Clinical trial NCT04296357: Health of IVF Versus IVM Children (FM-BABIES)
Official title: Follow-up of Children Born From In-vitro Maturation Versus In-vitro Fertilization: Follow-up of a Randomized Controlled Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infertility
IVF
IVM
Keywords: IVF
IVM
ASQ-3
Health of children
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2020-03-05
Enrollment: 231
Sex: ALL
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Live babies born following the IVF and IVM from our FM study (NCT03405701)

Brief summary: The investigators conduct a follow up of our randomized controlled trial (RCT) to investigate the development of children born from In-vitro fertilization (IVF) and In-vitro maturation (IVM), in order to give strong evidence about the safety of IVM in women with high antral follicle count or especially polycystic ovary syndrome (PCOS).

Detailed description: Since the birth of the first baby born from in-vitro maturation (IVM) in 1991, this technique has been considered an alternative solution for treating infertility beside conventional controlled ovarian stimulation for in-vitro fertilization (IVF). Since then, there are already more than 5000 children born from IVM, and that number is on the trend of increasing.

Regarding technique, immature oocytes (germinal vesicle - GV) were aspirated from secondary follicles sized from 2-10mm, under follicle-stimulating hormone (FSH) priming or no ovarian stimulation at all. Afterward, the maturation process was undertaken in an artificial medium, out of a living body. This technique, by reducing the usage of external hormones, is highly effective in minimizing the risk of ovarian hyperstimulation syndrome (OHSS) in women with high antral follicle count, especially polycystic ovarian syndrome, with a rate of OHSS recorded as low as 0 percent. Alongside that, the pregnancy rate, as well as the live birth rate of IVM, when proceeded well, is not lower than conventional IVF. Until now, there is only one randomized controlled trial comparing these two techniques directly.

Due to differences in the process of culturing between IVM and IVF, primarily the maturation is undertaken in an artificial medium, the health of children born from IVM received many interests. Numerous studies have been conducted to compare the development of children born from IVM and IVF. Neonatal outcomes of children born from IVM and IVF are considerably comparable. And the development of children born from these two techniques is not significantly different. All the information, as mentioned above, was not from randomized controlled trials but retrospective or prospective cohort studies. Thus, we conduct a follow up of our RCT to investigate the development of children born from IVM and IVM, to give strong evidence about the safety of IVM in women with high antral follicle count or especially PCOS.

Eligibility criteria: Inclusion Criteria:

* All live babies born following the In-vitro Maturation and In-vitro fertilization from our FM study.
* Parents agree to participate in the study.

Exclusion Criteria:

* Babies died under or at 24 months

Primary outcomes:
measure: The average total ASQ-3 score
timeFrame: Up to 24 months after birth
Secondary outcomes:
measure: Score of Communication
timeFrame: Up to 24 months after birth
measure: Score of Gross motor
timeFrame: Up to 24 months after birth
measure: Score of Fine motor
timeFrame: Up to 24 months after birth
measure: Score of Problem solving
timeFrame: Up to 24 months after birth
measure: Score of Personal-Social
timeFrame: Up to 24 months after birth
measure: The rate of children who have at least one red flag sign
timeFrame: From 6 months 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: Name of 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: Up to 24 months after birth
measure: Height
timeFrame: Up to 24 months after birth
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 24 months after birth
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Mỹ Đức Hospital
Study officials:
affiliation: Mỹ Đức Hospital
name: Lan N Vuong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vuong LN, Ho VNA, Ho TM, Dang VQ, Phung TH, Giang NH, Le AH, Pham TD, Wang R, Norman RJ, Smitz J, Gilchrist RB, Mol BW. Effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilisation in women with high antral follicle count: study protocol for a randomised controlled trial. BMJ Open. 2018 Dec 9;8(12):e023413. doi: 10.1136/bmjopen-2018-023413.
citation: Cha KY, Koo JJ, Ko JJ, Choi DH, Han SY, Yoon TK. Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program. Fertil Steril. 1991 Jan;55(1):109-13. doi: 10.1016/s0015-0282(16)54068-0.
citation: Das M, Son WY, Buckett W, Tulandi T, Holzer H. In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome. Reprod Biomed Online. 2014 Nov;29(5):545-51. doi: 10.1016/j.rbmo.2014.07.019. Epub 2014 Aug 12.
citation: Gremeau AS, Andreadis N, Fatum M, Craig J, Turner K, McVeigh E, Child T. In vitro maturation or in vitro fertilization for women with polycystic ovaries? A case-control study of 194 treatment cycles. Fertil Steril. 2012 Aug;98(2):355-60. doi: 10.1016/j.fertnstert.2012.04.046. Epub 2012 May 31.
citation: Ho VNA, Braam SC, Pham TD, Mol BW, Vuong LN. The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count. Hum Reprod. 2019 Jun 4;34(6):1055-1064. doi: 10.1093/humrep/dez060.
citation: Mostinckx L, Segers I, Belva F, Buyl R, Santos-Ribeiro S, Blockeel C, Smitz J, Anckaert E, Tournaye H, De Vos M. Obstetric and neonatal outcome of ART in patients with polycystic ovary syndrome: IVM of oocytes versus controlled ovarian stimulation. Hum Reprod. 2019 Aug 1;34(8):1595-1607. doi: 10.1093/humrep/dez086.
citation: Roesner S, von Wolff M, Elsaesser M, Roesner K, Reuner G, Pietz J, Bruckner T, Strowitzki T. Two-year development of children conceived by IVM: a prospective controlled single-blinded study. Hum Reprod. 2017 Jun 1;32(6):1341-1350. doi: 10.1093/humrep/dex068.
citation: Sauerbrun-Cutler MT, Vega M, Keltz M, McGovern PG. In vitro maturation and its role in clinical assisted reproductive technology. Obstet Gynecol Surv. 2015 Jan;70(1):45-57. doi: 10.1097/OGX.0000000000000150.
citation: Shu-Chi M, Jiann-Loung H, Yu-Hung L, Tseng-Chen S, Ming-I L, Tsu-Fuh Y. Growth and development of children conceived by in-vitro maturation of human oocytes. Early Hum Dev. 2006 Oct;82(10):677-82. doi: 10.1016/j.earlhumdev.2006.01.012. Epub 2006 May 11.
citation: Yu EJ, Yoon TK, Lee WS, Park EA, Heo JY, Ko YK, Kim J. Obstetrical, neonatal, and long-term outcomes of children conceived from in vitro matured oocytes. Fertil Steril. 2019 Oct;112(4):691-699. doi: 10.1016/j.fertnstert.2019.05.034. Epub 2019 Jul 29.
citation: Vuong LN, Nguyen MHN, Nguyen NA, Ly TT, Tran VTT, Nguyen NT, Hoang HLT, Le XTH, Pham TD, Smitz JEJ, Mol BW, Norman RJ, Ho TM. Development of children born from IVM versus IVF: 2-year follow-up of a randomized controlled trial. Hum Reprod. 2022 Jul 30;37(8):1871-1879. doi: 10.1093/humrep/deac115.