Background. Dysbiotic conditions among pregnant women may lead to the translocation of opportunistic microorganisms into breast milk through the enteromammary pathway, thereby increasing the risk of lactostasis, mastitis, and neonatal gastrointestinal disorders. Administering probiotics during this critical period may be an effective preventive strategy. Aim. To evaluate the impact of oral probiotics on the microbiota of breast milk, the incidence of lactation-related complications in new mothers, and the health status of newborns during the first six weeks of life. Materials and methods. A prospective randomized study was conducted involving 80 pregnant women. Participants were divided into three groups: a control group (physiological vaginal pH 3.8–4.5, n = 25); subgroup 2A (pH 4.5, received probiotics, n = 30); and subgroup 2B (pH 4.5, received no probiotics, n = 25). A breast milk culture was performed during the early postpartum period, and the incidence of lactostasis, mastitis, and neonatal gastrointestinal symptoms and infectious complications was assessed. Results. Pathogens in breast milk were identified in over half of the cases in the subgroup without probiotics, with Staphylococcus aureus being predominant. Other microorganisms, such as Streptococcus agalactiae, Escherichia coli, and Klebsiella pneumoniae, as well as microbial associations, were also isolated. In contrast, the frequency of pathogen detection was significantly lower in the probiotic-treated group, with no S. agalactiae or its associated forms isolated. Lactostasis and lactation mastitis, including purulent forms, were reported infrequently in both the probiotic and control groups. In the subgroup without probiotics, these complications occurred significantly more frequently. Moreover, newborns whose mothers received probiotics experienced fewer episodes of infantile colic and regurgitation, whereas severe enterocolitis was reported exclusively in infants from the group without probiotic support. Conclusion. Administering oral probiotics to pregnant women with baseline vaginal pH 4.5 aims to restore the intestinal microbiota. This improvement in intestinal microbiocenosis is associated with an indirect reduction in the frequency of pathogen detection in breast milk, a decreased occurrence of lactostasis and mastitis (including purulent forms) among new mothers, as well as a significant reduction in gastrointestinal symptoms (regurgitation and colic) in newborns, compared to those without probiotic intervention.
Background. Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) are common conditions that significantly impact the quality of life for women of reproductive age. Although standard treatments for BV and VVC are effective at alleviating acute symptoms, they often fail to restore the vaginal microbiota in the long term. Aim. To evaluate the efficacy and safety of oral multiprobiotics as part of the comprehensive therapy for BV and VVC. Materials and methods. A prospective, randomized, double-blind, placebo-controlled, parallel study was conducted involving 180 patients of reproductive age. The cohort comprised 90 individuals with confirmed BV and 90 with VVC. Patients were randomized into four groups: BV with probiotic (n = 50), BV with placebo (n = 40), VVC with probiotic (n = 50), and VVC with placebo (n = 40). The investigational agent was a multiprobiotic formulation containing Lactobacillus rhamnosus, L. plantarum, L. helveticus, L. gasseri, and L. crispatus. The treatment duration was one month. Parameters assessed included changes in clinical symptoms (using a 10-point scale), vaginal pH, vaginal microflora composition (analyzed via real-time polymerase chain reaction using Femoflor-16), and patient satisfaction with treatment outcomes. Results. The addition of the multiprobiotic from the initiation of standard therapy significantly contributed to the restoration of normal vaginal microbiota composition, evidenced by a substantial increase in the proportion of Lactobacillus spp. (p 0.001), normalization of vaginal pH and more pronounced relief of clinical symptoms compared to placebo (p 0.001), and increased patient satisfaction with the treatment outcomes (p 0.05). Specifically, the increase in Lactobacillus spp. in the BV + probiotic group was 33.3% vs. 14.4% in the placebo group (p 0.001), while in the VVC + probiotic group, it was 19.8% vs. 6.7% (p 0.001). According to Femoflor-16 data, the absolute increase in Lactobacillus spp. concentration in the BV + probiotic group was 1.8 times greater (+3.48lg vs. +1.94lg), and the reduction of BV-associated anaerobes was 1.8–2.3 times more significant than in the placebo group (all p 0.001). For the VVC + probiotic group, the elimination of Candida spp. was 1.4 times more pronounced (-3.86lg vs. -2.72lg; p 0.001), and the increase in lactobacilli was six times greater. Additionally, significant reductions in Staphylococcus spp., Streptococcus spp., and Enterobacteriaceae were documented in the probiotic group, with no similar changes observed in the placebo group. Patients diagnosed with VVC exhibited a significant decrease in pH levels by 0.46 units (p 0.001). Following therapy, the probiotic groups presented statistically significant reductions in clinical symptom severity when compared with the placebo groups (p 0.001). In BV patients, the intensity of abnormal discharge averaged 1.2 ± 0.8 points vs. 2.1 ± 1.2 points, and the unpleasant odor intensity averaged 0.8 ± 0.6 points vs. 1.5 ± 0.9 points. In VVC patients, the severity of itching and burning was recorded at 0.9 ± 0.7 points vs. 1.8 ± 1.1 points. Treatment satisfaction was notably higher in the probiotic groups: 88% vs. 70% for BV (p = 0.034) and 86% vs. 65% for VVC (p = 0.019). Conclusions. The findings of this study support the inclusion of oral multiprobiotics that contain combinations of L. rhamnosus, L. plantarum, L. helveticus, L. gasseri, and L. crispatus in comprehensive treatment regimens from the first day of therapy for BV and VVC, as this approach enhances treatment efficacy and may reduce the risk of relapse.
Background. The choice of combined hormonal contraception in overweight women of reproductive age requires an assessment of not only contraceptive efficacy but also metabolic safety, as abdominal obesity, atherogenic dyslipidemia, insulin resistance, and blood pressure are key modifiable cardiovascular risk factors. A monophasic combined oral contraceptive (COC) containing estetrol 15 mg and drospirenone 3 mg is considered a drug with a potentially more favorable metabolic profile compared to COCs containing synthetic ethinyl estradiol. However, data on the effect of Esteretta (estetrol 15 mg + drospirenone 3 mg) on metabolic parameters in overweight women in real-world clinical settings remain limited. Aim. To evaluate the dynamics of metabolic parameters and calculated indices of cardiovascular risk in women with normal and overweight body weight during the use of COC containing 15 mg estetrol and 3 mg drospirenone. Materials and methods. An open observational study was conducted at Clinical and Diagnostic Outpatient Clinic of Volgograd Regional Clinical Perinatal Center No. 2 in Volgograd. The study included 168 women of reproductive age seeking contraception. All patients were prescribed the COC Esteretta (estetrol 15 mg + drospirenone 3 mg). The study group included 82 overweight women (BMI 25.0–29.9 kg/m²), and the comparison group included 86 patients with normal body weight (BMI 18.5–24.9 kg/m²). The examination was conducted at baseline and after 3 and 6 months. Anthropometric parameters, blood pressure, lipid profile, fasting glucose, visceral adiposity index, triglyceride-to-high-density lipoprotein cholesterol ratio, plasma atherogenic index, triglyceride-glucose index, lipid accumulation index, and the presence of metabolic syndrome (MS) according to the 2026 RKO/RNMOT criteria were analyzed. Results. After 6 months, use of the Esteretta COC (estetrol 15 mg + drospirenone 3 mg) was associated with clinically insignificant changes in metabolic and calculated cardiometabolic parameters in both groups. The proportion of patients with age-related visceral adiposity index and triglyceride-to-high-density lipoprotein cholesterol ratio 1.196 did not increase and remained 0% at all visits in both groups. Using the 2026 RCO/RNMOT Consensus criteria, the estimated compliance with MS criteria in the overweight group was found in 13/82 (15.9%) patients at baseline and in 16/82 (19.5%) after 6 months, the change was not statistically significant (p = 0.250). In the normal weight group, the estimated compliance with MS criteria was not found in any patient at any visit. Conclusion. The use of the COC Esteretta (estetrol 15 mg + drospirenone 3 mg) for 6 months in overweight, non-obese women is not associated with a clinically significant deterioration in the cardiometabolic profile. However, regular (at least once every 6 months) monitoring of metabolic parameters and active lifestyle modification remain necessary in overweight women receiving hormonal contraception.
Background. Late reproductive age of a woman is one of the main reasons for failures in in vitro fertilization programs. Optimizing in vitro fertilization protocols by modifying the embryological stage based on the clinical situation, including a woman's age, opens new prospects for improving the effectiveness of assisted reproductive technology programs. Aim. To study the outcomes of assisted reproductive technology programs using oocytes of patients of late reproductive age with a reduced lactate culture medium and a standard culture medium. Materials and methods. The study included married couples, divided into two groups based on the women’s age: Group 1 (35–39 years) included 200 married couples, and Group 2 (40–42 years) included 140. Depending on the culture medium utilized to culture embryos, each of the age groups was further divided into two subgroups: the cohort of 35–39 years old into Subgroup 1 (n = 115), where the CSCM-NX medium with reduced lactate was used, and Subgroup 2 (n = 85) with the cultivation of embryos in a one-stage standard G-TL medium; the cohort of 40–42 years old was divided into Subgroup 1 (n = 70) and Subgroup 2 (n = 70), respectively. Results. There were no statistically significant differences in outcomes with different culture media among the 35–39-year-old group. However, in the group of 40–42 years old, the analysis of the embryological stage showed a statistically significant increase in the frequency of blastocyst formation (p = 0.04) and an increase in the number of blastocysts (p = 0.04), as well as trends to an increase in the frequency of clinical and biochemical pregnancy when culturing embryos in a medium with a reduced lactate compared to the standard medium. Conclusion. Improving the embryonic stage performance by culturing embryos in a reduced-lactate medium can increase the cumulative live birth rate in patients aged 40–42 years, supporting further study of this modification of the embryological stage in the older age cohort.
Background. Asymptomatic bacteriuria (ASB) is often diagnosed during pregnancy and may be associated with gestational complications. The standard therapy for ASB in pregnant women is the appointment of antibiotics. However, given the global increase in antibiotic resistance and the possible negative effect of antibiotics on the fetus, the question of the expediency of such treatment is questioned. In this regard, an urgent task is to study the effectiveness of alternative remedies, in particular, herbal preparations. Aim. To evaluate the efficacy and safety of phytotherapy in pregnant women with ASB based on clinical and microbiological studies. To determine the pathogenic potential of Escherichia coli strains, the main causative agent of urinary infection. Materials and methods. 97 pregnant women were included in the prospective study, the main group consisted of 65 pregnant women with a confirmed diagnosis of ASB, of which 40 patients received antibacterial therapy and 25 patients were treated with the complex herbal preparation Canephron® N. The control group included 32 pregnant women without ASB. The clinical efficacy of therapy, gestational outcomes, the relationship between ASB and the vaginal microbiota were evaluated, and the pathogenic potential of E. coli strains, the most common causative factor of this pathology, was determined. Results. There were no differences in the frequency of pregnancy complications and the nature of perinatal outcomes between women who received antibiotics and those who took Canephron® N and patients of the control group. The absolute majority of women in three groups completed full-term pregnancy at 39–41 weeks (p = 0.934). Assessing the condition of newborns, we found that there were no statistically significant differences between the groups and subgroups in terms of weight and height (p = 0.934), the number of underweight children (p = 0.897), newborns with developmental delay (p = 0.962) and morphofunctional immaturity (p = 0.772). During the detection of E. coli virulence genes, only 33.8% of pregnant women with ASB revealed potentially dangerous combinations of them and, as a result, an increased risk of infection in the absence of treatment. Vaginal infections and dysbiotic conditions are associated with ASB; they were more common in group I (p = 0.015): nonspecific vaginitis was noted in 63.1%, vulvovaginal candidiasis in 4.6%, bacterial vaginosis in 1.5%. In group II – nonspecific vaginitis – in 28.1%, vulvovaginal candidiasis – in 9.4%, bacterial vaginosis – in 3.1%. The presence of vaginal infections increases the probability of colonization of the bladder by opportunistic flora by more than 15 times (95% confidence interval 5,433–45,867; p 0.001). Conclusion. In most cases of ASB in pregnant women, Escherichia coli is caused with a low potential for pathogenicity. In this regard, it is justified to use Canephron® N preprate instead of antibiotics, which demonstrates high efficacy and good tolerability. Careful monitoring of the state of the vaginal microbiota is necessary and, if necessary, rehabilitation of the infection.
Background. Pregnancy and childbirth are primary contributors to pelvic floor (PF) trauma. The structural integrity of connective tissue is altered during pregnancy due to hormonal influences, including progesterone and relaxin, leading to increased elasticity and increased susceptibility to injury. Tissue damage can occur both from the pressure exerted by the pregnant uterus and from the progression of the fetus during labor. It is believed that the first pregnancy may reveal preexisting congenital abnormalities in PF structures, enabling the prediction of future prolapse and pelvic dysfunction and facilitating the planning of preventive strategies. Aim. To evaluate the role of individual risk factors on the development of symptoms related to PF dysfunction in women both during and after childbirth for the planning of examination and medical rehabilitation interventions for women at risk. Materials and methods. A retrospective cohort study was conducted involving 116 women who gave birth to their first child via vaginal delivery. Data were collected concerning maternal age, body mass index (BMI) during pregnancy, incidences of episiotomy, trauma to the birth canal, and the body weight of newborns. Descriptive statistics and multiple logistic regression methods were used for the statistical analysis. Results. Urinary incontinence was observed in 31.9% of women during pregnancy, while post-delivery, this proportion increased to 50.0%. Intestinal incontinence was reported by 7.8% of participants. The results from multiple logistic regression analysis indicated that elevated BMI was a significant risk factor for urinary incontinence during pregnancy (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.04–1.24; p = 0.004). For postpartum urinary incontinence, identified significant risk factors included BMI (OR 1.08, 95% CI 1.01–1.15; p = 0.016) and trauma to the birth canal (OR 2.74, 95% CI 1.03–7.27; p = 0.043). Notably, episiotomy did not protect against incontinence. Conclusion. Urinary incontinence emerged as the predominant symptom of PF dysfunction. The primary modifiable risk factors for PF dysfunction in postpartum women are increased BMI and birth canal trauma, while episiotomy did not show any protective advantages.
Background. Chronic endometritis (CE) is a multifaceted pathology, with ongoing revisions in the understanding of its etiology, pathogenesis, and treatment modalities. The lack of standardized, universally accepted algorithms for diagnosing and managing CE results in inconsistent diagnoses and patient care. While the role of bacterial infection is well established, it is recognized that antibacterial therapy does not yield favorable outcomes in every case. Increasing evidence suggests that various microorganisms, alongside bacteria, contribute significantly to this condition. Notably, CE associated with viral factors in the endometrium presents with various cytopathic effects, often resulting in persistent morphofunctional disorders of the uterine mucosa. Viral agents such as human papillomavirus (HPV) and herpes simplex viruses types 1 and 2 (HSV-1, HSV-2) can persist in the endometrium. In women with CE and reproductive failure (RF), the prevalence of HPV and HSV endometrial infections may reach up to 93.3%. Combination therapy, integrating antiviral medications with immunomodulatory agents, is emerging as a promising strategy to enhance interferon production and activate cellular immunity. Aim. To conduct a comparative analysis of the clinical efficacy of two therapeutic regimens: monotherapy with valacyclovir vs. a combination therapy with 1 mg of alloferon (Allokin-alpha®) and valacyclovir in patients with RF, associated with viral contamination of the endometrium and CE. Materials and methods. The prospective study involved 30 women diagnosed with CE and RF. A comprehensive morphological study of endometrial biopsy specimen was performed within days 19–23 of the menstrual cycle, along with an immunohistochemical assessment to identify viral antigens and evaluate p16ink4a protein expression. Following clinical and laboratory examinations that confirmed the diagnosis of viral CE, participants were randomized into two groups: Group 1 (n = 15) received valacyclovir monotherapy (500 mg twice daily for 10 days from Day 1 of the menstrual cycle for two months); Group 2 (n = 15) received combination therapy with valacyclovir (according to a similar regimen for two months) and alloferon (Allokin-alpha®) administered subcutaneously at 1 mg in 1 ml of 0.9% NaCl solution every other day from Day 1 of the menstrual cycle, totaling nine injections in the first month of treatment. Follow-up endometrial biopsies were collected for control examinations four months post-treatment, within the luteal phase of the cycle (Days 19–23). Results. At the preliminary stage, all patients were diagnosed with chronic virus-associated endometritis. Mono-infection was detected in 33.3% of cases, whereas combined viral infections, primarily HPV in association with HSV-1 and/or HSV-2, accounted for 66.7% of observations. A comparative analysis showed that the combination regimen was statistically superior to monotherapy in terms of treatment efficacy. Complete eradication of viruses from the endometrium was observed in 60% of patients receiving combination therapy, compared with 20% in the monotherapy group. Furthermore, no mixed viral associations were detected following combination treatment (p = 0.025). Morphological evaluations confirmed a marked regression of chronic inflammation in the combination therapy group, with mild lymphohistiocytic infiltration noted in 86.7% of patients. An important effect of combination therapy was a substantial reduction in p16ink4a expression in the endometrium (p = 0.011), thereby suggesting a restoration of cell cycle regulation. Follow-up assessments over 12 months post-treatment revealed significant differences in reproductive outcomes during this period (p = 0.026). Conclusion. The combination therapy involving alloferon and valacyclovir demonstrated superior efficacy when compared to valacyclovir monotherapy, as evidenced by pronounced improvements in the histological findings in the endometrium and a decrease in p16ink4a protein expression. This combined therapeutic approach presents a promising approach for enhancing reproductive outcomes in patients with viral CE.
Endometriosis is a chronic, estrogen-dependent condition characterized by a significant fibrosing component, which substantially impacts the pain, reproductive function, and overall quality of life for affected individuals. Given the limitations of current therapeutic options and the high recurrence rates, there is a justified need to explore pathogenetic strategies to modify fibrosis and chronic inflammation. This review evaluates the latest findings on the role of fibrosis in the pathogenesis of endometriosis, along with the nature of the inflammatory and immune responses and their associations with pain-related, reproductive, and adhesive complications accompanying the disorder. In particular, the focus is on bovhyaluronidase azoximer as an antifibrotic, anti-inflammatory, and immunomodulatory agent used in the combined treatment regimen for endometriosis, particularly during the postoperative phase. The findings from preclinical investigations, along with 11 clinical trials involving over 1,200 patients, demonstrate reductions in pain severity, improvements in reproductive outcomes, decreased frequency and severity of adhesion formation, and a favorable safety profile associated with bovhyaluronidase azoximer administration. In light of the collective data, this review discusses the potential to incorporate antifibrotic therapy into standard care protocols for patients with endometriosis, as well as the directions for future clinical research, including optimizing dosing protocols, establishing the appropriate duration of therapy, and assessing long-term outcomes.
Preserving the reproductive potential of women with endometrial diseases is an urgent task of modern reproductive medicine due to the increase in their prevalence and the fact that many women postpone pregnancy to a later age, which is especially common in developed countries. The article reviews the literature published in recent years on modern approaches to preserving fertility in patients with endometrial hyperplasia and low-grade endometrial adenocarcinoma, including organ-preserving therapies and methods to realize reproductive potential after treatment, as well as assessment of the endometrium after treatment and the use of assisted reproductive technologies. Organ-preserving therapy for endometrial hyperplasia aims to optimize oncological and reproductive outcomes while minimizing side effects. Hormone therapy used in these disorders contributes to a decrease in the receptive properties of the endometrium and reduces the probability of pregnancy. Therefore, despite attempts to optimize treatment, after hormonal therapy, patients with endometrial hyperplasia without atypia, as well as with atypical endometrial hyperplasia and low-grade endometrial adenocarcinoma of reproductive age, face problems in achieving pregnancy. The lack of standardized approaches to assessing the recovery of implantation properties of the endometrium makes it difficult to develop pregnancy planning programs after treatment for such patients of fertile age.
Cystocele remains one of the most prevalent forms of genital prolapse. Despite extensive study over the centuries, the pathogenetic mechanisms underlying this condition remain incompletely understood. In this review, we examined contemporary literature regarding the pathogenesis of anterior vaginal prolapse and cystocele. A comprehensive search was conducted in the PubMed, Cochrane Library, and eLibrary databases using the keywords "pelvic floor failure," "cystocele," and "cystocele pathogenesis," covering the period from 2000 to 2025. The pathogenesis of cystocele is complex, multifactorial, and progressive. It is primarily attributed to defective fibromodulin expression, which disrupts myofibril maturation and is associated with dysfunction of collagen synthesis and structural abnormalities in the pubocervical fascia. Key factors contributing to the development of cystocele include apical insufficiency, paravaginal defects, and damage to the musculus levator ani, alongside disruptions in the structural integrity of the pubocervical fascia.
