Health of Frozen Transferred Versus Fresh Transferred Children
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Freeze-only Children born from freeze-only group and frozen embryo transfer |
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.
Other: Physical development and General Health
Physical development and General health examination
Other: Developmental Red flags
Developmental Red flags Questionnaires
|
| Fresh Children born from fresh embryo transfer |
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.
Other: Physical development and General Health
Physical development and General health examination
Other: Developmental Red flags
Developmental Red flags Questionnaires
|
Outcome Measures
Primary Outcome Measures
- The average total ASQ-3 score [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 Outcome Measures
- Score of Communication [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
- Score of Gross motor [Up to 66 months after birth]
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
- Score of Fine motor [Up to 66 months after birth]
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
- Score of Problem solving [Up to 66 months after birth]
6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.
- Score of Personal-Social [Up to 66 months after birth]
6 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 sign [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
- Duration of breast-feeding [Up to 24 months after birth]
Duration of breast-feeding
- Infant age at which weaning starts [Up to 24 months after birth]
Infant age at which weaning starts
- Name of diseases that lead to hospital admission [Up to 66 months after birth]
Name of diseases that lead to hospital admission
- Number of hospital admission [Up to 66 months after birth]
Number of hospital admission
- Weight [Through study completion, an average of 1.5 months]
Weight on the examination date
- Height [Through study completion, an average of 1.5 months]
Height on the examination date
Other Outcome Measures
- Gestational age at delivery [At birth]
Gestational age at delivery
- Mode of delivery [At birth]
Vaginal birth or C-section
- Birth weight [At birth]
Weight of baby born
- Length circumference [At birth]
Head circumference after birth Head circumference after birth Head circumference after birth Length circumference after birth
- Head circumference [At birth]
Head circumference after birth
- Rate of congenital anomalies [At birth]
Any congenital anomalies detected in baby born
- Length of neonatal intensive care unit (NICU) admission [Up to 28 days after birth]
Number of admission days to NICU
- Rate of Respiratory distress syndrome [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
- Rate of Periventricular haemorrhage [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.
- Rate of Necrotizing enterocolitis [Up to 28 days after birth]
Necrotizing enterocolitis (NEC) will be diagnosed according to Bell.
- Rate of Proven sepsis [Up to 28 days after birth]
Proven sepsis, will be diagnosed on the combination of clinical signs and positive blood cultures.
- Rate of Composite of poor perinatal outcomes [Up to 28 days after birth]
Composite of poor perinatal outcomes, defined as intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.
- The rate of long-term illness and chronic conditions [Up to 66 months after birth]
Any long-term illness and chronic condition appears in a child
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mỹ Đức Hospital | Ho Chi Minh City | Tan Binh | Vietnam |
Sponsors and Collaborators
- Mỹ Đức Hospital
Investigators
- Principal Investigator: Lan N Vuong, MD, PhD, Mỹ Đức Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- 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. Erratum in: N Engl J Med. 2016 Nov 17;375(20):2010.
- Pelkonen S, Koivunen R, Gissler M, Nuojua-Huttunen S, Suikkari AM, Hydén-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.
- 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. Erratum in: N Engl J Med. 2021 Nov 4;385(19):1824.
- 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.
- 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.
- 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.
- CS/BVMĐ/19/08