Reference ranges of AMH and interaction with placental biomarkers in early pregnancy: the Generation R Study, a population-based prospective cohort study

Objective: The primary objective of this study is to establish maternal reference values of AMH in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is exploring the association between AMH and placental biomarkers.

Design: This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards.

Setting: City of Rotterdam, the Netherlands, out of hospital setting.

Patients: In 5806 women serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5–17.2). 

Intervention(s): None.

Main outcome measures: Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human Chorionic Gonadotrophin (hCG), soluble FMS-Like Tyrosine kinase-1 (sFLT), and Placental Growth Factor (PLGF).

Results: A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels.

Conclusion: In this large study we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT and PLGF suggests a better placental development with a lower vascular resistance in mothers with higher AMH levels. Hence AMH might be useful in predicting adverse pregnancy outcome due to impaired placental development.