Anti-Mullerian hormone (AMH, MIS)

Why this test?

For the differential diagnosis of the causes of cryptorchidism: delayed descent of the testicles or anarchy (as well as persistent Müllerian duct syndrome).

To diagnose the violation of gender differentiation and identify its cause.

For the diagnosis of non-obstructive azoospermia as a cause of male infertility.

To assess the functional reserve of the ovaries in order to plan pregnancy and predict the onset of menopause.

To identify groups of patients with insufficient or excessive response to ovulation stimulation during in vitro fertilization programs and correction of female infertility treatment.

For the diagnosis of granulosa cell tumors of the ovaries and testicles and control of their treatment, as well as for the diagnosis of Sertoli cell neoplasms.

In what cases is it prescribed?

With cryptorchidism - the absence of testicles in the scrotum in a newborn boy.

If the newborn has external genital structures that have both female and male characteristics.

In the differential diagnosis of obstructive and non-obstructive azoospermia.

When predicting the age of onset of infertility and menopause.

When selecting groups of patients:
a) with an insufficient response to ovulation stimulation and an unfavorable prognosis for the onset of pregnancy; 
b) with an excessive response to ovulation stimulation and an unfavorable prognosis for the development of ovarian hyperstimulation syndrome.

With symptoms of hyperestrogenism in women (uterine bleeding) and in men (gynecomastia).

Test information

Anti-Mullerian hormone (AMG) is normally synthesized only by the Sertoli cells of the testicles (both during embryonic development and after birth) and granulosa cells of the ovaries (only after birth). It got its name due to the unique property of preventing the development of female reproductive structures from the Muller duct. Although the sex of the child is determined at the time of conception, by the 6th week of pregnancy the fetus has undifferentiated gonads and the rudiments of internal genital structures of both sexes: the mesonephrotic duct (Wolff) and the paramesonephrotic duct (Müller). At first, the fetus develops according to the female type.

At the same time, the Müller duct stimulates the development of the uterus, fallopian tubes and the upper part of the vagina, and the cells of the Wolff duct are destroyed. Conversely, in the presence of suppressive factors, the Müllerian duct of Wolff is subject to destruction and gives rise to the epididymis, vas deferens and seminal vesicles - thus, the development of the reproductive system takes place according to the male type. One of these factors, as a result of which the anatomical male sex of the child is formed, is anti-Mullerian hormone. It is produced by the Sertoli cells of the testis from about the 7th week of embryonic development. Its main function is to stop the formation of female genital structures from the Mullerian duct. If a genetically male fetus has mutations in the anti-Müllerian hormone gene or mutations in the gene of its receptor, the development of the Müllerian duct continues and, along with internal male genital structures, female genital structures (uterus, fallopian tubes, or cervix) are formed. At the same time, the child has normally developed testicles, internal male genital structures (epididymis, vas deferens and seminal vesicles) and external male genital organs, the sex at birth is defined as male and it is not possible to suspect a developmental abnormality.

Another important function of the AMH is the descent of the testicles from the abdominal cavity into the scrotum. With deviations of AMH, descent of the testicles is disturbed. Delayed descent of the testicles (cryptorchism) is the most common pathology of the genitourinary system in boys, it occurs in 30% of premature and 5% of full-term children. As a rule, the descent of the testicles still occurs spontaneously before the 3rd month of life. If this does not happen before 6 months, an operation is performed to move the testicles from the abdominal cavity or inguinal canal to the scrotum (orchidopexy). Most patients with a deficiency or insensitivity to AMH have cryptorchidism, so they are prescribed such an operation. Often, it is during orchidopexy that additional internal female genital structures are detected and the persistent Müllerian duct syndrome is suggested. In addition to anatomical defects that increase the likelihood of inguinal hernia in children, this syndrome is associated with infertility.

Doctors observing a boy with cryptorchidism face certain difficulties. Such a pathology can occur both in the case of violation of the descent of the testicles, and in their absence. These deviations have a completely different prognosis and treatment, so their correct differential diagnosis is necessary. Ultrasound can detect testicular tissue in the abdominal cavity or inguinal canal only in 70-80% of cases, while AMH is specific (98%) and a sensitive (91%) indicator of the presence of testicular tissue. A positive AMH test in a boy indicates impaired testicular descent, which can be corrected with surgery. The absence of AMH makes it possible to diagnose anorchia (congenital bilateral absence of testicles), in which surgery is not indicated. In this regard, measurement of AMH can be used for differential diagnosis of cryptorchidism.

The concentration of AMH changes significantly during life. A boy's AMH level is low at birth, but increases significantly by 6 months. In childhood and adolescence, AMH gradually decreases and reaches its lowest values in adulthood. Unlike newborn boys, the level of AMH in female babies is normally very low (not determined) and remains so during childhood and adolescence. During puberty in girls, it increases slightly and during adulthood it corresponds to that in adult men. The level of AMH after menopause is not determined normally. Thus, concentrations of AMH in boys and girls in the newborn period and early childhood differ significantly, so AMH can be used to diagnose syndromes of violation of gender differentiation. If the child has external sexual structures with both female and male characteristics, AMH in combination with some other indicators allows not only to determine the true gender, but also to identify the cause of its differentiation. So, for example, isolated dysfunction of testosterone-producing Leydig cells is accompanied by underdevelopment of the external male genital organs, while the concentration of AMH synthesized by Sertoli cells remains normal. In contrast, underdevelopment of the external male genitalia resulting from underdevelopment of the testes, accompanied by loss of both Sertoli cells and Leydig cells, is characterized by a low AMH value. In newborn girls, the level of AMH is very low (not determined). In this regard, the analysis of AMH can be used in the diagnosis of violation of gender differentiation and identification of its cause.

Despite the fact that the main function of AMH is realized during the development of the embryo, this hormone performs a number of functions after birth. In the body of an adult, it takes part in the regulation of androgen synthesis. The level of serum AMH in men with non-obstructive azoospermia (absence of sperm in the ejaculate due to impaired sperm production) is 50% lower than in patients with obstructive azoospermia (absence of sperm in the ejaculate due to obstruction in the vas deferens). This laboratory indicator is an even more accurate method of differential diagnosis of two variants of azoospermia than the traditional analysis for follicle-stimulating hormone (FSH), so AMH can be used to identify the cause of male infertility.

In a woman's body, AMH participates in the maturation of follicles, as well as their selection for ovulation. It is synthesized by granulosa cells of follicles, suppresses the growth of neighboring primordial follicles, and also reduces the sensitivity of growing follicles to the action of FSH. All this contributes to the final maturation and ovulation of one follicle every month. Since the synthesis of AMH is carried out by growing follicles, their amount is estimated by its concentration. In turn, the number of such follicles reflects the number of primordial follicles, which are called the functional reserve of the ovaries. This reserve decreases with age, as well as with conditions accompanied by premature menopause (for example, with chemotherapy). Assessment of functional reserve with the help of AMG allows to answer many questions. Quite often, a modern woman deliberately postpones the birth of a child. At the same time, it has been proven that the probability of conceiving the first child within 1 year by a woman older than 31 years decreases by 6 times compared to younger women. By the age of 41, quantitative and qualitative changes in follicles in the vast majority of cases lead to so-called natural infertility, and it occurs much earlier than menopause. Therefore, the evaluation of the functional reserve of the ovaries allows to determine the approximate age of onset of menopause and infertility (infertility), which can be taken into account by young women when planning a pregnancy. A low level of AMH indicates the onset of menopause in the next 5 years. The advantages of the AMH test are that the concentration of this hormone does not change significantly during the menstrual cycle, and also remains constant from one cycle to another.

Evaluation of the functional reserve of the ovaries with the help of AMH is also carried out during the selection and preparation of patients for in vitro fertilization programs for the treatment of female infertility. Patients with insufficient functional ovarian reserve and low AMH respond worse to ovulation stimulation, and pregnancy occurs less often. On the other hand, AMH is used to assess the risk of overstimulation of ovulation. It is not only accompanied by abdominal discomfort and the production of a larger number of defective eggs, but can also lead to life-threatening condition - ovarian hyperstimulation syndrome. AMH allows to identify patients with a high risk of excessive stimulation of ovulation, which is necessary for further selection of the optimal scheme of infertility treatment.

AMH is a marker of ovarian tumors originating from granulosa cells (granulosa cell tumors). They account for about 3% of ovarian neoplasms. The most common is the so-called adult version of the tumor, which is observed in pre- and postmenopausal women (the average age at which the tumor is diagnosed is 51 years). At the same time, along with the increased production of AMH, the amount of estrogens increases significantly, which leads to endometrial hyperplasia, which is manifested by menstrual cycle disorders in premenopause. In postmenopause, hyperestrogenism is most often manifested by uterine bleeding or adenocarcinoma of the endometrium. In men, an excess of estrogen is accompanied by gynecomastia. Sertoli cell tumors are other rare hormonally active ovarian tumors. In both cases, the AMH level will be significantly elevated.
Repeated tests for AMH can be used at the stage of control of tumor treatment.