title: Two-year development of children conceived by IVM: a prospective controlled single-blinded study.
abstract: Is there a difference in mental development of children conceived by IVM in comparison to IVF or ICSI, independently, at the age of 2 years?
  
  
  
  No differences could be found in mental development of IVM children compared to IVF and IVM children compared to ICSI as well.
  
  
  
  Only few retrospective or non-controlled studies addressed the health of IVM children and did not show a negative impact of the IVM procedure.
  
  
  
  Prospective controlled single-blinded study including 63 pregnancies (21 per IVM, IVF and ICSI groups) with 70 children expected. Examinations of 62 embryos at first trimester screening, of 57 fetuses at 21st week of pregnancy, of 60 children at birth and of 37 children at their second birthday were performed during the study period from January 2009 until October 2016. Bayley score at the age of 2 was the primary outcome parameter. Data of 40 children after spontaneous conception from a previous prospective unrelated study were further used as control at 2 years examination and compared to the pooled ART group (IVM, IVF and ICSI).
  
  
  
  Twenty-one IVM pregnancies achieved in the study period were included. For each of them, the following IVF- and ICSI pregnancies were recruited as controls. Ultrasound examinations during pregnancy, examinations of newborns and of children around their second birthday were done by blinded prenatal specialists, pediatricians and neuropediatricians, respectively.
  
  
  
  Children conceived after IVM did not show differences during embryonic development, at birth nor in their neuropediatric development at the age of 2 compared to their counterparts after IVF and after ICSI (Bayley score 91.3 ± 21.0 for IVM, 96.8 ± 13.2 for IVF and 103.9 ± 13.1 for ICSI) and of the pooled ART group compared to children after spontaneous conception (96.6 ± 16.4 ART and 103.2 ± 9.4 spontaneous conception). When analyzing singleton pregnancies only, again no differences during pregnancy, at birth and at their 2-year evaluation were detected between IVM versus IVF and IVM versus ICSI.
  
  
  
  Due to the small sample size data must be interpreted with caution. To allow a confirmative answer that there are no health risks for children conceived by IVM, large multicenter cohort or registry-based studies are urgently needed.
  
  
  
  The study adds further information to previous uncontrolled or retrospective studies, which were unable to detect risks for the health of IVM children.
  
  
  
  The study was supported by the 'Deutsche Forschungsgemeinschaft' (DFG): STR 387/4-1. G.R. receives royalties from Pearson Assessment Germany (editor fee for Bayley-III). The other authors have no conflicts of interest to declare.
  
  
  
  Not applicable.
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Roesner
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Inselspital Bern, Effinger Strasse 102, 3010 Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: von Wolff
authors.affiliation: Ruprecht-Karls University of Heidelberg, Women's Hospital, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Elsaesser
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Roesner
authors.affiliation: Center for Child and Adolescent Medicine, Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Reuner
authors.affiliation: Center for Child and Adolescent Medicine, Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Pietz
authors.affiliation: Ruprecht-Karls University of Heidelberg, Institute of Medical Biometry and Informatics, Im Neuenheimer Feld 130.3, 69120 Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Department of Gynecological Endocrinology and Fertility Disorders, Ruprecht-Karls University of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Strowitzki
mesh_terms: D002657:Child Development; D004622:Embryo, Mammalian / Q000000981:diagnostic imaging; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects; D047109:Fetal Development; D005333:Fetus / Q000000981:diagnostic imaging; D005858:Germany; D006785:Hospitals, University; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D007231:Infant, Newborn; D008297:Male; D055495:Neurogenesis; D011247:Pregnancy; D016037:Single-Blind Method; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects; D016216:Ultrasonography, Prenatal
keywords: Bayley score; ICSI; IVF; IVM; health of children; mental development