Vol 10, No 2 (2023)

Currently, recurrent miscarriage is considered a polygenic multifactorial disease, that is, a condition in which the predisposition to miscarriage is related to various genetic factors. The realization of these factors depends largely on the environment. This paper analyzes the current world literature on the effect of single-nucleotide polymorphisms of genes associated with recurrent miscarriage. The literature review summarized data from recent meta-analyses regarding the association between recurrent miscarriage and genetic polymorphisms leading to endothelial dysfunction (vascular endothelial growth factor A gene and endothelial NO synthase genes), hereditary thrombophilia (Leiden mutation and polymorphisms in the methylene tetrahydrofolate reductase gene), immunological disorders (cytokine genes, including interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha), altered receptor interactions in the endometrium (progesterone receptor and ESR1 and ESR2 estrogen receptor genes), and imbalance between lipoproteins of different densities (apolipoprotein E gene). The study of genetic predisposition to miscarriage is necessary to identify high-risk cases, initiate timely and careful monitoring, and develop personalized preventive techniques.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common and to some extent mysterious diseases falling under the competence of gynecologists. PCOS occurs in 5–10% of women of reproductive age. This paper presented the long-term results of surgical treatment of patients with PCOS.

AIM: This study aimed to determine the efficiency of surgical treatment of the ovaries to restore reproductive function in women with PCOS.

MATERIALS AND METHODS: The initial diagnosis of PCOS was made at the outpatient examination. The study included 121 women of reproductive age diagnosed with PCOS when other factors of infertility and menstrual dysfunction were excluded. Patients with PCOS as an initial diagnosis for hospitalization and absence of tubal-peritoneal infertility and male infertility were included. All patients (n = 121) underwent surgical treatment and histological examination. Patients were referred for treatment to gynecological surgical hospitals. In particular, 54 (group 1), 48 (group 2), and 19 (group 3) women were treated in a municipal clinical hospital, research center, and commercial clinic, respectively. Statistical data analysis was performed with the STATISTICA Base software package using parametric and nonparametric methods. Arithmetic mean, standard deviations, medians, and percentiles of the indices were calculated. Confidence limits to the arithmetic mean were calculated based on Student’s distribution. The exact 95% confidence limits to frequencies and the reliability of differences in frequencies between the groups were determined using binomial distribution and the chi-square test, respectively. In addition, the Mann–Whitney (U) and Wilcoxon nonparametric tests were used because several indicators had significantly normal distributions. Differences were considered statistically significant at p <0.05.

RESULTS: Of the total number of patients (n = 121), 108 (89%) became pregnant postoperatively, and 13 (11%) did not. Moreover, 47 (39%) of the total number of patients became pregnant for up to 1 year and 61 (50%) for over a year, and 48 (39.6%) of 108 patients became pregnant post-in vitro fertilization (IVF, 1–2 attempts in 37 (32%) and more than 3 attempts in 11, or 9% patients). PCOS was confirmed in 6 (14%) patients; of these, spontaneous pregnancy occurred in 5 (83%), including 4 patients in the first year and 1 in over a year. These patients had clinical and biochemical signs of hyperandrogenism and insulin resistance.

PCOS-like conditions were diagnosed in 37 (86%) patients; of these, pregnancy occurred in 33 (89%), including spontaneous pregnancy in 10, or 27% (4 within 1 year and 6 over 1 year) patients. Post-IVF pregnancy was diagnosed in 23 (62%) patients (1–2 attempts in 20, or 54.1%, and more than 3 attempts in 3, or 8.1% women).

CONCLUSIONS: Surgical treatment of patients with PCOS is an independent treatment of this gynecological and metabolically burdened disease. This method has both indications and contraindications, and it has specific types, which require certain patient preparations, such as weight loss, blood glucose control, hyperinsulinemia analysis, and compensation of arterial hypertension, to increase treatment efficiency.

BACKGROUND: Cervical cancer is one of the leading cancers in women of reproductive age. The etiological role of the human papillomavirus (HPV) in cancer development is long known and undisputed. However, owing to the widespread use of combined oral contraceptives (COCs), scientists actively investigate possible mechanisms of interrelation between sex steroids and HPV in terms of cervical cancer risk.

AIM: This study aimed to assess the risk of cervical cancer in women of reproductive age, depending on the use of COCs for different durations.

MATERIALS AND METHODS: The study included 411 patients of reproductive age who were treated at the Center for Gynecology and Reproductive Technologies of the Russian Ministry of Health and the Department of Oncogynecology at the University Clinical Hospital No. 4 of the I.M. Sechenov First Moscow State Medical University between January 2015 and December 2021. All patients were divided into two groups. The study group included 291 patients with verified cervical cancer, and the control group included 120 patients without cancer.

RESULTS: The study group was significantly more likely to take COCs (56, or 19.2%) than the control group (11, or 6.5%; p=0.018). In addition, the study group had significantly longer treatment durations (p=0.011). Overweight (n = 52, or 17.9%) and grade II obesity (n = 11, or 3.8%, vs. 0; p=0.03) were significantly more common in the study group than in the control group (n = 8, or 4.7%; p=0.003). The result of the multivariate analysis showed that taking COCs negatively affect cervical cancer development (p=0.018; odds ratio (OR) 1.230; CI 1.064–1.423). The receiver operating characteristic analysis revealed that the use of COCs has a high predictive value for determining the risk of cervical cancer (area under the curve, AUC=0.742); the sensitivity and specificity of this predictor were 74.07% and 72.73%, respectively. In the assessment on the effect of duration of COC use on the risk of cervical cancer, the results showed that total use of COCs for over 7 years was associated with a higher risk of cervical cancer development (p=0.010; OR 1.68; CI 1.1–2.5).

CONCLUSIONS: Prescribing COCs in patients with HPV infection requires a personalized approach to consider etiologic factors of cervical cancer and reduce possible carcinogenic risks.

BACKGROUND: Reactive oxygen species play important and ambiguous role in carcinogenesis, and local oxidative metabolism may differ significantly from systemic metabolism and determine the processes occurring in tumor tissues.

AIM: This study aimed to examine the expressions of key oxidative metabolism genes, particularly CYB5R, POR, NOX4, SOD1, NF-κB, and NRF2, in ovarian neoplasm tissues, and determine cytochrome b5 reductase and cytochrome P450 reductase activity, blood neutrophil activity, and antioxidant indices in the blood plasma and peritoneal fluid.

MATERIALS AND METHODS: The study included two groups of patients: a study group (n = 10) with ovarian adenocarcinoma and a comparison group (n = 6) with benign ovarian neoplasms. The expressions of CYB5R1, CYB5R2/R4, CYB5R3, POR, BIRC3, NOX4, NRF2, NF-κB, SOD1, HMOX1, and BCL2 genes, cytochrome b5 reductase, and cytochrome P450 reductase activity, oxidative activity of blood neutrophils, and antioxidant potential of plasma and peritoneal fluid were evaluated in these two groups of women.

RESULTS: The expression levels of CYB5R3 and BCL2 were significantly lower in adenocarcinoma tissues. The activities of cytochrome b5 reductase and cytochrome P450 reductase increased in the group with adenocarcinoma. On average, the activity of blood neutrophils corresponded to the reference values. For blood plasma, the antioxidant capacity were not different, whereas the antioxidant capacity in the peritoneal fluid increased approximately twofold in ovarian cancer.

CONCLUSIONS: Significantly increased cytochrome b5 reductase activity in adenocarcinoma tissues may be a response to intracellular oxidative stress, whereas CYB5R3 gene expression may be reduced by a negative feedback mechanism. The activities of cytochrome P450 reductase and its gene change to a lesser extent in the presence of ovarian adenocarcinoma. The oxidative balance in the blood and peritoneal fluid correlated with the tissue expressions of NF-κB and NRF2.

The clinical signs of spondylolysis and spondylolisthesis most commonly appear at a young age in professional athletes and ballet dancers. The development and improvement of diagnostic methods and surgical treatment techniques for these pathologies lead to an increase in the number of patients of reproductive age with implants in the lumbosacral junction. A multidisciplinary approach in the management of pregnancy and determination of the delivery method in women with this pathology allows for safe reduction in the incidence of unwarranted operative delivery without worsening maternal and perinatal outcomes. This study presents the clinical case of a patient who had surgery for spondylolysis and spondylolisthesis and delivered successfully through natural childbirth at full-term gestation.

BACKGROUND: This study aimed to assess compliance to transfusion therapy recommendations in the clinical guidelines “Extrauterine (ectopic) pregnancy” with blood transfusion standards and the achievements of evidence-based medicine in transfusiology.

THE MAIN PART: The study assessed the compliance to recommendations on transfusion therapy in the clinical guidelines “Extrauterine (ectopic) pregnancy ― 2021–2022–2023 (01.07.2021)” with blood transfusion guidelines approved by the Russian Ministry of Health (laws, governmental decrees, orders of the Russian Ministry of Health, and instructions on medicines, and medical devices).

It was found that the issues of blood transfusion in the clinical recommendations “Ectopic (ectopic) pregnancy ― 2021–2022–2023 (01.07.2021)” need correction on the following points:

• replace the names of obsolete blood components with current ones;
• replace obsolete blood components with modern ones;
• provide recommendations on immunohematological examination of the recipient and selection of compatible blood components;
• exclude recommendations to use the cancelled “regulatory guillotine” orders of the the Ministry of Health of Russia;
• replace the term “factor VIII concentrate” with “cryoprecipitate” and use fibrinogen concentration rather than factor VIII activity to monitor the efficiency of cryoprecipitate;
• when describing a massive transfusion protocol, clarify that four units must be pooled to obtain a therapeutic dose of platelets, and five units extracted from a dose of whole blood must be pooled to obtain a therapeutic dose of cryoprecipitate;
• bring the recommendations in accordance with the instructions for the medical use of prothrombin complex concentrate and eptacog alfa activated;
• remove the recommendation to use fibrinogen concentrates not registered in Russia.

CONCLUSIONS: Precise recommendations for blood transfusion will improve the treatment of patients with ectopic pregnancy.