About the Anti-Müllerian Hormone (AMH) Uses in the Clinical Practice.

of evaluation of the OR, which is AFC performed by sonography. A possibility of a more objective way to access the OR is an important tool for the clinical practice. To date, the AMH is considered the earliest and most sensitive marker of OR, especially in assisted reproductive technology (ART) scenarios. 15 The main strength of AMH testing is to predict inadequate ovarian response, either poor ovarian response (POR) or excessive ovarian response. For instance, sensitivities range between 44 and 97%, and specificities range between 41 and 100%14 for a POR, if AMH levels are low (0.1–1.66 ng/mL).16 Anti-Müllerian hormone levels > 1.0 ng/mL but < 3.5 ng/mL, if the patient is in the appropriate age, are consistent with normal ovarian response to ovarian stimulation. 15 However, in cases of natural fertility, the AMH seems to have a more limited predictability. 16,17 Assessing OR in the general population might add extra costs to the health system. 17 However, showing an information about one ’s OR might lead individuals to modify life choices in terms of fertility decisions. 18–20 The assessment of AMH levels is useful and reliable, but more studies shall further endorse the dissem- ination of its use. Currently, the main indications for OR testing are applied in women undergoing infertility evaluation/treatment (in- cluding history of premature ovarian insuf ficiency, oocyte donation, fertility preservation due to social or personal issues or due to gonadotoxic treatments), prior to ovarian surgery in women in reproductive age, in polycystic ovary syndrome (PCOS), in perimenopause, and in women with mutation of BRCA-1o r FMR1 premutation (Fragile X syn- drome). In addition, OR assessment is useful in the individu- alization of ART ovarian stimulation. 15 The second approved use of AMH assessment is the predic - tion of ovarian response in ART treatment.14 To date, it is well established that both AMH and AFC are strong predictors of ovarian response in in vitro fertilization (IVF).21 The measure- ment of AMH is useful in the prediction of poor response and cycle cancellation due to inadequate ovarian response, as well as in hyper-response and ovarian hyperstimulation syndrome, in COS. 14 The AMH was shown to be a better marker in predicting ovarian response to COS than the age FSH, estradiol, and inhibin B.14 Recently, a study with a new human recombi- nant FSH (follitropin delta, rFSH), found that the AMH might be a tool in predicting an adequate ovarian response in COS, with lower doses of rFSH with similar number of blastocysts. 22 However, another study, using a different AMH more studies are necessary to assess thosefindings in different platforms. It seems that AFC and AMH may have complementary roles in the preassessment of infertile women. 23 An important issue for the clinical practice is related to technical aspects of the laboratorial assessment of the AMH serum levels. Several assays to detect the serum levels of the AMH were developed, but most of them are based on a sandwich type of immunometric or enzyme-linked immuno- sorbent assay (ELISA) tests with two monoclonal antibodies (ABs) that were both raised against recombinant human AMH (rhAMH). The ABs are able to recognize epitopes in the proregion (F2B/7A) and/or in the mature regions (F2B/ 12H). 24 However, there have been studies questioning the stability of AMH upon storage, sample handling and sample diluting, due to a complement system interference, that could falsely alter the serum titles.25 This problem has motivated the biggest manufacturer of AMH tests to withdraw its tests from the world market in 2013, but a few assays remained available. In a short period of time, the manufacturers addressed the problem by adding the ABs in solution, instead of a in solid phase and new automated platforms were created. The com- plement interference issue seemed to be adequately solved. 23 Although the implementation of automated platforms must be considered an advance, an international standard developed in accordance with the International Federation of Clinical Chem- istry is still needed because, the variation amongst platforms can interfere in the clinical interpretation. 23 Another issue for the diagnostic use of AMH is that its levels might be in fluenced by speci fic biological, reproduc - tive or environmental conditions. The serum levels of AMH tend to be decreased in several clinical situations: low levels of vitamin D, 26 use of oral contraceptive pills or GnRH agonists, endometriosis, endometriomas, history of ovarian surgery, smoking habit, mutations and permutation in the BRCA-1 and in the FMR1 genes, respectively. On the other hand, PCOS, granulosa cells tumors, and DSDs are associated with remarkable increases in the level of AMH. 23 All these situations must be considered when AMH tests are used. In conclusion, the assessment of AMH may be useful in several clinical situations, especially to evaluate the OR and to help to predict ovarian response in IVF cycles. However, an international standardization of the measuring methods is still necessary. Although an exciting amount of information is contributing to reveal its functions, the physiology of the AMH is not completely understood, and the elucidation of key steps of its physiological roles has the potential to increase its utility in the clinical practice.

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