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Health of Frozen Transferred Versus Fresh Transferred Children

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04099784
Enrollment
255
Registered
2019-09-23
Start date
2019-09-01
Completion date
2019-11-20
Last updated
2020-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infertility, IVF

Keywords

Fresh transfer, freeze-only, ASQ-3, health of children

Brief summary

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.

Detailed description

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.

Interventions

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 examination

Developmental Red flags Questionnaires

Sponsors

Mỹ Đức Hospital
Lead SponsorOTHER

Study design

Observational model
OTHER
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
1 Months to 66 Months
Healthy volunteers
Yes

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.

Design outcomes

Primary

MeasureTime frameDescription
The average total ASQ-3 scoreUp to 66 months after birthASQ-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

MeasureTime frameDescription
Score of CommunicationUp to 66 months after birth6 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
Score of Gross motorUp to 66 months after birth6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
Score of Fine motorUp to 66 months after birth6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
Score of Problem solvingUp to 66 months after birth6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
Score of Personal-SocialUp to 66 months after birth6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
The rate of children who have at least one red flag signFrom 2 to 5.5 years after birthHe 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
Duration of breast-feedingUp to 24 months after birthDuration of breast-feeding
Infant age at which weaning startsUp to 24 months after birthInfant age at which weaning starts
Name of diseases that lead to hospital admissionUp to 66 months after birthName of diseases that lead to hospital admission
Number of hospital admissionUp to 66 months after birthNumber of hospital admission
WeightThrough study completion, an average of 1.5 monthsWeight on the examination date
HeightThrough study completion, an average of 1.5 monthsHeight on the examination date

Other

MeasureTime frameDescription
Gestational age at deliveryAt birthGestational age at delivery
Mode of deliveryAt birthVaginal birth or C-section
Birth weightAt birthWeight of baby born
Length circumferenceAt birthHead circumference after birth Head circumference after birth Head circumference after birth Length circumference after birth
Head circumferenceAt birthHead circumference after birth
Rate of congenital anomaliesAt birthAny congenital anomalies detected in baby born
Length of neonatal intensive care unit (NICU) admissionUp to 28 days after birthNumber of admission days to NICU
Rate of Respiratory distress syndromeUp to 28 days after birthRespiratory 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
Rate of Periventricular haemorrhageUp to 28 days after birthPeriventricular 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.
Rate of Necrotizing enterocolitisUp to 28 days after birthNecrotizing enterocolitis (NEC) will be diagnosed according to Bell.
Rate of Proven sepsisUp to 28 days after birthProven sepsis, will be diagnosed on the combination of clinical signs and positive blood cultures.
Rate of Composite of poor perinatal outcomesUp to 28 days after birthComposite of poor perinatal outcomes, defined as intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.
The rate of long-term illness and chronic conditionsUp to 66 months after birthAny long-term illness and chronic condition appears in a child

Countries

Vietnam

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 27, 2026