Tactics of training with miscarriage of infectious genesis

For the habitual miscarriage of pregnancy is characterized by the presence in the body of the mother of persistent forms of bacterial and viral infection.

In the anamnesis - termination of pregnancy with various manifestations of infection: high temperature, premature discharge of water, endometritis after miscarriage or childbirth; acute and / or chronic inflammation of the genitals. If the infectious genesis of miscarriage is suspected, the survey includes the following parameters:

• bacteriological examination from the cervical canal;
• Gram stain smear microscopy;
• virusus - determination of urine virus antigens in urine sediment cells by indirect immunofluorescence;
• determination in the mucus of the cervical canal by the method of PCR - herpes simplex virus, cytomegalovirus, chlamydia, mycoplasmas, ureaplasma;
• the determination of antibodies to the herpes simplex virus (IgG) and cytomegalovirus (IgG) in the blood.

To select immunomodulatory therapy and determine the order of treatment is carried out:

• evaluation of the immune status: determination of sub-populations of T-cell immunity; the level of immunoglobulins IgG, IgM, IgA classes;
• evaluation of interferon status: serum IFN, interferon reaction of lymphocytes (spontaneous, virus-induced (IFNa), mitogen-induced (IFNy) and lymphocyte sensitivity to IFN inducers;
• histochemistry of immunocompetent cells for the selection of a complex of metabolic therapy.

Manifestations of acute infection, or exacerbation of chronic, are always accompanied by changes in the hemostatic system, so control of hemostasis and normalization of all parameters are extremely important for the treatment of infection. Treatment and prophylactic measures for the infection of the patient, and more correctly, the couple, depend on the severity of the infection process, the immune and interferon status, and the financial capabilities of patients.

Unfortunately, this has to be taken into account. To reduce the cost of treatment due to its quality is not worth it, but to exaggerate the role of these or other very expensive means is not advisable.

When assessing the vaginal biocenosis in a group of women with suspected infectious genesis of miscarriage, it was found that normocynosis was in 38.7% of women, vaginosis was detected in 20.9%, vaginitis in 22.1% and candidosis in 18.2%. In the control group of women with intact reproductive function normycinosis was in 85%, candidiasis - in 10% and vaginosis - in 5%.

When an infection was detected in the cervical canal, it was found that in a group of women with suspected infectious genesis of miscarriage, 36.6% persistence of ureaplasma was detected by the PCR method, mycoplasma in 15.2%, and 20.9% in chlamydia. In a bacteriological study in the mucus of the cervical canal, conditionally pathogenic microorganisms were determined in 77.1% of women, mainly: escherichia, enterococci, mycoplasma, obligate anaerobes (bacterioids, peptostreptococci), streptococci in group B, D, and others.

The microbiological studies of ribbon scrapings of the endometrium in the 1st phase of the menstrual cycle showed that the asymptomatic persistence of microorganisms in the endometrium was found in 67.7% and was not found in the control group. Obligatory anaerobes accounted for 61.4% (bacterioids, eubacteria, peptostreptococci, etc.), microaerophils - 31.8% (genital mycoplasmas, diphtheria), facultative anaerobes - 6.8% (Group B Streptococcus, epidermal staphylococcus).

Only 10.8% of women have monocultures, the rest have associations of 2-6 species of microorganisms. In quantitative estimation of the growth of microorganisms, it was found that massive seeding (10 ³ -10 ⁵ cfu / ml) occurred only in 10.2% of women with extremely burdened anamnesis, in the remaining women the amount of microflora in the endometrium was within 10 ² -5х10 ² CFU / ml endometrial homogenate.

When viruses were detected by PCR in mucus of the cervical canal and specific antibodies in the blood, carrier of herpes simplex virus was found in 45.9% of women and a recurrent form of genital herpes was found in 19.6% of women, cytomegalovirus carriage in 43.1%, recurrent infection - in 5.7% of the examined women. In these circumstances, termination of pregnancy, apparently, is due not so much to the persistence of infectious agents (opportunistic microorganisms and viruses) as to features of the patient's immune system. The following algorithm of therapy outside of pregnancy is suggested.

• Stage 1 - individually selected antibiotics, trihoyol, antimycotics in therapeutic doses from 1 to 7-9 day of the cycle.

Most researchers in the detection of chlamydia, mycoplasmosis, ureaplasmosis are treated with a combination of doxycycline 100 mg 2 times a day, trichopole (metronidozole) 0.25 3 times a day, nystatin - 0.5 g 4 times a day. 1 to 7-9 day of the cycle. If there is a possibility of determining sensitivity to antibiotics, then an individual approach will be preferable.

In chlamydia, treatment with antibiotics such as carbohydrate may be more successful by 0.15 to 3 times a day for 7 days; or sumamed (azithromycin) on 0,5 - 2 times a day; erythromycin 0.5 - 4 times a day for 9 days. Recently, the preparation of vilprafen (josamycin) is recommended for 0.5 to 3 times a day for 9 days, especially with mycoplasma and ureaplasma.

Proteolytic enzymes are participants in virtually all immune processes:

• affect the individual components of the immunity system, immunocompetent cells, antibodies, complement, etc .;
• have immunomodulatory effect on the normalization of all parameters, the immune system;
• have a direct stimulating effect on the processes of phagocytosis, the secretory activity of macrophages, natural killers.

Immunomodulating effect of enzymes is manifested in the achievement of optimal activity of various cells participating in immunological reactions. Enzymes, even in small concentrations, contribute to the cleavage and removal of circulating immune complexes (CIC), this is especially important in the combination of infection and autoimmune disorders.

An important property of enzymes is their effect on the hemostasis system and, first of all, their ability to dissolve fibrin deposits in blood vessels, thereby restoring blood flow, facilitating the process of thrombus destruction. This feature of enzymes is extremely useful, as in chronic inflammatory processes there is a depletion of its own fibrinolytic potential in the body.

Enzymes, destroying immune complexes, make microorganisms more accessible for the action of antibiotics.

According to our data, combined therapy with the inclusion of systemic enzyme therapy (at a dose of 5 tablets 3 times a day 40-45 minutes before meals, washed down with 1 glass of water) is more successful and allows you to achieve better results, in a shorter period to prepare for pregnancy 92% of women . In a comparative group completely randomized with the use of the same drugs, but without systemic enzyme therapy, only 73% of patients had a successful preparation for pregnancy.

When infected with Group B Streptococcus during pregnancy, premature discharge of water, premature birth, chorioamnionitis, bacterial postpartum endometritis is possible. Diseases of newborns (pneumonia, sepsis, meningitis) occur in 1-2% of infected mothers.

When infected with streptococcus group B, the drug of choice is ampicillin. With urinary tract infection - ampicillin in a dose of 1-2 g every 6 hours 3-7 days.

In the asymptomatic course of chronic carriage of Group B Streptococcus, ampicillin is prescribed 0.25 4 times a day, 3-7 days. Simultaneously with antibiotics, antimycotics are needed, since repeated treatment often leads to the development of dysbiosis not only vaginal, but more often intestinal. Therefore, after treatment with antibiotics and antimycotics, it is necessary to make smears to assess the effect of systemic treatment on vaginal processes. From modern antimycotics, derivatives of fluconazole (diflucan) are now recommended. It is possible to recommend other drugs not less effective, but not so expensive: nystatin, nizoral, thioconazole, etc.

If the vaginal pathology was present simultaneously with the detected infection in the endometrium and in the cervix, then after the therapy it is necessary to make smears to make sure that additional local treatment is not required. With favorable smears, it is possible to recommend the use of eubiotics vaginally (acylact, lactobacterin) and inward in the form of biochephoric or lactobacterin, primadofilis, etc.

When detecting bacterial vaginosis:

• whitened with an unpleasant odor, a feeling of discomfort, itching;
• in the smear on Gram - lactobacteria are practically absent, "key cells" are detected, there are practically no or few leukocytes, pH> 4.5;
• bacteriological examination reveals a large number of microorganisms> 10 ³ cfu / ml, predominantly gram-negative bacteria: gardnerelles, bacterioids, mobiluncus, etc.

For the treatment of vaginosis, a set of measures is needed, including the overall effect on the body and local treatment. We use metabolic complexes or vitamins, sedatives, normalization of the hormonal profile (cyclic hormone therapy with the drug femoston).

Vaginal treatment: vaginal cream dalacin (clindamycin) 2% application in the vagina, at night treatment course 7 days. If there is no candidiasis in the anamnesis, or if antimycotics were prescribed simultaneously, after the course of dalacin - acylactate or lactobacterin in suppositories, vaginally 10 days.

Alternative treatment - metronidazole 0.5 - vaginal tablets 7days, ginalgin - vaginal tablets.

Ginalgin is a combined preparation (chlorohinaldol 100 mg and metronazol 250 mg) in the form of vaginal tablets 1 tablet per night for 10 days. When applying ginalgina can be a local reaction in the form of itching, which passes after the completion of therapy.

Some authors recommend the use of vaginal suppositories "Betadine" (200 mg of polyvinylpyrrolidone, 100 mg of iodine) 2 times a day for 14 days; terzhinan - combined preparation (ternidazole 200 mg, neomycin sulfate 100 mg, nystatin 100 thousand units, prednisolone 3 mg) per 1 suppository at night 10 days; makmiror complex (nifuratel and nystatin) for 1 suppository or 2-3 grams of cream per night for 10 days.

When revealing vaginal candidiasis, we assign clotrimazole - vaginal tablets (suppositories) to 100 mg once a day for 6 days, vaginal tablets at a dose of 500 mg 1 time per night 1-day. Simultaneously, especially with recurrent candidiasis, we recommend taking diflucan 150 mg or more, or taking other antimycotics (nizoral, nystatin, fluconazole, etc.). Clotrimazole is effective not only against fungi, but also against gram (+) cocci, bacteroides, trichomonads.

An alternative method of treatment is pimafucin, in the form of vaginal suppositories and oral tablets; Klion-Dpo 1 vaginal tablet for 10 days; betadine; makmiror complex, terzhinan.

When recurring candidiasis, when traditional treatment does not help or helps for a short period of time, it is advisable to make a crop to identify the species of fungi and their sensitivity to various antimycotic drugs. So, when identifying fungi of the genus Glabrata, it is more effective to treat with ginopevar in the form of vaginal suppositories for the night of 10 days.

Recently, due to the insensitivity of some species of fungi to antimycotics, a very old method is recommended in the new version of boric acid 600 mg in gelatin capsules vaginally from 2 to 6 weeks. With recurrent candidiasis, treatment of the sexual partner is necessary.

If before the treatment the immunity parameters were within the limits of the norm, then the treatment can be supplemented by the use of metabolic complexes or vitamins, fortifying agents and completed at this stage by the resolution of pregnancy.

After the completion of antimicrobial treatment of general and local, with the reduction of all parameters of T-cell immunity, it is advisable to conduct immunomodulatory therapy. Use T-activin 2.0 ml intramuscularly every other day 5 injections, then 2.0 ml every 5 days for 5 more injections.

In the imbalance of the T-cell link of immunity, the drug imunofan, simultaneously the immunomodulator and inducer of interferon is used. A distinctive feature of this drug is that it activates the lowered parameters, while the elevated ones reduce it.

Imunofan is prescribed in a dose of 1.0 ml IM in 2 days only 10 injections.

At the second stage of treatment, it is necessary to evaluate the interferon status and, when identifying the reduced parameters of the a- and y-IFN products, recommend a course of treatment with an interferon inducer taking into account the sensitivity of immunocompetent cells. We have experience with the application of ridostin, lorifane, imunofan, tsikloferona, derinata, tamerite.

Loriffan is a high-molecular inducer of interferon of natural origin, belongs to the early inducers of interferon, is effective for respiratory viral infections, various forms of herpes. The drug has an immunomodulatory effect, stimulates specific and nonspecific links of immunity, T-cell and humoral immunity, has antibacterial and antitumor effect. It is prescribed in the form of intramuscular injections 1 time per day with an interval of 3-4 days, the course of treatment is not more than 2 weeks. Of the side effects, a brief increase in temperature should be noted. When pregnancy is contraindicated.

Ridostin is a high-molecular inducer of natural interferon. Stimulates the production of early interferon (alpha and beta) has an antiviral, antibacterial, antitumor effect. Effective in herpesviral infections, chlamydia. Ridostin is given in the form of intramuscular injections of 2 ml per 1, 3, 6, 8 and 10 days of the cycle. Contraindicated in pregnancy.

Cycloferon - a synthetic analogue of the natural alkaloid - a low-molecular interferon-alpha inducer possesses antiviral, immunomodulating, anti-inflammatory and antitumor activity. Cycloferon is highly effective in rheumatic and systemic connective tissue diseases, suppressing autoimmune reactions and exerting an anti-inflammatory effect. Cycloferon penetrates into cells and accumulates in the nucleus and cytoplasm of the cell, with which the mechanism of action is connected. The main producers of interferon under the action of tsikloferona are T-lymphocytes, natural killer cells. Normalizes the balance between subpopulations of T cells. Cycloferon is effective against hepatitis, herpes, cytomegalovirus, including autoimmune diseases. Has a pronounced anti-Chlamydial effect. It is prescribed intramuscularly for 1 ml (0.25) for 1, 2, 4, 6, 8, 11, 14 day of the cycle. Repeat the course if necessary, we spend 6-12 months. In chronic forms of viral infection, it can be used in maintenance doses of 0.25 intramuscularly 1 time in 5 days to 3 months. When pregnancy is contraindicated.

Neovir is a low molecular weight synthetic superindineator of IFN. With parenteral administration, neovir causes rapid formation of early interferon-alpha, beta, and y in the body of high titers. The drug has antiviral and antitumor effect. Neovir is effective in acute infections, including acute herpesvirus infection, hepatitis. With chronic viral infections, it is less effective than with acute viral infections. The course of treatment is 3 injections of 250-500 mg with an interval of 16-24 hours. The course of treatment can be repeated after 48 hours. When pregnancy is contraindicated.

Polyoxidonium - a synthetic drug with immunostimulating effect, increases the immune resistance of the organism in relation to local and generalized infections. Its action is based on the activation of phagocytosis and antibody formation. It is prescribed intramuscularly at doses of -12 mg once a day for 5-10 injections per course of treatment. Before injection, the drug is dissolved in 1 ml of saline or 0.25 ml of a 0.5% solution of novocaine. When pregnancy is contraindicated.

Imunofan is a hexopeptide with a molecular weight of 836 D. Imunophane immediately after administration is destroyed to its constituent amino acids. The drug has immunomodulatory, detoxicating, hepatoprotective effect and causes inactivation of free radical and peroxide compounds. Distinguish the fast phase of the action of imunofan in the first 2-3 hours and the duration of 2-3 days after administration, the middle and slow phase. In the first hours detoxification effect is manifested, antioxidant protection is enhanced, lipid peroxidation is normalized, the disintegration of phospholipids of the cell membrane and the synthesis of arachidonic acid are inhibited. During the middle phase (from 3 to 10 days), the phagocytosis reaction and the death of intracellular bacteria and viruses increase. As a result of the activation of phagocytosis, there may be a slight exacerbation of the foci of chronic inflammation, sustained due to the persistence of viral or bacterial antigens. During the slow phase (from 10 days to 4 months), the immunoregulatory effects of the drug are manifested - the restoration of disturbed parameters of cellular and humoral immunity. The effect of the drug on the production of specific antiviral antibodies is equivalent to the action of certain vaccines. The drug stimulates the production of IgA when it is deficient, does not affect the production of IgE and, thus, does not enhance allergic reactions - immediate type hypersensitivity. The action of imunofan does not depend on the production of PdE2 and it is possible to use together with anti-inflammatory drugs a steroid and non-steroidal series.

Imunofan is administered intramuscularly or subcutaneously in 1.0 ml of 0.005% solution once a day in 2 days, only 10-15 injections.

The drug is not contraindicated in pregnancy, except for Rh-conflict pregnancy (possibly increasing the titer of antibodies). In pregnancy, we use imunofan in the II and III trimesters with 1.0 ml intramuscular daily courses No. 5-10, depending on the clinical situation: with the exacerbation of a viral bacterial infection complicated by the prolapse of the bladder of ischemic-cervical insufficiency, with suspicion of chorioamnionitis, with increasing the content of proinflammatory cytokines in the peripheral blood and / or in the mucus of the cervical canal, with acute respiratory viral infections in patients with habitual miscarriages.

Tamerite - a combination of synthetic drugs, has anti-inflammatory, immunomodulating and antioxidant effects. The basis is the action of tamerite on the functional and metabolic activity of macrophages and neutrophils. It is used in the form of intramuscular injections in a dose of 1 ampoule (100 mg), diluted with 2-3 ml of water for injection, a course of 5-10 injections every other day. It is used for the treatment of chronic inflammatory processes, including the autoimmune component in pathogenesis.

Derinat - a biologically active substance obtained from milk of sturgeon fish, 1.5% solution of sodium deoxyribonucleate. Has an immunomodulatory effect on the cellular and humoral levels; stimulates reparative processes, hemopoiesis, has an anti-inflammatory effect, has a weak anticoagulant effect. It can be used in the treatment of chronic adnexitis, vaginitis, and prostatitis.

It works very well for chronic virus carrying, syndrome of chronic fatigue. Patients note improvement of health, working capacity.

The drug is used by 5.0 ml intramuscularly after 2 days, only 5 injections. The drug is painful, you must enter it slowly.

Unfortunately, there are no clinical trials on the use of derinata in pregnancy. Judging by its composition, it is a natural product that can not have a pathogenic effect. Nevertheless, while it is not allowed to be used in pregnancy as intramuscular injections.

Drops of derinata are used for the prevention of acute respiratory infections and acute respiratory infections 2-3 drops 2-3 times a day. Drops have an immunomodulatory effect and protect against acute and exacerbation of chronic infections transmitted by airborne droplets. Drops can also be used during pregnancy.

Selection of inducers of interferon is carried out individually on the sensitivity of blood cells to different drugs.

According to studies, ridostin, lorifane, imunofandicloferon, tamerite are more effective and sensitivity to them is almost the same in 85% of patients. Neovir and polyoxidonium, according to research, were ineffective in our patients, these are the preparations of the acute phase of inflammation, and patients with habitual miscarriage have a chronic, low-symptom infection.

Simultaneously with interferon inducers, antiviral therapy is performed with the use of the preparation viferon-2 in the form of rectal suppositories for 1 suppository 3 times a day for 10 days.

Viferon is a complex drug that contains interferon and antioxidant components - ascorbic acid and alpha-tocopherol. In addition, viferon combines the qualities of interferon and interferon inducer.

Treatment at the 2 nd stage is also performed against the background of metabolic therapy of systemic enzyme therapy. After the completion of the second stage of treatment, a control evaluation of the effectiveness of the treatment is conducted:

• bacteriological examination from the cervix;
• smears on Gram;
• PCR-diagnostics from the cervix: herpes simplex viruses, cytomegaloviruses, chlamydia, mycoplasma, ureaplasma;
• evaluation of immune and interferon status.

At normalization of all parameters pregnancy can be resolved.

If the effectiveness of the therapy is insufficient, endovascular laser irradiation of the blood, plasmapheresis, can be suggested.

ELOK - endovascular laser irradiation of blood is performed with the help of the ULF-01 device, generating helium-neon radiation with a wavelength of 0.65 nm and an output power of 1 mW. For intravascular irradiation of blood, a monofilament quartz fiber is used, introduced through the puncture needle into the ulnar vein. The duration of the procedure is 5 minutes on average. Treatment is conducted once a day with a course of 7 sessions.

After the completion of the course of therapy, normalization of the haemostasiological parameters is noted, since laser light of low power leads to an increase in fibrinolytic activity.

In the course of all stages of therapy, metabolic therapy complexes are prescribed, which are selected individually on the basis of a study of histochemistry of lymphocytes. It is known that the enzymatic status of lymphocytes of human peripheral blood is its phenotypic feature and characterizes its somatic state not only at the time of the study, but also with a degree of reliability in the near future. In addition, it has a reliable correlation with the clinical symptoms of many diseases and can be used for the purpose of their early diagnosis and prognosis. Intracellular exchange in leukocytes is subject to changes depending on the phase of the menstrual cycle: an increase in the activity of enzymes during the period of ovulation is regarded as an intensification of energy metabolism throughout the body. When studying the activity of enzymes in women with habitual miscarriage, it was revealed that in the dynamics of the menstrual cycle, a significant depression of oxidation-reduction enzymes, especially the alpha-glycerophosphate dehydrogenase of GDD) is observed. The absence of a peak in the activity of enzymes in the ovulation phase was detected, and the activity of succinate dehydrogenase (SDG) decreased in the second phase of the cycle.

Unlike normative parameters, the activity of acidic phosphatase (CF) in women with miscarriage and chronic viral-bacterial infection is significantly increased in all phases of the cycle.

Pregnancy is accompanied by an effort of tissue metabolism processes, as well as the conjugation of enzymatic activity of lymphocytes in the phase of ovulation and the first weeks of pregnancy. Depression of enzymes is an unfavorable factor in predicting a planned pregnancy. In terms of preparation for pregnancy, the normalization of cytochemical indicators is one of the criteria for preparedness for conception. The courses of metabolic therapy are recommended not only for the future mother, but also for the father. If individual selection of metabolic therapy is impossible, it is possible to use the average type of therapy most acceptable for our patients.

Course of metabolic therapy:

I complex - 5-6 days from 8-9 days of the cycle for 13-14 days:

• kokarboksilaza 100 mg 1 time in / m or benfotiamin 0.01 - 3 times;
• riboflavin mononucleate 1.0 w / m 1 time per day;
• calcium pantetanate 0.1-3 times;
• Lipoic acid 0.25 - 3 times;
• Vitamin E 1 capsule (0.1) - 3 times.

II complex - from 15 to 22 day of the cycle:

• Riboxin 0.2 - 3 times a day;
• pyridoxal phosphate (pyridoxine) 0.005 - 3 times;
• folic acid 0,001 - 3 times;
• fitin 0.25 - 3 times;
• potassium oratate 0.5 - 3 times before meals;
• vitamin E 1 cap (0.1) - 3 times.

Despite the fact that a lot of vitamins enter the complex of metabolic therapy, it is not unique to replace these complexes with polyvitamins, since the complexes are designed to restore the Krebs cycle, and then the normalization of oxidation-reduction processes in cells. When taking multivitamins, there is no such sequence. But we recommend the intake of vitamins between the complexes of metabolic therapy. When detecting patients with infectious genesis of NLF miscarriage, the therapy complex can be supplemented with the appointment of cyclic hormone therapy (Femoston) or Dufaston, and Utrozhestan - in the second phase of the cycle.

Thus, the implementation of antibacterial therapy, immunomodulatory therapy and complexes of metabolic therapy allow to normalize the parameters of immunity and prepare a woman for pregnancy.

Pregnancy can be resolved if: the parameters of hemostasis are within the norm, there are no pathogenic microorganisms in the cervix of the uterus during bacteriological examination and the PCR method, there are no antibodies of IgM class to HSV and CMV, the parameters of the virus are quite satisfactory, the activity of viruses is not more than +, normal immunity and interferon status, normocinosis of the vagina and the parameters of the spermogram of the husband within the norm.