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

R H M Dykgraaf; S Schalekamp-Timmermans; M C Adank; S A A van den Berg; B M N van de Lang-Born; T I M Korevaar; A Kumar; B Kalra; G V Savjani; E A P Steegers; Y V Louwers; J S E Laven

doi:10.1530/EC-22-0320

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

Endocr Connect. 2023 Feb 14;12(3):e220320. doi: 10.1530/EC-22-0320. Print 2023 Mar 1.

Authors

R H M Dykgraaf¹, S Schalekamp-Timmermans^{2

3}, M C Adank^{2

3}, S A A van den Berg^{4

5}, B M N van de Lang-Born^{4

5}, T I M Korevaar⁵, A Kumar⁶, B Kalra⁶, G V Savjani⁶, E A P Steegers^{1

2}, Y V Louwers¹, J S E Laven¹

Affiliations

¹ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
² Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
³ Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁴ Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁵ Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
⁶ Ansh Labs, Webster, Texas, USA.

Abstract

Objective: The primary objective of this study is to establish maternal reference values of anti-Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore 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 lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.

Keywords: early pregnancy; human chorionic gonadotrophin (hCG); nomogram; ovarian reserve; placental biomarker; placental growth factor (PLGF); soluble fms-like tyrosine kinase-1 (sFLT),.