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Development of children born from IVM versus IVF: 2-year follow-up of a randomized controlled trial

Lan N. Vuong 1,2,*, Minh H.N. Nguyen 2 , Nghia A. Nguyen 2,3 , Trung T. Ly 4, Van T.T. Tran 4, Nam T. Nguyen 4, Hieu L.T. Hoang 4, Xuyen T.H. Le 4 , Toan D. Pham 2 , Johan E.J. Smitz 5 , Ben W. Mol 6 , Robert J. Norman 7 , and Tuong M. Ho 2,4

Published: 20 May, 2022

Author information

1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
2 HOPE Research Center, My Duc Hospital, Ho Chi Minh City, Vietnam
3 Department of Pediatrics, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
4 IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam
5 Follicle Biology Laboratory, Free University of Brussels (VUB), Brussels, Belgium
6 Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia
7 Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia


Is there any difference in developmental outcomes in children born after capacitation IVM (CAPA IVM) compared with conventional IVF?
Overall development up to 24 months of age was comparable in children born after CAPA IVM compared with IVF.
IVM has been shown to be a feasible alternative to conventional IVF in women with a high antral follicle count (AFC). In addition to live birth rate, childhood development is also a relevant metric to compare between the two approaches to ART and there are currently no data on this.
This study was a follow-up of babies born to women who participated in a randomized controlled trial comparing IVM with a pre-maturation step (CAPA IVM) and IVF. Developmental assessments were performed on 231 children over 24 months of follow-up.
Participants in the randomized controlled trial had an indication for ART and a high AFC (≥24 follicles in both ovaries). They were randomized to undergo one cycle of either IVM (n = 273) or IVF (n = 273). Of these, 96 women and 118 women, respectively, had live births. Seventy-six women (94 children, 79.2%) and 104 women (137 children, 88.1%), respectively, completed Ages & Stages Third Edition Questionnaire assessment (ASQ-3), and underwent evaluation of Developmental Red Flags at 6, 12 and 24 months of age.
Baseline characteristics of participants in the follow-up study between the IVM and IVF groups were comparable. Overall, there were no significant differences in ASQ-3 scores at 6, 12 and 24 months between children born after IVM or IVF. The proportion of children with developmental red flags was low and did not differ between the two groups. Slightly, but significantly, lower ASQ-3 problem solving and personal–social scores in twins from the IVM versus IVF group at 6 months were still within the normal range and had caught up to the IVF group in the 12- and 24-month assessments. The number of children confirmed to have abnormal mental and/or motor development after specialist assessment was four in the IVM group and two in the IVF group (relative risk 2.91, 95% CI 0.54–15.6; P = 0.23).
This study is an open-label follow-up of participants in a randomized controlled trial, and not all original trial subjects took part in the follow-up. The self-selected nature of the follow-up population could have introduced bias, and the sample size may have been insufficient to detect significant between-group differences in developmental outcomes.
Based on the current findings at 2 years of follow-up, there does not appear to be any significant concern about the effects of IVM on childhood development. These data add to the evidence available to physicians when considering different approaches to fertility treatment, but require validation in larger studies.
This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number FWO.106-YS.2017.02. L.N.V. has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; B.W.M. has acted as a paid consultant to Merck, ObsEva and Guerbet and is the recipient of grant money from an NHMRC Investigator Grant; J.E.J.S. reports lecture fees from Ferring Pharmaceuticals, Biomérieux and Besins Female Healthcare, grants from Fund for Research Flanders (FWO) and is co-inventor on granted patents on CAPA-IVM methodology in the USA (US10392601B2) and Europe (EP3234112B1); T.D.P., M.H.N.N., N.A.N., T.T.L., V.T.T.T., N.T.N., H.L.T.H. and X.T.H.L. have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.


in vitro maturation, in vitro fertilization, childh