Clinical trial NCT04099784: Health of Frozen Transferred Versus Fresh Transferred Children
Official title: Follow-up of Children Born From Freeze-only Versus Fresh Embryo Transfer: a Follow-up of a Randomized Controlled Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility
IVF
Keywords: Fresh transfer, freeze-only, ASQ-3, health of children
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2019-09-23
Enrollment: 255
Sex: ALL
Minimum age (years): 1
Maximum age (years): 66
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Live babies born following the frozen embryo transfer and fresh embryo transfer from our Freeze-only study (NCT02471573)

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The average total ASQ-3 score
timeFrame: Up to 66 months after birth
Secondary outcomes:
measure: Score of Communication
timeFrame: Up to 66 months after birth
measure: Score of Gross motor
timeFrame: Up to 66 months after birth
measure: Score of Fine motor
timeFrame: Up to 66 months after birth
measure: Score of Problem solving
timeFrame: Up to 66 months after birth
measure: Score of Personal-Social
timeFrame: Up to 66 months after birth
measure: The rate of children who have at least one red flag sign
timeFrame: From 2 to 5.5 years after birth
measure: Duration of breast-feeding
timeFrame: Up to 24 months after birth
measure: Infant age at which weaning starts
timeFrame: Up to 24 months after birth
measure: Name of diseases that lead to hospital admission
timeFrame: Up to 66 months after birth
measure: Number of hospital admission
timeFrame: Up to 66 months after birth
measure: Weight
timeFrame: Through study completion, an average of 1.5 months
measure: Height
timeFrame: Through study completion, an average of 1.5 months
Other outcomes:
measure: Gestational age at delivery
timeFrame: At birth
measure: Mode of delivery
timeFrame: At birth
measure: Birth weight
timeFrame: At birth
measure: Length circumference
timeFrame: At birth
measure: Head circumference
timeFrame: At birth
measure: Rate of congenital anomalies
timeFrame: At birth
measure: Length of neonatal intensive care unit (NICU) admission
timeFrame: Up to 28 days after birth
measure: Rate of Respiratory distress syndrome
timeFrame: Up to 28 days after birth
measure: Rate of Periventricular haemorrhage
timeFrame: Up to 28 days after birth
measure: Rate of Necrotizing enterocolitis
timeFrame: Up to 28 days after birth
measure: Rate of Proven sepsis
timeFrame: Up to 28 days after birth
measure: Rate of Composite of poor perinatal outcomes
timeFrame: Up to 28 days after birth
measure: The rate of long-term illness and chronic conditions
timeFrame: Up to 66 months after birth
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Mỹ Đức Hospital
state: Tan Binh
Study officials:
affiliation: Mỹ Đức Hospital
name: Lan N Vuong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen ZJ, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, Yang J, Liu J, Wei D, Weng N, Tian L, Hao C, Yang D, Zhou F, Shi J, Xu Y, Li J, Yan J, Qin Y, Zhao H, Zhang H, Legro RS. Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome. N Engl J Med. 2016 Aug 11;375(6):523-33. doi: 10.1056/NEJMoa1513873.
citation: Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, Zhu Y, Deng X, Qi X, Li H, Ma X, Ren H, Wang Y, Zhang D, Wang B, Liu F, Wu Q, Wang Z, Bai H, Li Y, Zhou Y, Sun M, Liu H, Li J, Zhang L, Chen X, Zhang S, Sun X, Legro RS, Chen ZJ. Transfer of Fresh versus Frozen Embryos in Ovulatory Women. N Engl J Med. 2018 Jan 11;378(2):126-136. doi: 10.1056/NEJMoa1705334.
citation: Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, Nguyen LK, Norman RJ, Mol BW. IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries. N Engl J Med. 2018 Jan 11;378(2):137-147. doi: 10.1056/NEJMoa1703768.
citation: Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian LF, Lv Q, Ma X, Zhang H, Legro RS, Chen ZJ. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019 Mar 30;393(10178):1310-1318. doi: 10.1016/S0140-6736(18)32843-5. Epub 2019 Feb 28.
citation: Pelkonen S, Koivunen R, Gissler M, Nuojua-Huttunen S, Suikkari AM, Hyden-Granskog C, Martikainen H, Tiitinen A, Hartikainen AL. Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006. Hum Reprod. 2010 Apr;25(4):914-23. doi: 10.1093/humrep/dep477. Epub 2010 Feb 2.
citation: Spangmose AL, Malchau SS, Henningsen AA, Forman JL, Rasmussen S, Loft A, Schmidt L, Pinborg A. Academic performance in adolescents aged 15-16 years born after frozen embryo transfer compared with fresh embryo transfer: a nationwide registry-based cohort study. BJOG. 2019 Jan;126(2):261-269. doi: 10.1111/1471-0528.15484. Epub 2018 Oct 24.
citation: Vuong LN, Ly TT, Nguyen NA, Nguyen LMT, Le XTH, Le TK, Le KTQ, Le TV, Nguyen MHN, Dang VQ, Norman RJ, Mol BW, Ho TM. Development of children born from freeze-only versus fresh embryo transfer: follow-up of a randomized controlled trial. Fertil Steril. 2020 Sep;114(3):558-566. doi: 10.1016/j.fertnstert.2020.04.041. Epub 2020 Jun 16.