Method for prediction of ovulatory menstrual cycles in females with oligomenorrhea in past medical history

IPC classes for russian patent Method for prediction of ovulatory menstrual cycles in females with oligomenorrhea in past medical history (RU 2549985):

G01N33/74 - involving hormones

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FIELD: medicine.

SUBSTANCE: blood serum anti-Mullerian hormone (AMH) is measured on the 3-5^th day of the menstrual cycle by the immunoenzyme method, and an antral follicle count of 2-5 mm in diameter is derived on the 5-7^th day of the menstrual cycle by means of transvaginal ultrasonic examination. The ovulatory menstrual cycles are predicted, if the measured AMH is from 5.0 to 8.0 ng/ml, while the antral follicle count in the ovary makes up to 10.

EFFECT: obtaining reliable results for the purpose of prescribing an adequate treatment in the adolescence and reproductive age aiming at detecting the ovulatory menstrual cycles and preventing endocrine sterility.

1 tbl, 2 ex

The invention relates to medicine, namely to gynecology.

Primary oligomenorrhea is a violation of menstrual function, which is characterized by the number of spontaneous menses per year ≤8 since menarche. According to preventive examinations of adolescent girls menstrual dysfunction is 39.5%, in the structure of disorders oligomenorrhea takes place after 2 dysfunctional uterine bleeding [1]. The establishment of a regular menstrual cycle in adolescent girls occurs within 6 to 24 months [5]. The number of ovulatory cycles is 20-25% in the first year after menarche and to 60% in the fifth year. In complex treatment and rehabilitation in adolescence in 25% of adolescent girls a normal menstrual cycle. In this regard, the prediction of ovulatory menstrual cycles in women with primary oligomenorrhea in history upon the occurrence of reproductive age matters in a timely treatment for the establishment of ovulatory menstrual cycles and prevention of infertility endocrine Genesis.

Known "Method of predicting the restoration of the menstrual cycle in women with uterine bleeding in adolescents" [4]. In the serum by ELISA to determine the level of caspase-8. If this figure is lower or equal 0,2135 ng/ml, the prognosis is copied to�of the menstrual cycle is unfavorable, bleeding will be of a recurrent nature. The caspase-8 plays an important role in all diseases associated with impaired apoptosis, primarily in the development of malignant tumors and other neoplastic processes, so it is not highly specific.

Known "Method of predicting the recovery of menstrual function in female patients with anorexia nervosa" [3]. The method consists in the fact that in patients with anorexia nervosa to determine the serum level of interleukin-1β by ELISA and, if this indicator is 25,84 PG/ml or less at a normal BMI (19 to 25 kg/m²), predict the normalization of menstrual function. It is assumed that interleukin-1β (IL-1β) is a regulator of neuroendocrine functions and is involved in insulin secretion and appetite regulation. Thus, we believe that the disadvantage of this method is the lack of evaluation of ovarian function in the regulation of the menstrual cycle.

Closest to the claimed method (prototype) selected "a Method of predicting the effectiveness of treatment of patients with polycystic ovary syndrome Metformin and/or weight reduction" [2]. The essence of the method lies in the fact that the patient determine the level of anti-Mullerian hormone (AMH). With his increasing no more than 1/3 of the upper limit of normal predicted positive�th menstrual response to treatment. This method has high sensitivity (81.3 per cent), but based only on clinical data and one biochemical indicator. Unlike our method, used in patients with polycystic ovaries. Our proposed method also includes the evaluation of ultrasound examination of the ovaries and is used in women with normal body weight and no clinical signs of hyperandrogenism.

Object of the invention is to provide a method for predicting ovulatory menstrual cycles in women with primary oligomenorrhea in history and preserved in the reproductive age.

Summary of the invention. Proposed a method for predicting ovulatory menstrual cycles in women of reproductive age with primary oligomenorrhea in history, which is characterized by an investigation of the amount of AMH in the serum for 3-5 day independent of the menstrual cycle or progesterone-induced menstrualnopodobnoe cavoodle. An ultrasound at 5-7 day menstrual cycle the ovaries is carried out by counting the number of antral follicles with a diameter of 2-5 mm. While the AMG performance from 5.0 to 8.0 ng/ml and the number of antral follicles up to 10 predicted ovulatory menstrual cycles.

We examined 45 women with primary oligomenorrhea in history and preserved in reproductive age� (main group). 30 of them comprehensive treatment and rehabilitation were conducted in adolescence (subgroup 1), 15 women first turned to the doctor in the reproductive age complaining of irregular menstrual cycle (≤8 menses per year) period with menarche (2 subgroup). The control group consisted of 30 women of reproductive age with normal menstrual cycle. Chronological age of a core group of women 20,96±0,63 years, control group 21,00±0.57 years. Gynecological age 8,20±0.65 years and of 7.48±0,70 year groups, respectively.

The paper used the following research methods: medical history, General physical examination with anthropometry, special gynecological examination. The content of magnesium was studied by enzyme-linked immunosorbent assay (ELISA) on days 3-5 of the menstrual cycle, transvaginal ultrasonography was performed at 5-7 day menstrual cycle. The results of the study are presented in the table.

Table
The content of AMH in serum and the number of antral follicles 2-5 mm in diameter in the ovaries (M±Δ)
Group, subgroup	AMH (ng/ml)	The number of follicles (n)
Control (n=30)	To 5.04±0,61	10,10±1,10
The main (n=45):	6,39±0,96*	12,5±1,86*
1 subgroup (n=30)	5,23±0,77	11,43±2,50
2 subgroup (n=15)	8,04±1,78**	16,8±1,98***
Note: * - p<0,05, - p<0.01, * - p<0,001 - reliability of differences compared with the control group.

The content of AMH in serum in women 2 subgroups significantly higher than in the control group (p<0.01).

The number of antral follicles in the ovaries with a diameter of 2-5 mm in women 1 subgroup does not have statistically significant differences with the control group, women 2 subgroups the number of antral follicles 2-5 mm in diameter compared with the control group (p<0,001).

The inventive method is carried out as follows. Examines the content of AMH in serum on days 3-5 of the menstrual cycle by ELISA using enzyme immunoassay kit MIS/AMH GEN ELISA (control values of AMH 2,9±0,6 and 8.2±1.6 ng/ml), and the number of antral follicles 2-5 mm in diameter on 5-deny menstrual cycle with transvaginal ultrasonography in the slice when scanning the right and left ovary from the inner to the outer edge of the longitudinal projection apparatus Voluson 730 Expert (GE, CMA). When AMH values from 5.0 to 8.0 ng/ml on days 3-5 of the menstrual cycle and the number of antral follicles with a diameter of 2-5 mm to 10 at 5-7 day menstrual cycle predicted ovulatory menstrual cycles. This method allows to carry out treatment, aimed at the establishment of ovulatory menstrual cycles and infertility prevention endocrine Genesis.

Example 1.

Patient S. 21. Social status - a student. Complaints of menstruation. She was born breech, body weight at birth 3600 grams. History of chickenpox, chronic gastritis. Menarche at 13 years moderate, painless with delays of up to 1-2 months. Surveyed in 15 years gynecologist involving the pediatrician, endocrinologist, neurologist, ophthalmologist in an outpatient setting. Diagnosed with Primary oligomenorrhea". BMI 19. Conducted a study of the hormonal profile, hyperandrogenism were excluded. The purpose of regulation of the menstrual cycle received combined oral contraceptives the course of 3 months and rehabilitation with the help of cyclodiene, acupuncture, su-Jok therapy in a rehabilitation center. Sex life with 18 years of age, gynecological age of 8 years.

In the reproductive age remained the menstrual cycle. When special gynecological�the first study revealed no pathology. AMH in serum was 6.4 ng/ml. the Number of antral follicles 2-5 mm in diameter in the ovaries 10. These indicators are predictors of a normal ovarian reserve. The purpose of regulation of the menstrual cycle conducted short-term treatment with low-dose combined oral contraceptives. After discontinuation of hormonal medication in the next menstrual cycle when echographic study on day 22 in the right ovary was visualized yellow body with a diameter of 18 mm with heavy blood flow along the periphery, the index of resistance in the vessels of 0.54.

Thus, treatment in adolescence, aimed at the regulation of the menstrual cycle, helped preserve the ovarian reserve and to prevent the development of polycystic ovaries. Support short course of hormonal treatment in reproductive age was effective because after the abolition identified ovulatory menstrual cycle. The prognosis of pregnancy is favorable.

Example 2.

Patient B., 22 years. Social status - a student. Physical illness - chronic gastritis. Menarche is 12 years, 6 days, moderate, painless, irregular, with delays of up to 2 months. In adolescence medical help was not sought. Sex life from the age of 18. In this age when inspecting an obstetrician-genealogie revealed an ovarian cyst, were treated with low-dose combined oral contraceptives for three months. Ultrasound examination revealed regression of the cyst.

In the reproductive age menstrual rhythm is not installed, oligomenorrhea was observed. When examining the content of AMH in the serum on day 3 independent of the menstrual cycle of 12.1 ng/ml. Ultrasound examination of the pelvic organs on the 7th day of the menstrual cycle: the volume of the right and left ovary on 18,1 cm³the number of follicles in the cut 2-5 mm in diameter and 12 to 16 in the ovaries, respectively. Conclusion: I phase of the menstrual cycle. Multifollicular the structure of the ovaries. Ultrasound examination on day 24 of the menstrual cycle: multifollicular changes in the ovaries. Anovulatory cycle.

Thus, the lack of treatment in patients with primary oligomenorrhea in adolescence has resulted in the formation of retention cysts in the ovary at the age of 18. At 22, the content of AMH in the serum was of 12.1 ng/ml, which is above the test values. The number of antral follicles 2-5 mm in diameter in the ovaries of 28. On the basis of the increase in AMH and antral follicle count 2-5 mm in diameter can be predicted anovulatory menstrual cycle, which was confirmed by ultrasound. The patient should SAG�and diagnostic search for diagnosis and conduct etiopathogenetic treatment.

The technical result of the invention is to obtain reliable results for the appointment of adequate treatment in adolescence and the reproductive years, aimed at the establishment of ovulatory menstrual cycles and infertility prevention endocrine Genesis.

Sources of information

1. Gurkin Y. A. pediatric and adolescent gynecology. Honey. information. Agency - the 2009. - 692 p.

2. Pat. EN 2427842. A method of predicting the effectiveness of treatment of patients with polycystic ovary syndrome Metformin and/or weight reduction / Popov P. V., Grineva E. N., Zadarska I. E. et al.; publ. 27.08.2011.

3. Pat. EN 2442170. A method for predicting the recovery of menstrual function in female patients with anorexia nervosa / V. Andreeva O., lewkowicz M., Linde V. A. et al.; publ. 10.02.2012.

4. Pat. EN 2477858. A method of predicting the restoration of the menstrual cycle in women with uterine bleeding in adolescents / V. Andreeva O., Masalova A. A., Linde V. A., lewkowicz M. A.; publ. 20.03.2013.

5. Villarroel S., Merino P. M., P. López et al. Polycystic ovarian morphology in adolescents with regular menstrual cycles is associated with elevated anti-Müllerian hormone / Hum. Reprod., 2011. 26 (10): 2861-2868.

A method of predicting ovulatory menstrual cycles in women with primary oligomenorrhea in history, characterized by the study of anti-Mullerian hormone (AMH) serum kravina 3-5 days of the menstrual cycle by ELISA and the number of antral follicles with a diameter of 2-5 mm at 5-7 day menstrual cycle transvaginal ultrasound, forecasting with ovulatory menstrual cycles when the concentration of AMH from 5.0 to 8.0 ng/ml and the number of antral follicles in the ovaries to 10.