RU2342173C1 - Treatment method for chronic endometritis - Google Patents

Abstract

FIELD: medicine, gynecology.

SUBSTANCE: vulva sanitation is conducted. Then ultrasound exposure of vagina is conducted during 60 seconds, through intermediate antiseptic solution infused into the cavity. Whereupon 100 IU poludane dissolved in 5 ml sterile injection solution, is introduced into uterine cavity. At the same time ultrasound exposure of endometrium is conducted during 60 seconds. The low-frequency ultrasound with 26.5 kHz frequency and 50 mcm amplitude is applied in continuous mode. Treatment procedures are effected every morning at first phase of menstrual cycle, 1.5 to 2 hours after the meal. The course includes 5 procedures.

EFFECT: increased therapy efficiency due to complications reduction, steady treatment result, curing period shortening, and medicament load easing.

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Description

The invention relates to medicine, specifically to gynecology, and relates to methods for treating chronic endometritis (CE).

Most chronic endometritis is latent and has no clinical manifestations of infection. In general, 35-40% of patients have no clinical symptoms. The most constant manifestations of CE include, in 50-85% of cases, menstrual dysfunction of the type of menorrhagia and metrorrhagia, pre - and postmenstrual bleeding. In 30% of cases, a violation of reproductive function associated with miscarriage in the early stages, as well as infertility and unsuccessful attempts of IVF (in vitro fertilization). In 80% of cases, patients complain of pain localized in the lower abdomen with radiation to the lumbar or sacral spine [1]. Inflammatory diseases of the pelvic organs lead to impaired immunity. In addition to affecting the general immune system, infectious agents cause serious changes in local immunity, which are manifested by an increase in the number of Ig G, M, A, which contributes to the rejection reactions of the embryo. The quantitative content of immunoglobulins M, G, A in the endometrial secretion with CE is 100 times higher than immunoglobulins in healthy women, which in turn necessitates the use of immunomodulators in the treatment of CE. A histological examination of endometrial scraping remains the most reliable way to diagnose CE, the "gold standard" [2].

Known methods of treating CE with medications (antibacterial drugs [3], immunomodulators in the form of injections, suppositories, tablets [4]; hormone therapy - in the form of cyclic hormone therapy [5], intrauterine irrigation [6]) and preformed physiotherapeutic methods of treatment - microwaves centimeter range, magnetic field, UHF, pulsed ultrasound, electrophoresis of iodine and others [7]. However, with these methods of treatment, a high percentage of complications is noted, due to which it is necessary to interrupt the course of treatment (drug intolerance - allergic reactions, impaired gastrointestinal function). The use of physiotherapeutic methods may exacerbate the chronic process, which requires the mandatory use of antibacterial agents and possible hospitalization. The duration of the course of the above physiotherapeutic procedures (10-12 days), which creates certain inconveniences for patients. Also known methods are characterized by low efficiency due to the impossibility of directly affecting the endometrium and creating a depot of the drug in it.

The closest (prototype) is a method of treating CE using intrauterine irrigation, when an immunomodulator half-dan is used as a dialysis solution [8]. However, this method has the following disadvantages:

- the inability to deposit the dosage form in the endometrium,

- it is used only as part of complex therapy of chemotherapy with the use of antibiotics, systemic immunomodulators, which can cause a number of side effects in the form of drug intolerance, dyspeptic manifestations, intestinal dysbiosis, exacerbation of the inflammatory process, increase in body temperature during immunomodulating therapy,

- the duration of treatment is at least 7-10 days,

- low efficiency when used as monotherapy,

- an insufficient number of studies does not allow us to judge the complications of therapy and the expansion of the scope.

The problem solved by this invention is to increase the effectiveness of treatment by reducing the number of complications, obtaining a more stable therapeutic effect, reducing treatment time and drug load, as well as expanding the scope. The problem is solved by a new method of treating chronic endometritis by introducing a half-dan immunomodulator (100 ME) into the uterine cavity, and at the same time, the endometrium is scored with low-frequency ultrasound (LCH), with a frequency of ultrasonic vibrations of 26.5 kHz, an amplitude of ultrasonic vibrations of 50 microns and an exposure time of 60 seconds in continuous mode, in the I phase of the menstrual cycle (8-12 days), once a day, in the morning after breakfast, only five procedures. What is new is that intrauterine half-dan (polyadenylurenedyl acid 100 ME) is administered and the endometrium is simultaneously voiced with low-frequency ultrasound (LCH), with a frequency of ultrasonic vibrations of 26.5 kHz, an amplitude of ultrasonic vibrations of 50 μm and a sound exposure of 60 seconds in continuous mode, in I the phase of the menstrual cycle (8-12 days), once a day, in the morning 1.5-2 hours after a meal, only five procedures. In the patent and medical literature analyzed by the authors, this combination of distinctive features was not found, which made it possible to achieve the indicated positive effect, which consists in increasing the effectiveness of treatment by reducing the number of complications, a more stable therapeutic effect, shortening the treatment time and drug load, and expanding the scope.

This method has passed a clinical trial in the gynecological department of the Center for Women's Health (OOO "MADEZ"). Thus, this technical solution meets the criteria of the invention of "novelty", "inventive step", "industrially applicable".

The method is as follows: conduct phased scoring of the vagina and endometrium through a liquid intermediate drug medium.

At the first stage of treatment, the vulva is treated with a 0.5% alcohol solution of chlorhexidine in order to reorganize it.

At the second stage of treatment, ultrasonic treatment of the vagina through an intermediate solution of an antiseptic is carried out with the aim of its rehabilitation [14]. A vaginal dilator is introduced into the vaginal cavity with expansion of the folds of the vaginal mucosa. The cavity is filled with an aqueous solution of chlorhexidine 0.05%, a waveguide tool is inserted and primary sanitation of the vagina and vaginal part of the cervix is performed by sounding them for 60 seconds, with a frequency of ultrasonic vibrations of 26.5 kHz and an amplitude of oscillation of the emitting end of the waveguide tool 60 μm. After completion of the scoring process, the spent solution is evacuated from the vagina.

At the third stage, NPh3 phonophoresis of the drug substance (polyadenylurenedyl acid - half-dan) is carried out in the endometrium, in order to create a depot of the drug substance in the endometrium for 60 s in a continuous mode, with a frequency of ultrasonic vibrations of 26.5 kHz and an oscillation amplitude of the emitting end of the waveguide tool 50 microns.

For this, under aseptic conditions:

- the cervix is fixed with bullet forceps,

- the uterine probe determines the length of the uterine cavity,

- an intrauterine expander-limiter is inserted into the uterine cavity to a depth determined by the installation of a position fixator,

- to the extender connect a supply tube connected to a container for a medicinal solution,

- a waveguide tool is introduced into the cavity of the expander-limiter,

- scoring of the endometrium begins simultaneously with the circulation of the drug substance in the uterine cavity. Treatment of patients according to the proposed method is carried out in the morning, 1.5-2 hours after a meal, once a day for five days.

Some patients with hypersensitivity before the procedure for voicing the endometrium undergo paracervical blockade with a 2% lidocaine solution.

A specific example of the method

Patient P., 37 years old, went to the gynecologist of the Center for Women's Health (LLC "MADEZ") with complaints of a lack of pregnancy for 7 years, a cycle disorder such as menorrhagia, intermenstrual bleeding, miscarriage of early pregnancy history, two unsuccessful IVF attempts. History: menarche at 11 years old, the menstrual cycle was established after 1 year, menstruation was regular, after 27 days, 5 days, heavy on the first day, moderately painful (first day). Pregnancy - 4, medical abortion - 1, delivery on time - 1, spontaneous miscarriages in the period of 6 and 9 weeks - 2. Infertility for 7 years. In 2002, laparoscopy and hysteroscopy were performed, obstruction of the fallopian tubes and chronic endometritis were revealed. The treatment was carried out using antibacterial therapy, physiotherapy (microwaves of the centimeter range), hormonal treatment. After treatment 2 attempts of IVF, to no avail. Objectively: a patient with a hypersthenic physique, height - 164 cm, weight - 75 kg. Gynecological examination revealed an increase in the uterus up to 5-6 weeks, prolapse of the walls of the vagina of I degree. Ultrasound of the pelvic organs: conclusion - uterine fibroids of small sizes, echo signs of chronic endometritis and the adhesive process of the small pelvis. On the 10th day of the menstrual cycle, a pipel was performed - endometrial biopsy, histological conclusion: chronic endometritis without exacerbation, hyperplastic variant.

The patient was treated according to the proposed method, by complex intrauterine use of the immunomodulator half-dan (polyadenylurenedyl acid 100 ME) and low-frequency ultrasound (NCHU), with a frequency of ultrasonic vibrations of 26.5 kHz, an amplitude of ultrasonic vibrations of 50 μm and a sound exposure of 60 seconds in continuous mode, in the I phase of the menstrual cycle (8-12 days), once a day, in the morning after breakfast, only five procedures. After treatment, the patient did not observe a single episode of intermenstrual bleeding; in the control study of aspirate from the uterine cavity after 3 months there was no lymphohistiocytic infiltration characteristic of CE, the endometrium corresponded to the phase of the menstrual cycle. After treatment, the patient was taken into the IVF program according to the short protocol (A-GTRH + rivers-FSH). Two embryos were transferred to the uterine cavity, pregnancy with one fetus. Currently, pregnancy is 22 weeks, proceeds without complications.

The immunomodulator half-dan (polyadenyloredilic acid) was chosen because of its ability to induce the synthesis of endogenous interferon. It stimulates the formation of mainly alpha interferon, to a lesser extent beta and gamma interferons. It has a pronounced immunomodulating and antiviral effect. Half-dan was originally used in ophthalmology for the treatment of keratoiridocyclitis (keratouveitis), keratoconjunctivitis, keratitis, adenoviral and herpetic conjunctivitis, iridocyclitis, chorioretinitis, since when it is used, a high concentration occurs not only in blood serum, but also in lacrimal fluid [9]. However, there are reports of its effective use in the treatment of other diseases [10, 11], including genital herpes [12].

The drug stimulates not only natural cytotoxicity, but also the functioning of other immunocompetent cells, in the regulation of the activity of which interferon plays a significant role [13]. A dose of 100 ME was selected as sufficient to achieve a clinical and histological effect and did not cause side effects.

The therapeutic effect of NPhUZ is achieved by implementing the pathogenetic effects of low-frequency ultrasonic treatment of foci of infection through an intermediate solution of a drug substance. These effects are determined by: cavitation, vortex-like acoustic flows, variable sound pressure, initiated in a powerful ultrasonic field and further determining the intensification of mass transfer processes in the volume of the drug solution and at the interfaces (extraction and impregnation) due to diffusion and rheological processes. A high-quality sanitation of the foci of infection, improvement of microcirculation, detoxification and impregnation of the drug substance deep into biological tissues is achieved [14]. Parameters are suggested as sparing. The duration of the procedures is necessary and sufficient to obtain a sustainable therapeutic effect. An increase in the duration of exposure will lead to an excessive load on the body. The exposure regimen was selected based on the analysis of clinical observation data for 75 patients aged 18 to 45 years with a histologically verified diagnosis of CE. All patients by random sampling were divided into three groups depending on the methods of treatment received:

- the first group consisted of patients (26 people) who underwent intracavitary administration of a half-dozen of 100 ME diluted in five milliliters of a sterile solution for injection, once a day, for five days;

- the second group - patients (25 people) who underwent intrauterine treatment of NCHU, with a frequency of ultrasonic vibrations of 26.5 kHz, an amplitude of ultrasonic vibrations of 50 μm and a sound exposure of 60 seconds in continuous mode, in the first phase of the menstrual cycle (8-12 days) , once a day, in the morning after 1.5-2 hours after eating, only five procedures;

- the third group - women (24 people) who underwent combination therapy when using the intrauterine device half-dan (polyadenylurelic acid 100 ME) with simultaneous sounding of the endometrium with low-frequency ultrasound (LFU), with a frequency of ultrasonic vibrations of 26.5 kHz, an amplitude of ultrasonic vibrations of 50 μm and exposure of sound for 60 seconds in a continuous mode, in the first phase of the menstrual cycle (8-12 days), once a day, in the morning 1.5-2 hours after eating, only five procedures.

Patients of the three groups did not have statistically significant differences in socio-demographic characteristics, the presence of somatic and gynecological pathologies and the nature of the complaints presented at the time of initiation of therapy. The effectiveness of the treatment was evaluated according to the results of a histological examination, which was carried out before treatment and 3 months after treatment, in the first phase of the menstrual cycle.

The most pronounced dynamics in the change in the histological picture was among patients in the third group (p <0.00001). In all three groups, before treatment, CE was detected in 100% of cases. After treatment in the first group, histological signs of CE remained in 22 (84.62%) patients; in the second group - in 10 (40%), and in the third group only in 5 (20.83%) patients. In addition, within 6 months, 9 (60%) of 15 (100%) patients in the third group suffering from infertility had a desired pregnancy, in group I in 1 (7.69%) of 13 (100%) and Group II only in 4 (25%) of 16 (100%) patients. Thus, as clinical trials have shown, this method has the following advantages: it increases the effectiveness of treatment by reducing the number of complications associated with the traditional treatment of CE with antibiotics and systemic immunomodulators (drug intolerance, dyspeptic manifestations, intestinal dysbiosis, exacerbation of the inflammatory process, fever body and others), has a more stable therapeutic effect, halves the treatment time, reduces the drug load and ra expands the scope of its application due to the possibility of use in patients with the presence of diseases such as uterine fibroids of small sizes, internal endometriosis.

Bibliography

1. Eckert LO, Hawes SE, Wolner-Hanssen PK, et al. Endometritis: the clinical-pathologic syndrome. Am J Obstet Gynecol, 2002; 186: 690-5.

2. Kiviat NB, Wolner-Hanssen P, Eschenbach DA, et al. Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis. Am J Surg Pathol, 1990; 14: 167-75.

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Claims (1)

A method of treating chronic endometritis, including the introduction of a half-dan, characterized in that the vulva is first sanitized, then the vagina is ultrasonically treated for 60 seconds through an intermediate solution of an antiseptic introduced into its cavity, after which 100 IU of half-dan, dissolved in 5, are introduced into the uterine cavity ml of a sterile solution for injection, and at the same time the endometrium is voiced for 60 s, acting continuously with low-frequency ultrasound, with an oscillation frequency of 26.5 kHz, an amplitude of 50 μm, Corollary is carried out in the first phase of the menstrual cycle, once a day, in the morning, after 1.5-2 hours after a meal, a course of 5 treatments.