Пост | Api-Norm Natural

Vl. V. Podolsky, V.V. Podolsky

The goal is to develop and determine the effectiveness of pre-gravid training methods for women of childbearing age suffering from infertility.

Patients and methods. 50 women of childbearing age with infertility were examined, and divided into groups:

I group — with primary infertility
II group — with secondary infertility

Bacteriological studies were conducted to assess the species and quantitative composition of the vaginal microflora in women after a course of treatment for vegetative disorders of the nervous system. Depending on the obtained results of the state of microbiocenosis of the urogenital organs in women who had inflammation of the genital organs, at the first stage basic treatment is prescribed, developed for women with this pathology, and the effectiveness of which has been proven. In the second stage, the drug Api-Norm is prescribed in the form of vaginal suppositories, and sexual partners of these women - Api-Norm in the form of rectal suppositories.

Statistical processing of the obtained research results was carried out with the help of the standard computer packages "Data Analysis" and Microsoft Excel for Windows 2007.

The value of the arithmetic mean was calculated - the value (М), the average error of the average value (m), and the level of probability of discrepancies (p). The reliability of the obtained data was assessed by the generally accepted method using the Student's criterion. Reliability was considered established if its probability was equal to at least 95% (0.05).

The results. The obtained data indicate an excess of diagnostic levels of opportunistic microflora in the vast majority of the studied women. It was noted that in women with secondary infertility, qualitative and quantitative indicators of opportunistic microflora, higher than diagnostic levels, occur more often than in women with primary infertility, which may indicate the presence of chronic inflammatory diseases of the genital organs. An insufficient number of lactobacilli is one of the reasons for the impossibility of stabilizing the microbiocenosis of the genital organs in the studied women. The use of modern methods of microbiocenosis correction makes it possible to reduce the level of microbial contamination of the genital tract in such women.

Conclusions. The use of Api-Norm vaginal suppositories in the complex pre-gravid preparation of women suffering from infertility, their preparation for safe motherhood, as well as the use of Api-Norm rectal suppositories in the treatment and prevention of inflammatory diseases in the sexual partners of these women, indicates high efficiency, which allows recommending this drug for complex therapy.

Introduction

According to official statistics, the frequency of infertility in Ukraine ranges from 3 to 3.5 per 1,000 for women, and from 0.3 to 0.4 for men, but unwanted infertility in different regions of Ukraine ranges from 8 to 20% of families. Infertile marriage is a social problem that manifests itself in a decrease in social activity and the working capacity of the population. This problem also has psychological aspects, since the failure to get pregnant worries a woman, and her family relationships become unstable.

Among the causes of infertility, chronic inflammatory diseases of the genital organs (hereinafter referred to as CIDGO) are very common (up to 25%). Changes in the endocrine system, which are already factors of endocrine infertility, occur against the background of CIDGO.

The microbiocenosis of the genital tract of a woman of childbearing age (hereinafter referred to as WCA) consists of gram-positive and gram-negative aerobes, facultatively anaerobic and obligately anaerobic microorganisms, and 95–98% of all microorganisms are H202-producing strains of lactobacilli. A decrease in the level of contamination of the genital tract with lactobacilli is accompanied by an active proliferation of conditionally pathogenic microflora.

Gram-positive cocci (epidermal and aureus staphylococcus, enterococcus, and streptococci of various serological groups) are registered with the highest frequency in CKD. The coccal microflora has the ability to adapt to adverse environmental conditions, antiseptics, and antibiotics. Dominant positions are occupied by staphylococci, which have a wide range of factors of aggression and their own defense. Staphylococcus aureus synthesizes lethal toxins, dermonecrotoxin, leukocidin, hemolysin, and enterotoxin. The pathogenicity factors of staphylococci include their ability to produce plasmacoagulase, lecithinase, and cause hemolysis of erythrocytes.

Also, causative agents of infectious processes can be gram-negative bacilli of the intestinal group and anaerobes of various species. The virulence of enterobacteria is associated with bacterial exo- and endotoxins. They cause lysis of erythrocytes and leukocytes and also lead to proteolysis of cells.

Along with bacteria, fungi of the genus Candida participate in the formation of inflammatory processes. The development of candidiasis is aggravated by hormonal disorders, viral infection, immunodeficiencies, changes in metabolism, and inadequate therapy. In the development of vaginal candidiasis, filamentation and subsequent adhesion of Candida to the vaginal mucosa are important stages. The main factor in the virulence of Candida fungi is their genotypic and phenotypic instability, as well as the secretion of proteinases, which leads to adhesion and invasion of the pathogen into the mucous membrane. Factors causing the activation of the adhesive properties of Candida fungi are drugs that are often used in obstetrics and gynecology practice. Antibacterial drugs increase the virulence of fungi due to the suppressive effect on immunological reactivity.

Gardnerella occurs with high frequency in women of childbearing age. These facultatively anaerobic bacteria have the ability to produce toxic bioproducts: mucolytic enzymes and hemolysin. When the proliferation of Gardnerella vaginalis increases against the background of suppression of its main antagonists — lactobacilli, it acquires pathogenic properties, which are manifested in the production by some strains of the enzyme spalidase, which is active against globular glycoproteins of the mucous membrane of the vagina. It is believed that the leukotoxic factor produced by Gardnerella causes structural and functional disorders of leukocytes.

The developed methods of treatment of CIDGO in WCA with infertility have proven to be highly effective. However, HCVS in this group of women have a tendency to frequent relapses. In this regard, it is important to carry out treatment and preventive measures to prevent recurrences of CIDGO in women with infertility and to prepare them for safe motherhood.

Research materials and methods

50 women of childbearing age with infertility were examined, and divided into groups:

I group — with primary infertility
II group — with secondary infertility

Bacteriological studies were conducted in order to assess the species and quantitative composition of the vaginal microflora in women after a course of treatment for vegetative disorders of the nervous system.

Microbiological analyses and accounting of the results were carried out in accordance with the Order of the Ministry of Health of the USSR No. 535 of 1985 and the Order of the Ministry of Health of Ukraine No. 234 of May 10, 2007.

The following differential diagnostic media were used for mucus culture: blood agar, yolk-salt agar, Endo, Saburo media, and MRS media for lactobacilli.

Sowing was carried out by the method of sector sowing on dense nutrient media, which made it possible to determine the degree of microbial insemination and to reveal the maximum possible spectrum of aerobic and facultatively anaerobic microflora.

The taxonomic position of microorganisms is determined according to "Bergey's Bacteria Identifier". Microorganisms were identified by their cultural and morphological characteristics.

Determination of the number of lactic acid bacteria was carried out after 24–48 hours. incubation at a temperature of 37±1°C. In smears that were stained by Gram, lactobacilli had the appearance of gram-positive rods.

To determine staphylococci, yolk-salt agar was used, on which staphylococci were used in the form of yellow or white convex colonies. The pigmentation of the colonies and the presence of lecithinase activity were taken into account during the study.

Identification of detected microorganisms was carried out on an automatic microbiological analyzer BD BBL Crystal (USA).

Sabouraud's medium was used to identify yeast-like fungi. Cups with sieves were incubated in a thermostat at a temperature of 37 ± 1°C for three days, then colonies characterized by morphology (dense, opaque, milky) were microscopically examined in a 40% solution of caustic soda. In smears, yeast-like fungi have the appearance of large oval gram-positive cells located singly, in clusters, or chains.

Depending on the obtained results of the state of microbiocenosis of the urogenital organs in women with infertility who had CKD, a basic treatment developed for women with this pathology and the effectiveness of which has been proven is prescribed at the first stage. In order to prevent and treat exacerbations of CKD and in the complex pre-gravid preparation for safe motherhood of women who suffer from infertility, in the second stage, the drug Api-Norm is prescribed for 1 candle intravaginally at night, 1 time a day for 10 days, and then 2 times a week a total course of 15 suppositories. This drug in the form of rectal suppositories is also prescribed to sexual partners of women suffering from infertility, 1 suppository rectally at night once a day for 10 days, and then 2 times a week for a total course of 15 suppositories.

Api-Norm vaginal suppositories contain a balanced multicomponent composition based on beekeeping products and plant components. The drug has a combined anti-inflammatory, antispasmodic, adaptogenic, anti-infective, antioxidant, and wound-healing effect; prevents the development of complications and possible relapses in diseases of the internal organs of the pelvis; activates, modulates, and supports the body's own protective mechanisms, including cellular immunity; penetrates deep into tissues, saturates them with natural components, trace elements, and vitamins; compatible with many other preventive and therapeutic drugs.

Thanks to the special technology of obtaining constituent components and their activation, Api-Norm differs from other drugs of similar orientation in high activity and increased bioavailability of active substances. Due to the well-chosen components, the properties of the components of the drug reduce the likelihood of side effects and allergic reactions.

Plant components and beekeeping products included in Api-Norm have a high level of effectiveness and safety from the point of view of evidence-based medicine.

We chose this drug because the components of multicomponent vaginal suppositories have a positive effect on the condition of women's reproductive organs. It includes:

Sea buckthorn oil has an anti-inflammatory, pain-relieving, antibacterial (especially against staphylococci and Proteus) effect. Promotes epithelization and granulation of tissues, and accelerates wound healing. Normalizes degenerative changes of mucous membranes. Contains a complex of vitamins.
Calendula extract has regenerative, antibacterial, antiviral, analgesic, anti-inflammatory, and bacteriostatic (especially against streptococci and staphylococci) effects. Suppresses the migration of leukocytes in places of inflammation. It is used for disorders of the menstrual cycle, ulcers, erosions, and white hair.
Propolis extract has antioxidant, antiviral, antibacterial, anti-inflammatory, wound-healing, antispasmodic, and antiseptic effects. Its composition includes more than fifty biologically active substances, a large number of vitamins, and trace elements. Increases the number of immunoglobulins (increases specific immunity). Enhances the effect of natural and synthetic antibiotics and antimycotics. Stabilizes cell membranes. Delays the growth of cancer and pathological cells.
St. John's wort extract has an antibacterial, antiseptic, pain-relieving effect, and also enhances the regenerative capacity of tissues. Reduces spasms and fragility of blood vessels. The important active substances of St. John's wort are essential oils, flavonoids (rutin, quercitrin, hyperoside), and hypericin.
Natural beeswax has an anti-inflammatory, antiseptic, and softening effect, and is a source of vitamin A and trace elements important for cellular immunity. Increases the biological activity of the constituent plant extracts.

Api-Norm rectal suppositories, which were prescribed to sexual partners of women suffering from infertility, have a combined anti-inflammatory, antispasmodic, adaptogenic, anti-infective, antioxidant, and wound-healing effect; have an antitumor effect, delay the development of hyperplasia, reduce the risk of cancer; prevent the development of complications and possible relapses in diseases of the prostate gland and other internal organs of the pelvis; activate, modulate and support the body's protective mechanisms, including cellular immunity; penetrate deep into tissues, saturate them with trace elements and vitamins; compatible with many other preventive and therapeutic drugs. Medical preventive measures for sexual partners of women suffering from infertility are important because they ensure the effectiveness of medical and preventive measures for these women

Rectal suppositories are slightly different from those prescribed for women and contain:

Black poplar extract has antioxidant, anti-inflammatory, antimycotic, and antimicrobial effects. Promotes epithelization and granulation of tissues. The content of populin glycoside determines the pain-relieving properties. The antihistamine properties of the extract reduce the risk of allergic reactions from other components.
Comfrey extract has a regenerative, analgesic, anti-inflammatory, hemostatic, and enveloping effect, and exhibits antitumor activity. Among its main active substances are allantoin, zinc, vitamin B12, triperten. Antioxidant properties prevent the development of malignant neoplasms.
Propolis extract has antioxidant, antiviral, antibacterial, anti-inflammatory, wound-healing, antispasmodic, and antiseptic effects. Its composition includes more than fifty biologically active substances, a large number of vitamins, and trace elements. Increases the number of immunoglobulins (increases specific immunity). Enhances the effect of natural and synthetic antibiotics and antimycotics. Stabilizes cell membranes. Delays the growth of cancer and pathological cells.
St. John's wort extract has an antibacterial, antiseptic, pain-relieving effect, and also strengthens the regenerative capacity of tissues. Reduces spasms and fragility of blood vessels. The important active substances of St. John's wort are essential oils, flavonoids (rutin, quercitrin, hyperoside), and hypericin. Natural beeswax has an anti-inflammatory, antiseptic, and softening effect, and is a source of vitamin A and trace elements important for cellular immunity. Increases the biological activity of the constituent plant extracts.
Ascorbic acid, which is part of Api-Norm (17 mg per 1 suppository), is an antioxidant, plays an active role in regulating redox processes, carbohydrate metabolism, blood coagulation, and tissue regeneration; increases the body's resistance to infections, reduces vascular permeability, reduces the need for other vitamins (B1, B2, A, E, folic acid, pantothenic acid). Enhances absorption and increases the bioavailability of flavonoids. The statistical processing of the obtained research results was carried out using the standard computer package "Data Analysis" Microsoft Excel for Windows 2007. The value of the arithmetic mean was calculated - the value (М), the average error of the average value (m), and the level of probability of discrepancies (p). The reliability of the obtained data was assessed by the generally accepted method using the Student's criterion. Reliability was considered established if its probability was equal to at least 95% (0.05).

Research results and their discussion

Bacteriological examination of vaginal secretions in women with primary infertility showed that Gram-positive cocci predominated in the microbiocenosis. Epidermal staphylococcus with hemolytic properties was cultured most often (23.8%), and its concentration was lg 5.94±0.04 CFU/ml, respectively. At the same time, the frequency of detection of microflora of this type in women with secondary infertility was slightly higher (25.8%), the quantitative indicator also exceeded the diagnostic level and was higher than in women with primary infertility — lg 6.45±0.02 CFU/ Jr

The frequency of seeding of Staphylococcus aureus in FP with primary infertility was 22.2%, while the value of the quantitative indicator was equal to lg 5.55±0.03 CFU/ml, in FP with secondary infertility, Staphylococcus aureus was seeded in 25% of cases in the amount of lg 6, 25±0.04 CFU/ml.

Among the representatives of enterobacteria, the following were cultured with a high frequency in FVV with primary and secondary infertility:

Escherichia coli — 22.6% and 25%;
Escherichia coli with hemolytic properties — 22.2% and 26.6%;
Klebsiella — 21.4% and 22.2%;
Enterobacteria — 22.2% and 21%.

Quantitative indicators of vaginal insemination by enterococci in FPV with primary and secondary infertility also exceeded the diagnostic threshold and were, respectively:

Escherichia coli — lg 5.65±0.02 CFU/ml and lg 6.25±0.04 CFU/ml;
Escherichia coli with hemolytic properties — lg 5.55±0.02 CFU/ml and lg 6.65±0.03 CFU/ml;
Klebsiella — lg 5.35±0.02 CFU/ml and lg 5.55±0.02 CFU/ml;
Enterobacteria — lg 5.55±0.04 CFU/ml and lg 5.25±0.03 CFU/ml.

Also, among the representatives of opportunistic microflora in FP with primary and secondary infertility in the amount exceeding the diagnostic threshold, the following were found, respectively:

S. viridans — lg 5.05±0.02 CFU/ml and lg 5.35±0.02 CFU/ml;
S. faecalis — lg 5.65±0.04 CFU/ml and lg 5.45±0.04 CFU/ml;
S. agalactiae — lg 4.95±0.04 CFU/ml and lg 5.25±0.02 CFU/ml.

The frequency of sowing Candida fungi was 25%. These results proved a significant increase in the microbiocenosis of the genital tract of women in the content of opportunistic microorganisms, which can be an etiological factor in the development of inflammation of the genital tract and reduce the chances of the desired pregnancy.

Three- and four-component associations of opportunistic microorganisms were found in a large number (65%) of the examined. The associations most often included staphylococci with pathogenic properties and enterobacteria (Klebsiella, Escherichia coli with hemolytic properties) in combination with enterococcus and Candida fungi.

The study of the presence of lactobacilli showed that in women with primary and secondary infertility, they were detected in concentrations that did not reach the indicators of healthy women — lg 3.05±0.02 CFU/ml and lg 2.25±0.02. The state of protective microflora plays a significant role. Lactobacilli have a number of useful properties. They suppress the toxicity of some microorganisms, produce substances of an antibiotic nature, act as antagonists to many conditionally pathogenic bacteria, and stimulate the synthesis of secretory lgA and lysozyme (Tab1).

The results of the examination of WCA with infertility after treatment showed a decrease in the frequency of seeding of opportunistic microflora in patients of both groups, respectively: S. epidermidis (hem.), — 17% and 17.8%, S. aureus — 16.2% and 17%; and streptococci — S. agalactiae — 11.4% and 12.2%, S. viridans — 13% in both groups, S. faecalis — 16.2% and 15.8%. The quantitative level of gram-positive cocci did not exceed the diagnostic level.

The frequency and quantification of enterobacteriaceae in infertile ICUs were significantly lower compared to gram-negative bacilli before treatment. The frequency of registration of E. coli was 13% in both groups, Klebsiella — 14.6% and 13.8%, respectively. Quantitative indicators of these types of enterobacteria were within normal limits: Klebsiella — respectively, lg 3.65±0.02 CFU/ml and lg 3.45±0.02 CFU/ml; E. coli — lg 3.45±0.04 CFU/ml and lg 3.45±0.03 CFU/ml. The detection frequency of Candida fungi was 17% and 17.8%, respectively. The quantitative level of Candida fungi seeding in women with primary infertility was lg 4.25±0.03 CFU/ml, and in women with secondary infertility — lg 4.45±0.04 CFU/ml and did not exceed the diagnostic level. The frequency of lactobacilli seeding after the treatment increased to 17.8% and 18.6% in women of the examined groups, respectively (Tab 2).

* — The difference is statistically significant between indicators in women of childbearing age with primary infertility before and after treatment (p>0.05);

** — The difference is statistically significant between indicators in women of childbearing age with secondary infertility before and after treatment (p>0.05).

Conclusions

In women with primary and secondary infertility, there is an increase in the concentration of opportunistic microflora, which can be the cause of the inflammatory process and affect the onset and course of pregnancy.

Colonies of opportunistic microorganisms are detected more often and in larger quantities in FPV with secondary infertility, which may indicate the presence of chronic inflammation and decreased immunity.

An insufficient number of lactobacilli is one of the reasons for the impossibility of stabilizing the microbiocenosis of the genital organs in women with primary and secondary infertility.

The use of modern methods of microbiocenosis correction makes it possible to reduce the level of microbial contamination of the genital tract in women with primary and secondary infertility.

The use of Api-Norm vaginal suppositories in the complex pre-gravid preparation of women suffering from infertility, their preparation for safe motherhood, as well as the use of Api-Norm rectal suppositories in the treatment and prevention of inflammatory diseases in the sexual partners of these women, indicates high efficiency, which allows recommending this Api-Norm suppositories for complex therapy.