The Clinical Value and Interpretation of Anti-Müllerian Hormone in Women With Cancer

Abstract

Cancer treatments can be damaging to the ovary, with implications for future fertility and reproductive lifespan. There is therefore a need for a biomarker than can usefully provide an assessment of the ovary and its potential for long-term function after cancer treatment, and ideally also be of value pre-treatment, for the prediction of post-treatment function. In this review we assess the value of anti-Müllerian hormone (AMH) in this context. Measurement of AMH at the time of cancer diagnosis has been shown to be predictive of whether or not there will remain some ovarian function post-treatment in women with breast cancer, in conjunction with age. AMH may however be reduced at the time of diagnosis in some conditions, including lymphoma, but probably not in women with breast cancer unless they are carriers of BRCA1 mutations. Following chemotherapy, AMH is often much reduced compared to pretreatment levels, with recovery dependent on the chemotherapy regimen administered, the woman's age, and her pretreatment AMH. Recent data show there may be a long duration of relative stability of AMH levels over 10 to 15 years prior to decline rather than a rapid decline for many young women after cancer. Post-treatment AMH may have utility in determining that ovarian function will not recover, contributing to assessment of the need for ovarian suppression in women with hormonesensitive breast cancer. AMH measurement provides an index of treatment gonadotoxicity, allowing comparison of different treatment regimens, although extrapolation to effects on fertility requires caution, and there are very limited data regarding the use of AMH to estimate time to menopause in the post-cancer setting.

Does the Anti-Mullerian Hormone Decline Rate Improve the Prediction of Age at Menopause?

“…The majority of models assumed a steady rate of follicular atresia over time, resulting in a comparable decreasing pattern for each woman ( 17 , 27 ). Although the level of AMH is primarily determined by the initial primordial follicle pool size ( 27 ), its level may be influenced by biological characteristics, reproductive factors, or environmental/lifestyle factors ( 9 – 14 , 28 ), leading to a complex pattern of AMH decline.…”

“…Besides, there is uncertainty regarding the added value of repeated AMH measurements for improving the prediction of age at menopause. It is well documented that the ovarian reserve status is not constant throughout one’s life and is influenced by different intrinsic and extrinsic factors ( 9 – 14 ); therefore, it is hypothesized that serial AMH measurements may indirectly estimate these changes.…”

Cryopreservation of paediatric ovarian tissue with an updated version of the Edinburgh criteria for appropriate patient selection

“…However, there is some controversy about measurement of AMH levels, because they do not necessarily predict the chance of future live births (Iwase et al 2016); physiologically, the peak of AMH is after adulthood (24.5 years old in 3,260 measurements) (Kelsey et al 2011). Therefore, the measurement of AMH levels for assessment of ovarian reserve in children and adolescents has limitations, although it may allow some assessment of ovarian reserve in prepubertal girls, as well as young adults, after chemotherapy (Miyoshi et al 2016, Anderson and Su 2020, Lotz et al 2020. Furthermore, AMH levels are initially low immediately posttreatment, and they then take a few years (1-3 years) to recover (Anderson and Su 2020).…”

“…Therefore, the measurement of AMH levels for assessment of ovarian reserve in children and adolescents has limitations, although it may allow some assessment of ovarian reserve in prepubertal girls, as well as young adults, after chemotherapy (Miyoshi et al 2016, Anderson and Su 2020, Lotz et al 2020. Furthermore, AMH levels are initially low immediately posttreatment, and they then take a few years (1-3 years) to recover (Anderson and Su 2020). In the present the timing of AMH measurement was initially set at a year after treatment, because the precise timing of measurement remains undetermined.…”

Disparities in Female Pediatric, Adolescent and Young Adult Oncofertility: A Needs Assessment

“…Standardization of current assays has resolved the latter concern. AMH provides an index of treatment gonadotoxicity, and allows comparison of different treatment regimens, but the data cannot be extrapolated to fertility, and data regarding the use of AMH to estimate time to menopause after cancer is limited [53]. Therefore, although AMH correlates with AFC and reliably predicts response to ART, AMH does not reliably predict live birth rates [48,54].…”