The mostly used parameter in evaluating the safety of children is the perinatal status of infants, not the development of these children.

Searching literature, in 2010, S. Pelkonen published a large cohort study indicating that freezing the embryos do not change the rate of prematurity, low birthweight and being small for gestational age (Pelkonen et al., 2010). Looking further in our freeze-only study, our sub-analysis indicates that the livebirth weight of infants born from frozen embryos is 300 gram heavier than that from fresh embryos (Vuong et al., 2018). Following 4 studies comparing fresh and frozen embryo transfer, children from frozen embryos are similar or higher in term of newborn weight, and there is no study investigate the onward development of childrens born from these two strategies. The only proof on the development of children born from fresh verus frozen embryo is from one study with no randomization which states that children from fresh and frozen embryos share similar academic performance at the age 15-16 (Spangmose et al., 2019). We found no study investigate the impact of different embryo transfer strategies on the growth of children resulting from either fresh or frozen embryos.

In order to give strong recommendation on the efficacy and safety of fresh versus frozen embryo transfer, we conduct this study in order to investigate the physical and mental development of children from fresh versus frozen embryo transfer. Based on our Freeze-only study (Vuong et al., 2018), the women without polycystic ovary syndrome undergoing the first or second IVF were randomly assigned to receive either fresh or frozen embryos on day 3 after oocyte retrieval, which leads to the similarity in characteristics of these two groups. Hence, the result from analysing these offsprings would be preciously valuable.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Live babies born from the first transfer of both freeze-only and fresh embryo transfer group from our Freeze-only study.
  • Parents agree to participate in the study.

Exclusion criteria

  • Babies died after perinatal period.

Treatment and study plan

Developmental score according to The Ages & Stages Questionnaires®, Third Edition - ASQ®-3

Other

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.

Physical development and General Health

Other

Physical development and General health examination

Developmental Red flags

Other

Developmental Red flags Questionnaires

Primary outcomes

  1. The average total ASQ-3 score

    Time frame: Up to 66 months after birth

    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.

Secondary outcomes

  1. Score of Communication

    Time frame: Up to 66 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 aspects in each stages has alternative threshold

  2. Score of Gross motor

    Time frame: Up to 66 months after birth

    6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.

  3. Score of Fine motor

    Time frame: Up to 66 months after birth

    6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.

  4. Score of Problem solving

    Time frame: Up to 66 months after birth

    6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.

  5. Score of Personal-Social

    Time frame: Up to 66 months after birth

    6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.

  6. The rate of children who have at least one red flag sign

    Time frame: From 2 to 5.5 years after birth

    He or she has at least one red flag sign by age

    From 2 to < 3 year-old:

    • Has very unclear speech
    • Doesn't understand simple instruction • Doesn't speak in sentences
    • Doesn't make eye contact
    • Loses skills he/she once had

    From 3 to < 4 year-old:

    • Can't jump in place
    • Doesn't play pretend or make-believe • Speaks unclearly
    • Can't retell a favorite story
    • Doesn't use "me" and "you" correctly
    • Loses skills he/she once had

    From 4 to < 5.5 year-old:

    • Is easily distracted, has trouble focusing on one activity for more than 5 minutes • Doesn't talk about daily activities or experiences
    • Shows extreme behavior
    • Loses skills he/she once had
  7. Duration of breast-feeding

    Time frame: Up to 24 months after birth

    Duration of breast-feeding

  8. Infant age at which weaning starts

    Time frame: Up to 24 months after birth

    Infant age at which weaning starts

  9. Name of diseases that lead to hospital admission

    Time frame: Up to 66 months after birth

    Name of diseases that lead to hospital admission

  10. Number of hospital admission

    Time frame: Up to 66 months after birth

    Number of hospital admission

  11. Weight

    Time frame: Through study completion, an average of 1.5 months

    Weight on the examination date

  12. Height

    Time frame: Through study completion, an average of 1.5 months

    Height on the examination date

Other outcomes

  1. Gestational age at delivery

    Time frame: At birth

    Gestational age at delivery

  2. Mode of delivery

    Time frame: At birth

    Vaginal birth or C-section

  3. Birth weight

    Time frame: At birth

    Weight of baby born

  4. Length circumference

    Time frame: At birth

    Head circumference after birth Head circumference after birth Head circumference after birth Length circumference after birth

  5. Head circumference

    Time frame: At birth

    Head circumference after birth

  6. Rate of congenital anomalies

    Time frame: At birth

    Any congenital anomalies detected in baby born

  7. Length of neonatal intensive care unit (NICU) admission

    Time frame: Up to 28 days after birth

    Number of admission days to NICU

  8. 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

  9. 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.

  10. Rate of Necrotizing enterocolitis

    Time frame: Up to 28 days after birth

    Necrotizing enterocolitis (NEC) will be diagnosed according to Bell.

  11. 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.

  12. 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.

  13. The rate of long-term illness and chronic conditions

    Time frame: Up to 66 months after birth

    Any long-term illness and chronic condition appears in a child

Sponsors and collaborators

Lead sponsor

Mỹ Đức Hospital

Other

Registry information

Official study title

Follow-up of Children Born From Freeze-only Versus Fresh Embryo Transfer: a Follow-up of a Randomized Controlled Trial

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Sep 23, 2019
Registry last updated
Mar 3, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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