Challenges in Measuring AMH in the Clinical Setting

Abstract

Serum anti-Mullerian hormone (AMH) is a widely used marker of functional ovarian reserve in the assessment and treatment of infertility. It is used to determine dosing of gonadotropins used for superovulation prior to in vitro fertilization, as well as to determine the degree of damage to ovarian reserve by cytotoxic treatments such as chemotherapy. AMH is also now used to predict proximity to menopause and potentially provides a sensitive and specific test for polycystic ovarian syndrome. Twenty one different AMH immunoassay platforms/methods are now commercially available. Of those compared, the random-access platforms are the most reliable. However, to date there has not been an agreed common international AMH reference preparation to standardize calibration between the various immunoassays. Recently, a purified human AMH preparation (code 16/190) has been investigated by the World Health Organization as a potential international reference preparation. However, this was only partially successful as commutability between it and serum samples was observed only in some but not all immunoassay methods. Development of a second generation reference preparation with wider commutability is proposed.

Correlations between follicular fluid AMH and IVF/ICSI outcomes among polycystic ovary syndrome women using different controlled hyperstimulation protocols

“…Currently, twenty-one different commercial immunoassays are available to detect AMH levels. Yet, there is no international reference preparation of AMH to standardize calibration between the various immunoassays and harmonize the results [73,74]. Even though a puri ed human AMH preparation (code 16/190) has been investigated by the World Health Organization as a potential international reference preparation, its commutability was unsatisfactory [73,74].…”

“…Yet, there is no international reference preparation of AMH to standardize calibration between the various immunoassays and harmonize the results [73,74]. Even though a puri ed human AMH preparation (code 16/190) has been investigated by the World Health Organization as a potential international reference preparation, its commutability was unsatisfactory [73,74]. One of the reasons for the poor commutability is that the standardized preparation did not include all AMH isoforms [74].…”

Potential pitfalls of reproductive direct-to-consumer testing

“…The measurement of the AMH, which is a key component of nearly all DTC tests currently marketed to evaluate fertility or ovarian reserve, also has significant limitations both in terms of the reliability and validity of currently available AMH assays and its clinical utility in a low-risk population. From a laboratory standpoint, there are currently more than 20 different AMH immunoassay platforms available, with others also in development ( 12 ). Values from different assays are highly correlated but vary with regard to the numeric value, depending on the test used.…”

“…There may also be additional proteolytic cleavages of AMH that may lead to unknown isoforms of AMH that may affect results ( 14 ). Second, interference by the complement system in blood, particularly C1q, has also been shown to interfere in the measurement of AMH in some assays, and premixture with a buffer to reduce the interference may be required ( 12 , 15 ). Finally, AMH tests may also vary in terms of protocol, sample preparation and stability, assay time, and detection system.…”

“…Finally, AMH tests may also vary in terms of protocol, sample preparation and stability, assay time, and detection system. Laboratories seldom determine their own reference range, and there is also no international reference material to calibrate or compare different assays, despite recent attempts by the World Health Organization to generate a reference reagent for AMH ( 12 , 16 , 17 ).…”