RU2709229C1 - Method of treating "thin" endometrium - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to obstetrics and gynecology, and can be used in treating female infertility and chronic uterine inflammation. Method of treating the "thin" endometrium involves an intrauterine introduction of the ultrasonicated cavity medicinal solutions for 4–5 minutes using an ultrasonic therapy apparatus at a frequency of ultrasonic oscillations of 25 kHz and an ultrasonic vibration level of 50 units. Ultrasonic treatment is ensured by a constant outflow of content from the uterine cavity. Complex therapy is performed, which involves intravenous drop-by-drop introduction of human placental hydrolyzate 6.0–8.0 ml dissolved in 250 ml of 0.9 % sodium chloride with infusion duration of 1.5 hours. Human placental hydrolyzate is administered twice week for 5 weeks, wherein the ultrasonic therapy apparatus is represented by an AUZX-100-"PHOTEC" ultrasonic therapy apparatus.

EFFECT: method provides higher clinical effectiveness of the "thin" endometrium with simultaneous safety of the placenta hydrolyzate.

6 cl, 2 ex

Description

The present invention relates to medicine, in particular to obstetrics and gynecology, and can be used in the treatment of female infertility, as well as in the treatment of chronic uterine inflammation.

In the treatment of female infertility, one of the most important areas is increasing the thickness of the endometrium.

Sufficient endometrial thickness is necessary for normal implantation of the embryo in the uterine cavity. The thinner the endometrium, the less chance of a favorable implantation outcome.

If the thickness of the endometrium, measured on the 18-21st day of the menstrual cycle, is less than 8 mm, then such an endometrium is considered to be a “thin” endometrium, and it should be treated in order to increase it.

Currently, various methods of treating the “thin” endometrium are known, aimed at increasing the thickness of the endometrium, consisting in the appointment of antibacterial agents, female sex hormones, drugs that improve uterine blood flow, physiotherapeutic procedures.

However, the analysis of the accumulated clinical material indicates the insufficient effectiveness of the proposed treatment methods in order to increase the thickness and receptivity of the endometrium, as well as their safety.

A known method of local treatment of inflammatory diseases of the uterine cavity and a device for its implementation (RF patent No. 2537779, A61N7 / 00), in which the uterine cavity is washed with a medicinal solution with the supply of cavitated fluid to the uterine cavity using an ultrasound generator for 3-5 minutes, at a frequency of ultrasonic vibrations of 25 kHz, while in the process of ultrasonic treatment provide a constant outflow of contents from the uterine cavity.

This method allows to achieve a certain thickness of the endometrium, but this thickness is not sufficient for normal implantation of the ovum.

There is also a method of treating infertility in women with external genital endometriosis (RF patent No. 2253489, A61N5 / 067), in which surgical destruction of endometrioid heterotopies, antibiotic therapy and subsequent hormone-depleting therapy are performed.

In particular, they spend 7 days on the background of taking antibiotics, analgesics and Wobenzym, starting from the first postoperative day, irradiating blood through a monofilament quartz fiber, lasting 15 minutes for the first 5 procedures.

This method allows to increase the effectiveness of treatment, since it uses complex therapy, but it requires surgical intervention, taking a large number of antibiotics, and is also not safe and quite difficult to perform.

Closest to the claimed method is a method of local treatment of postpartum endometritis described in the patent of Russian Federation No. 2634471, A61N7 / 00, which is selected as a prototype.

This method involves the intrauterine administration of an ultrasonic cavitated Betaleikin drug solution with 0.9% physiological saline at a ratio of 1 μg of the drug per 400 ml of physiological saline, and 2 procedures are performed every other day at an ultrasonic oscillation frequency of 25 kHz of the ultrasound therapy apparatus, the infusion volume is not less than 300 ml

This method is quite simple to implement, but not effective enough.

The objective of the proposed invention is the creation of such a highly effective method of treatment of "thin" endometrium, which allows to achieve significant growth of the endometrium, the value of which allows implantation of the fetal egg in the uterine cavity, and to reduce the growth time of the endometrium.

The technical result of the invention is to increase the effectiveness of the method of treatment of "thin" endometrium, while ensuring its safety.

The technical result achieved is achieved due to the fact that in the method of complex therapy of the “thin” endometrium, including intrauterine administration of ultrasonically cavitated drug solutions during an exposure of 4-5 minutes, using an ultrasound therapy apparatus with an ultrasonic vibration frequency of 25 kHz and an ultrasonic vibration level of 50 units , the infusion rate of at least 60 ml / min, and the infusion volume of at least 300 ml, while in the process of ultrasonic treatment provide a constant outflow of contents from the uterine cavity, there is a complex therapy, which also includes intravenous drip of a human placenta hydrolyzate of 6.0-8.0 ml, dissolved in 250 ml of a 0.9% sodium chloride solution, with an infusion duration of 1.5 hours, while the placenta hydrolyzate is administered human exercise twice a week for 5 weeks.

Preferably, in the method, the ultrasonic therapy device AUZX-100-FOTEK is used as an ultrasound therapy apparatus, which makes it possible to perform an action on the endometrium with a cavitation stream, supplemented by cavitation sparging of the drug solution in the uterine cavity, ensuring constant circulation of the solution inside the uterus.

It is advisable that in the method sterile 0.9% sodium chloride solution, or an aqueous 0.05% chlorhexidine solution, or 0.5% dioxidine solution in a 1:20 dilution with 0.9% sodium chloride solution be used as ultrasonic cavitated drug solutions .

Preferably, the preparation Laennec® is used as a human placenta hydrolyzate in the method.

It is desirable that in the method the procedure of one cycle of administration of cavitated ultrasound drug solutions was carried out for five days daily, starting from 5-9 days of the menstrual cycle.

It is advisable that in the method, at the end of each treatment cycle, the size of the endometrium and the need for a subsequent treatment cycle are determined.

For a more complete disclosure of the invention, the following is a description of a specific possible embodiment with specific examples of its application, which allow us to evaluate the high efficiency and safety of using this method of treatment of "thin" endometrium.

For this method, the ultrasonic surgical apparatus AUZX-100- “FOTEK”, manufacturer of LLC “FOTEK”, the city of Yekaterinburg of the Russian Federation, with acoustic unit AA211 can be preferably used.

Beginning of procedures: 5 - 9 day of the menstrual cycle.

Ultrasound treatment is carried out in 2 to 3 courses (the number of courses is determined by assessing the thickness of the endometrium during treatment).

In the first course of procedures for ultrasonic treatment, you can use: sterile 0.9% sodium chloride solution, aqueous 0.05% chlorhexidine solution or 0.5% dioxidine solution in a 1:20 dilution with 0.9% sodium chloride solution (1 ampoule of 10 ml of a 0.5% solution of dioxidine per 200 ml of a 0.9% solution of sodium chloride).

In the second course of procedures (carried out, if necessary, in the next menstrual cycle after 1 course), the solutions indicated above for the first course of treatment are used.

In the third year (carried out, if necessary, in the next menstrual cycle after 2 courses) a sterile 0.9% sodium chloride solution is used.

Courses of procedures are carried out in each menstrual cycle.

The amount of solution to be processed: 200 - 300 ml.

The frequency of ultrasonic vibrations: 25 kHz.

Level of ultrasonic vibrations: 50 units.

The operating mode of the apparatus: “EXIT UZ”, “ASPIRATION”, IRRIGATION ”.

Mode for ultrasonic exposure: "BASIC".

Location of the container with the solution: the infusion stand is raised so that during the procedure, the lower edge of the container with the solution suspended on it is at least 90 cm from the acoustic unit introduced into the uterine cavity. This is necessary in order to ensure a sufficient supply rate of the treatment solution for the procedure.

The fluid flow rate for the procedure is maximum and is determined by the size of the uterine cavity, averaging 300 ml. The roller clamp on the system must be fully open. It is necessary to ensure that the solution is fed smoothly into the channel of the unit, and the feed rate of the solution is at least three drops per second (controlled by the drip chamber of the infusion system).

Processing time 4-5 minutes

The average number of procedures in the course of treatment is 5 (performed daily, once a day).

Medicines are selected individually. If a woman has intolerance to one of them, then he is replaced with an analog. There are no cases of anaphylactic or allergic reactions to the procedure.

A local effect on the endometrium by ultrasonic irrigation of the uterine cavity with cavitated drug solutions can increase the effectiveness of treatment, reduce the drug load on the patient, and reduce the duration of treatment by an average of 2 to 3 times. The use of the method in pregravid preparation and in preparation for the IVF procedure helps to restore the reproductive function of women, increases the frequency of the desired pregnancy (both during conception in a natural way and when using assisted reproductive technologies).

At the same time, the treatment procedure is quite comfortable and safe for the patient and does not require large time and material costs.

The inventive method is as follows:

1. On the device AUZH-100- "FOTEK" the appropriate operating mode is selected.

2. The patient is placed in a gynecological chair.

3. Bimanual research is performed.

4. The external genitalia is treated with an antiseptic solution.

5. Using a mirror, Cusco exposes the cervix.

6. Prior to treatment, a uterine cavity is probed with a uterine probe in order to determine its size and length of the cervical canal.

7. If there is a strong bend between the body and the cervix, it is recommended to straighten it. For this, the vaginal part of the cervix is pulled by bullet forceps to the entrance to the vagina anteriorly (with uterine retroflexion) or posteriorly (with uterine anteflexia).

8. Anesthesia and expansion of the cervical canal is not required. The exception is women with a closed canal, whose expansion usually is required before the first procedures. For this, the cervix is fixed by bullet forceps, and the cervical canal is dilated by Gegar's dilators up to 6 - 6.5 mm. If you do not use expanders, fluid outflow will be impaired, which can cause pain.

9. Since the expansion procedure can be painful, in this case, local anesthesia of the cervix is first performed using a spray of 10% Lidocaine solution or gel for external use (Katedzhel with lidocaine, Instillillagel, Lidochlor, Septalor). The gel is applied to the cervical region and the external pharynx of the cervical canal. Anesthetic effect develops within 5 to 10 minutes after application of the gel.

10. When the cervical canal is prepared for the introduction of the acoustic node, a test spray of the solution in the external environment is mandatory. You must make sure that the temperature of the stream is comfortable for the patient (by spraying the solution into the palm of his hand).

11. Then, the distal end of the acoustic node AA211, without touching the walls of the vagina, in order to reduce the risk of infection penetrating the ascending pathway, is carefully inserted through the cervical canal into the uterine cavity taking into account the deviation of the uterus in one direction or another (anteflexia, retroflexion, lateroflexion).

12. During the procedure, the acoustic unit is held by the doctor’s hands to avoid displacement in the uterine cavity. Using the acoustic node AA211 apparatus AUZX-100- "FOTEK" is carried out irrigation of the mucous membrane of the uterine cavity with a cavitated solution. Throughout the procedure, with the help of a drip chamber on the infusion system, it is necessary to ensure that the solution is supplied to the channel of the acoustic unit uninterruptedly and the rate of solution supply is at least three drops per second, otherwise overheating of the instrument under the casing and thermal burns of the walls are possible uterus and cervical canal.

13. In the process of ultrasonic treatment, the solution from the uterus flows out through the drainage holes in the protective casing of the acoustic unit. Additional outflow of fluid is also carried out between the walls of the cervical canal and the protective casing, so the walls of the cervical canal should not too tightly cover the tip inserted into the uterine cavity. A full and free outflow of solution irrigated into the uterus is an indispensable condition for the procedure. Otherwise, the contents of the uterine cavity can be thrown into the abdominal cavity through the fallopian tubes.

14. For the comfort of the doctor and patient, an aspirator can be used at the same time. It allows you to remove fluid from the vagina into a separate container. Leaking fluid from the uterine cavity usually accumulates in the vagina. It can be periodically removed from the vagina by changing the inclination of the gynecological mirror or using aspiration tips.

15. After the procedure, the acoustic unit is removed from the uterine cavity and, when disassembled, is subjected to disinfection and sterilization.

At the same time, a human placenta hydrolyzate (Laennec® preparation) is administered intravenously dropwise for 1.5 hours, 6.0-8.0 ml intravenously, dissolved in 250 ml of a 0.9% sodium chloride solution 2 times a week for 5 weeks.

Efficiency monitoring is carried out by ultrasound monitoring with measurement of endometrial thickness and blood flow dopplerometry three times during the menstrual cycle.

The technique of exposure to ultrasound is not used for bleeding of unknown origin due to the risk of its amplification. Ultrasonic cavitation during menstruation can lead to increased bleeding due to the thermal effect and micromassage of the uterine cavity. Under the influence of ultrasound, blood flow increases, arterioles expand. Therefore, menstruation can go into bleeding. Subject to recommendations on the procedure, the risk of complications is minimal.

A method for stimulating endometrial regeneration can be performed on an outpatient basis.

Thus, the method of treating “thin” endometrium by combining intrauterine irrigation with a cavitated solution and intravenous drip of Laennec® is an effective, non-invasive, affordable, easily reproducible on an outpatient basis, a fairly simple and safe treatment method that does not require complicated equipment, long time and significant economic costs. Provides patients with a low degree of pain and the absence of complications.

A method of treating a “thin” endometrium involves a combination of irrigation of the endometrium with a cavitated solution and intravenous drip of the placenta hydrolyzate (Laennec® preparation).

According to the proposed method for the treatment of “thin” endometrium, 12 patients were treated at the Clinic of Actual Medicine LLC in Moscow. All patients for at least 6 months before the start of the observation repeatedly received standard therapy for chronic endometritis (antibacterial, hormonal, immunomodulating, physiotherapy).

Patients received an irrigation of the walls of the uterine cavity with a 0.05% chlorhexidine solution or a sterile 0.9% sodium chloride solution treated with low-frequency ultrasound. Conducted from 1 to 3 courses of irrigation of the walls of the uterine cavity, including 5 procedures 1 time per day daily. The courses of treatment were carried out without interruption in each menstrual cycle.

In both groups, the size of the median M-echo during ultrasound examination before the start of the proposed method of treatment did not differ significantly. In the main group, its average value was 5.0 mm (4.5 - 6.2 mm). After the 2nd and 3rd courses of treatment, the average thickness of the endometrium was 8.7 mm.

It was found that the complex application of the irrigation of the endometrium with a cavitated solution and intravenous drip of the human placenta hydrolyzate (Laennec® drug) in women with thin endometrium has a positive effect, and in most patients there is a significant increase in endometrium by the end of the treatment period, which increases the likelihood of pregnancy in the future. The effectiveness of this technique is more than 75%, in the complete absence of any serious complications, in particular bleeding, trauma to the cervix. This is extremely important from the point of view and prevention of both infectious complications and the development of isthmic-cervical insufficiency in the future. There are also no adverse reactions.

The following are specific examples of using the claimed treatment method.

Example 1

Patient P. 36 years. I went to the Clinic with complaints about the absence of pregnancy for 8 years of regular sexual life without contraception. A history of 2 failed IVF attempts (2017, 2018). Since 2017, with an ultrasound examination of the endometrium in the II phase of the menstrual cycle, linear, with a thickness of not more than 5.2 mm.

Objectively, the uterus and appendages without features. An ultrasound examination of the pelvic organs on the 24th day of the menstrual cycle has a three-layer endometrium, a thickness of 5.8 mm.

2 courses of ultrasonic treatment of the uterine cavity were performed. The first course using a 0.05% chlorhexidine solution for 5 daily procedures, starting from the 6th day of the menstrual cycle. The second course using 0.9% sodium chloride solution. After performing anesthesia with Katedzhel lidocaine and expanding the cervical canal to No. 6 with Geghar expanders, the acoustic unit AA211 of the AUZX-100-FOTEK apparatus was inserted into the uterine cavity beyond the internal pharynx in a protective case. Then, using the roller regulator of the infusion system, the drug solution was sprayed into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were started and the endometrium was irrigated with “voiced” drug solution for 5 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml / min. the total infusion volume was 300 ml of solution. The patient did not experience any discomfort during the procedure. At the same time, intravenous drip of a human placenta hydrolyzate (Laennec® preparation) was carried out for 1.5 hours, 6.0 ml each, dissolved in 250 ml of a 0.9% sodium chloride solution 2 times a week for 4 weeks. Control ultrasound of the endometrium after treatment on the 22nd day of the menstrual cycle - the endometrium is three-layered, 9 mm thick. It is recommended that you contact a reproductologist for an ART: IVF program.

Example 2

Patient M., 40 years old. I went to the clinic with complaints of a lack of pregnancy for 2 years of regular sexual activity without contraception. A history of childbirth in the outcome of the ART program: IVF (2013); 3 unsuccessful IVF attempts (2016, 2017, 2018). Since 2017, with an ultrasound examination of the endometrium in the second phase of the menstrual cycle, it is three-layer, with a thickness of not more than 5.0 mm.

Objectively, the uterus and appendages without features. An ultrasound examination of the pelvic organs on the 22nd day of the menstrual cycle has a three-layer endometrium, a thickness of 5.7 mm.

1 course of ultrasonic treatment of the uterine cavity with a 0.5% Dioxidine solution in a 1:20 dilution with 0.9% sodium chloride solution was carried out, 5 daily procedures starting from the 6th day of the menstrual cycle. Without anesthesia and expansion of the cervical canal, the acoustic unit AA211 of the AUZX-100-FOTEK apparatus was inserted into the uterine cavity beyond the internal pharynx in a protective case. Then, using the roller regulator of the infusion system, the drug solution was sprayed into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were started and the endometrium was irrigated with “voiced” drug solution for 4 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml / min, the total infusion volume was 300 ml of solution. The patient did not experience any discomfort during the procedure. At the same time, intravenous drip of a human placenta hydrolyzate (Laennec® preparation) was carried out for 1.5 hours in 8.0 ml, dissolved in 250 ml. 0.9% sodium chloride solution 2 times a week for 5 weeks. Control ultrasound of the endometrium after treatment on the 23rd day of the menstrual cycle - the endometrium is three-layered, 9.1 mm thick. It is recommended that you contact a reproductologist for an ART: IVF program.

Thus, the application of the proposed method for the treatment of "thin" endometrium with the above exposure parameters allowed to reduce the drug load on the patient, reduce the duration of treatment and increase its effectiveness. Moreover, the technique has good tolerability, is comfortable and safe for the patient, does not require large material costs for its implementation.

  The proposed method for the treatment of "thin" endometrium can significantly increase the effectiveness of its use due to the use of complex therapy in this method, which includes ultrasonic treatment of the uterine cavity with cavitated ultrasound drug solutions with simultaneous intravenous administration of a human placenta hydrolyzate in the form of a Laennec® drug solution.

As is obvious to those skilled in the art of medicine, the invention is readily developed in other specific forms without departing from the spirit of the invention.

Moreover, the present embodiments should be considered merely illustrative, and not limiting, and the scope of the invention is represented by its formula, and it is assumed that it includes all possible changes and the scope of equivalence to the claims of this invention.

Claims (6)

1. A method of treating a “thin” endometrium, including intrauterine administration of ultrasonic cavitated drug solutions for 4-5 minutes using an ultrasound therapy apparatus at an ultrasonic vibration frequency of 25 kHz and an ultrasonic vibration level of 50 units, an infusion rate of 60 ml / min and an infusion volume of not less than 300 ml, while in the process of ultrasonic treatment provide a constant outflow of contents from the uterine cavity, characterized in that they carry out complex therapy, which also includes intravenous e dropwise administration of human placenta hydrolyzate 6.0-8.0 ml, dissolved in 250 ml of 0.9% sodium chloride solution, with an infusion duration of 1.5 hours, while the introduction of a human placenta hydrolyzate is carried out twice a week for 5 weeks. 2. The method according to p. 1, characterized in that the ultrasonic therapy apparatus AUZX-100-FOTEK is used as an ultrasound therapy apparatus, which allows the endometrium to be affected by a cavitation jet, supplemented by cavitation bubbling of the drug solution in the uterine cavity with constant circulation of the solution inside the uterus. 3. The method according to p. 1, characterized in that the sterilized 0.9% sodium chloride solution, or an aqueous 0.05% chlorhexidine solution, or 0.5% dioxidine solution at a dilution of 1:20 s is used as ultrasound-cavitated drug solutions 0.9% sodium chloride solution. 4. The method according to p. 1, characterized in that the preparation Laennec® is used as a human placenta hydrolyzate. 5. The method according to p. 1, characterized in that the procedure for one cycle of the introduction of cavitated ultrasound drug solutions is carried out for five days daily, starting from 5-9 days of the menstrual cycle. 6. The method according to p. 5, characterized in that at the end of each treatment cycle determine the size of the endometrium and the need for a subsequent treatment cycle.