Accepted for/Published in: JMIR Research Protocols
Date Submitted: May 9, 2023
Open Peer Review Period: May 9, 2023 - Jul 4, 2023
Date Accepted: Nov 23, 2023
(closed for review but you can still tweet)
Validation of Anti-Müllerian Hormone Cut-Off for Polycystic Ovarian Morphology (PCOM) in the Diagnosis of Polycystic Ovary Syndrome (PCOS) in the HARMONIA Study: Protocol for a Prospective, Non-Interventional Study
ABSTRACT
Background:
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women and is diagnosed using the Rotterdam criteria, including diagnosis of polycystic ovarian morphology (PCOM) by transvaginal ultrasound (TVUS). Due to high cost, availability, and the impact of operator and ultrasound equipment on reliability of antral follicle count (AFC) by TVUS, an unmet need exists for a diagnostic test to determine PCOM without TVUS. A strong positive correlation between elevated anti-Müllerian hormone (AMH) levels and AFCs has been demonstrated in women with PCOS. The retrospective APHRODITE study derived and validated an AMH cut-off of 3.2 ng/mL for the Elecsys® AMH Plus/Elecsys AMH assays to diagnose PCOM in patients with PCOS.
Objective:
This study aims to further validate the AMH cut-off for PCOM determination that was derived and validated in the APHRODITE study.
Methods:
This large, prospective, multi-center, population-based, non-interventional study will evaluate the previously established AMH cut-off for determination of PCOM during diagnosis of PCOS using the Elecsys AMH Plus immunoassay (Roche Diagnostics International Ltd) in an independent population. Participants were women born July 1985–Dec 1987 in Northern Finland; the study partially links to the Northern Finland Birth Cohort 1986. Enrolled women were assessed for current PCOS status and divided by phenotype if positive. Each participant had one study visit to collect serum samples, record clinical data, and underwent a gynecological examination including TVUS. All data were collected by highly trained midwives/specialized gynecologists. Sensitivity, specificity, and agreement measures were used to validate the previously determined cut-off in the whole population and in subpopulations based on phenotype and relevant demographic/clinical factors. The minimum target sample size was ~1800 women, including ~10% with PCOS.
Results:
At the time of manuscript submission, participant recruitment had concluded and 1803 women were enrolled into the study. Data collection is complete and biostatistical analysis is planned for 2023.
Conclusions:
To limit variability, there were few TVUS operators and only two TVUS machines of the same type. Selection bias was limited as this was a population-based study and participants were not seeking treatment for PCOS symptoms. Validating the AMH cut-off in a large, population-based study will provide further evidence on utility of the Elecsys AMH Plus/Elecsys AMH assays in PCOM diagnosis, as an alternative to TVUS. Measuring AMH for PCOM diagnosis could reduce delayed/missed diagnoses due to specialist, operator-dependent TVUS examinations. Clinical Trial: NCT05527353
Citation
Request queued. Please wait while the file is being generated. It may take some time.
Copyright
© The authors. All rights reserved. This is a privileged document currently under peer-review/community review (or an accepted/rejected manuscript). Authors have provided JMIR Publications with an exclusive license to publish this preprint on it's website for review and ahead-of-print citation purposes only. While the final peer-reviewed paper may be licensed under a cc-by license on publication, at this stage authors and publisher expressively prohibit redistribution of this draft paper other than for review purposes.