Vol 71, No 3 (2022)

The review presents the results of experimental studies that have revealed the molecular mechanisms underlying implantation and placentation controlled by cytokines, chemokines, adhesion molecules, hormones, as well as transcription and growth factors, and have indicated the key regulatory and protective role of melatonin. It has been shown that low production of the hormone and lack of its circadian rhythm underlie the disruption of endogenous antioxidant protection and contribute to oxidative stress leading to the development of preeclampsia. The necessity of using melatonin as a neuroimmunoendocrine marker of pathology is emphasized in this review article, which will allow for developing new approaches to its use for the prevention and treatment of preeclampsia, as well as its adverse consequences, such as obesity, type 2 diabetes mellitus, renal failure, and cardiovascular pathology.

BACKGROUND: The problem of infertility has not only medical, but also socio-demographic significance. To date, the global scale of the spread of various forms of infertility is beyond doubt among specialists around the world. This, in turn, causes an increase in the frequency of prescribing assisted reproductive technologies, but the question of the relationship between the prescribing of drugs used to treat infertility and the risk of developing cancer of the uterine body remains poorly understood.

AIM: The aim of this study was to assess the possible relationship between in vitro fertilization, the use of ovulation stimulation drugs and the risk of developing uterine cancer in women with infertility.

MATERIALS AND METHODS: This literature systematic review is based on resources from the following databases: Medline, ClinicalKey, Google Scholar, Embase, the Cochrane Library, and eLIBRARY for the period 1999–2022. The search for publications was carried out using keywords defined in accordance with the PICO principle (P, population or patients; I, intervention; C, comparison; O, outcomes): “female”, “women”, “infertility”, “infertility treatment”, “in vitro fertilization”, “IVF”, “assisted reproductive technology”, “ART”, “ovarian stimulation”, “ovarian hyperstimulation”, “clomiphene citrate”, “hCG”, “hMG”, “tamoxifen”, “uterine”, “endometrial”, “cancer”, “carcinoma neoplasm”, “uterine neoplasm”. The following SQL operators were used during the search: AND and OR.

RESULTS: The search resulted in 37 representative publications, with eight studies selected for meta-analysis.

CONCLUSIONS: This systematic review and meta-analysis have demonstrated the ambiguity of the design and results of studies on the possible relationship of uterine cancer and assisted reproductive technology methods published to date. The issue under review is urgent due to the high frequency of infertility and an increase in the frequency of gynecologic cancers. The conducted studies confirm that it is impossible to evaluate the carcinogenic effect of ovulation inducers or in vitro fertilization methods without adjusting for the infertility factor, as well as risk factors for uterine cancer. There is still a high need for further research, particularly for studying the safety profile of infertility treatment methods in relation to long-term cancer risks.

This review article summarizes the results of modern clinical studies performed domestically or abroad, which provide information on maternal pregestational diabetes (type 1 or 2) shaping a spectrum of congenital malformations of the fetus. Advances in the treatment of diabetes mellitus have reduced the risk of fetal congenital malformations in pregnant women with the disease, but an increase in its incidence among women of childbearing age indicates that this cause of congenital malformations is becoming more relevant every year. This review article presents four diabetes-mediated pathways for the genesis of fetal congenital malformations: those associated with metabolic imbalance or oxidative stress, genetically mediated and caused by insufficient inhibition of apoptosis. Thus, based on clinical studies and meta-analysis over the past ten years, it has been demonstrated that women with pregestational diabetes mellitus are at the highest risk of developing fetal congenital malformations. Achievement of diabetes compensation and physiological nutritional status in such patients determines the favorable course of all stages of pregnancy.

BACKGROUND: Cervical cancer is one of the four most common cancers today and is the second most common cancer among women in developing countries. According to World Health Organization estimates, in 2018, the number of new cases in these countries was 570,000 (84% of all new cases globally). About 311,000 women died of cervical cancer in 2018, with more than 85% of these deaths occurring in low- and middle-income countries. The detection of the disease in its later stages has not significantly reduced since 2018 (32.6% of all cases).

AIM: The aim of this study was to compare the information contents of conventional and liquid cytology methods in women with verified human papillomavirus of high oncogenic risk.

MATERIALS AND METHODS: We retrospectively analyzed 50 outpatient records of women aged 23 to 65 years who underwent colposcopy (cervical biopsy) based on the results of cervical screening. To establish the diagnosis, all patients underwent examination of smears from the cervix and cervical canal using conventional (n = 25) and liquid (n = 25) cytology methods. A molecular genetic study was carried out to detect high-oncogenic human papillomavirus types (16, 18, 31, 33, 35, 45, 51, 56, 58) in scraping of the cervix by real-time polymerase chain reaction. Women in the both study groups also underwent colposcopy with histological examination of the cervical biopsy specimen. The analysis of the obtained data was carried out using methods of parametric and nonparametric statistics. Inclusion criteria included cytological examination, verified human papillomavirus of high oncogenic risk, and colposcopy. Exclusion criteria included pregnancy and acute infectious diseases.

RESULTS: According to the results of histological examination, the percentage of coincidence of cytological and histological diagnosis in the group of women who underwent conventional cytological examination was 48%. The total number of discrepancies in this group was 13 (52.0 ± 9.99%). The number of women infected with human papillomavirus in the both study groups was almost the same (18 in the conventional cytology group and 19 in the liquid cytology group). The most common types of human papillomavirus among the examined patients were the 16^th type (9 women) and the 18^th type (6 women).

CONCLUSIONS: To date, cytological research methods have not lost their relevance, the liquid cytology method being a reliable screening test with high specificity, which reduces the number of unsatisfactory preparations for analysis and false negative results. The most informative for women with type 2 or type 3 of transformation zone is the use of the liquid cytology method.

BACKGROUND: Postoperative scar endometriosis is diagnosed in 0.03–1.5% of women and is 0.42–4.0% of the total number of endometriosis lesions. The increase in the frequency of surgical delivery and the difficulties of early clinical diagnosis determine the relevance of clinicopathologic analysis of postoperative scar endometriosis.

AIM: The aim of this study was to conduct a comprehensive comparative analysis of the clinical course, diagnostic criteria, results of surgical and combined treatment, as well as morphological and morphofunctional features of postoperative scars endometriosis.

MATERIALS AND METHODS: We analyzed complaints, anamnesis, general clinical, gynecological and instrumental examination data, as well as results of the morphological examination of the surgical material from 21 patients with postoperative scar endometriosis. Immunohistochemical study of the surgical material was performed according to the avidin-biotin complex method using monoclonal mouse antibodies to alpha-smooth muscle actin (Dako, Denmark).

RESULTS: The average age of patients with postoperative scar endometriosis was about 33.6 ± 6.3 years. In 19 out of 21 patients (90.47%), this pathology occurred in the scar after caesarean section. The main clinical manifestation of the disease was pain syndrome. All patients complained of periodic pain in the area of the postoperative scar, which worsened on the eve and during menstruation. According to its nature and intensity, the patients characterized the pain as dull (33.3%), aching (14.3%), paroxysmal (19.1%), or “twitching” (33.3%). In some cases (28.6%), the pain syndrome was accompanied by nausea and vomiting. Many women (71.4%), in addition to the pain, noted the appearance of dark brown (bloody) discharge from the scar during menstruation. In macro- and microscopic examination, postoperative scar endometriosis foci formed nodes of different sizes without a clear capsule. This was due to proliferation of connective tissue fields found in all observations with a large number of collagen fibers located around and between heterotopias. Immunohistochemical study of postoperative scar endometriosis revealed perifocal proliferation of myofibroblasts, which surrounded endometrioid heterotopias in the form of “couplings” and was characterized by positive expression of alpha-smooth muscle actin. Concentric myofibroblast proliferates in the form of nodules were found in the cytogenic stroma of endometriosis foci.

CONCLUSIONS: Early diagnosis and treatment of endometriosis are important in terms of preventing the fibrosis and sclerosis of the affected tissues and organs, which lead to their deformation and dysfunction.

BACKGROUND: Despite the achievements of modern obstetrics and neonatology, the problem of preterm birth remains one of the most pressing.

AIM: The aim of this study was to evaluate the influence of risk factors on the outcome of threatened preterm birth.

MATERIALS AND METHODS: This prospective cohort study included the analysis of clinical and anamnestic data of 130 patients delivered at various gestational ages. The main group comprised 68 women with preterm delivery, with the control group consisting of 62 women with timely delivery.

RESULTS: The outcome of preterm birth is adversely affected by overweight in the group of modifiable risk factors, by history of premature birth in the immediate family in the group of non-modifiable risk factors, and by a previous COVID-19, anemia and autonomic nervous system disorders in the group of potentially modifiable risk factors. The most reliable prognostic marker for the development of preterm labor was the shortening of the cervical length of less than 2.5 cm according to ultrasound.

CONCLUSIONS: The formation of risk groups based on the analysis of clinical, anamnestic, medical, and social data, as well as somatic and gynecological diseases can help avoid the development of adverse outcomes of preterm birth.

This article provides information on the Northern School of Obstetricians and Gynecologists established in the city of Arkhangelsk, Russia thanks to the scientific legacy of E.-A.Ya. Krassovsky, N.V. Yastrebov, K.F. Slavyansky, D.O. Ott and V.V. Preobrazhensky. World-famous scientists, as heads of obstetric and gynecological clinics in St. Petersburg, Russia made a huge contribution to the creation and future development of the northernmost medical institute not only in the European Arctic Russia, but also in the world, as well as to the opening of the Department of Obstetrics and Gynecology in 1934. In 2022, the Northern State Medical University (formerly Arkhangelsk State Medical Institute, Arkhangelsk State Medical Academy) is to celebrate its 90^th anniversary.