P-657 Elecys anti-Müllerian hormone thresholds for defining ovarian response categories; comparison of published and novel values in 7,988 treatment naïve women
Authors: Gromski P , Shaw M , Child T , Trew G , Nelson S 
Published: June 2023

Abstract

Study question
Test the accuracy of published and novel AMH thresholds in predicting (low, sub-optimal, optimal and high) ovarian response categories in first treatment cycles.

Summary answer
Published AMH thresholds for poor and excessive ovarian response perform adequately, however, prediction of suboptimal or optimal oocyte yields is difficult reflecting their limited range.

What is known already
AMH is an established predictor of ovarian response, and can identify women at risk of poor (&lt;4 oocytes) or excessive (&gt;15 oocytes) response. With the development of suboptimal (4 to 9 oocytes) and optimal (10 to 14 oocytes) response categories, a series of AMH ranges for the Roche Elcesys AMH assay has been proposed to predict response for all four categories (AMH &lt;6.4pmol/l, 4.9–11.3 pmol/l, 11.3–20.9 pmol/l, and &gt;14.2 pmol/l). To date there has been no internal or external validation of these single centre derived thresholds, and it is unknown whether they are generalisable to other clinic populations.

Study design, size, duration
Observational cohort study from 8 UK clinics, incorporating 7,998 women undertaking their first ovarian stimulation cycle for assisted conception or fertility preservation between 2016 and 2022, with a pre-treatment AMH measured using the Roche Elecsys AMH assay. Both GnRH agonist and antagonist cycles were included, with triggering by either recombinant hCG or GnRH agonist once 3 follicles were ³18mm in size with oocyte retrieval performed 36h later.

Participants/materials, setting, methods
To give equal opportunity to the published and novel thresholds, patients were divided into training (5,330) and testing (2,668) sets. Novel cut-off points for a low, sub-optimal, optimal and high response were derived in the training set. The performance of these novel thresholds and those of published values were then assessed and compared in the testing set by their respective AUC, and precision as defined as the fraction of correct predictions for a certain class.

Main results and the role of chance
Baseline patient characteristics (mean, SD) were 35.1±4.7 years; BMI 25.5±4.4 kg/m2, with a median AMH 15.2 pmol/l (IQR 8, 26) and a median of 11 (IQR 6,16) oocytes retrieved. These baseline characteristics and outcomes were similar after splitting in the training and testing datasets. Baseline AMH and oocytes collected were moderately correlated (r = 0.54, p &lt; 0.001). 465 (5.8%) cycles were cancelled due to not meeting trigger criteria and classed as poor/low responders. The novel thresholds for low oocyte yield (≤10.05 pmol/l) provided similar performance (AUC 0.70 95%CI 0.66-0.74, sensitivity 0.69, specificity 0.74) to the published thresholds (AUC 0.67, 95%CI 0.62-0.72) in the testing population. Similarly, the novel high (15.9pmol/l) threshold (AUC 0.78, 95%CI 0.75-0.81, sensitivity 0.78, specificity 0.64) exhibited similar performance to the published threshold AUC 0.77, 95%CI 0.74,0.81) in the testing population. Deriving novel thresholds for prediction of 4 categories of response (6.7, 12.9, 18.9pmol) was associated with slightly better precision for low, suboptimal and high categories (p &lt; 0.001), with the fraction of correct predictions for a certain category of response for the novel cut-points; 69.0 % low, 11.7% suboptimal, 14.1% optimal and 78.3% high, as compared to 52.0%, 27.8%, 12.9% and 83.8% respectively for the published values.

Limitations, reasons for caution
While designing the ovarian stimulation strategies clinicians were aware of the baseline AMH and targeted a perceived optimal response for cumulative live birth (∼15 oocytes), which may have contributed to the performance of both the established and novel AMH thresholds.

Wider implications of the findings
In a large heterogenous population of women undergoing their first treatment cycle, we confirm the appropriateness of the previously published Elecsys AMH values for prediction of low (&lt;6.4pmol/l) and high (&gt;14.2pmol/l) oocyte yields.

Trial registration number
N/A