RU2185211C2 - Method for treating the cases of male atouimmune infertility - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves administering intravenous irradiation of patient blood in peripheral veins by means of device. Blood is treated with ultraviolet radiation during 30 min. The treatment course is 6 daily sessions long. Continuous membrane-type plasmapheresis is administered beginning from the second day every other day 30 min after blood irradiation. Plasmapheresis treatment course is 3 procedure long. EFFECT: enhanced effectiveness in repairing spermatogenesis and spermatozoa fertility.

Description

 The invention relates to medicine, namely to urology, andrology, immunology and can be used in the treatment of infertility in men.

 The normal function of spermatogenic cells is possible due to the presence of a special barrier with selective permeability between the blood and the contents of the seminiferous tubules, the hematotesticular barrier, which is formed by its own membrane of the seminiferous tubules and the cytoplasm of Sertoli cells, it plays a significant role in the pathogenesis of autoimmune infertility in men. Mature spermatids and especially spermatozoa have antigenic properties. Therefore, a violation of the hematotesticular barrier (trauma, ischemia, infection, etc.) leads to the formation in the blood of antibodies to spermatogenic epithelium of the seminiferous tubules with the development of autoimmune infertility.

 A decrease in fertility occurs in the presence of antisperm antibodies and sperm lymphocytes sensitized to antigens (Chernyshev V.P., 1989; Tiktinsky O.L., Mikhaylichenko V.V., 1999). As a result of this, there is a violation of the function of spermatogenic epithelium, spermatogenesis, which is manifested in a decrease in the number of motile spermatozoa, a decrease in the number of spermatozoa in 1 ml of ejaculate.

 The most common tactics for treating autoimmune diseases are based on two-component drug therapy - corticosteroids and cytostatics (Tiktinsky O. L., Mikhaylichenko V.V., 1999). Abroad, they began to use intravenous administration of large doses of immunoglobulins. Oral administration of specific autoantigens is also used. The latter is designed to stimulate immune responses by the type of response to vaccination with the suppression of pathological autoimmune processes of the underlying disease.

 However, such therapy is not without a large number of adverse reactions. Corticosteroids lead to Cushingoid Syndrome; cytostatics - to significant metabolic disorders, including healthy organs and systems; large doses of immunoglobulins, in addition to the high cost of such treatment, are fraught with the danger of transmitting viral diseases. Taking autoantigens through the mouth also carries the risk of a number of complications, up to stimulating autoimmune reactions, which makes this method very problematic in the treatment of autoimmune diseases.

 A known method of treating autoimmune infertility in men, taken as a prototype, based on the use of prednisone (Tiktinsky O.L., Mikhaylichenko V.V., 1999). However, such therapy in most cases is symptomatic, the treatment is long, for several months, low effective. Prodnisolone slightly inhibits the production of antibodies, reduces the response of tissues to antibodies, leaving them in the circulation and target organs "for the rest of their lives", also inhibits the function of the adrenal glands, gonads, disrupts the electrolyte balance, and spermatogenesis normalizes very slowly and not always effectively.

 The purpose of the invention is to increase the effectiveness of treatment of autoimmune infertility in men, to improve quantitative (volume, sperm count) and qualitative (motility, morphology, fertilizing ability) indicators of spermatogenesis, to reduce treatment time. Quickly and effectively remove antisperm antibodies from the patient’s blood, deprive the patient of adverse reactions from treatment.

 The goal is achieved in that for the effective removal of antisperm antibodies from the patient’s blood, the combined effect of the two components is combined — ultraviolet irradiation of the blood (improves microcirculation, activates the output of immune complexes in the blood) and plasmapheresis (removal of antibodies, immune complexes and their pathological metabolites from the body) . Such therapy reduces treatment time, is free from adverse reactions, is more effective, and quickly normalizes spermatogenesis.

 The method is as follows.

 In order to improve microcirculation and excretion of fixed immune complexes into the vascular bed for six days, every day, once a day, the patient is exposed to ultraviolet irradiation of peripheral vein blood for 30 minutes using an OVK-3- (04) device / quartz fiber irradiator) , with a power of 50 mW, in the wavelength range of 360-450 nm and using a monofilament fiber made of quartz glass with an outer diameter of 0.8 mm (according to the method of A.V. Marchenko, 1999), which activates the release of immune complexes into the blood. Starting from the second radiation session 30 minutes after it (time of maximum output of immune complexes in the blood), the patient is given 3 sessions of continuous membrane plasmapheresis on a PMF-800 plasma filter every other day in a plasma volume of 20 ml per kg of patient’s body weight per session (which is quite safe even when compensated only by crystalloid solutions) to remove immune complexes.

 For a complete rehabilitation of the internal environment, a course of 3 plasmapheresis sessions is usually required. After the third session, a significant release of pathological products into the circulation is no longer observed, and it is thus possible to achieve a balance of interests - their maximum elimination in the absence of negative consequences of plasmapheresis.

 Clinical example 1. Patient P., 25 years old, medical history 1224, appealed for infertility in marriage; in the spermatogram: sperm count 60 million in 1 ml, mobile forms of sperm cells - 40%, degenerative forms - 35%. Antisperm antibodies in blood serum - 1750 IU / L (N - up to 70 IU / L). Diagnosed with Autoimmune Infertility. Asthenozoospermia.

 In stationary conditions, a course of treatment was carried out according to our methodology. In the control blood test after the course, after one month and after 2 months, the titer of sperm antibodies was 0 IU / L. In the control spermatogram after the course of treatment, the number of spermatozoa is 70 million in 1 ml, mobile forms - 75%, degenerative forms - 20%.

 Clinical example 2. Patient S., 28 years old, turned on an outpatient basis according to the absence of children in the marriage for 5 years. The patient underwent surgery for varicocele. When examined in a spermatogram, the sperm count is 30 million per 1 ml, mobile forms - 60%, degenerative forms - 25%. In blood serum, the titer of antisperm antibodies was 278 IU / L. Diagnosis: Autoimmune infertility, oligozoospermia. An outpatient treatment according to the proposed method. After treatment, the titer of antisperm antibodies in serum decreased to 25 IU / L. In the control spermatogram after the course of treatment, the sperm count is 60 million in 1 ml, mobile forms 70%, degenerative forms 15%.

 Clinical example 3. Patient B., 26 years old, turned about infertility in marriage. A history of trauma to the left testicle. When examined in a spermatogram: sperm count is 45 million per 1 ml, mobile forms - 25%, degenerative forms - 30%. The titer of antisperm antibodies in serum was 188 IU / L. Diagnosis: Autoimmune infertility, oligozooastenospermia. After the treatment according to our method, the titer of antisperm antibodies decreased to 0 IU / L and this indicator remained in the patient for six months. In the control spermatogram after the course of treatment, the number of spermatozoa is 80 million in 1 ml, active - 60%, degenerative forms - 10%.

 The indicated method was used in 69 patients with autoimmune infertility (24 patients with oligozoospermia, 45 patients with asthenozoospermia). All patients received a decrease in the titer of antisperm antibodies in the blood serum and a statistically significant increase in the number of sperm in 1 ml by 1.5-2 times and the percentage of mobile forms, a decrease in degenerative forms.

 Spermatogenesis indicators steadily improved with dynamic observation, which is confirmed by the onset of pregnancy in the wives of 36 patients.

 Our proposed method is based on the removal of antibodies from the blood of patients using plasmapheresis after their activation using ultraviolet blood and is devoid of the above disadvantages. Either complete or partial blockage of antibody production can be achieved. Given the rather slow rate of accumulation of autoantibodies (for many weeks and months), by conducting efferent therapy periodically, usually twice a year, it is possible to achieve a fairly stable normalization of spermatogenesis in patients with autoimmune infertility.

 A comparative analysis of the claimed solution object with the prototype shows that the claimed method differs from the known ones in that it allows to achieve a stable therapeutic effect in the treatment of male autoimmune infertility. The inventive method was used both in oligozoospermia (low sperm count) and asthenozoospermia (low active form) with a high titer of antisperm antibodies in the patient's blood serum. The combined use of two components (ultraviolet blood irradiation and plasmapheresis) in the treatment of autoimmune infertility gives an ultimately total effect and gives the claimed solution a new property.

 These differences allow us to conclude that the method meets the criterion of "inventive step".

 Signs that distinguish the claimed method from the prototype, are not identified in other methods in the study of this and related fields of medicine and, therefore, provide the claimed method with the criterion of "novelty."

 Our proposed method allows the treatment of infertility in men in both inpatient and outpatient settings, which expands the therapeutic possibilities of conservative treatment of male autoimmune infertility.

 The methodically claimed method best meets the objectives of complex ethiopathogenetic therapy, which can significantly increase the therapeutic effect of the treatment of infertility in men.

Sources of literature
1. Tiktinsky O. L., Mikhaylichenko V.V. "Andrology". St. Petersburg, Media Press, 1999.S. 372-400 (prototype).

 2. Korenkov D.G. Marusanov V.E., Alexandrov V.P., Mikhaylichenko V.V. "Plasmapheresis in the treatment of autoimmune infertility in men." Sat scientific works Conf. 70th anniversary of prof. S.A. Simbirtseva. St. Petersburg LITTLE. St. Petersburg, 1999.S. 78.

 3. Chernyshev V.P. "Immuno-andrology". Kiev, 1989.S. 182-185.

 4. Marchenko A. V. "Intravascular photomodification of blood in surgery and related areas." Abstract. Diss. Doct. medical science. St. Petersburg, 1999.

Claims (1)

 A method of treating autoimmune infertility in men by lowering the titer of antisperm antibodies in the patient’s blood, characterized in that they use intravenous peripheral ultraviolet irradiation of the patient’s blood with an OVK-3- (04) device with an irradiation duration of 30 minutes, the number of sessions 6 per treatment course, daily, sec then, starting from the second day, 30 minutes after irradiation of blood, a continuous membrane plasmapheresis is applied a day later, three plasmapheresis per course.