Aim : to evaluate efficacy of a comprehensive diagnostic approach for cervical intraepithelial neoplasia (CIN) based on a combination of colposcopy, cytology and human papillomavirus (HPV) testing using advanced digital technology, and to assess a role of p16INK4a/Ki-67 immunohistochemical markers in challenging cases of differential diagnosis. Materials and Methods . A single-center prospective analysis covering the period from 2023 to 2026 was conducted. Data from 84,712 women who underwent visual screening were processed using a custom-developed digital module. There were enrolled 247 women identified as CIN suspected based on a positive result in at least one of three tests: colposcopy, cytology, or HPV DNA testing. They underwent an examination using the comprehensive diagnostic approach (CDА). Results . CIN was excluded in 165 (66.8 %) cases, low-grade squamous intraepithelial lesion (LSIL) was detected in 63 (25.5 %), high-grade squamous intraepithelial lesion (HSIL) – in 14 (5.7 %) cases and stage I cervical cancer was diagnosed in 5 (2,0 %) women. While assessing accuracy, the HPV DNA test turned out to be the most optimal showing 93.1 % (sensitivity (Se) – 92.7 %; specificity (Sp) – 93.3 %), followed by cytology – 91.9 % (Se – 85.4 %; Sp – 95.2 %) and colposcopy – 78.5 % (Se – 96.3 %; Sp – 69.7 %). In 17 complex clinical cases, immunohistochemical (IHC) testing of p16/Ki-67 markers enabled clear differentiation between reactive lesions, such as LSIL with focal or weak p16/Ki-67 expression ≤ 20 % in the lower third of the epithelium, and pronounced precancerous transformation (HSIL) with diffuse p16/Ki-67 expression throughout the entire epithelium. This completely eliminated diagnostic uncertainty in challenging clinical situations. Conclusion . CDА for CIN using three widely available tests (visual colposcopic, cytology, and HPV DNA testing) on a digital platform approaches the accuracy of histological diagnosis. In complex and controversial cases, IHC testing for p16/Ki-67 markers serves as an objective method for stratifying patients into mild (LSIL) and severe (HSIL) forms, eliminating over- and underdiagnosis as well as optimizing treatment.
Aim : to reveal a relationship between immunohormonal parameters and increased cytotoxic T-lymphocyte levels in peripheral venous blood in women of reproductive age with early miscarriage at 3–6 weeks, living in the European North of the Russian Federation. Materials and Methods . A retrospective observational study was conducted, 107 women of reproductive age 20–30 years old living in the European North of the Russian Federation (Arkhangelsk region, 64˚33' s) were examined: 55 of them were practically healthy women at the time of examination, with a history of term pregnancy and birth of a healthy child, and 52 patients with single miscarriage in the early stages of 3–6 weeks. The hemogram, count of lymphocytes with CD3+CD8+, CD4+, CD10+, CD16+, CD56+, CD3+CD16+CD56+, CD3-CD16+CD56+ receptors, level of sCD16, sCD56, cytokines such as interleukins (IL) IL-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), immunoglobulins of classes A, M, G, E, circulating immune complexes (CIC), levels of sex hormones – follicle-stimulating (FSH) and luteinizing (LH) hormones, prolactin, progesterone, estradiol, testosterone were assessed. The data were analyzed using descriptive statistics, comparative and logistic regression analyses, with odds ratio (OR), relative risk (RR), and 95 % confidence interval calculated. Results . 65.39 % of women with early miscarriages had elevated levels of cytotoxic T-lymphocytes, combined with high count of natural killer (57.69 %) cells, sCD56, and sCD16 (98.08%). In the peripheral venous blood of the patients, degenerative forms of blood cells with toxogenic granularity, nuclear apoptosis, and cytosolic vacuolization were detected, as well as hypochromic erythrocytes, echinocytes, acanthocytes, and aggregation of erythrocytes and platelets, evidencing about suppressed bone marrow cell functional activity as an unfavorable sign of pregnancy course. Conclusion . The immunohormonal parameters associated with increased levels of cytotoxic lymphocytes in women with miscarriage included high level of natural killers, mature T-lymphocytes, proliferative lymphocytes, increased concentrations of sCD16, sCD56, and endothelin-1 along with lower levels of FSH and LH.
Introduction . The perimenopausal transition is accompanied by progressive decline in ovarian function, variability of sex steroid secretion, menstrual cycle disturbances, abnormal uterine bleeding (AUB), and vasomotor and psychoemotional symptoms. Despite age-related decline in fertility, a risk of unintended pregnancy remains in sexually active women of late reproductive age thereby emphasing a choice of effective and safe contraception as a clinically important task. Aim : to analyze and summarize current literature assessing 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) use during the transition from contraception to menopausal hormone therapy (MHT) in perimenopausal women, focusing on contraceptive efficacy, endometrial protection, safety, tolerability, and its place among alternative strategies. Materials and Methods . A narrative literature review in PubMed/MEDLINE, ScienceDirect, eLibrary, and Google Scholar databases was carried out. Publications addressing the use of the 52-mg LNG-IUS in late reproductive-age and perimenopausal women were included primarily assessing contraceptive efficacy, AUB control, endometrial protection during estrogen-containing MHT, safety, tolerability, and patient-oriented outcomes. Results . The 52-mg LNG-IUS is a highly effective long-acting reversible contraceptive method with additional non-contraceptive benefits, including reduction of menstrual blood loss, treatment of heavy menstrual bleeding, and prevention of endometrial hyperplasia. In perimenopause, the system may simultaneously provide contraception and AUB control; when estrogen therapy is initiated, it may serve as a local progestogen component of MHT and protect the endometrium. This approach may be particularly relevant for women with contraindications to estrogen-containing contraception, a need for a long-term delivery method, and concomitant menstrual cycle disorders. Conclusion . The 52-mg LNG-IUS may be considered a clinically relevant tool for transition from contraception to MHT in perimenopausal women. However, data on long-term oncological, cardiovascular, and metabolic outcomes remain heterogeneous. Chosing this strategy should be individualized according to age, bleeding pattern, endometrial status, risk profile, contraindications to alternative methods, and patient preferences.
Aim : to compare the discriminative ability and calibration of nested-architecture machine learning (ML) models and the Fetal Medicine Foundation (FMF) algorithm for predicting early-onset (< 34 weeks) and late-onset (≥ 34 weeks) preeclampsia (PE) in the first trimester of pregnancy in Russian population. Materials and Methods. with 23,247 singleton pregnancies was carried out. The biophysical sample comprised 22,230 observations, and the biochemical subsample included 7,581 observations. Nested ML models were developed: M0 (maternal characteristics) → M2 [(M0 + biophysical markers – mean arterial pressure (MAP) and uterine artery pulsatility index (UtAPI)] → M4 (M2 + biochemical markers – placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and pregnancy-associated plasma protein-A (PAPP-A)]. A comparison was made with the FMF algorithms – prior FMF risk (FMF prior) and posterior FMF risk (FMF posterior). Metrics included: AUC-ROC (Area Under the Receiver Operating Characteristic curve) with 95 % confidence interval (CI) calculated by the bootstrap method (n = 2000); the observed-to-expected ratio (O:E ratio); incremental value of biomarkers – change in C-statistic (ΔC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and sensitivity at fixed false-positive rates. Statistical significance of AUC differences was assessed using the DeLong test. Results. The AUC of model M4 for early-onset PE (EOPE) was 0.972 (95 % CI = 0.947–0.991) compared with 0.951 for FMF posterior (p = 0.368); for late-onset PE (LOPE), the AUC was 0.871 (95 % CI = 0.833–0.906) versus 0.822 for FMF posterior (p = 0.009). After Platt scaling recalibration, the ML models demonstrated adequate calibration (O:E ≈ 1.0). FMF posterior demonstrates inadequate calibration for LOPE in the Russian population (O:E = 3.34; 95 % CI = 2.61–4.21), indicating 3.34-fold more LOPE cases than predicted by the model. Biophysical markers provided 4-fold greater incremental value for EOPE (ΔC = +0.029 vs. +0.007), while biochemical markers were more valuable for LOPE (ΔC = +0.020 vs. +0.001). For EOPE the UtAPI was a lead predictor (odds ratio (OR) = 3.28; 95 % CI = 2.68–4.70), for LOPE – previous PE (OR = 1.90; 95 % CI = 1.72–2.09). Conclusion . ML models significantly outperform the FMF algorithm in discriminating late preeclampsia and provide substantially better calibration in Russian population. The inadequacy of the FMF algorithm for LOPE (O:E = 3.34 indicates 3.3-fold more LOPE cases than predicted) justifies the need for specialized models for this phenotype. Differential incremental value of biomarkers was established: biophysical markers (UtAPI) are critical for EOPE, biochemical markers (PlGF, sFlt-1) – for LOPE, supporting the concept of contingent screening.
Aim : to systematically evaluate the evidence on psychosocial stress impacting on the microbiocenosis of the female reproductive tract and to delineate the underlying pathogenetic mechanisms. Materials and Methods . A comprehensive literature review was conducted across PubMed/MEDLINE, Google Academy, and eLibrary databases covering a 25-year period. Search terms for query included "stress," "vaginal microbiome/microbiocenosis/microflora," "cervical microbiome," and "uterine microbiome" in both Russian and English. Original studies, systematic reviews, and meta-analyses were included; animal experiments, conference abstracts, non-full-text publications, and off-topic articles were excluded. Results . Chronic psychosocial stress activates the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system, leading to hypercortisolemia and elevated catecholamine levels. Key pathogenetic mechanisms include Th1-to-Th2 (T-helpers 1/T-helpers 2) immune shift followed by consequently suppressed cell-mediated immunity, estrogen deficiency-driven reduction of vaginal epithelial glycogen, impaired glucose metabolism, and direct catecholamine-mediated enhancement of bacterial virulence and proliferation. In the lower reproductive tract, stress is an independent predictor of bacterial vaginosis, recurrent vulvovaginal candidiasis, genital herpes reactivation, and high-risk human papillomavirus (HPV) persistence with increased risk of cervical intraepithelial neoplasia and invasive cervical cancer. Stress also elevates susceptibility to sexually transmitted infections. In the upper reproductive tract, depression and anxiety are associated with increased incidence of pelvic inflammatory disease and reduced implantation success in assisted reproductive technology programs. Conclusion . Psychosocial stress is an independent, modifiable risk factor for reproductive tract dysbiosis. Assessing psychosocial status should be integrated into clinical evaluation of women with inflammatory and dysbiotic conditions of the reproductive tract, and psychological intervention should be considered a component of comprehensive treatment strategies.
