Health of Frozen Transferred Versus Fresh Transferred Children

Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04099784
• Other study ID #: CS/BVMÐ/19/08
• Status: Completed
• Start date: September 1, 2019
• Est. completion date: November 20, 2019

Study information

• Verified date: November 2019
• Source: M? Ð?c Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: November 20, 2019
• Est. primary completion date: November 15, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Month to 66 Months

Eligibility

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.

Related Conditions & MeSH terms

• Infertility
• IVF

Intervention

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.
• Physical development and General Health
Physical development and General health examination
• Developmental Red flags
Developmental Red flags Questionnaires

Locations

Country	Name	City	State
Vietnam	M? Ð?c Hospital	Ho Chi Minh City	Tan Binh

Sponsors (1)

Lead Sponsor	Collaborator
M? Ð?c Hospital

Country where clinical trial is conducted

Vietnam, 

References & Publications (6)

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. — View Citation

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gestational age at delivery	Gestational age at delivery	At birth
Other	Mode of delivery	Vaginal birth or C-section	At birth
Other	Birth weight	Weight of baby born	At birth
Other	Length circumference	Head circumference after birth Head circumference after birth Head circumference after birth Length circumference after birth	At birth
Other	Head circumference	Head circumference after birth	At birth
Other	Rate of congenital anomalies	Any congenital anomalies detected in baby born	At birth
Other	Length of neonatal intensive care unit (NICU) admission	Number of admission days to NICU	Up to 28 days after birth
Other	Rate of Respiratory distress syndrome	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	Up to 28 days after birth
Other	Rate of Periventricular haemorrhage	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.	Up to 28 days after birth
Other	Rate of Necrotizing enterocolitis	Necrotizing enterocolitis (NEC) will be diagnosed according to Bell.	Up to 28 days after birth
Other	Rate of Proven sepsis	Proven sepsis, will be diagnosed on the combination of clinical signs and positive blood cultures.	Up to 28 days after birth
Other	Rate of Composite of poor perinatal outcomes	Composite of poor perinatal outcomes, defined as intraventricular haemorrhage, respiratory distress syndrome, necrotizing enterocolitis or neonatal sepsis.	Up to 28 days after birth
Other	The rate of long-term illness and chronic conditions	Any long-term illness and chronic condition appears in a child	Up to 66 months after birth
Primary	The average total ASQ-3 score	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.	Up to 66 months after birth
Secondary	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
Secondary	Score of Gross motor	6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.	Up to 66 months after birth
Secondary	Score of Fine motor	6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.	Up to 66 months after birth
Secondary	Score of Problem solving	6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.	Up to 66 months after birth
Secondary	Score of Personal-Social	6 questions, if the answer is Yes, score = 10, Sometimes = 5 and Not yet = 0.	Up to 66 months after birth
Secondary	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 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	From 2 to 5.5 years after birth
Secondary	Duration of breast-feeding	Duration of breast-feeding	Up to 24 months after birth
Secondary	Infant age at which weaning starts	Infant age at which weaning starts	Up to 24 months after birth
Secondary	Name of diseases that lead to hospital admission	Name of diseases that lead to hospital admission	Up to 66 months after birth
Secondary	Number of hospital admission	Number of hospital admission	Up to 66 months after birth
Secondary	Weight	Weight on the examination date	Through study completion, an average of 1.5 months
Secondary	Height	Height on the examination date	Through study completion, an average of 1.5 months