RU2748490C1 - Method for treatment of "thin" endometrium in women of reproductive age using autologous platelet-rich plasma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to gynecology, and is intended for treatment of uterine forms of infertility. For treatment of “thin” endometrium, women of reproductive age with “thin” endometrium in the proliferative phase of the menstrual cycle (up to 10 days) are injected with autologous platelet-rich plasma (PRP) controlled by office hysteroscopy in a small operating room under intravenous anesthesia. Autologous PRP therein is injected at a volume of 35 to 40 ml with an MIT needle buried directly in the endometrium at a depth of 2 to 3 mm.

EFFECT: use of the invention allows restoring normal structure and functional activity of the endometrium by locally affecting the uterine mucosa without the need for a multiple intrauterine infusion procedure in each cycle, also providing a local and precise effect of growth factors contained in autologous PRP on the uterine mucosa and a controlled insertion depth.

1 cl, 3 ex

Description

The invention relates to medicine, in particular to gynecology, and can be used in the clinic for reproductive technologies in the treatment of uterine infertility.

One of the most pressing problems in modern gynecology is the problem of infertility. In women with impaired reproductive function, the uterine factor of infertility is 24-62% [Silantyeva E.S. Physical methods of structural and functional remodeling of the endometrium in women with reproductive dysfunction: dis. Dr. med. Sciences: 14.00.01. 14.00.51. M., 2008. 261s.]. In the structure of intrauterine pathological changes, the leading role is played by chronic endometritis, characterized by a long and low-symptom course and causing infertility, unsuccessful attempts at in vitro fertilization (IVF) and miscarriage [Treatment of female and male infertility. Assisted reproductive technologies. Ed. IN AND. Kulakova, B.V. Leonova, L.N. Kuzmichev. M .: MIA, 2005.592s .; Lisina O.N. Intrauterine pathology in women with infertility: author. dis. can. honey. Sciences: 14.00.01. M., 1993, 24p.].

In clinical practice, adequate endometrial growth is required for successful implantation and normal embryo development.

Pathology of the endometrium leads to a violation of its secretory transformation, damage to the receptive apparatus, defects in implantation of a fertilized egg, which is clinically manifested by infertility or spontaneous miscarriage in the first half of pregnancy [Sidelnikova V.M. Habitual fetal loss. M .: Triada-X, 2005. 304s.].

Currently, there is no consensus on the methods of treatment aimed at increasing the thickness of the endometrium.

Among the existing methods of treating "thin" endometrium, conservative, associated with the use of drugs, and physiotherapy can be distinguished.

A known method of treating "thin" endometrium in women of reproductive age in the framework of pregravid preparation before the IVF program and embryo transfer by using exogenous estrogen [Chen MJ, Yang JH, Peng FH, Chen SU, Ho HN, Yang Y S. Extended estrogen administration for women with thin endometrium in frozen-thawed in-vitro fertilization programs. J Assist Reprod Genet 2006; 23: 337-342].

Known methods of treating "thin" endometrium, including the use of low-dose aspirin and vitamin E [Khairy M, Banerjee K, El-Toukhy T, Coomarasamy A and Khalaf Y. Aspirin in women undergoing in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 2007; 88: 882-831 .; Takasaki A, Tamura H, Miwa I, Taketani T, Shimamura K and Sugino N. Endometrial growth and uterine blood flow: a pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril 2010; 93: 1851-1858]. The use of intravaginal sildenafil citrate promotes endometrial growth in 70% of women with "thin" endometrium, but the rate of successful implantation and ongoing pregnancy reaches only 29% and 45%, respectively [Sher G and Fisch J D. Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertile Steril 2002; 78: 1073-1076].

Unfortunately, the described medical methods of treatment do not always allow achieving a complete restoration of the structure of the endometrium and its functional activity.

Among the physiotherapeutic methods for treating "thin" endometrium, electrotherapy and magnetotherapy should be noted. Electrotherapy methods include electrical impulse therapy and interference currents (with concomitant gynecological diseases that do not require surgical treatment at the moment). The method consists in conducting a course of electrical impulse therapy with the ELM-01 Andro-Gin hardware-software complex, interference therapy with the AIT-01 apparatus or therapy with a traveling magnetic field with the AMUS-01-Intramag Z apparatus for patients with a "thin" endometrium starting from 5 -7 days of the menstrual cycle. The use of these physical methods of treatment in the treatment of reproductive dysfunction, according to the authors, contributes to its restoration only in 55% of patients [Silantyeva E.S. Physical methods of structural and functional remodeling of the endometrium in women with reproductive dysfunction: dis. Dr. med. Sciences: 14.00.01. 14.00.51. M., 2008. 261s.].

Despite all the diversity, some women with "thin" endometrium have no response to the use of these methods of treatment. Consequently, there is a need to search for new comprehensive approaches to solving the problem of "thin" endometrium.

A new approach in the treatment of "thin" endometrium is the use of autologous platelet-rich plasma (PRP). Platelet-rich plasma is produced from fresh whole blood, which is taken from a peripheral vein, stored in an anticoagulant solution, and processed to increase platelets by separating various blood components. Platelet autoplasma modulates and regulates the function of primary, secondary and tertiary growth factors, influencing all stages of regeneration simultaneously.

For the first time, the use of PRP to increase the thickness of the endometrium in IVF programs was used by Y. Chang et al. in 2015. The study included 5 women with endometrial thickness <7 mm after standard systemic hormone therapy (SGT) in the IVF program. In this study, intrauterine infusion of PRP was performed after CHT. According to the results of the study, all women after the use of PRP became pregnant [Chang Y., Li J., et al. Autologous platelet - rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization // Int.JClin.Med. 2015. No. 8(1).P.1286-1290].

This method of treatment is the closest solution to the problem of "thin" endometrium, however, its technical problem is the need for intrauterine infusion procedures several times in each cycle and the impossibility of introducing a volume of autologous PRP sufficient for the clinical effect (during irrigation, it is administered within 5 ml).

The objective of the invention is to eliminate the indicated technical problems.

The technical result of the invention is the restoration of the normal structure and functional activity of the endometrium by local action on the uterine mucosa without the need for intrauterine infusion procedures several times in each cycle. It also provides a local and precise effect of the growth factors contained in the autologous PRP on the uterine mucosa and the controlled insertion depth. In addition, the technical result is the possibility of introducing a sufficient amount for the clinical effect of the volume of autologous PRP.

The specified technical result is achieved due to the fact that the claimed method for the treatment of "thin" endometrium in women of reproductive age, including the injection of autologous platelet-rich plasma (PRP), women with "thin" endometrium in the proliferative phase of the menstrual cycle (up to 10 days) under the control of office hysteroscopy in a small operating room under intravenous anesthesia, characterized in that autologous PRP is injected in a volume of up to 35-40 ml with a MIT needle directly into the endometrium to a depth of 2-3 mm.

Implementation of the invention

The task and the technical result are solved by a method based on the introduction of autologous PRP directly into the endometrium with an endoscopic needle under the control of a hysteroscope.

This needle was developed to correct vesicoureteral reflux and urinary incontinence in children. The authors propose for the first time to use this needle to inject PRP into the thickness of the uterine mucosa under the control of a hysteroscope for the treatment of "thin" endometrium in women of reproductive age (<7 mm in the II phase of the menstrual cycle). At the same time, the possibility of accurate injection of PRP directly into the endometrium is realized, while effectively controlling the depth of penetration of the needle.

The introduction of autologous PRP in a volume of up to 35-40 ml with a MIT needle directly into the endometrium to a depth of 2-3 mm provides a local and precise effect of the growth factors contained in the autologous PRP on the uterine mucosa and a controlled depth of injection.

In contrast to the prototype, the claimed invention provides the possibility of introducing a sufficient amount for the clinical effect of the volume of autologous PRP in a volume of 35-40 ml.

The whole procedure is carried out in a small operating room with the patient lying on a gynecological chair. Intravenous anesthesia is used. Under aseptic conditions, the cervix is exposed in mirrors and fixed with bullet forceps by the front lip. The length of the body of the uterus is measured. A hysteroscope is inserted into the uterine cavity. Under the control of office hysteroscopy, a disposable endoscopic needle "MIT" is inserted into the uterine cavity. Intrauterine injections of PRP are made to a depth equal to the thickness of the endometrium, previously established during ultrasound of the pelvic organs. Growth factors are delivered to the tissues in the injectable form of autoplasma and are concentrated by injecting large amounts of plasma. The operation takes an average of 20 minutes. After the administration of autologous PRP, the patient is monitored for 6 hours. If the condition is satisfactory, the patient can be discharged home. List of equipment: centrifuge, blood collection kit, tubes for PRP preparation, endoscopic needle, hysteroscope.

The treatment regimen includes one or two administrations of autologous PRP into the endometrium under the control of a hysteroscope. Whole blood is collected for the preparation of autologous PRP on days 6-9 of the menstrual cycle. The introduction of autologous PRP is performed in the proliferative phase up to the 10th day of the menstrual cycle under the control of a hysteroscope into the mucous layer of the uterus. The mechanism of action of autologous PRP is the release of granules containing growth factors (VEGF, PDGF, EGF, etc.) during the destruction of platelets, inflammatory mediators, which promotes the launch of regeneration processes and biological synthesis in tissues. Growth factors stimulate cell growth and proliferation.

The essence of the proposed method is illustrated by clinical examples.

Clinical example 1

Patient M, 32 years old, came to the clinic with complaints of miscarriage and spotting discharge from the genital tract after menstruation.

During the examination in the clinic: no pathological changes were revealed during the bimanual examination. According to the results of ultrasound of the pelvic organs, there are data for chronic endometritis, the thickness of the endometrium in the II phase of the menstrual cycle (M-echo on day 21 m.c.) is 7 mm.

On the 8th day of the menstrual cycle, the patient was taken whole blood for the preparation of autologous PRP. On the 9th day m.ts. hysteroscopy was performed with injection of autologous PRP in a volume of 35 ml with an endoscopic needle into the thickness of the uterine mucosa. The procedure was performed in a small operating room under intravenous anesthesia. After the procedure, the patient was monitored for 6 hours, after which she was discharged home in a satisfactory condition. There were no complications of the operation. Subsequent observations showed the growth of the endometrium according to the ultrasound of the pelvic organs (a month after the procedure, the thickness of the endometrium on day 21 m.c. was 9 mm) and in the next cycle, the onset of physiological uterine pregnancy, which continues today.

Clinical example 2

Patient M, 43 years old, came to the appointment with complaints of repeated failures of embryo implantation in cryoprotocols, withdrawal from the protocol due to insufficient growth of the endometrium, scanty spotting menstruation over the past few years. The nature of menstruation changed after the last curettage of the uterine cavity due to a missed pregnancy.

During the examination in the clinic: the general physical examination did not reveal any abnormalities, with the bimanual examination no pathological changes were revealed. According to the results of ultrasound of the pelvic organs, the thickness of the endometrium in the II phase of the menstrual cycle (M-echo on day 19 m.c.) was 6 mm.

On the 5th day of the menstrual cycle, the patient was taken whole blood for the preparation of autologous PRP. On the 6th day m.ts. hysteroscopy was performed with injection of autologous PRP in a volume of 35 ml with an endoscopic needle into the thickness of the uterine mucosa and irrigation of the uterine cavity with autologous PRP in a volume of 5 ml. The procedure was performed in a small operating room under intravenous anesthesia. The duration of the operation was 15 minutes. After the procedure, the patient was monitored for 6 hours, after which she was discharged home in a satisfactory condition. There were no complications after surgery. In the next cycle, the patient received estrogens and endometrial thickness according to the ultrasound of the pelvic organs on day 21 m.ts. was 9 mm. The patient was transferred 1 thawed embryo (4AA) into the uterine cavity. Pregnancy has come.

Clinical case 3

Patient N, 34 years old, applied to the clinic with complaints of miscarriage and a medical record from another clinic with a diagnosis of chronic endometritis.

During the examination in the clinic: no pathological changes were revealed during the bimanual examination. According to the results of ultrasound of the pelvic organs, there are data for chronic endometritis, the thickness of the endometrium in the II phase of the menstrual cycle (M-echo on day 20 m.c.) is 6 mm.

On the 6th day of the menstrual cycle, the patient underwent a sampling of whole blood for the preparation of autologous PRP. On the 7th day m.ts. hysteroscopy was performed with injection of autologous PRP in a volume of 40 ml with an endoscopic needle into the thickness of the uterine mucosa. The procedure was performed in a small operating room under intravenous anesthesia. After the procedure, the patient was monitored for 6 hours, after which she was discharged home in a satisfactory condition. There were no complications of the operation. Subsequent observations showed the growth of the endometrium according to the ultrasound of the pelvic organs (a month after the procedure, the thickness of the endometrium on day 21 m.c. was 10 mm) and after one cycle a physiological uterine pregnancy occurred, which continues today.

Clinical examples show that injection of autologous platelet-rich plasma (PRP) in women with "thin" endometrium in the proliferative phase of the menstrual cycle (up to 10 days) under the control of office hysteroscopy in a small operating room under intravenous anesthesia , with the introduction of autologous PRP in a volume of up to 35-40 ml with a MIT needle, directly into the thickness of the endometrium to a depth of 2-3 mm, provides the restoration of the normal structure and functional activity of the endometrium by local action on the uterine mucosa without the need for an intrauterine infusion procedure. once in every cycle.

Claims (1)

A method of treating a "thin" endometrium in women of reproductive age, which includes an injection of autologous platelet-rich plasma (PRP) in women with a "thin" endometrium in the proliferative phase of the menstrual cycle (up to 10 days) under control office hysteroscopy in a small operating room under intravenous anesthesia, characterized in that autologous PRP is injected in a volume of 35-40 ml with a MIT needle directly into the thickness of the endometrium to a depth of 2-3 mm.