REPRODUCTIVE HEALTH AND ART
Currently, scientific knowledge about various Lactobacillus species, which are representatives of the resident flora of the vagina, is actively expanding. We know, lactobacilli are an integral part of the female genital tract. Currently, about 20 different types of lactobacilli are known. Most of the lactobacilli already studied contribute to maintaining vaginal health by providing protection from pathogenic microorganisms, the development of dysbiosis, pregnancy complications, including premature birth. The protective function is provided primarily by the formation of Dand L-forms of lactic acid, which maintains an optimal acidic pH, from the glycogen of the vaginal epithelium. Lactobacillus spp. also prevent adhesion and invasion of pathogens into epithelial cells, synthesize bacteriocins, and inhibit the release of proinflammatory cytokines. However, to date, there is already evidence that not all representatives of lactobacilli have a positive effect on the health of the female body. Thus, patients with the CSTIII morphotype, dominated by L. iners, are especially predisposed to the development of vaginal dysbiosis, and the dominance of L. acidophilus in patients is probably associated with infertility. Currently, there is no reliable evidence of the positive and/or negative effects of many lactobacilli on the female body, and existing studies on a number of bacteria are limited and contradictory. In this regard, it is relevant to further study the characteristics and properties of Lactobacillus spp., colonizing the vagina, for a more accurate understanding of the role of lactobacilli in the vagina and the application of the knowledge gained in clinical practice for the treatment and prevention of various disorders of the normal vaginal microbiome.
The article presents a review of the literature and our own data on the etiology and pathogenesis of iron deficiency and iron deficiency anemia in patients with obesity. Obesity is considered as a subclinical systemic chronic inflammation, which is associated with an increase in the level of hepcidin, which is a key mediator of anemia during inflammation. Patients with obesity should undergo periodic screening of iron status and ferrokinetic parameters. Today, new oral iron preparations with increased tolerability and improved absorption are used in clinical practice. These include sucrosomial iron preparations. Sucrosomial iron (SI) is an innovative oral iron-containing carrier in which iron pyrophosphate is enclosed in a phospholipid matrix coated with sucrester, which protects sucrosomial iron from the effects of gastric juice, excluding contact with the mucous membrane of the gastrointestinal tract. Resistance to the action of gastric juice allows intact sucrosomes to reach the mucous membrane of the small intestine, where they are absorbed through special M cells, followed by the release of iron in liver cells. This allows prescribing SI to patients with iron deficiency and inflammatory bowel diseases, celiac disease, cancer and patients with obesity. Sucrosomial iron should be considered as an alternative treatment for iron deficiency in obese women. SI is innovative, allowing to bypass the “hepcidin barrier”, convenient for administration, effective for treatment, well tolerated than traditional oral iron salts.
Choline is an essential nutrient, but intake among pregnant women is insufficient – only 7% of them consume adequate amounts of choline. The discrepancy between choline requirements and actual intake raises questions about the need for choline supplementation and its potential benefits for pregnant women. The diet of the expectant mother, rich in choline, in the preconception period ensures folliculogenesis and better quality of oocytes, changes the foetal epigenome, counteracting genomic defects during intrauterine development and reducing the susceptibility to metabolic changes in adulthood. Choline is a source of methyl groups and its consumption reduces the risk of NTDs by 7 times, so a promising trend in nutritional support of pregnancy and prevention of NTDs is the intake of folates and choline in combination with other micronutrients. Choline promotes the growth, proliferation and functioning of placental cells, transport of macronutrients, and has an anti-inflammatory effect. The risk of low foetal weight is reduced by 69% when choline is added to the mother’s regular diet. A significant connection has been shown between high levels of choline in the mother and a 2-fold reduction in the risk of preeclampsia, premature birth and a significant effect on the neurodevelopment and mental health of the child – improving neurocognitive functions and reducing the risk of autism and attention deficit hyperactivity disorder. A choline supplement at a dose of 130 mg/day as part of the vitamin-mineral complex Femibion 1 is sufficient to meet the needs for this nutrient during the preconception period and in the first trimester of pregnancy. The need for choline supplementation in the pregravid period and the first trimester of pregnancy is because on folliculogenesis and oocyte protection, epigenetic programming, the effectiveness of preventing congenital malformations of the foetus, participation in metabolic and physiological processes in the placenta, reducing the risk of placenta-associated complications, influence on the development of nervous tissue and brain of the foetus and newborn.
According to the World Health Organization tuberculosis remains a global health issue for both adult and pediatric populations worldwide. Among women the peak incidence occurs during the active reproductive age, with pregnant women being 1.5–2 times more likely to be affected and experience more severe symptoms than non-pregnant women. In the Altai Region, the epidemiological situation of tuberculosis is characterized by instability, with the incidence rate among women reaching
30.5 per 100 000 of the corresponding population in 2022. Delayed diagnosis and treatment can lead to serious complications, including fatal outcomes for both mother and fetus. This article describes a clinical observation of a case of urogenital and pulmonary tuberculosis diagnosed three months after premature abdominal delivery. The course of pregnancy was complicated by acute pleuritis at 13–14 weeks, however, negative results of bacteriological culture of pleural fluid led to the absence of specific tuberculosis treatment and the development of chronic subcompensated placental dysfunction. Three months after delivery, a 34-year-old patient was admitted to the gynecological department of the emergency hospital with abnormal uterine bleeding. The diagnosis was confirmed by histopathology of an endometrial sample revealing tuberculous granulomas without caseous necrosis with epithelioid giant cells of Pirogov – Langhans. Subsequently, generalized tuberculosis was diagnosed in the preterm infant. The negative impact of undiagnosed combined urogenital and pulmonary tuberculosis on the course and outcome of pregnancy is demonstrated, including the development of anemia, placental dysfunction, preterm delivery, puerperal complications, and adverse perinatal outcomes.
Pathological vaginal discharge is one of the main reasons for visiting gynecologists. Despite the abundance of drugs, not all are compliant and quickly effective for pronounced itching and swelling in the introitus area. One of the most common causes of pathological leukemia is vaginal infections, which are represented by three main clinical forms: bacterial vaginosis (BV) – up to 50% of all cases; vulvovaginal candidiasis (CVV) – 20–25% and trichomonas vaginitis (TV) – 15–20% of cases, respectively. In this regard, retrospective analysis shows that patients with BV, KV, TV most often actively turn to a gynecologist or venereologist However, the fact that the cause of pathological whites in more than 30% of cases can be a mixed infection creates problems in treatment with the use of monodrugs (many relapses up to 40% or more). Therefore, for their treatment, it is considered rational to use the concept of the etiotropic approach, based on the local effect of combined vaginal drugs. The role of a combined topical drug, including those with a rapid anesthetic effect, was evaluated. Neo-Penotran Forte L is a logical combination of antibacterial agents and a local anesthetic used to treat manifest forms of vaginal infections and provide rapid relief of intolerable symptoms.
Anemia is the most common disease in the world, affecting about 30–40% of people. Children, adolescents, and women are most often affected by anemia. The main causes of true iron deficiency (ID and IDA) are insufficient iron intake, increased iron loss (chronic bleeding), increased iron requirement, and impaired iron absorption (gastrointestinal diseases). Chronic diseases, inflammatory conditions, autoimmune diseases, obesity cause an increase in the synthesis of hepcidin in the liver and block the entry of iron into the bloodstream, leading to functional iron deficiency. Anemia of chronic diseases (ACD) or anemia of chronic inflammation (the second most common anemia) is associated with the fact that iron is present in the body, but the absorption of iron in various areas is limited. Until recently, it was believed that treatment with iron supplements in the absence of iron deficiency does not bring benefit to patients with ACD. The opinion has been repeatedly expressed about the harm of iron therapy, since iron is necessary for the growth of some pathogenic microorganisms and tumor cells. However, the real clinical significance of these mainly theoretical provisions is unknown. Therefore, the prescription of iron preparations for anemia is justified and logical. Ferrous sulfate (ferrous iron) is most often prescribed orally due to its low cost, high bioavailability and effectiveness. The drug Tardiferon, containing iron sulphate 247.25 mg (in terms of iron (II) 80.00 mg), is widely used in patients with IDA and ID, since divalent iron has a high ability to overcome the intestinal barrier by “passive” transport and quickly create high concentrations in the blood, restoring the level of hemoglobin and iron stores in the body. The drug Tardiferon has a relatively low dose of iron – 80 mg with slow-release technology to avoid irritating effects on the intestine, contributing to good tolerability. A number of studies confirmed a high safety profile – patients did not refuse to take the drug due to side effects. Timely examination and identification of patients with anemia allows you to prescribe an effective correction. The drug Tardiferon promotes rapid restoration of hemoglobin and iron stores in the body and has good tolerability.
Introduction. Progesterone levels are a critical factor for embryo implantation in in vitro fertilization (IVF) programs, including thawed embryo transfer programs. Overweight/obese patients often have lower blood progesterone concentrations in the luteal phase during IVF cycles, which requires an individual approach to planning luteal support in this category of patients.
Aim. To compare the pregnancy ratе and miscarriage rates up to 12 weeks of pregnancy in overweight/obese patients who underwent a program of transfer of thawed embryos into the uterine cavity, depending on the type and route of administration of gestagens.
Materials and methods. The study included 76 overweight or obese patients. All patients were treated for infertility using a program for transferring a thawed embryo into the uterine cavity; luteal phase support was carried out either using micronized progesterone, identical to natural, – the drug Utrogestan in a daily dose of 800 mg intravaginally (40 patients), or combination therapy was prescribed – vaginal gel with progesterone 90 mg in combination with the synthetic progestin dydrogesterone in a daily dose of 30 mg, taken orally (36 patients).
Results. The rates of pregnancy and miscarriage in the first trimester were comparable in both groups and did not depend on differences in luteal support.
Conclusions. The formation of the luteal phase of the cycle in patients with overweight/obesity is equally effective using various forms of gestagens. The use of micronized progesterone may be preferable in patients with overweight/obesity in terms of the ability to monitor blood progesterone levels, a more favorable metabolic profile when used vaginally, and the possibility of switching to oral administration of the drug in the event of the development of adverse local events.
Introduction. Multiple sclerosis (MS) is a chronic disease of the central nervous system predominantly affecting women of reproductive age. It is known that there is a high incidence of low urinary tract infections in MS. However, information about microbiology of the genital tract in women with MS is extremely limited.
Aim. To study the qualitative and quantitative composition of the vaginal microflora in patients with MS.
Materials and methods. 19 patients with relapsing-remitting MS of the main group and 19 healthy women of the control group, the qualitative and quantitative composition of the microflora in the vaginal secretion was determined using the polymerase chain reaction method in real time (a set of reagents was used to study the biocenosis of the urogenital tract in women, Femoflor 16, DNA-Technology, Moscow), a gynecological smear from the vagina was performed. The neurological status was assessed using the EDSS scale and The questionnaire on pelvic organ function. The following statistical indicators were determined: frequency, spread, average and χ² test.
Results. A status of normocenosis was observed in the majority of women with MS (14 subjects, 73.7%), Lactobacillus bacteria were found in 16 subjects (84.2%), and an increased number of facultative anaerobes was identified in 7 subjects (37.4%), there were no significant differences with the comparator group. Bacteriological examination findings from vaginal smears did not show any signs of inflammation in either group. A high incidence of vaginal infections in anamnesis was reported in women with neurogenic lower urinary tract dysfunction (16 subjects, 84.2%).
Conclusion. Data on the state of the vaginal biocenosis of women with MS has been presented for the first time. It was found the preservation of normocenosis with a tendency to shift the balance towards dysbiotic processes in the vagina.
Iron deficiency anaemia is one of the most common diseases among women, and is most often caused by posthemorrhagic conditions. Gynaecological diseases requiring surgical treatment play a determinant role in the genesis of heavy iron loss in women. Anaemia can prevent from the timely surgery, and failure to eliminate local causes of blood loss can deteriorate the patients’ condition and quality of life. Anaemia is currently regarded as a serious risk factor for the outcomes of surgical treatment, which can and should be eliminated. At the same time, substitution transfusion that was previously often used to manage anaemia in less time is not only ineffective and has a temporary effect, but can itself cause such serious complications as haemolysis, infection, anaphylaxis. Therefore, it is recommended to apply an approach that combines diagnosis and treatment of anaemia, reduces blood loss and improves the general condition of patients. This approach can lead to about 40% reduction in the incidence of complications. The review summarizes the main features of iron deficiency anaemia in gynaecology and the most effective approaches to therapy. Early onset of modern oral ferrotherapy allows to assign treatment courses of required duration without side effects and prevents severe iron deficiency. Parenteral administration of iron carboxymaltose has significantly reduced the duration of treatment and improved its effectiveness in severe recurrent and perioperative anaemia. Timely management of anaemia allows not only to perform surgical intervention in time, when indicated, but also to reduce the likelihood of complications and improve the women’s quality of life.
INFECTIONS
Of all types of cancer in the female reproductive system, cervical cancer has the greatest social significance due to its impact on young patients, often even those who have not yet completed their reproductive function, and it is the third leading cause of cancer-related death. Considering the lack of etiological therapy for human papillomavirus and associated diseases, the high demand for effective methods of medical therapeutic support, and the absence of a gold standard treatment apart from destructive and excisional methods, it seems reasonable to consider the use of nutrients with anticancer effects in the treatment of low-grade cervical intraepithelial neoplasia both as an addition to the watchful waiting strategy and in the use of ablative treatment methods, as well as their adjuvant appointment in the case of obligatory precancer. Based on domestic and foreign literature sources from electronic databases such as PubMed, CyberLeninka, and Elibrary, this review presents data on the use of trans-resveratrol and indole-3-carbinol in HPV-associated diseases. The combination of two mutually complementary anticancer antioxidants – indole-3-carbinol, which primarily has antiproliferative effects, and trans-resveratrol, which restores cellular apoptosis mechanisms, comprehensively affects the pathogenetic mechanisms of the virus-induced pathological process: it has been proven to reduce the expression of oncogenes E6 and E7, increase the expression of tumor suppressor proteins – p53, pRb, PTEN, and decrease markers of proliferation PCNA and Ki-67. The combination of 200 mg of indole-3-carbinol and 60 mg of trans-resveratrol for the prevention of persistent papillomavirus infection and the treatment of cervical intraepithelial neoplasia has impressive potential; however, further research is needed to determine the most effective application schemes.
PREGRAVID PREPARATION AND PREGNANCY
Despite significant progress achieved in healthcare, preterm birth is an urgent problem in modern obstetrics. The preterm birth can be caused by various risk factors: for example, an ascending infection can trigger the onset of uterine contractions, cervical shortening followed by infection of the fetal membranes, amniotic fluid, and, in rare cases, the fetus itself. In most cases, the infectious and inflammatory process is the etiopathogenetic factor of isthmic-cervical insufficiency (ICI), one of the common causes of late miscarriages and preterm births. The period between 14 and 20 weeks of gestation is the most critical time for the development of ICI. The dynamic ultrasound cervicometry once every 7–14 days from week 16 through week 24 of pregnancy is recommended to the patients with ICI, as well as pregnant women in the high-risk group. Most professional societies guidelines addressing this issue recommend all pregnant women to perform routine transvaginal cervicometry during the second ultrasound screening for the timely formation of risk groups and optimization of approaches to the patient management. The following groups of drugs are used to prevent preterm birth: micronized progesterone, slow calcium channel blockers, β-adrenergic agonists, and non-steroidal anti-inflammatory drugs. The use of progesterone drugs to prevent preterm birth has generated much debate. Thus, the availability of several forms of progesterone and various routes of administration determine the complexity of the drug therapy. Micronized progesterone is the only progesterone drug that was approved for use after 20 weeks of gestation. The vaginal micronized progesterone has been found to be highly effective in the prevention of preterm birth, significantly reduce neonatal mortality and improve infant morbidity outcomes.
A disturbed vaginal ecosystem is characterized by reduced or non-existing lactobacillary flora and damaged vaginal epithelium. It may not always be apparent whether alterations of the vaginal epithelium or pathogenic microorganisms are the primary cause of a disturbed vaginal ecosystem. Estriol plays a key role in developing and maintaining a healthy vaginal epithelium, stimulating cell growth and differentiation, increases epithelial thickness, and also promotes glycogen synthesis, which is required to maintain an acidic environment. Estriol deficiency results in the vulvovaginal atrophy and the development of atrophic vaginitis. In turn, Lactobacillus acidophilus maintains a healthy microbiome, protecting against infections and creating an acidic environment unfavourable for the growth of pathogens. In recent years, an increasing interest has been developed in probiotics with the belief that probiotics could be able to restore the vaginal microbiota health. A review of scientific articles on the use of an ultra-low-dose vaginal estriol 0.03 mg in combination with Lactobacillus acidophilus to normalize the vaginal microbiota and treat vaginal infections has been conducted. An analysis of published clinical studies and meta-analyses on the use of probiotics in vaginal infections showed the mechanisms of action of probiotics, their biological role and clinical effects. The integration of probiotics into the treatment and prevention of bacterial vaginosis is growing more urgent. The results of numerous studies and meta-analyses confirmed their high efficacy and safety. The supplementation of standard antibiotic therapy with probiotics improves cure rates, restores normal vaginal microflora and reduces the risk of relapse. Therefore, further studies on the use of probiotics to develop more effective and personalized treatment strategies providing long-term results are needed. The publication of new evidence will make it possible to introduce best practices into clinical practice and ensure a healthier future for patients worldwide.
Introduction. The results of a number of studies indicate the comorbidity of endometriosis with various diseases, such as uterine fibroids, endometrial cancer, migraine, depression, infertility, bronchial asthma, and stomach diseases.
Aim. Present literature data on the comorbidity of endometriosis and various diseases.
Materials and methods. A review of the literature for 2021–2023 in the databases PubMed (National Library of Medicine), Cochrane Library, CyberLeninka, Medline, as well as in scientific citation databases (Scopus, Web of Science).
Results and discussion. This paper analyzes data on the comorbidity of endometriosis and various diseases such as uterine myoma, endometrial cancer, migraine, depression, infertility, bronchial asthma, and gastric diseases. It was found that the comorbidity of endometriosis and the described diseases is based on common risk factors (early age of menarche, late menopause, absence of childbirth in the anamnesis, chronic inflammatory diseases of the pelvic organs, smoking, chronic stress, exposure to phthalate esters), molecular pathogenetic mechanisms (changes in gene expression, sex hormone levels, aberrant immune response, subclinical inflammatory response, hyperestrogenism, characteristic of both endometriosis and comorbid diseases), as well as genes involved in the development of these diseases. According to the results of full genomic studies, more than 170 polymorphic loci associated with the development of endometriosis and various comorbid diseases have been identified, and a positive correlation between endometriosis and these diseases has been revealed.
Conclusion. These studies dictate the need to take into account in clinical practice the syntropy of endometriosis with other diseases, which, in turn, requires a multidisciplinary approach to the management of patients with endometriosis.
Introduction. Differentiating conditions accompanied by the development of thrombotic microangiopathy (TMA) in obstetrics is still rather challenging. Our present opinion is that the effect of childbirth on the TMA symptom regression is the key to differential diagnosis. If hemolysis and thrombocytopenia regress after childbirth, we can talk about HELLP syndrome. If not, we should think about atypical hemolytic uremic syndrome (aHUS). aHUS is an extremely rare disease characterized by TMA predominantly involving acute kidney injury. However, the diagnostic task can also be difficult due to possible overlapping one process with another: for example, HELLP syndrome can trigger aHUS, but which of the patients is more susceptible to this transformation is unclear.
Aim. To identify clinical and laboratory criteria that can be used to early detect aHUS immediately after childbirth.
Materials and methods. A total of 230 patients were enrolled in the study, of whom 71 women were diagnosed with aHUS, 124 patients with HELLP syndrome, and 35 patients without signs of TMA were enrolled in the control group. We assessed and compared the main clinical, anamnestic and laboratory findings.
Results. Women with HELLP syndrome and aHUS were comparable in terms of age, frequency of operative delivery and gestational age at delivery, and adverse perinatal outcomes. Peak serum creatinine and LDH values after delivery were the most useful to early predict aHUS. Serum creatinine > 142 μmol/L and LDH > 1391 U/L were associated with the transformation of HELLP syndrome into aHUS.
Conclusion. We concluded that standard laboratory data, most specifically peak serum creatinine and LDH, may be used to aid in the early diagnosis of aHUS.
Obesity is a chronic multifactorial heterogeneous disease characterized by high prevalence, progressive increase in morbidity, high cardiometabolic risk. The prevalence of obesity is increasing from year to year and does not tend to decrease. Up to 60% of women of reproductive age are overweight, and a quarter of them are obese. In addition to cardiovascular pathology, type 2 diabetes, gastrointestinal diseases, oncological processes, obesity can affect the reproductive function of women, reduce fertility and be an independent cause of infertility, as well as reduce the effectiveness of assisted reproductive technology programs. This paper analyzes studies on the problem of reproductive system disorders, the effectiveness and safety of assisted reproductive technology programs in patients with overweight / obesity. The review includes data from foreign and domestic articles in the Pubmed, Elsevier, Cochrane Library, e_library databases published over the past 10 years. As a result of the analyzed publications, it was concluded that the implementation of IVF programs in patients with overweight/obesity presents certain difficulties at each stage of the program: the duration and cost of ovarian stimulation increases, the number and quality of the obtained oocytes and embryos decreases, the displacement of the “implantation window” is more often noted, decreased endometrial receptivity, which together causes a decrease in the pregnancy rate (PR) in this category of patients. It should be noted that in women with visceroabdominal obesity, with more pronounced metabolic abnormalities – dyslipidemia, carbohydrate metabolism disorders, reproductive disorders are expressed to a greater extent than in patients with a more favorable femoral phenotype type of obesity, which requires an individual approach to the treatment of infertility using IVF methods depending on the clinical and etiopathogenetic category of patients.
PRE- AND POSTMENOPAUSE
Introduction. The postmenopausal period being a significant part of a modern woman’s life. The persistence of menopausal disorders clinic can be combined with the hypovitaminosis D state, which, in turn, can further aggravate the existing symptoms. Vitamin D supplementation may be one of the pharmacological approaches to correct menopausal disorders.
Aim. To evaluate the contribution of hypovitaminosis D to the clinic of menopausal disorders; to determine the clinical efficacy of using cholecalciferol in late postmenopausal residents of Yekaterinburg.
Materials and methods. During the period from 2018 to 2021, 144 late postmenopausal patients from 56 to 79 years old living in Yekaterinburg and do not need outside help in everyday life took part. The following parameters of anthropometry, the severity of modified menopausal index (MMI), hospital anxiety and depression scales (HADS), Mini-Mental State Examination (MMSE), an assessment of serum 25(OH)D level (chemiluminescent immunoassay; Access 2, Beckman Coulter, USA) were studied. Clinical efficacy of cholecalciferol was evaluated in 68 patients in the prospective cohort study design. Micellated water-soluble form of cholecalciferol in standard doses recommended by the Russian Association of Endocrinologists (RAE) was used.
Results. Vitamin D deficiency and insufficiency are associated with increased parameters of body weight (p = 0.048), waist circumference (p = 0.018) and hips (p = 0.016), increased cases of decreased performance (p = 0.046) and subclinical symptoms anxiety (p = 0.033). Supplementation of standard therapeutic and maintenance doses of cholecalciferol for 6 months contributed to a significant reduction in neurovegetative component of modified menopausal index in 54.4% of cases (p = 0.035) and improvement in cognitive function parameters in 50.0% of cases (p = 0.023) in late postmenopausal patients.
Conclusions. The use of cholecalciferol in adequate doses can be considered as an important component of complex therapy for women in late postmenopausal period.
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