Antimullerian Hormone, Serum

Specimen Type: Serum
Collection Container: Serum gel
Specimen Volume: 1 mL

Collection Container: Red top

CAUTIONS 

Interference was observed at biotin concentrations above 30 ng/mL. Specimens should not be collected from patients receiving therapy with high biotin doses until at least 12 hours following the last biotin administration.

The following drugs may interfere with this test: Cetrotide (cetrorelix), Ovitrelle, Endometrin (progesterone), and follistatin. Do not use this test to analyze specimens from patients who have received 1 or more of these products within 1 to 2 weeks of testing.

There is not a high-dose hook effect at anti-Mullerian hormone (AMH) concentrations up to 1400 ng/mL.

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may also interfere in this assay. Caution should be used in interpretation of results and the laboratory should be alerted if the result does not correlate with the clinical presentation.

For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination, and other findings.

AMH immunoassays are not standardized, and values obtained with different assay methods or kits may be different and cannot be used interchangeably.

If using as a tumor marker, test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease.

REFERENCE VALUES 

Males
<2 years: 18-283 ng/mL
2-12 years: 8.9-109 ng/mL
>12 years: <13 ng/mL

Females
<3 years: 0.11-4.2 ng/mL
3-6 years: 0.21-4.9 ng/mL
7-11 years: 0.36-5.9 ng/mL
12-14 years: 0.49-6.9 ng/mL
15-19 years: 0.62-7.8 ng/mL
20-24 years: 1.2-12 ng/mL
25-29 years: 0.89-9.9 ng/mL
30-34 years: 0.58-8.1 ng/mL
35-39 years: 0.15-7.5 ng/mL
40-44 years: 0.03-5.5 ng/mL
45-50 years: <2.6 ng/mL
51-55 years: <0.88 ng/mL
>55 years: <0.03 ng/mL

INTERPRETATION 

Menopausal women or women with premature ovarian failure of any cause, including after cancer chemotherapy, have very low anti-Mullerian hormone (AMH) levels.

While the optimal AMH concentrations for predicting response to in vitro fertilization are still being established, it is accepted that AMH concentrations in the perimenopausal to menopausal range indicate minimal to absent ovarian reserve. Depending on patient age, ovarian stimulation is likely to fail in such individuals.

AMH may be used as a surrogate to antral follicle count (AFC) at day 2 to 4 of the menstrual cycle to determine ovarian reserve. Women with an AFC greater than 15 are identified as having high ovarian reserve. In this context, a Roche AMH concentration greater than 1.77 ng/mL at day 2 to 4 of the menstrual cycle identified women with an AFC greater than 15 with 88.3% sensitivity and 68.3% specificity.(1)

Controlled ovarian stimulation (COS) with exogenous gonadotropin is an essential step of in-vitro fertilization protocols. Using the Roche AMH assay, a cut-off of 2.10 ng/mL is correlated with the response categories in women undergoing COS using a gonadotropin-releasing hormone antagonist protocol. A 2.10 ng/mL cutoff provided reliable prediction of hyperresponse to COS.(2) Sensitivity for the detection of hyperresponsive individuals was 81.3%, and the negative predictive value for ruling out hyperresponse was 96.6%. The 2.10 ng/mL cutoff identified 88.9% of individuals with a poor response.(2)

In individuals with polycystic ovarian syndrome, AMH concentrations may be 2- to 5-fold higher than age-appropriate reference range values. Such high levels predict anovulatory and irregular cycles.

In children with intersex conditions, an AMH result above the normal female range is predictive of the presence of testicular tissue, while an undetectable value suggests its absence.

In boys suspected of cryptorchidism, a measurable AMH concentration is predictive of undescended testes, while an undetectable value is highly suggestive of anorchia or functional failure.

Klinefelter syndrome is characterized by accelerated germ cell depletion and occurs in approximately 10% to 12% of men presenting with nonobstructive azoospermia. In these patients, serum AMH concentrations are within the reference interval until puberty, and thereafter, AMH concentrations decline to abnormally low or undetectable levels.

Pubertal delay and congenital hypogonadotropic hypogonadism (HH) share the same clinical manifestation of delayed sexual maturation in prepubertal boys. Levels of gonadotropin and testosterone are very low in prepubertal boys and, therefore, have little clinical significance; thus, AMH measurements are useful in the differential diagnosis of pubertal delay and congenital HH. In individuals with congenital HH, AMH concentrations are abnormally low, while in pubertal delay, AMH concentrations will be within the prepubertal reference interval.

Granulosa cell tumors of the ovary may secrete AMH, inhibin A, and inhibin B. Elevated levels of any of these markers can indicate the presence of such a neoplasm in a woman with an ovarian mass. Levels should fall with successful treatment. Rising levels indicate tumor recurrence or progression.

USEFUL FOR 

Assessing ovarian status, including ovarian reserve and responsiveness, as part of an evaluation for infertility and assisted reproduction protocols

Assessment of menopausal status, including premature ovarian failure

Evaluation of infants with ambiguous genitalia and other intersex conditions

Evaluating testicular function in infants and children

Monitoring individuals with antimullerian hormone-secreting ovarian granulosa cell tumors


CLINICAL INFORMATION 

Antimullerian hormone (AMH), also known as Mullerian-inhibiting substance, is a dimeric glycoprotein hormone belonging to the transforming growth factor-beta family. It is produced by Sertoli cells of the testis in male patients and by ovarian granulosa cells in female patients. Expression during male fetal development prevents the Mullerian ducts from developing into the uterus, resulting in development of the male reproductive tract. In the absence of AMH, the Mullerian ducts and structures develop into the female reproductive tract. AMH serum concentrations are elevated in boys under 2 years old and then progressively decrease until puberty when there is a sharp decline. In female individuals, serum AMH concentrations are very low at birth, peaking after puberty, and decrease progressively thereafter with age, eventually becoming undetectable at menopause.

Because of the gender differences in AMH concentrations, its changes in circulating concentrations with sexual development, and its specificity for Sertoli and granulosa cells, AMH measurement has utility in the assessment of gender, gonadal function, fertility, and as a gonadal tumor marker.

In female individuals, AMH is considered an ovarian reserve marker. It correlates with the primordial follicle pool, has an inverse correlation with chronologic age, predicts ovarian response in assisted reproductive therapy, and has been suggested to be predictive of the timing of the onset of menopause. In contrast to other markers of ovarian reserve that show significant fluctuations during the menstrual cycle, serum AMH concentrations have been shown to be relatively stable. Women with higher concentrations of AMH have a better response to ovarian stimulation and tend to produce more retrievable oocytes than women with low or undetectable AMH. Women at risk of ovarian hyperstimulation syndrome after gonadotropin administration can have significantly elevated AMH concentrations. Polycystic ovarian syndrome can elevate serum AMH concentrations, because it is associated with the presence of large numbers of small follicles.

AMH measurements are commonly used to evaluate testicular presence and function in infants with intersex conditions or ambiguous genitalia and to distinguish between cryptorchidism and anorchia in male infants.

Serum AMH concentrations are increased in some individuals with ovarian granulosa cell tumors, which comprise approximately 10% of ovarian tumors. AMH, along with related tests including inhibin A and B (INHA / Inhibin A, Tumor Marker, Serum; INHB / Inhibin B, Serum; INHAB / Inhibin A and B, Tumor Marker, Serum), estradiol (EEST / Estradiol, Serum), and cancer antigen 125 (CA25 / Cancer Antigen 125 [CA 125], Serum), can be useful for diagnosing and monitoring these individuals.