Children Born From IVM-CAPA vs IVF or Natural Conception

IVF Clinical Trial

Official title:

Follow-up of Children Born From CAPA-IVM IVF or Natural Conception: a Prospective Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04048486
• Other study ID #: CS/BVMÐ/19/07
• Status: Completed
• Start date: August 7, 2019
• Est. completion date: December 15, 2019

Study information

• Verified date: October 2020
• Source: M? Ð?c Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

CAPA-IVM is a new promising IVM technique involving the use of a new compound to facilitate the oocyte and embryo competence. CAPA-IVM preserved the maintenance of trans-zonal projections and significantly improved maturation rate and blastocyst yield. NGS analysis of 20 good quality CAPA-IVM blastocysts did not reveal increased aneuploidy compared to age-matched routine ICSI patients. The first CAPA-IVM baby was born in 2017 at My Duc Hospital, Vietnam and up to now, there are 33 babies born from this technique. There is no study to investigate the development of babies born from CAPA-IVM.

Description:

Assisted reproductive technologies (ART), such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and in vitro maturation (IVM), are widely used to solve human infertility, and have provided great benefits for millions of couples who have struggled with infertility disorders. The use of ART has been growing persistently and more than 8 million babies worldwide have been born via ART since the first IVF conceived child was born in 1978 (ESHRE monitoring).

During the last two decades, many studies have shown that children born following assisted reproductive techniques (ART) have an increased risk of adverse obstetric, perinatal and short-term follow-up outcomes when compared to naturally conceived (NC) infants (Jackson RA 2004, Helmerhorst et al., 2004; Pinborg et al., 2013; Adams et al., 2015). The etiologies of this association are mainly related to higher proportion of multiple pregnancies due to double embryo transfer option and greater rate of unfavorable comorbidities of infertile women (older age, high BMI, diabetes…). But with the trend toward single embryo transfer in current IVF practice, there are existing evidences supporting that the perinatal risks of singleton gestations following IVF treatment are still higher than those that result from a spontaneous conception (McDonald et al., 2009; Pandey et al., 2012).

Long-term development of children born by ART is also a concerned issue. It is evident that children born as a result of IVF treatment have an excess rate of congenital abnormalities, higher risk of developing metabolic, cardiovascular disorders and subclinical hyperthyroidism in later life (Roger Hart and Robert J. Norman, 2013, part I). Regarding mental health and development outcomes, cerebral palsy and slight neurodevelopmental delay are potential long-term associations with ART (Roger Hart and Robert J. Norman, 2013, part II). However, these adverse outcomes can be explained by obstetric factors (higher rate of prematurity and intrauterine growth restriction) rather than IVF. This leads to the concern about research biases in studies of long-term development of children born by ART where multiple gestations, prematurity, neonatal hospitalization and growth restriction were not well-controlled. Another concern about long-term follow-up studies of IVF children is the limitation of literatures and high-quality clinical trials that investigate the general health outcomes of children born by ART. The majority of valuable data only exist on the short-term outcome of infants born as a result of IVF treatment (Kalra and Barnhart, 2011) even though it is possible that some suspected disorders might only be identifiable beyond the first year of life (Oliver et al., 2012).

When studying about the long-term development of children following ART, a very important factor need to be considered is the medium of culture. There have been existing theories that proposed the mechanism of how epigenetic environment can up or down-regulate a set of genes which then results in the changes in embryonic growth or even the long-term development of children in later stage of life. Different ART methods may cause possible changes in DNA methylation patterns which in turn affect development of the placenta and fetus. This is the "developmental origins of health and disease hypothesis" (DOHaD) explaning why exposure to an adverse environment (possibly the culture medium) may result in unfavorable development and illnesses profiles in the ART offspring (Barker, 2007).

CAPA-IVM is a new promising IVM technique involving the use of a new compound to facilitate the oocyte and embryo competence. CAPA-IVM preserved the maintenance of trans-zonal projections and significantly improved maturation rate and blastocyst yield. NGS analysis of 20 good quality CAPA-IVM blastocysts did not reveal increased aneuploidy compared to age matched routine ICSI patients. The first CAPA-IVM baby was born in 2017 at My Duc Hospital, Vietnam and up to now, there are 33 babies born from this technique. There is no study to investigate the development of babies born from CAPA-IVM.

The investigators therefore conduct this study to investigate the physical and mental development of babies born from CAPA-IVM, IVF or natural conception.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 15, 2019
• Est. primary completion date: September 30, 2019
• Gender: All
• Age group: 1 Month to 66 Months

Eligibility

Inclusion Criteria:

• Live babies born from CAPA-IVM

• Live babies born from IVF

• Live babies born from natural conception

• Parents agree to participate

Exclusion Criteria:

• Babies born from oocyte donation cycles

• Babies born from sperm donation cycles

• Babies born from PGT cycles

Related Conditions & MeSH terms

• IVF
• IVM

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 (10)

Barker DJ. The origins of the developmental origins theory. J Intern Med. 2007 May;261(5):412-7. Review. — View Citation

Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II--Mental health and development outcomes. Hum Reprod Update. 2013 May-Jun;19(3):244-50. doi: 10.1093/humupd/dmt002. Epub 2013 Feb 28. Review. — View Citation

Hart R, Norman RJ. The longer-term health outcomes for children born as a result of IVF treatment: Part I--General health outcomes. Hum Reprod Update. 2013 May-Jun;19(3):232-43. doi: 10.1093/humupd/dms062. Epub 2013 Feb 28. Review. — View Citation

Helmerhorst FM, Perquin DA, Donker D, Keirse MJ. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ. 2004 Jan 31;328(7434):261. Epub 2004 Jan 23. Review. — View Citation

Kalra SK, Barnhart KT. In vitro fertilization and adverse childhood outcomes: what we know, where we are going, and how we will get there. A glimpse into what lies behind and beckons ahead. Fertil Steril. 2011 May;95(6):1887-9. doi: 10.1016/j.fertnstert.2011.02.044. Epub 2011 Mar 16. Review. — View Citation

McDonald SD, Han Z, Mulla S, Murphy KE, Beyene J, Ohlsson A; Knowledge Synthesis Group. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol. 2009 Oct;146(2):138-48. doi: 10.1016/j.ejogrb.2009.05.035. Epub 2009 Jul 4. Review. — View Citation

Oliver VF, Miles HL, Cutfield WS, Hofman PL, Ludgate JL, Morison IM. Defects in imprinting and genome-wide DNA methylation are not common in the in vitro fertilization population. Fertil Steril. 2012 Jan;97(1):147-53.e7. doi: 10.1016/j.fertnstert.2011.10.027. Epub 2011 Nov 23. — View Citation

Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A. Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Hum Reprod Update. 2012 Sep-Oct;18(5):485-503. doi: 10.1093/humupd/dms018. Epub 2012 May 19. Review. — View Citation

Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Söderström-Anttila V, Nygren KG, Hazekamp J, Bergh C. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update. 2013 Mar-Apr;19(2):87-104. doi: 10.1093/humupd/dms044. Epub 2012 Nov 14. Review. — View Citation

Stephens SM, Arnett DM, Meacham RB. The use of in vitro fertilization in the management of male infertility: what the urologist needs to know. Rev Urol. 2013;15(4):154-60. Review. — 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	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	5-min Apgar score	The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. The five criteria are summarized using words chosen to form a backronym (Appearance, Pulse, Grimace, Activity, Respiration).	At 5 minute after birth
Other	Rate of 5-min Apgar score <7	Rate of Apgar score at 5 minute after birth <7	At 5 minute after birth
Other	Rate of Admission to neonatal intensive care unit	Admission to neonatal intensive care unit of baby	Within 7 days after birth
Other	Length of 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
Primary	The average total ASQ-3 score	ASQ-3 (Ages and Stages Questionares®) has 5 aspects: Communication, Gross motor, Fine motor, Problem solving and Personal-Social; Each aspesct 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.; 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 Fine motor	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 Problem solving	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 Personal-Social	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	The presence of red flag signs by age	For children less than 4 months; Rolling prior to 3 months; Persistent fisting at 3 months; Failure to alert to environmental stimuli; For children from 4 to 6 months; Poor head control; Failure to reach for objects by 5 months; Absent smile; For children from 6 to 12 months; Absent babbling by 6 months; W-sitting at 7 months; Inability to localize sound by 10 months; Persistent mouthing of objects at 12 months; Lack of consonant production by 15 months; For children from 12 to 24 months; Lack of imitation by 16 months; Lack of protodeclarative pointing by 18 months; Hand dominance prior to 18 months; Inability to walk up and down stairs at 24 months; Advanced non-communicative speech (meaningless communication repertoires); Delayed Language Development milestone (50 single words at 24 months)	Up to 24 months 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	Diseases that lead to hospital admission	Diseases that lead to hospital admission	Up to 24 months after birth
Secondary	Number of hospital admission	Number of hospital admission	Up to 24 months after birth
Secondary	Weight	Weight at 3, 6, 12, 18, 24 months and on the examination date	At 3, 6, 12, 18, 24 months and on the examination date
Secondary	Height	Height at 3, 6, 12, 18, 24 months and on the examination date	At 3, 6, 12, 18, 24 months and on the examination date

External Links

•   Adams: A meta-analysis of neonatal health outcomes
•   De Geyter