Evaluation of the level of antimulyullovogo hormone in the diagnosis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) includes a wide range of characteristic clinical and biochemical indices. The mechanisms of the formation of this disease are still poorly understood, but its main feature is disrupted folliculogenesis, in which there is no development of the dominant follicle, which leads to anovulation and cystic degeneration of the ovaries. Growth of follicles from the primordial stage to the ovulation of the dominant follicle remains the most important part of research in human reproduction.

Folliculogenesis can be divided into three periods. In the first hormone-independent period, a pool of growing follicles occurs, when the latter grow from the primordial stage to the secondary stage. The facts that determine the onset of growth and differentiation of primordial follicles have not yet been determined. However, a number of authors suggest that this is a kind of intracellular hormone-independent factor associated with the formation of intercellular contacts and supporting the follicles at rest. In the second period of folliculogenesis, basal growth of follicles occurs from the secondary stage to the stage of large antral (1-2 mm in diameter). This stage of growth of follicles can occur only in the presence of basal levels of pituitary gonadotropins, primarily FSH, and is called the hormone-sensitive phase. At present, a factor has been singled out, according to which it is possible to judge the hormone-sensitive phase of folliculogenesis. This factor is the antimulylerovy hormone (AMG) - glycoprotein, which belongs to the family of transforming growth factors p. It is believed that in women antimulylerovy hormone is synthesized by granulosa cells of preantral and small antral follicles (less than 4 mm), and also participates in the transition of "resting" primordial follicles to the phase of active growth. Moreover, the anti-Muller hormone, together with FSH, controls the selection of new follicles that are at the stage of early antral follicles. As you know, direct measurement of the pool of primordial follicles is impossible, nevertheless, their number is indirectly reflected by the number of growing follicles. Consequently, a factor secreted predominantly by growing follicles will reflect the size of the primordial pool. Thus, the anti-Muller hormone, which is secreted by growing follicles and can be tested in the serum, is a marker of the functional activity of the ovaries and a diagnostic criterion for the preservation of the follicular apparatus.

The third, or hormone-dependent, period of folliculogenesis is characterized by the formation of a pool of small antral follicles and their growth, selection, maturation of the dominant follicle and proper ovulation. If the first two stages are under the influence of intraovarial factors in the absence of gonadotropins, the last stage is directly regulated by the pituitary gland. Violation of the function of the hypothalamic-pituitary-adrenal and ovarian systems can lead to disruption of folliculogenesis, the accumulation of small antral follicles, which contribute significantly to the development of hyperandrogenism, the production of antimueller hormone and the formation of a syndrome of polycystic ovaries.

So far, the most commonly used parameters for assessing the state of the ovarian reserve and for diagnosing the polycystic ovary syndrome are the calculation of the volume of the ovaries and the count of the number of antral follicles. It would seem that there is no doubt that the volume of the ovaries indirectly reflects the ovarian reserve, since it depends on the number of growing follicles, which in turn is determined by the size of the primordial pool. However, the opinions of scientists differ when considering the volume of ovaries as an adequate test for the diagnosis of polycystic ovary syndrome. And if some authors claim that the volume of ovaries is of significant importance in diagnosing polycystic ovary syndrome and predicting a response to stimulation, others concluded that the definition of the volume of ovaries in this plan is not very informative. Most researchers agree that counting the number of small antral follicles is a more accurate method of diagnosing ovarian hyperandrogenism.

Measurement of the volume of the ovaries and the calculation of the number of antral follicles is performed by ultrasound (ultrasound) of the ovaries and is a common method of diagnosis of the polycystic ovary syndrome. However, in 25% of fertile women with no clinical symptoms of hyperandrogenism with normal menstrual cycles, ultrasound imaging is similar to polycystic ovary syndrome. This allowed us to question the value of ultrasound diagnostics and gave grounds to consider an increase in volume and a change in the structure of the ovaries only by indirect signs of the syndrome of polycystic ovaries. In the literature there are more and more reports that in the modern diagnosis of polycystic ovary syndrome the more accurate and specific is the determination of the content of antimulylerovogo hormone in the blood. It is assumed that the level of antimulylerovogo hormone does not depend on the pituitary gonadotropins, does not change sharply during the menstrual cycle and, consequently, reflects the processes occurring in the ovary itself.

The presented contradictory data testify to the complexity of the diagnosis of polycystic ovary syndrome. In this regard, it is extremely important to adequately assess the diagnostic criteria of the disease.

The aim of the study was to make a comparative analysis of the level of antimueller hormone, the volume of ovaries and the number of antral follicles as diagnostic criteria for polycystic ovary syndrome.

30 patients with polycystic ovary syndrome aged 18 to 29 years (mean age 24.4 ± 0.2 years) were examined in the IPPE clinic. The diagnosis of polycystic ovary syndrome was based on the criteria of the World Consensus of the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine. Definition of the syndrome of polycystic ovaries is determined by the presence of chronic anovulation and hyperandrogenia of ovarian genesis. Clarification and verification of the diagnosis of polycystic ovary syndrome was carried out after additional hormonal examination and ultrasound. The comparison group included 25 patients with tubal peritoneal infertility without surgical interventions on the ovaries, which in the past repeatedly underwent courses of anti-inflammatory therapy. The mean age of the examinees was 26.2 ± 0.2 years. The control group included 30 healthy women aged 24.4 ± 0.2 years with normal menstrual function, who applied to clarify the state of the reproductive system before planning pregnancy.

Measurement of the anti-Muller hormone level was performed in the blood serum on the 2-3rd day of the menstrual cycle by ELISA using the commercial kit of the firm "DSL" (USA). Evaluation of antimulylerovogo hormone was carried out according to literature data on the following levels: <1 ng / ml - low level of antimulylerovogo hormone; from 1 to 4 ng / ml - the average level of antimulylerovogo hormone; more than 4 ng / ml - a high level of antimulylerovogo hormone.

The folliculogenesis parameters were monitored using the Aloka prosound SSD-3500SX (Japan). The volume of the ovaries was calculated on the basis of three measurements according to the formula:

V = 0.5236 x L x W x D,

Where L is the length, W is the width, and T is the thickness. Depending on the volume of the ovaries, three groups are distinguished: the volume of the ovaries is less than 5 cm3, 5-10 cm3 and more than 10 cm3. In our work we used literature data, according to which, depending on the number of follicles, three groups of ovaries are distinguished: inactive (less than 5 follicles), normal (5-12 follicles) and polycystic (more than 12 follicles).

Diagnostic criterion of ultrasound for polycystic ovary syndrome is an increase in the volume of the ovaries more than 9 cm3 and the presence of peripheral hypoechoic structures (follicles) with a diameter of 6-10 mm. In one cut, there must be at least 8 undeveloped follicles in the absence of signs of growth of the dominant follicle.

Statistical processing of the obtained data was carried out by variational statistics methods using a standard statistical calculation package. The reliability of the discrepancies in the mean values was determined by the Student's t-test. The discrepancies were considered reliable at p <0.05. To study the relationship between the indicators, a correlation method was used to determine the correlation coefficient (r) and establish its significance according to the t-test with a 95% reliability level (p <0.05). The data are presented as X ± Sx.

The results of the study showed that the level of antimueller hormone in the control group of women without disturbance of the reproductive system ranged from 2.1 to 5 ng / ml and averaged 3.6 ± 02 ng / ml. This indicator was taken as the norm, which coincides with the literature data. It should be noted that the values of this hormone in 80% of women in the control group corresponded to the average and in 20% to high levels. At the same time, 93.3% of women had normal (5-10 cm3) ovaries, while 6.7% had enlarged ones. In 83.3% of the control group, the number of antral follicles was average.

Young women with a tubal peritoneal factor of infertility did not differ from the women in the control group by the average parameters of the ovarian reserve. Our results of ovarian ultrasound showed that the average volume of the ovaries in them was not significantly different from the control group (7.6 ± 0.3 and 6.9 ± 0.2 cm3, p> 0.05). However, an individual study determined a high proportion of patients (16%) with a reduced (<5 cm3) ovarian volume. The normal volume of the ovaries (5-10 cm3) in the study group was 1.5 times less common, while the enlarged (> 10 cm3) was three times more likely than in the control group. The average number of antral follicles also did not differ significantly in both groups (6.9 ± 0.3 and 6.2 ± 0.2, p> 0.05), although the proportion of patients with low follicle content was higher, and with normal - lower , than in the control group. The average level of anti-Muller's hormone did not differ from the parameters of the control group. However, 12% of the surveyed AMG comparison group was below the level of healthy women, and 28% had normal values. It can be assumed that the revealed changes in the parameters of the ovarian reserve are a consequence of the transferred inflammatory diseases.

In the examined women with polycystic ovary syndrome there was an increase in all the parameters of the ovarian reserve considered. The level of antimueller hormone was 3.5 times higher than in the control and comparison group, and ranged from 9.8 ng / ml to 14 ng / ml, and averaged 12.6 ± 0.2 ng / ml. The ovary volume in patients with polycystic ovary syndrome was 13.9 ± 0.3 cm3 and was significantly (p <0.05) higher than in the control and comparison groups (respectively, 6.9 ± 0.2 and 7.6 ± 0.3 cm3). Individual analysis showed that the volume of the ovary more than 10 cm3 was noted in 21 (70%) patients with polycystic ovary syndrome, while in the remaining 9 (30%) it was less than 10 cm3, but more than 8 cm3. The number of antral follicles in the ovary in patients with polycystic ovary syndrome averaged 15.9 ± 0.3, which was also significantly higher than that of the examined women of other groups. The correlation analysis established a direct correlation between the antimueller hormone and the ovarian volume (r = 0.53, p <0.05) and the number of antral follicles (r = 0.51, p <0.05).

Thus, the results of the assessment of the parameters of the ovarian reserve provided undeniable evidence that the antimuller hormone, the volume of the ovaries and the number of antral follicles are sufficiently informative tests in the diagnosis of reproductive pathology and in particular of the polycystic ovary syndrome. The data obtained by us coincide with the results of studies presented in the literature, the importance of determining the volume of ovaries and the number of antral follicles in the diagnosis of polycystic ovary syndrome. Despite this, the quantitative determination of such parameters should be treated critically, since ultrasound, according to many researchers, poorly reflects the pool of antral follicles, in addition requires the improvement of ultrasound equipment and expert experience. At the same time, the most accurate diagnostic test for polycystic ovary syndrome should be considered antimulylerovy hormone, the level of which is above 10 ng / ml can be considered a diagnostic criterion of polycystic ovary syndrome.

Cand. Honey. Sciences of TL Arkhipkina. Evaluation of the level of antimueller hormone in the diagnosis of polycystic ovary syndrome // International Medical Journal - №4 - 2012

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