Health of IVF Versus IVM Children (FM-BABIES)

Infertility Clinical Trial

— FM-BABIES  

Official title:

Follow-up of Children Born From In-vitro Maturation Versus In-vitro Fertilization: Follow-up of a Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04296357
• Other study ID #: CS/BVMÐ/20/05
• Status: Completed
• Start date: March 1, 2020
• Est. completion date: January 5, 2022

Study information

• Verified date: February 2022
• Source: M? Ð?c Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 231
• Est. completion date: January 5, 2022
• Est. primary completion date: January 5, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 24 Months

Eligibility

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

Related Conditions & MeSH terms

• Infertility
• IVF
• IVM

Intervention

Diagnostic Test:
• 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

Diagnostic Test:
• Developmental Red flags
Developmental Red flags Questionnaires

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
M? Ð?c Hospital

Country where clinical trial is conducted

Vietnam, 

References & Publications (10)

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 — View 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 — View 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.fe — View 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. — View 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 Re — View 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/dex0 — View 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. Review. — View 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. Epub 2006 May 11. — View 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. — View 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. — 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 24 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 24 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 24 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 24 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 24 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 24 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 24 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 For children at 6 months: he or she; Do not know to flip before 3 months; Still holding hands constantly at 3 months; Do not pay attention to the stimulation from the environment; Poor head control; No access to objects/ toys before 5 months; No laughter; For children at 12 months: he or she; No babbling before 6 months; Unable to sit down in a W-style at 7 months; Unable to identify audio source before 10 months; Still holding things in your mouth often for 12 months; For children at 24 months: he or she; Do not speak consonants before 15 months; Do not know imitate before 16 months; Do not know to point fingers to attract attention about objects that he or she cares about; Show right-handedness before 18 months; Unable to ascend and descend stairs at 24 months; Repeat the machinery of others' words; Not reached the single 50 marks yet by 24 months	From 6 months 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	Name of diseases that lead to hospital admission	Name of 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 on the examination date	Up to 24 months after birth
Secondary	Height	Height on the examination date	Up to 24 months after birth