Biomarkers of ovarian reserve in childhood and adolescence: A systematic review

Abstract

Introduction: Certain medical disorders as well as their management may affect gonadal function. Recent advances in the management of these conditions accompanied by the availability and success of methods of fertility preservation has highlighted the need for assessment of ovarian reserve in childhood and adolescence. Serum anti-Mullerian hormone (AMH) and antral follicle count are well established markers of ovarian reserve and serum inhibin has also been used. However, literature on reference ranges for ovarian reserve markers in this age-group is relatively scarce. Thus, our aim was to evaluate published data to estimate reference values of ovarian reserve makers in childhood and adolescence.

Material and methods: We performed a systematic review of the literature reporting ovarian reserve markers in childhood and adolescence. We included only those studies examining markers of ovarian reserve in the normal healthy population between the ages of 0 and 19 years. PROSPERO registration: CRD42018119064.

Results: Serum AMH emerged as the most common biomarker assessed. Serum AMH was detectable at birth and, after a transient increase in infancy, increased steadily in childhood. Following a slight decrease at puberty, levels were constant throughout adolescence with a peak in adolescence or early adulthood. The mean serum AMH values during infancy, childhood and adolescence were 10.55, 22.32 and 31.84 pmol/L, respectively. The corresponding median values were 9.85, 24.49 and 26.32 pmol/L. It was not possible to construct age-specific reference intervals because of methodological heterogeneity, variations in the assay used to measure AMH and differing interval width for age used in included studies. Serum inhibin showed an increase from childhood to adolescence, with median serum inhibin values of 53.86 pg/mL in adolescence. Antral follicle count showed a significant positive correlation with serum AMH and a median value of 30.52 in adolescence.

Conclusions: We summarize the trends and levels of biomarkers of ovarian reserve from birth until young adulthood. Peak levels of serum AMH are reported in adolescence or early adulthood. We have reported median/mean values for serum AMH in different age-groups based on data pooled from several studies, which may be used as a reference when evaluating ovarian reserve in childhood and adolescence especially when considering fertility preservation.

Keywords: adolescence; anti-Mullerian hormone; antral follicle count; childhood; ovarian reserve.