Clinical trial NCT04048486: Children Born From IVM-CAPA vs IVF or Natural Conception
Official title: Follow-up of Children Born From CAPA-IVM IVF or Natural Conception: a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: IVM
IVF
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2019-08-07
Enrollment: 66
Sex: ALL
Minimum age (years): 1
Maximum age (years): 66
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Live babies born from CAPA-IVM, IVF or natural conception

Brief 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.

Detailed 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.

Eligibility criteria: 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

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 presence of red flag signs by age
timeFrame: Up to 24 months 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: Diseases that lead to hospital admission
timeFrame: Up to 24 months after birth
measure: Number of hospital admission
timeFrame: Up to 24 months after birth
measure: Weight
timeFrame: At 3, 6, 12, 18, 24 months and on the examination date
measure: Height
timeFrame: At 3, 6, 12, 18, 24 months and on the examination date
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: 5-min Apgar score
timeFrame: At 5 minute after birth
measure: Rate of 5-min Apgar score <7
timeFrame: At 5 minute after birth
measure: Rate of Admission to neonatal intensive care unit
timeFrame: Within 7 days after birth
measure: Length of 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
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: 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.
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. doi: 10.1136/bmj.37957.560278.EE. Epub 2004 Jan 23.
citation: Pinborg A, Wennerholm UB, Romundstad LB, Loft A, Aittomaki K, Soderstrom-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.
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.
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.
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.
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.
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.
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.
citation: Barker DJ. The origins of the developmental origins theory. J Intern Med. 2007 May;261(5):412-7. doi: 10.1111/j.1365-2796.2007.01809.x.