Povidone-iodine solution for local and external use 10%, 120ml (Yuzhfarm)

Povidon Jod

Release form, composition and packaging

Solution for external use 10% in the form of a dark brown liquid with a characteristic odor of iodine. 100 ml povidone-iodine 10 g. Excipients: nonoxynol, glycerol, disodium hydrogen phosphate 12-hydrate, citric acid, sodium hydroxide, demineralized water.

Foaming solution for external use 7.5% in the form of a dark brown liquid with a characteristic odor of iodine; Foams when shaken. 100 ml povidone-iodine 7.5 g. Excipients: lauric acid diethanolamide, ammonium nonylphenylethoxylate sulfonic acid, sodium phosphate 12-hydrate, citric acid, demineralized water.

Solution for local use concentrated 8.5% 1 ml povidone-iodine 85 mg Ointment for external use 10% dark brown, homogeneous, with a characteristic odor of iodine. 100 g povidone-iodine 10 g Excipients: macrogol 4000, purified water. Vaginal suppositories 1 sup. povidone-iodine 200 mg Clinical and pharmacological group: Antiseptic for external and local use.

pharmachologic effect

Antiseptic and disinfectant drug. Released from the complex with polyvinylpyrrolidone upon contact with the skin and mucous membranes, iodine forms iodamines with bacterial cell proteins, coagulates them and causes the death of microorganisms. It has a rapid bactericidal effect on gram-positive and gram-negative bacteria (with the exception of Mycobacterium tuberculosis). It is also active against fungi, viruses, and protozoa. It has a longer action compared to a solution of inorganic iodine.

Pharmacokinetics

When applied externally, the reabsorption of iodine from the surface of the skin or mucous membrane or wounds is extremely insignificant.

Indications

Solution for external use 10%

• treatment and prevention of wound infections in surgery, traumatology, combustiology, dentistry;
• treatment of bacterial, fungal and viral skin infections, prevention of superinfection in dermatological practice;
• treatment of bedsores, trophic ulcers, diabetic foot;
• disinfection of the skin and mucous membranes of patients in preparation for surgical interventions, invasive studies (including punctures, biopsies, injections);
• disinfection of the skin around drainages, catheters, probes;
• disinfection of the oral cavity during dental operations;
• disinfection of the birth canal during minor gynecological operations (including artificial termination of pregnancy, insertion of an intrauterine device, coagulation of erosion and polyp).

Foaming solution for external use 7.5%

• disinfectant baths - for complete and partial treatment of the patient before operations;
• hygienic treatment of patients;
• hand hygiene when in contact with infected patients;
• processing of instruments (not metal) and patient care items.

Concentrated topical solution 8.5%

• for rinsing the mouth and throat.

Ointment for external use 10%

• bacterial and fungal skin infections;
• burns;
• trophic ulcers;
• bedsores;
• infectious dermatitis;
• abrasions;
• wounds.

Vaginal suppositories

• candidiasis;
• trichomoniasis;
• nonspecific vaginitis.

Dosage regimen

Solution for external use 10% For treating the skin and mucous membranes, use undiluted for lubrication, rinsing or as a wet compress. For use in drainage systems, the solution is diluted 10 to 100 times.

Foaming solution for external use 7.5% To disinfect the hands of surgical personnel, apply 5 ml of undiluted solution to pre-washed hands and distribute it evenly to the elbows, rubbing for 2.5 minutes with palms or a brush until foam forms (the foam is washed off with sterile water or removed with a sterile napkin); then the treatment is repeated.

To disinfect the skin of the surgical field, apply the drug to shaved and moistened skin with water and rub it in to form foam. 1 ml of the drug is enough to apply to the skin surface of 50-70 cm2 by rubbing for 5 minutes. The foam is removed using a sterile gauze pad soaked in water, after which the skin is lubricated with an undiluted solution and dried.

Concentrated solution for topical use 8.5% To rinse the mouth and throat, dilute 1 teaspoon of solution in 1/4 glass of water. Rinsing is carried out several times a day. Ointment for external use 10% The ointment is applied in a thin layer to the affected area 2-3 times a day, can be used under an occlusive dressing.

Vaginal suppositories

Prescribed 1-2 pieces/day. Duration of treatment is 14 days or as directed by a doctor. Before using vaginal suppositories, sanitation is necessary.

Side effect

Possible: allergic reactions. Local reactions: in some cases, allergic reactions to iodine - hyperemia, burning, itching, swelling, pain (drug discontinuation required). Systemic reactions: when used on a large area of ​​the wound surface and mucous membranes, systemic reabsorption of iodine is possible, which can cause neutropenia, as well as change the results of tests of functional activity of the thyroid gland; with long-term use (more than 7-10 days), symptoms of iodism are possible (including a metallic taste in the mouth, increased salivation, swelling of the eyelids or larynx).

Contraindications

• hyperthyroidism;
• thyroid adenoma;
• heart failure;
• chronic renal failure;
• Dühring's dermatitis herpetiformis;
• simultaneous use of radioactive iodine;
• premature and newborn babies;
• children under 8 years of age (ointment for external use);
• pregnancy;
• lactation;
• hypersensitivity to iodine and other components of the drug.

Pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Use for renal impairment

Contraindicated in chronic renal failure.

special instructions

If side effects develop, discontinuation of the drug is required. The presence of blood and pus may reduce the antimicrobial effect of the drug. Do not use for bites from insects, domestic or wild animals. The patient should be warned about the need to consult a doctor if systemic reactions occur. It is necessary to ensure that no excess solution remains under the patient. A colored film is formed at the site of application, which remains until the entire amount of active iodine is released, i.e. its disappearance means the drug has ceased to act. Coloring on leather and fabrics is easily washed off with water. Do not heat before use.

Overdose

Symptoms: local irritation, allergic reactions. Treatment: reducing the frequency of use or completely stopping the use of the drug.

Drug interactions

Povidone iodine is incompatible with other disinfectants and antiseptics, especially those containing alkalis, enzymes and mercury. In an acidic environment, the activity of the drug decreases.

Storage conditions and periods

List B. Solutions should be stored in a place protected from light, tightly closed, at a temperature of 0° to 25°C. The ointment should be stored in its original packaging at a temperature between 0° and 25°C. The shelf life of the drug in the form of a solution for external use 10%, an ointment for external use 10% and vaginal suppositories is 3 years. The shelf life of a solution for external use, foaming 7.5%, and a solution for topical use, concentrated 8.5%, is 2 years.

Povidone-iodine solution for local and external use 10%, 120ml (Yuzhfarm)

Registration Certificate Holder

YUZHFARM (Russia)

Dosage form

Medicine - Povidone-Iodine

Description

Solution for local and external use

dark brown in color, with a characteristic odor of iodine.

100 ml

povidone-iodine 10 g

Excipients

: glycerol - 1.275 g, nonoxynol 9 - 0.312 g, sodium hydrogen phosphate dodecahydrate - 0.32 g, citric acid monohydrate - 0.1 g, sodium hydroxide - 0.117 g, purified water - up to 100 ml.

10 ml - bottles (1) - cardboard packs. 15 ml - bottles (1) - cardboard packs. 30 ml - bottles (1) - cardboard packs. 50 ml - bottles (1) - cardboard packs. 100 ml - bottles (1) - cardboard packs. 120 ml - bottles (1) - cardboard packs. 250 ml - bottles (1) - cardboard packs. 400 ml - bottles (1) - cardboard packs. 450 ml - bottles (1) - cardboard packs. 500 ml - bottles (1) - cardboard packs. 1000 ml - bottles (1) - cardboard packs. 100 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 120 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 250 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 400 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 450 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 500 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals). 1000 ml - bottles from 4 to 50 pcs. — cardboard boxes (for hospitals).

Indications

For treating the patient’s skin before and after operations, research (biopsy, puncture, blood drawing, injections, etc.), pre- and postoperative treatment of the hands of surgeons, medical personnel, hygienic treatment of hands when caring for infected patients, treatment of instruments and patient care items.

For local use: infections of the nasopharynx, treatment of infected skin lesions (burns, wounds, ulcers, abrasions), prevention of infection of wound surfaces, treatment of nonspecific vaginitis, trichomoniasis.

Contraindications for use

Hyperthyroidism, thyroid adenoma, renal failure, pregnancy, lactation (breastfeeding), hypersensitivity to iodine. Cannot be used to treat the skin of premature and newborn babies.

pharmachologic effect

Antiseptic. It is iodine in the form of polyvinylpyrrolidone iodine complex. The concentration of active iodine is from 0.1% to 1%. Has a wide spectrum of antimicrobial action. Active against bacteria (including Mycobacterium tuberculosis), fungi, viruses, protozoa. Polyvinylpyrrolidone iodine is an iodophor that binds iodine. Upon contact with the skin and mucous membranes, iodine is gradually and evenly released, exerting a bactericidal effect on microorganisms. At the site of application of povidone-iodine preparations, a thin colored layer remains, which remains until all the iodine is released, after which its effect ceases.

Drug interactions

Pharmaceutically incompatible with disinfectants containing mercury; oxidizing agents, alkali salts and acidic substances.

Dosage regimen

Individual, depending on the indications and dosage form used.

Side effect

Local manifestations of hypersensitivity to iodine (itching, hyperemia) are possible, which requires discontinuation of treatment.

special instructions

Povidone-iodine solution should not be used in combination with other antiseptics or enzymatic ointments. Before systematic use of povidone-iodine preparations, trial use is advisable. In the presence of blood, the bactericidal effect of povidone-iodine may be reduced. Avoid contact of povidone-iodine preparations with the eyes.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Contraindicated during pregnancy and lactation.

Use for renal impairment

Restrictions for impaired renal function - Contraindicated.

Contraindicated in renal failure.

Use in children

Restrictions for children - Contraindicated.

Cannot be used to treat the skin of premature and newborn babies.

The effect of povidone-iodine on the eradication of highly oncogenic HPV types in women with cervical lesions

Relevance

Over the past decade, significant advances have been made in understanding the role of human papillomavirus (HPV) in the development of cervical cancer (CC) and other anogenital cancers. HPV is the main etiological agent of cervical dysplasia and carcinoma [1]. CC is the third most common gynecological cancer in developed countries. In Russia, the number of deaths from cervical cancer has increased by 3,500 women per year. Approximately half of patients with cervical cancer are women of reproductive age (under 50 years old) [2]. Recently, more than 200 women aged 20–39 years die annually for this reason. HPV is a common virus that is transmitted horizontally through heterosexual contact. Approximately 80% of all women are infected with HPV at some point in their lives, but in about 90% the human papillomavirus (PVI) infection resolves spontaneously within a few years. In the absence of independent elimination, cervical cancer may develop. Almost 100% of squamous intraepithelial lesions and CC, about 43% of vulvar tumors and 70% of vaginal tumors are associated with PVI, which annually causes 530 thousand new cases of CC and 21 thousand cases of vulvar and vaginal cancer worldwide [3]. In the absence of a screening strategy, there is an increase in the incidence of cervical cancer and vulvar cancer in young women [4]. HPV is a double-stranded DNA virus belonging to the genus Papilloma
in the family
Papovaviridae
[5]. It has been established that HPV is the most common sexually transmitted infection and is the main cause of cervical squamous intraepithelial lesions and invasive cervical cancer. There are more than 100 types that infect the epithelium of the reproductive tract. Transmission of HPV occurs primarily through skin-to-skin contact and probably through disruption of the epidermis, where the virus can infect basal squamous epithelial cells [6].

Types of HPV and their role in the development of cancer processes

To date, more than 100 HPV genotypes have been identified in the female reproductive tract. 13 HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) are recognized as highly oncogenic (13HR) cancer-causing types. However, other types of HPV may also be associated with cancer. According to N. Munoz, two additional types of HPV - 73 and 82 - should be considered carcinogenic. G. Halec et al. demonstrated from a systematic review that HPV types 26, 53, 66, 67, 68, 70, 73 and 82 may be oncogenic [7]. One of the most important issues is that polymerase chain reaction (PCR)-based diagnostics used in epidemiological studies have limitations. Firstly, the PCR method detects not only highly oncogenic, but also other types of HPV. Second, some PCR tests using consensus primers have shown inconsistent results in identifying HPV types because the detection sensitivity of some HPV types is lower than that of others. Low-risk HPV types such as 6, 11, 40, 42, 43, 44, and 54 are associated with genital warts and low-risk anogenital lesions [8]. High-risk HPV types 16 and 18 together account for about 70% of cervical cancer cases, while low-risk HPV types 6 and 11 are responsible for 90% of genital warts [9]. The immune system plays an important role in controlling the development of cancer. The HPV genome encodes two oncoproteins - E6 and E7, capable of inactivating p53 proteins, and retinoblastoma (pRB) - regulators of cell proliferative activity. They are necessary for the emergence and maintenance of the malignant cell phenotype [10]. The adaptive immune response protects against HPV-induced diseases [11]. The progression of HPV-induced disease is associated with the lack of strong HPV-specific CD4+ and CD8+ T cell responses. Chemotherapy or radiation therapy influences immune regulatory activity and, in combination with vaccination, potentiates effective local HPV-specific T-cell immunity in mouse tumor models. Successful treatment of HPV-induced lesions can be achieved with low-dose cyclophosphamide, which modifies local immunity. Given the importance of the local microenvironment in the persistence of HPV-induced lesions and tumors, treatments that can locally shift the balance of immunoeffectors, such as cyclooxygenase-2 inhibitors, through the production of prostaglandin E2 and transforming growth factor β may be effective [12]. Vulvar carcinoma has two distinct carcinogenic pathways, one of which is associated with HPV type 16. It is the fourth most common invasive gynecological cancer, affecting mainly older women and is more common in Western countries [13]. Prognostic factors for the course of the disease include the presence or absence of metastases in the lymph nodes, as well as tumor size and recurrence. Relapse (hematogenous metastases) is observed in 40% of patients. The prognostic role of HPV in vulvar cancer is debated, with some studies showing better survival in women with HPV-positive vulvar tumors, others not [14]. An important issue remains the organization of screening programs. Such programs are being implemented effectively in New Zealand. National recommendations for a cervical cancer screening program recommend that all women aged 20 to 69 years who have ever had sexual intercourse be given a cervical smear within 3 years. If this is a primary screening smear or more than 5 years have passed since the previous test, it is recommended that the second smear be repeated one year after the first, and then after 3 years. After the introduction of this screening program, the incidence of cervical cancer decreased significantly, currently amounting to 5.4 per 100 thousand women [15]. In addition, a large study on the distribution of HPV genotypes in cervical samples was carried out in New Zealand. The material was collected from women with highly oncogenic HPV types (in 2009–2011) or suffering from invasive cervical cancer (in 2004–2010). The most common HPV types causing cervical neoplasia (cervical intraepithelial neoplasia - CIN 2 and 3) were HPV types 16 (51%), 52 (19%), 31 (17%), 33 (13%) and 18 (12 %). However, there was a trend toward increased rates of infection with HPV types 16 and 18 compared to other HPV genotypes in women aged 20–29 years. The most common HPV genotypes associated with invasive CC were HPV 16 (51%), 18 (21%), 31 (4%), 45 (3%) and 52 (3%) [16]. In 2008, New Zealand introduced the National Women's Immunization Program with the quadrivalent HPV vaccine (genotypes 6, 11, 16, 18). More recently, in 2013–2016, a study showed a decrease in the proportion of cervical intraepithelial neoplasia (CIN 2) associated with HPV 16/18 in a cohort of young New Zealand women, which may be associated with the implementation of the national HPV vaccination program. This study was significant because it was the first documented change in HPV genotype in women with cervical lesions after initiation of a vaccination program [17]. HPV type 16 is the most common genotype identified worldwide in patients with invasive CC, followed by HPV type 18. Eight HPV genotypes (16, 18, 31, 33, 35, 45, 52 and 58) lead to higher rates of CC progression [18]. The clinical guidelines of the Japanese Society of Obstetrics and Gynecology and the Japanese Association of Obstetricians and Gynecologists provide an algorithm for the management of patients with CIN, which includes HPV genotyping to determine the risk of progression to CIN 3 [19]. However, the relationship between HPV genotype and cancer prognosis remains controversial. Some studies have shown that HPV 18-positive tumors are associated with poor prognosis [20]. Other authors have stated that Chinese and British patients with tumors associated with HPV 16 and/or 18 have better survival, while in Taiwan favorable results were obtained for HPV 58- and 31-positive tumors [21]. On the contrary, other scientists have not found any associations between the HPV genotype and the prognosis of cervical cancer in Russian and Korean populations [22]. A cervical cytology study performed at three institutions in Japan demonstrated that HPV 18-positive tumors were associated with poor survival in women. Longer follow-up (102 months) confirmed that HPV 16-positive tumors correlated with better survival compared with HPV 18-positive tumors. These conflicting results may be due in part to geographic differences in HPV type prevalence [23].

Factors that increase susceptibility to HPV

Microbes are considered the main trigger factor for the development of malignant neoplasms. The Human Microbiome Project (HMP) has determined that 20% of all fatal malignancies are microbiologically induced. The ectocervix is ​​colonized by microbes, whereas the endocervix and upper genital tract are considered virtually sterile in healthy women. Changes in the cervicovaginal microbiome and processes such as bacterial vaginosis, cervical inflammation and increased vaginal pH influence susceptibility to cervical HPV. Women in different ethnic groups have different vaginal microbiomes [24]. Most cervicovaginal infections and vaginal discomfort are caused by Gardnerella vaginalis
or
Atopobium vaginae
[25], as well as Candida albicans [26].
The cervical epithelium becomes vulnerable to infectious microbial agents such as HPV [27]. With the development of modern sequencing techniques, it is becoming clear that the microbiome influences susceptibility to cancer through the production of harmful metabolites and their impact on cellular function, since deregulated metabolism and inflammation are hallmarks of cancer [28]. The relationship of specific microbes (prokaryotic and eukaryotic) with HPV infections and cervical neoplasia remains one of the significant research issues. It is known that the microbiome of healthy women is dominated by Lactobacilli
.
This constant vaginal species produces lactic acid in the form of fermentation of products, which leads to a decrease in vaginal pH to 3.5–4.5, creating a chemical barrier to pathogens [29]. High levels of L. iners
are associated with the risk of developing HPV-associated cervical lesions.
An increase in body mass index correlates with an increase in the abundance of L. iners
, which makes obesity a significant factor in the development of CIN [30].
L. iners are more adaptable to pH changes and a variety of metabolic conditions than other lactobacilli. L. kitasatonis
and
L. crispatus
in the cervix in combination with highly oncogenic HPV types increase the risk of developing CIN 3. Floral diversity correlates with the severity of CIN.
The presence of Sneathia sanguinegens, Anaerococcus tetradius,
and
Peptostreptococcus anaerobius
in the vaginal microbiome of Caucasian, Asian, and Black women is often associated with the development of CIN.
P. micros
is an uncommon taxon commonly found in the oral cavity, found in the salivary microbiome and common in the presence of cervical lesions.
It has been suggested that P. micros can penetrate the cervicovaginal tract as a result of oral sex [31]. A direct connection of HPV with the dominance of three fungi of the genera Candida
,
Malassezia
and
Sporidiobolaceae was discovered.
Malassezia are lipophilic fungi that parasitize the upper layers of human skin and cause superficial fungal infections such as atopic dermatitis and psoriasis.
Malassezia
is often found on the foreskin and glans penis in men. Malassezia produce bioactive indolysines, including aryl hydrocarbon receptor (AhR) activators. AhR receptors mediate many skin functions, including promoting cell division, and it has been suggested that Malassezia may be involved in skin carcinogenesis. A recent study found that certain cervicovaginal tract microbiome structure correlates with both highly tumorigenic types of PVI and CIN severity in a population of women of reproductive age. Therefore, searching for features of the cervicogenital microbiome may be an important step in understanding the biology of cervical neoplasia and developing new therapeutic regimens targeting the microbiota [32].

Treatment of dysplastic changes in the cervix

Because CIN primarily affects women of reproductive age, there is a need for early identification and improved treatment strategies for the most clinically significant CIN. Persistent infection with highly oncogenic HPV types is a necessary condition for the progression of cervical pathology. Primary (vaccination) and secondary prevention (cervical screening) can have a decisive impact on cancer prevention [32]. The search for drugs aimed at treating dysplastic changes in the cervix is ​​an important area of ​​gynecology. Iodine is an antiseptic that has been used in medical practice for more than 150 years. Povidone-iodine
is one of the most powerful and effective iodine-containing antiseptics with a wide spectrum of action.
The main difference of this drug is that when it is taken, microbial resistance does not arise; it is less likely than antibiotic-containing drugs to cause an allergic reaction. The antiseptic effect of povidone-iodine is associated with a strong oxidative effect. Under the influence of povidone-iodine, pores form in the membranes of microbial cells, which leads to disruption of the integrity of the cell membrane, damage to the cell and loss of viability. The drug has several advantages over other antiseptics. Firstly, it more effectively stops the proliferation of microorganisms even in large dilutions. Secondly, povidone-iodine has the widest antiviral spectrum of action, including enteroviruses, polio and herpes viruses, as well as adenoviruses and influenza virus. Povidone-iodine is a stable drug, its effectiveness does not change under the influence of physicochemical conditions at the site of inflammation, caused by changes in pH, proteins, blood, and the action of enzymes. In gynecological practice, it is most often used to treat inflammatory processes and prevent the development of complications after invasive interventions [33]. The drug has been demonstrated to induce the death of HeLa epithelial cells in rats. Additional evidence supporting the potent antitumor effects of the iodine molecule and iodolactones was established through cell culture studies. They found a significant reduction in cell growth in breast cancer. A decrease in proliferation under the influence of iodine molecules was also noted in other human malignant cell lines (neuroblastoma, glioma, melanoma, lung, colon, and pancreatic carcinomas) [34]. Comparative analysis of the antiproliferative/cytotoxic ability of I2, potassium iodide (KI), a combination solution of KI+I2, povidone-iodine and I2+ [KI+glycerol] on human carcinoma cells showed that povidone-iodine may be a potential tool for directly interfering with tumor growth. cells [35]. A randomized study conducted in the USA found that all 88 patients aged 23–67 years (mean 34.8 years) with abnormal cytology and the presence of a highly oncogenic HPV type after 2 courses of cervical cryotherapy and local treatment with povidone-iodine after 6 months after therapy, HPV was not detected [36]. Studies have shown that the use of the drug Betadine
® after treatment with condyloma with a solution for external use with a local necrotizing effect increases the effectiveness of treatment, reduces the incidence of bacterial infection and recurrence of PVI of the vaginal and cervical mucosa. In connection with the above, the feasibility of complex treatment of cervical pathology, including povidone-iodine, is obvious [37].

Conclusion

Understanding the characteristics of the persistence of PVI in the epithelium of the cervix and the associated process of development of diseases in this area determines the tactics of treating cervical injuries associated with HPV. There are many methods for treating genital HPV, but the recurrence rate of this disease is high. Therefore, a very promising direction is the development of complex therapy to prevent recurrence of HPV-associated cervical diseases. The use of povidone-iodine (for example, the drug Betadine®) in the complex therapy of PVI increases the effectiveness of treatment, reduces the incidence of bacterial infection, as well as the frequency of recurrence of PVI of the vaginal and cervical mucosa. Information about the authors: 1 Dubrovina Svetlana Olegovna - Doctor of Medical Sciences, Professor, Chief Researcher of the Research Institute of Obstetrics and Pediatrics; 2Krasilnikova Liliya Viktorovna – candidate of medical sciences, obstetrician-gynecologist; 1 Ardintseva Oksana Aleksandrovna - graduate student; 3 Varicheva Marianna Vladimirovna - obstetrician-gynecologist; 4Tsirkunova Nina Sergeevna - obstetrician-gynecologist, head of the gynecological department; 1 Afrikyan Oleg Arturovich - 6th year student; 1 Afanasova Pelageya Nikolaevna - 6th year student; 5 Gadzhibekova Naina Balabekovna - obstetrician-gynecologist. 1 Federal State Budgetary Educational Institution of Higher Education Rost State Medical University of the Ministry of Health of Russia. 344022, Russia, Rostov-on-Don, lane. Nakhichevansky, 29. 2 DAVINCI GROUP LLC. 344091, Russia, Rostov-on-Don, st. Tolmacheva, 117. 3 Municipal Budgetary Healthcare Institution "City Hospital No. 20 of Rostov-on-Don." 344091, Russia, Rostov-on-Don, Kommunistichesky Ave., 39. 4 Municipal Budgetary Institution "City Hospital No. 6 of Rostov-on-Don." 344025, Russia, Rostov-on-Don, st. Saryan, 85/38. 5 MBUZ "GBSMP". 347930, Russia, Rostov region, Taganrog, Bolshoy prosp., 16. Contact information: Ardintseva Oksana Aleksandrovna, e-mail: [email protected] . Transparency of financial activities: none of the authors has a financial interest in the materials and methods presented. conflict of interest . The article was received on November 26, 2018. About the authors : 1 Svetlana O. Dubrovina - MD, PhD, Professor, Principal Researcher of the Scientific Research Institute of Obstetrics and Pediatrics; 2 Liliya V. Krasilnikova - MD, PhD, obstetrician-gynecologist; 1 Oxana A. Ardintseva - graduate student; 3 Marianna V. Varicheva - obstetrician-gynecologist; 4 Nina S. Tsirkunova - obstetrician-gynecologist, Head of the Department of Gynecology; 1 Oleg A. Afrikyan - 6th year student; 1 Pelageya N. Afanasova - 6th year student; 5 Naina B. Gadzhibekova - obstetrician-gynecologist. 1 Rostov State Medical University. 29, per. Nakhichevanskiy, Rostov-on-Don, 344022, Russian Federation. 2 LLC "DAVINCI GROUP". 117, Tolmacheva sr., Rostov-on-Don, 344091, Russian Federation. 3Rostov-on-Don City Hospital No. 20. 39, Kommunisticheskiy pass., Rostov-on-Don, 344091, Russian Federation. 4 Rostov-on-Don City Hospital No. 6. 85/38, Saryana str., Rostov-on-Don, 344025, Russian Federation. 5 City Emergency Hospital. 16, Bolshoy prosp., Taganrog, Rostov region, 347930, Russian Federation. Contact information: Oxana A. Ardintseva, e-mail: [email protected] . Financial Disclosure: no author has a financial or property interest in any material or method mentioned. Received 11/26/2018.