RU2792572C1 - Method for the rehabilitation of patients with "thin" endometrium after ivf failures - Google Patents

Abstract

FIELD: obstetrics; gynaecology.

SUBSTANCE: invention can be used to restore the structure of the endometrium in women after IVF failures. The method includes a treatment regimen that involves 3 courses of low-frequency ultrasonic cavitation of the uterine cavity with antiseptic and cytoprotector solutions in combination with cyclic hormonal therapy, the procedure for one course of administration of drug solutions cavitated by ultrasound is carried out for five days daily, starting from the 5–9th day of the menstrual cycle. The 1st course consists of 5 procedures of low-frequency ultrasonic cavitation with an antiseptic solution of Chlorhexidine 0.05% diluted 1:10 with 0.9% NaCl solution, the 2nd and 3rd courses consist of 5 procedures of low-frequency ultrasonic cavitation of the uterine cavity with Cytochrome C in a 1:10 dilution with 0.9% NaCl solution in combination with cyclic hormonal therapy with estradiol and progesterone preparations, at the end of the 2nd and 3rd courses of treatment, the size of the endometrium and the need for a subsequent treatment cycle are determined.

EFFECT: ensuring normalization of the morphofunctional structure of the endometrium and restoration of endometrial receptivity and further reduction of the risk of reproductive failures.

1 cl, 4 ex

Description

The invention relates to medicine, namely to obstetrics and gynecology, and can be used to restore the structure of the endometrium in women after IVF failures.

Relevance.

The problem of infertility and miscarriage is one of the most urgent in gynecology, since it has not only medical, but also great social significance. Violation of the full implantation of the human embryo due to non-receptive endometrium is the most significant cause of reproductive failures of ART, occupying up to 70% in their structure. An urgent problem is the lack of unified clinical protocols for the treatment of endometrial diseases associated with a violation of its receptivity. These circumstances dictate the need to develop and scientifically substantiate new methods of treating diseases accompanied by impaired endometrial receptivity. One of the methods of preformed impact on biological tissues is low-frequency ultrasound.

Analogues

A known method of local treatment of inflammatory diseases of the uterine cavity and a device for its implementation (RF patent No. 2537779, A61N 7/00), in which the uterine cavity is washed with a medicinal solution with the supply of cavitated fluid into 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, a constant outflow of contents from the uterine cavity is ensured.

There is also known a method of local treatment of postpartum endometritis, described in the patent of the Russian Federation No. 2634471, A61N 7/00. This method includes intrauterine administration of an ultrasound-cavitated solution of Betaleukin with 0.9% saline at a ratio of 1 μg of the drug per 400 ml of saline, while 2 procedures are performed every other day at an ultrasonic vibration frequency of 25 kHz of the ultrasound therapy apparatus, infusion volume of at least 300 ml.

Criticism of analogues

Known methods of treatment do not create a sufficient concentration of substances in the uterine cavity, others, in addition to their main effect, have sufficient side effects. None of the methods gives a sufficient size of the endometrium by the end of the course of treatment.

Prototype

Closest to the claimed method is a method for the treatment of "thin" endometrium N2709229, A61N 7/00 (Khabarov Sergey Vyacheslavovich, 2019). This method of treating "thin" endometrium includes intrauterine administration of drug solutions cavitated by ultrasound for 4-5 minutes using an ultrasound therapy apparatus at an ultrasonic frequency of 25 kHz and an ultrasonic vibration level of 50 units. At the same time, in the process of ultrasonic treatment, a constant outflow of contents from the uterine cavity is ensured. Complex therapy is carried out, which also includes intravenous infusion 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. In this case, the introduction of the hydrolyzate of the human placenta is carried out twice a week for 5 weeks.

Criticism of the prototype

The proposed method for the treatment of thin endometrium has its significant drawbacks:

there is no local effect of the drug on the pathological endometrium;

it is not possible to create a high concentration of the drug in the uterine cavity;

there is no sufficient impregnation of the drug itself into the deeper tissues;

there is no cavitation of the drug itself, that is, the hydrolyzate of the placenta enters intravenously by drip, and not into the uterine cavity.

Purpose of the invention

The aim of the invention is to create an effective method for the treatment of "thin" endometrium, which allows to achieve a significant growth of the endometrium, the size of which allows the implantation of the ovum into the uterine cavity, the restoration of the morphofunctional structure of the endometrium, as well as the rehabilitation of women after IVF failures in women with reproductive failures. The purpose of the invention is achieved by using a complex treatment - the introduction of ultrasound-cavitated medicinal solutions into the uterine cavity.

The essence of the invention

This goal is achieved through therapy, which includes intrauterine administration of ultrasound-cavitated drug solutions. For ultrasonic treatment of the uterine cavity, a solution containing 10 mg of Cytochrome C and 100 ml of 0.9% saline is used. The treatment scheme involves 3 courses of intrauterine administration of drug solutions cavitated by ultrasound, 5 procedures are performed every day from the 5th to the 9th day of the menstrual cycle at a frequency of ultrasonic vibrations of 25-30 kHz, an amplitude of oscillations of the ultrasound waveguide-instrument of 60-120 microns, a consumption of a medicinal solution of 100- 150 ml / min, exposure exposure 3-5 minutes, infusion volume of at least 300 ml. EFFECT: method ensures normalization of the morphological and functional structure of the endometrium and restoration of endometrial receptivity and, in the future, the possibility of reducing the risk of reproductive failures.

Cytoprotector, as a metabolic agent, has a direct antihypoxic and trophic effect on the "thin" endometrium, stimulates regeneration processes that promote implantation processes.

The treatment regimen involves 3 courses of low-frequency ultrasonic cavitation of the uterine cavity with antiseptic and cytoprotector solutions in combination with cyclic hormonal therapy.

In the proposed method, the procedure for one course of administration of drug solutions cavitated by ultrasound is carried out for five days daily, starting from the 5th-9th day of the menstrual cycle.

The 1st course consists of 5 procedures of low-frequency ultrasonic cavitation with an antiseptic solution of Chlorhexidine 0.05% diluted with 0.9% NaCl solution.

The 2nd and 3rd course consists of 5 procedures of low-frequency ultrasonic cavitation of the uterine cavity with Cytochrome C at a dilution of 1:10 with 0.9% NaCl solution in combination with cyclic hormonal therapy with estradiol and progesterone preparations.

According to the proposed method, at the end of each cycle of treatment, the size of the endometrium is determined, and the need for a subsequent course of treatment.

For this method, the Ultrasonic Surgical Apparatus AUZKh-100-FOTEK, manufactured by FOTEK LLC, Yekaterinburg, Russian Federation, with an AA211 acoustic unit can be used.

The beginning of the procedures: 5-9 days of the menstrual cycle.

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

In all courses of procedures for ultrasonic treatment, a sterile 0.9% sodium chloride solution diluted with 10 ml of cytoprotector Cytochrome C solution is used. Courses of procedures are carried out in each menstrual cycle.

The amount of solution for processing: 100-110 ml.

Frequency of ultrasonic oscillations: 25 kHz.

The level of ultrasonic vibrations: 50 units.

Fluid consumption for the procedure 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 supplied to the node channel uninterruptedly, and the solution supply rate is at least three drops per second (controlled by the drip chamber of the infusion system).

Processing time 4-5 min.

The average number of procedures in the course of treatment is 3 - 5 and are carried out daily, once a day.

Medications are selected individually. If a woman has intolerance to one of them, then it is replaced with an analogue. There were no cases of anaphylactic or allergic reaction to the procedure.

Local impact on the endometrium by ultrasonic irrigation of the uterine cavity with cavitated medicinal solutions can increase the effectiveness of treatment, reduce the drug load on the patient, and reduce the duration of treatment by an average of 2-3 times. The use of the method in preconception preparation and in preparation for the IVF procedure contributes to the restoration of the reproductive function of women, increases the frequency of the desired pregnancy (both when conceived naturally, 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.

Efficiency control is carried out by Y3 monitoring with measurement of endometrial thickness and Doppler blood flow three times during the menstrual cycle.

Examples of specific implementation of the method

Example 1

Patient P., 36 years old. Appealed to the Clinic with complaints about the lack of pregnancy for 8 years of regular sexual activity without contraception. History of 2 unsuccessful IVF attempts (2017, 2018). Since 2017, during ultrasound examination, the endometrium in the II phase of the menstrual cycle is linear, with a thickness of not more than 5.2 mm. Objectively, the uterus and appendages are without features. Ultrasound examination of the pelvic organs on the 24th day of the menstrual cycle showed three-layer endometrium, thickness 5.8 mm.

Conducted 2 courses of ultrasound treatment of the uterine cavity. The first course using a 0.05% solution of Chlorhexidine 10.0 ml together with a 0.9% solution of sodium chloride 100.0 (diluted 1:10) for 5 daily procedures, starting from the 5th day of the menstrual cycle. The second course was the use of cytoprotector Cytochrome C with 0.9% sodium chloride solution diluted 1:10 in combination with cyclic hormonal therapy. After applying anesthesia with Cathejel with lidocaine and dilating the cervical canal to No. 6 with Gegar dilators, the acoustic unit AA211 of the AUZKh-100-FOTEK apparatus in a protective case was inserted behind the internal os into the uterine cavity. Then, using the roller regulator of the infusion system, a jet supply of the drug solution was established into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were triggered, and the endometrium was irrigated with the “sounded” drug solution for 5 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml/min. the total volume of infusion was 100 ml of solution. The patient did not report any discomfort during the procedure. Control ultrasound of the endometrium after the treatment on the 22nd day of the menstrual cycle - three-layer endometrium, thickness 9 mm, which is objectively normal for the implantation of the fetal egg. It is recommended to contact a reproductive specialist for the ART program: IVF.

Example 2

Patient M., 39 years old. She went to the clinic with complaints about the lack of pregnancy for 2 years of regular sexual activity without contraception. History of childbirth at the end of the ART program: IVF (2013); 3 unsuccessful IVF attempts (2016, 2017, 2018). Since 2017, during ultrasound examination, the endometrium in the II phase of the menstrual cycle is three-layered, no more than 5.0 mm thick. Objectively, the uterus and appendages are without features. Ultrasound examination of the pelvic organs on the 22nd day of the menstrual cycle showed a three-layer endometrium, thickness 5.7 mm.

Conducted 2 courses of ultrasound treatment of the uterine cavity. The first course using a 0.05% solution of Chlorhexidine 10.0 ml together with a 0.9% solution of sodium chloride 100.0 (diluted 1:10) for 5 daily procedures, starting from the 5th day of the menstrual cycle. The second course was the use of cytoprotector Cytochrome C with 0.9% sodium chloride solution diluted 1:10 in combination with cyclic hormonal therapy with Divigel and Utrozhestan 200 (the scheme could be prescribed by a reproductologist). Without anesthesia and expansion of the cervical canal, the acoustic unit AA211 of the AUZKh-YuO-FOTEK apparatus in a protective case was inserted behind the internal os into the uterine cavity. Then, using the roller regulator of the infusion system, a jet supply of the drug solution was established into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were triggered, and the endometrium was irrigated with the “sounded” drug solution for 4 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml/min. the total volume of infusion was 100 ml of solution. The patient did not report any discomfort during the procedure. Control ultrasound of the endometrium after the treatment on the 23rd day of the menstrual cycle - three-layer endometrium, thickness 9.1 mm, which is normal for implantation of the fetal egg. It is recommended to contact a reproductive specialist for the ART program: IVF.

Example 3

Patient P., 29 years old. Appealed to the antenatal clinic with complaints about the lack of pregnancy for 6 years of regular sexual activity without contraception. History of 1 unsuccessful IVF attempt (2018). Since 2017, during ultrasound examination, the endometrium in the II phase of the menstrual cycle is linear, no more than 6.3 mm thick.

Objectively, the uterus and appendages are without features. Ultrasound examination of the pelvic organs on the 22nd day of the menstrual cycle showed three-layer endometrium, thickness 5.8 mm.

Conducted 3 courses of ultrasound treatment of the uterine cavity. The first course using a 0.05% solution of Chlorhexidine 10.0 ml together with a 0.9% solution of sodium chloride 100.0 (at a dilution of 1:10) for 5 daily procedures, starting from the 6th day of the menstrual cycle. The second and third courses with the use of 0.9% sodium chloride solution with cytoprotector Cytochrome C at a dilution of 1:10. After applying anesthesia with Cathejel with lidocaine and dilating the cervical canal to No. 6 with Gegar dilators, the acoustic unit AA211 of the AUZKh-100-FOTEK apparatus in a protective case was inserted behind the internal os into the uterine cavity. Then, using the roller regulator of the infusion system, a jet supply of the drug solution was established into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were triggered, and the endometrium was irrigated with the “sounded” drug solution for 5 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml/min. the total volume of infusion was 300 ml of solution. The patient did not report any discomfort during the procedure. At the same time, cyclic hormonal therapy with Divigel and Duphaston was carried out (the scheme was prescribed by a reproductologist). Control ultrasound of the endometrium after the treatment on the 22nd day of the menstrual cycle - three-layer endometrium, thickness 9 mm, which corresponds to normal implantation. It is recommended to contact a reproductive specialist for the ART program: IVF.

Example 4

Patient M., 25 years old. Appealed to the clinic with complaints about the lack of pregnancy for 4 years of regular sexual activity without contraception. History of childbirth 1 unsuccessful IVF attempt (2019). Since 2018, during ultrasound examination, the endometrium in the II phase of the menstrual cycle is three-layered, with a thickness of not more than 6.0 mm.

Objectively, the uterus and appendages are without features. Ultrasound examination of the pelvic organs on the 22nd day of the menstrual cycle showed three-layer endometrium, thickness 5.7 mm.

Conducted 3 courses of ultrasonic treatment of the uterine cavity with a solution of Cytochrome C at a dilution of 1:10 with 0.9% sodium chloride solution, 5 daily procedures, starting from the 5th day of the menstrual cycle. Without anesthesia and expansion of the cervical canal, the acoustic unit AA211 of the AUZKh-100-FOTEK apparatus in a protective case was inserted behind the internal os into the uterine cavity. Then, using the roller regulator of the infusion system, a jet supply of the drug solution was established into the irrigation channel of the ultrasonic instrument, ultrasonic vibrations were triggered, and the endometrium was irrigated with the “sounded” drug solution for 4 minutes at an ultrasonic vibration frequency of 25 kHz and an infusion rate of about 60 ml/min. the total volume of infusion was 300 ml of solution. The patient did not report any discomfort during the procedure. At the same time, cyclic hormonal therapy was carried out with estradiol and progesterone preparations (Divigel and Duphaston (the scheme was prescribed by a gynecologist-reproductologist). Control ultrasound of the endometrium after treatment on the 22nd day of the menstrual cycle - three-layer endometrium, thickness 8.7 mm, which is normal for implantation of the fetal egg It is recommended to contact a reproductive specialist for the ART program: IVF.

Features of the invention, distinguishing from the prototype

Proposed as an invention, a method for the rehabilitation of women after IVF failures and treatment of "thin" endometrium differs from the prototype in that:

with this method, the flow of medicinal solutions into the uterine cavity is carried out directly with the help of the acoustic unit of the Fotek apparatus; and according to the prototype, only saline solution enters through the acoustic node, this difference allows the drug to act directly on the endometrium, without using the parenteral route of administration of an additional drug;

according to the proposed method, cavitation is carried out using a cytoprotector preparation, which has a direct pathogenetic effect on the thin endometrium; and according to the prototype, cavitation is carried out with saline, and the agent itself is administered intravenously;

according to the proposed method, the cytoprotector solution is impregnated deep into the underlying tissues and has a direct therapeutic effect on the tissues, without a systemic effect on the entire body, and according to the prototype, the main drug is administered parenterally;

The positive effect of the invention

Thus, the use of the proposed method for the treatment of "thin" endometrium with the above parameters of exposure allows to reduce the drug load on the patient, reduce the duration of treatment and increase its effectiveness. This method is well tolerated, comfortable and safe for the patient, does not require large material costs for its implementation.

EFFECT: method ensures normalization of the morphological and functional structure of the endometrium and restoration of endometrial receptivity and, in the future, the possibility of reducing the risk of IVF failures. Local impact on the endometrium by ultrasonic irrigation of the uterine cavity with cavitated medicinal solutions can increase the effectiveness of treatment, reduce the drug load on the patient, and reduce the duration of treatment by an average of 2-3 times. The use of the method in preconception preparation and in preparation for the IVF procedure helps to restore the reproductive function of women, increases the frequency of desired pregnancy (both when conceived naturally, and when using assisted reproductive technologies

- practically no allergic reaction was detected to the cytoprotector preparation;

- the drug also has an antihypoxic, trophic effect, stimulates regeneration processes;

- the drug accelerates endogenous redox reactions and metabolic processes in tissues, improves oxygen utilization and reduces tissue hypoxia in various pathological conditions.

Information taken into account:

Patent 2709229, A61N 7/00 Sergey Vyacheslavovich Khabarov, 2019 - prototype

Claims (1)

A method for the rehabilitation of patients with "thin" endometrium after IV failure, including complex therapy, including cavitation, characterized in that the treatment regimen involves 3 courses of low-frequency ultrasonic cavitation of the uterine cavity with antiseptic and cytoprotector solutions in combination with cyclic hormonal therapy, the procedure for one course of administration of cavitated ultrasound medicinal solutions are carried out for five days daily, starting from the 5th-9th day of the menstrual cycle, the 1st course consists of 5 procedures of low-frequency ultrasonic cavitation with an antiseptic solution of Chlorhexidine 0.05% diluted 1:10 with 0.9% NaCl solution, 2 -th and 3rd courses consist of 5 procedures of low-frequency ultrasonic cavitation of the uterine cavity with Cytochrome C at a dilution of 1:10 with 0.9% NaCl solution in combination with cyclic hormonal therapy with estradiol and progesterone preparations, at the end of the 2nd and 3rd courses treatment determine the size of the endometrium and the need for a subsequent cycle of le cheniya.