Pubertal development in children and adolescents born after IVF and spontaneous conception

Hum Reprod. 2008 Dec;23(12):2791-8. doi: 10.1093/humrep/den309. Epub 2008 Aug 9.


Background: Previous studies demonstrated a link between adverse conditions during prenatal life and the development of diseases in adult life. It is still unclear whether IVF conception could permanently affect early prenatal development in humans, with post-natal health consequences. The objective of the present study is to examine pubertal development in 8-18-year-old IVF singletons and controls born from subfertile parents who attended one Dutch fertility clinic were included.

Methods: IVF singletons and controls born from subfertile parents who attended one clinic in the Dutch OMEGA study were included. Pubertal stage by Tanner's classification, age at menarche and menstrual cycle characteristics were studied in the total population (n = 233: 115 IVF-conceived boys and 118 IVF-conceived girls, each with age-matched comparison groups). Bone age and sex hormone levels were examined in two distinct pubertal subpopulations.

Results: Pubertal stage and age at menarche were not significantly different between IVF and control children. In the pubertal subpopulation, a higher bone age-chronological age (BA-CA) ratio and a larger BA-CA difference were observed in IVF-conceived girls compared with controls (1.04 +/- 0.07 versus 1.02 +/- 0.08, P = 0.022; 0.54 +/- 0.82 versus 0.18 +/- 1.00 year, P = 0.021, respectively). Furthermore, dehydroepiandrosterone sulphate (DHEAS) and LH levels were significantly higher in IVF-conceived girls than in control subjects (2.5 versus 1.9 micromol/l, P = 0.017, and 1.5 versus 0.6 U/l, P = 0.031, respectively).

Conclusions: Bone age appeared to be advanced in pubertal IVF-conceived girls, but not in boys, compared with controls. Increased DHEAS and LH concentrations were found among IVF girls.

MeSH terms

  • Adolescent
  • Bone Development / physiology
  • Child
  • Cohort Studies
  • Dehydroepiandrosterone Sulfate / blood
  • Female
  • Fertilization in Vitro*
  • Fertilization*
  • Humans
  • Luteinizing Hormone / blood
  • Male
  • Menarche / physiology
  • Puberty / physiology*
  • Retrospective Studies
  • Sex Factors


  • Dehydroepiandrosterone Sulfate
  • Luteinizing Hormone