Evaluation of antimüllerian hormone levels in the diagnosis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) includes a wide range of characteristic clinical and biochemical parameters. The mechanisms of the disease formation are still poorly understood, but its main feature is impaired folliculogenesis, in which the development of the dominant follicle is absent, which leads to anovulation and cystic degeneration of the ovaries. Follicular growth from the primordial stage to 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 is formed, 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 certain intraovarian hormone-independent factor associated with the formation of intercellular contacts and maintaining follicles in a state of rest. In the second period of folliculogenesis, basal growth of follicles occurs from the secondary stage to the large antral stage (1-2 mm in diameter). This stage of follicle growth can only occur in the presence of basal levels of pituitary gonadotropins, primarily FSH, and is called the hormone-sensitive phase. Currently, a factor has been identified by which one can judge the hormone-sensitive phase of folliculogenesis. This factor is anti-Müllerian hormone (AMH), a glycoprotein that belongs to the family of transforming growth factors p. It is believed that in women, anti-Müllerian hormone is synthesized by granulosa cells of pre-antral and small antral follicles (less than 4 mm), and also participates in the transition of "resting" primordial follicles to the active growth phase. Moreover, anti-Müllerian hormone, together with FSH, controls the process of selection of new follicles that are at the stage of early antral follicles. As is known, direct measurement of the pool of primordial follicles is impossible, however, their number is indirectly reflected by the number of growing ones. Therefore, a factor secreted predominantly by growing follicles will reflect the size of the primordial pool. Thus, anti-Müllerian hormone, which is secreted by growing follicles and can be tested in blood 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 ovulation itself. If the first two stages occur under the influence of intraovarian factors in the absence of gonadotropins, then the last stage is directly regulated by the pituitary gland. Dysfunction of the hypothalamic-pituitary-adrenal and ovarian systems can lead to disruption of folliculogenesis, accumulation of small antral follicles, which make a significant contribution to the development of hyperandrogenism, production of anti-Müllerian hormone and the formation of polycystic ovary syndrome.

To date, the most commonly used parameters for assessing the state of the ovarian reserve and for diagnosing polycystic ovary syndrome are calculating the volume of the ovaries and counting 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, scientists have different opinions when considering the volume of the ovaries as an adequate test for diagnosing polycystic ovary syndrome. And if some authors claim that the volume of the ovaries is of significant importance in diagnosing polycystic ovary syndrome and predicting the response to stimulation, others have come to the conclusion that determining the volume of the ovaries is not very informative in this regard. Most researchers agree that counting the number of small antral follicles is a more accurate method for diagnosing ovarian hyperandrogenism.

Measurement of ovarian volume and calculation of the number of antral follicles is performed by ultrasound examination (US) of the ovaries and is a common method for diagnosing polycystic ovary syndrome. However, in 25% of fertile women without clinical symptoms of hyperandrogenism, having normal menstrual cycles, an ultrasound picture similar to polycystic ovary syndrome is visualized. This has led to questioning the value of ultrasound diagnostics and has given grounds to consider an increase in volume and changes in the structure of the ovaries only indirect signs of polycystic ovary syndrome. There are increasingly more reports in the literature that in modern diagnostics of polycystic ovary syndrome, determining the content of anti-Müllerian hormone in the blood is more accurate and specific. It is assumed that the level of anti-Müllerian hormone does not depend on pituitary gonadotropins, does not change sharply during the menstrual cycle and, therefore, reflects the processes occurring in the ovary itself.

The presented contradictory data indicate the complexity of diagnosing polycystic ovary syndrome. In this regard, an adequate assessment of the diagnostic criteria of this disease is extremely important.

The aim of the study was to conduct a comparative analysis of the level of anti-Müllerian hormone, ovarian volume and the number of antral follicles as diagnostic criteria for polycystic ovary syndrome.

A total of 30 patients with polycystic ovary syndrome aged 18 to 29 years (mean age 24.4±0.2 years) were examined at the clinic of the State Institution “IPEP”. The diagnosis of polycystic ovary syndrome was made based on the criteria of the World Consensus of the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine. The definition of polycystic ovary syndrome is determined by the presence of chronic anovulation and hyperandrogenism 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 tuboperitoneal infertility without surgical interventions on the ovaries, who had repeatedly undergone courses of anti-inflammatory therapy in the past. The average age of the examined patients was 26.2±0.2 years. The control group included 30 healthy women aged 24.4±0.2 years with normal menstrual function who sought clarification of the state of the reproductive system before planning a pregnancy.

The level of anti-Müllerian hormone was measured in the blood serum on the 2nd-3rd day of the menstrual cycle using the ELISA method using a commercial kit from DSL (USA). The assessment of anti-Müllerian hormone indicators was carried out according to the literature data at the following levels: < 1 ng/ml - low level of anti-Müllerian hormone; from 1 to 4 ng/ml - average level of anti-Müllerian hormone; over 4 ng/ml - high level of anti-Müllerian hormone.

Folliculogenesis parameters were monitored using the Aloka prosound SSD-3500SX device (Japan). Ovarian volume was calculated based on three measurements using the formula:

V = 0.5236 x L x W x D,

Where L is the length, W is the width, 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).

The diagnostic criterion of ultrasound examination for polycystic ovary syndrome is an increase in ovarian volume of more than 9 cm3 and the presence of peripheral hypoechoic structures (follicles) with a diameter of 6-10 mm. In one section there should be at least 8 non-developing follicles in the absence of signs of growth of the dominant follicle.

Statistical processing of the obtained data was carried out by methods of variation statistics using a standard package of statistical calculations. The reliability of discrepancies in average values was determined by Student's t-test. Discrepancies were considered reliable at p < 0.05. To study the relationship between the indicators, the correlation method was used with the determination of the correlation coefficient (r) and establishing its significance by 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 anti-Müllerian hormone in the control group of women without reproductive system disorders varied 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 average levels, and in 20% - to high levels. At the same time, 93.3% of women had normal (5-10 cm3) ovarian volume, and 6.7% had an increased volume. In 83.3% of women in the control group, the number of antral follicles had average values.

Young women with tubal-peritoneal infertility factor practically did not differ from women in the control group in average parameters of ovarian reserve. Our results of ovarian ultrasound examination showed that the average ovarian volume in them did not differ significantly from that in the control group (7.6±0.3 and 6.9±0.2 cm3; p> 0.05). However, individual study revealed a high proportion of patients (16%) with reduced (< 5 cm3) ovarian volume. Normal ovarian volume (5-10 cm3) in the study group was 1.5 times less common, while increased (> 10 cm3) was three times more common 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 counts was higher and with normal counts was lower than in the control group. The average level of anti-Müllerian hormone did not differ from the control group. However, in 12% of the examined comparison group, AMH was lower than the level of healthy women, and in 28% it exceeded normal values. It can be assumed that the detected changes in ovarian reserve values are a consequence of past inflammatory diseases.

The examined women with polycystic ovary syndrome had an increase in all the considered parameters of the ovarian reserve. The level of anti-Müllerian 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 ovarian 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 (6.9±0.2 and 7.6±0.3 cm3, respectively). Individual analysis showed that the ovarian volume of 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 also significantly exceeded the indicators of the examined women of other groups. The conducted correlation analysis established a direct correlation between anti-Müllerian hormone and the volume of the ovaries (r = 0.53; p < 0.05) and the number of antral follicles (r = 0.51; p < 0.05).

Thus, the results of the conducted assessment of the ovarian reserve parameters provided undoubted evidence that anti-Müllerian hormone, ovarian volume and the number of antral follicles are quite informative tests in the diagnosis of reproductive pathology and, in particular, polycystic ovary syndrome. The data we obtained coincide with the results of studies presented in the literature on the importance of determining the ovarian volume 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 antral follicle pool, in addition, it requires improvement of ultrasound equipment and the experience of a specialist. At the same time, the most accurate diagnostic test for polycystic ovary syndrome should be considered anti-Müllerian hormone, the level of which above 10 ng / ml can be considered a diagnostic criterion for polycystic ovary syndrome.

Cand. med. sciences T. L. Arkhipkina. Evaluation of the level of anti-Müllerian hormone in the diagnosis of polycystic ovary syndrome // International Medical Journal - No. 4 - 2012

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