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\begin{document}

\title{Reference ranges of AMH in early pregnancy: the Generation R Study, a
population-based prospective cohort study}



\author[1]{Ramon Dykgraaf}%
\author[1]{Joop Laven}%
\author[2]{Sarah Timmermans}%
\author[1]{Maria Adank}%
\author[1]{Sjoerd van den Berg}%
\author[1]{Brigitta van de Lang - Born}%
\author[3]{T I M Korevaar}%
\author[4]{Ajay Kumar}%
\author[4]{Bhanu Kalra}%
\author[4]{Gopal Savjani}%
\author[5]{Eric Steegers}%
\author[1]{Yvonne Louwers}%
\affil[1]{Erasmus Medical Center}%
\affil[2]{Erasmus Medical Centre}%
\affil[3]{The Generation R Study Group, Erasmus Medical Center,Netherlands}%
\affil[4]{Ansh Labs LLC}%
\affil[5]{Erasmus University Medical Centre}%


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  \date{June 04, 2024}


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\begin{abstract}
Objective: The 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. Design: The
Generation R Study is an ongoing population-based prospective cohort
study from early pregnancy onwards. Setting: Rotterdam, the Netherlands,
out of hospital setting. Population: In 5806 women serum AMH levels were
determined in early pregnancy (median 13.5 weeks; 95\% range 10.5-17.2).
Methods: The model-based AMH reference ranges for maternal age and
gestational age were created using GAMLSS. Associations between AMH and
several first trimester biomarkers were analyzed using multivariate
linear regression analyses. Main outcome measures: AMH levels in early
pregnancy and the association with placental biomarkers, hCG, sFLT, and
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 hCG and sFLT. 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 the first trimester 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. AMH
might be useful in predicting adverse pregnancy outcome due to impaired
placental development. Keywords: Ovarian reserve, placental biomarker,
nomogram, first trimester, human Choriogonadotrophin (hCG), soluble
FMS-Like Tyrosine kinase-1 (sFLT), Placental Growth Factor (PLGF).%
\end{abstract}%



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