No 5 (2021)

The data available in the current literature on non-invasive methods for diagnosing the quality of an embryo and its genetic status were systematically analyzed. The review includes data from foreign and Russian articles published in Pubmed on this topic over the past 3 years. The improvement in the outcome of the IVF program is determined by many factors, including the quality of an embryo. The expansion of knowledge in relation to its development and physiology largely due to various current data processing methods and technologies can determine not only the level of embryonic morphological development, but also to predict the potential for further development. The non-invasiveness, safety, and efficiency of the method are the main criteria for current diagnosis of the potential of the embryo. Numerous studies of the embryo culture medium meet these requirements and seem promising in the selection of high-quality embryos. Conclusion. The study of the molecular composition of culture media for the embryo makes it possible to comprehensively consider its life cycle, to assess the relationship of cellular metabolism to deep regulatory mechanisms. The development of omix technologies could gain insights into the molecular profile of the embryo culture medium, by identifying and characterizing the biomarkers that are potentially important for the onset of pregnancy. Further improvement of methods for analyzing culture media, processing the data, and increasing the future scope of research can provide a new, non-invasive predictor for the quality of the embryo and its implantation potential.

Gestational diabetes mellitus (GSD) is the most common complication of pregnancy. As one of the causes of perinatal and neonatal diseases, GSD presents a high risk of chronic metabolic and cardiovascular diseases to both the mother and her baby. Currently, the diagnosis of GSD is based on venous plasma glucose levels at the end of the second trimester of pregnancy and at the beginning of the third trimester. But it should be noted that medical interventions to correct hyperglycemia in these periods are not effective enough and are frequently late to prevent adverse pregnancy outcomes in the mother and fetus. Early detection of GSD and, consequently, timely correction of carbohydrate metabolism disorders contribute to the optimization of perinatal outcomes. That is why the problem of diagnosing carbohydrate metabolism disorders in early pregnancy is particularly relevant. This paper reviews the data currently available in the literature on GSD screening and early diagnosis. Conclusion. Further investigations are needed for the prediction and early diagnosis of GSD to determine the most appropriate strategy for the clinical management of women with carbohydrate metabolism disorders.

The review is devoted to the problem of recurrent urinary tract infections (RUTIs) in women. It considers risk factors for RUTIs and the role of abnormal vaginal microbiota in this disease. E. coli have special virulence factors that cause urinary tract infection and colonization by adhesion to urothelial cells: the pronounced virulence of Type 1 factor (or Type 1 pili), which triggers an inflammatory response by attracting neutrophils to the bladder. Despite the fact that RUTIs are not considered a life threatening disease, they have a significant impact on quality of life, disabling effects on women's health, intimate and social relationships, self-rating and work ability, and also lead to irritability, fatigue, and inability to concentrate until depression develops. There are modern views on bacterial vaginosis and the associated new pathogenesis of RUTIs. The existing relationship between the factors of RUTIs, sexual practice, and the composition of the vaginal microbiome requires correction of the composition of the vaginal flora and the implementation of preventive measures and non-antimicrobial treatment. The major mechanisms of RUTI development are reinfection and bacterial persistence. Female RUTIs are associated with a steady upward entrance of the microflora from the periurethral region. Antibiotics are the most common treatment regimen for urinary tract infections (UTIs), at the same time they are becoming increasingly ineffective due to the emergence of antibiotic-resistant microorganisms. The global emergence of multidrug-resistant UPEC strains over the past decade highlights the need for alternative therapeutic and preventive strategies to combat UTIs. Conclusion. Thus, a vicious circle is formed: the patient takes antibiotics often or even continuously for the treatment of cystitis, which leads to the development of vaginal dysbiosis, bacterial vaginosis, candidiasis, and vulvar and urethral discomfort. The presented results of clinical trials have confirmed the rationale, efficiency, and safety of taking vitamin D, D-mannose, and proanthocyanidins in the treatment, prevention, and rehabilitation of patients with UTIs.

Polycystic ovary syndrome (PCOS) is a pathological symptom complex characterized by oligo-anovulation, hyperandrogenism and impaired ovarian structure and function. PCOS occurs in 8-13% of early reproductive-age patients. Despite numerous studies, there is no common understanding of the causes of PCOS. In the pathogenesis of the disease, special attention is paid to concurrent hormonal disorders in the presence of metabolic ones. The manifestation of the metabolic syndrome is noted in an average of 20% of patients with PCOS by the age of 20 years and in 35-50% by the age of 30 years; the vast majority (35-90%) of them are recorded to have insulin resistance (IR). At the same time, 38-88% of patients with PCOS are overweight. Studying the signaling pathways involved in the development of the symptom complex has established a relationship between the vicious circle of IR and hyperandrogenism. This literature review places a special emphasis on impaired intracellular insulin signaling in the pathogenesis of PCOS. There is an update on fast and very fast PI3K/AKTpathways, slow and very slow MAPK and mTOR pathways of intracellular insulin signaling, which affect the processes of glycolysis and glucogenesis, lipolysis and lipogenesis, systemic inflammation and oxidative stress, proliferation and apoptosis, which occurs in the development of PCOS. The paper presents available data on the mechanisms of impact of mitochondrial dysfunction and oxidative stress on IR aggravation, hyperandrogenism, and abnormal folliculogenesis in PCOS. It considers the role of activation of the nuclear factor NF-kB signaling pathway in inflammation and synthesis of proinflammatory cytokines in conjunction with the accumulation of glycation end products and reactive oxygen species in changing steroidogenesis and increasing hyperandrogenism in PCOS. Conclusion. Thus, the review summarizes the update on the insulin signaling pathways involved in the development of PCOS, which confirm the mutual aggravation and progression of IR and hyperandrogenism.

Since 1980, breast cancer (BC) has dominated in the pattern of female cancer incidence. After successfully completing the main stage of BC treatment, patients very often survive the age at natural menopause. However, it is this form of malignant tumor that requires enormous healthcare resources to maintain the health, quality of life, and rehabilitation of women. Approximately two-thirds of BC cases are hormone-positive, i.e. they contain estrogen and/or progesterone receptors, requiring hormone (anti-estrogen) therapy. Taking hormonal drugs, such as aromatase inhibitors and tamoxifen, is associated with the development of moderate to severe menopausal disorders. To correct menopausal symptoms after completion of the main stage of BC therapy is a complex clinical task. Vasomotor symptoms can be severe and debilitating in some women, whereas menopausal hormone therapy is contraindicated. In patients with chemotherapy-induced premature menopause, loss of bone mineral density is very often accelerated and there is a need for appropriate correction. Vulvovaginal atrophy is a source of sexual dysfunction. To maintain not only somatic health and physical activity, but also to improve quality of life in patients with a family history of cancer should be the focus of clinical attention. Conclusion. The paper presents a list of alternative non-hormonal treatments for menopausal disorders in patients with a personal history of BC.

Objective. To study the features of respiratory and cardiovascular disorders in preterm infants born to mothers with abnormally invasive placenta (AIP) in comparison with preterm infants of similar gestational age (GA) born to mothers without AIP. Materials and methods. This was a retrospective cohort study of843premature newborns, 59 of them were born to mothers with AIP. All newborns were divided into two groups: the study group included 59preterm infants of GA 33-36/6 weeks born to mothers with AIP and the control group consisted of 784preterm infants of corresponding GA born to mothers without AIP. Additionally, all newborns were divided into subgroups depending on GA: 33-34 weeks and 35-36/6 weeks. There was a comparative analysis of GA, birth weight and length, Apgar score at 1 and 5 minutes, the incidence of respiratory distress syndrome (RDS), congenital pneumonia, transient tachypnea, the need and duration of using invasive mechanical ventilation (IMV) and high-frequency oscillatory ventilation (HFOV), surfactant administration, vasopressor and inotrope therapy, length of stay in the NICU. Results. Preterm infants of the study group had much greater body weight and length. The leading cause of respiratory disorders in the study group was RDS, which significantly exceeded the incidence of RDS in the control group (by 1.5 times). The need for IMV (RR [95% CI] 1.6 [1.05; 2.4]), HFOV (RR [95% CI] 1.79 [1.29; .47]), surfactant administration (RR [95% CI] 2.12[1.19;3.78]), dopamine administration (RR [95% CI] 1.75[1.32;2.32]), dobutamine administration (RR [95% CI] 1.96[1.37;2.81]) were significantly higher in the study group. There was a 1.7-fold increase in the frequency of HFOV use and a 2.5-fold increase in the frequency of cardiotonic therapy use in the subgroup of newborns aged 33-34 weeks in the study group compared to the similar subgroup in the control group. In the subgroup of infants of GA 35-36/6 weeks who were born to mothers with AIP, there was a higher frequency of RDS (by 3.6 times), more frequent use of HFOV (RR [95% CI] 1.8 [1.2; 2.79]) and surfactant replacement therapy (RR [95% CI] 4.8 [1.35; 17.3]) compared to the control group. Conclusion. Abnormally invasive placenta affects the incidence of respiratory and cardiovascular disorders in preterm infants. RDS was the main cause of respiratory disorders in preterm infants born to mothers with AIP. Cardiovascular disorders are an additional factor that accounts for the severity of the condition of infants born at 33-34 weeks of gestation.

Aim. To develop and apply haplotype-based single nucleotide polymorphisms (SNP) analysis for preimplantation genetic testing for monogenic diseases (PGT-M) using chips developed by Affymetrix, Inc., USA. Materials and methods. Twenty-three families with monogenic pathology underwent testing with an integrated approach simultaneously using PGT-M (fragment analysis of STR markers, SNP haplotyping, Sanger sequencing, real-time PCR) and PGTfor aneuploidy (PGT-A) (NGS and aCGH). Results. Out of 93 embryos sent for testing, 55 were euploid. In three families, OGT-M was not performed due to the complete absence of euploid embryos after OGT-A. In the remaining 20 observations, 38 embryos (20 without mutations and 18 with heterozygous carriers) were transferred into the uterine cavity. Interpretation of SNP haplotyping results was more straightforward and reliable than the STR analysis. This technique is universal and does not require individual development for each case. The results of SNP haplotyping are described in detail for two cases, including PGT-M for achondroplasia (autosomal dominant inheritance) and galactosemia (recessive inheritance). Conclusion. The versatility and reliability of the developed approach significantly accelerate obtaining the results, facilitating their interpretation, and reducing the likelihood of possible errors. Also, OGT-M should be preceded by OGT-A for the prevention of chromosomal pathology.

Aim. To investigate the relationship between bisphenol A levels in infertile patients and the outcomes of assisted reproductive technologies (ART). Materials and methods. Three hundred one married couples underwent assisted reproductive technology treatment. Blood and follicular fluid (FF) levels of bisphenol A were determined by chromatography-mass spectrometry. The study analyzed the impact of bisphenol A level on early embryogenesis parameters and ART outcomes. Results. Bisphenol A was detected in 92.9% (277/298) of blood and 16.8% (49/292) of FFsamples. No statistical relationship was found between the blood and FF bisphenol levels in the same patients. There were no differences in main early embryogenesis parameters and pregnancy rates in the quartile subgroups of blood bisphenol A. When dividing patients into groups based on the presence or absence of a detectable (i.e., 0.1 ng/ml and higher) bisphenol A in FF, no statistically significant differences in embryological parameters were revealed. Among 48 patients with available bisphenol A data both in the blood and FF, 24 had higher FF bisphenol A levels, and in the other 24 patients, it was higher in the blood. Patients with bisphenol A levels in FF higher than that in the blood had decreased number and quality of oocytes and embryos. Conclusion. Increased level of bisphenol A in FF compared with its level in the blood is associated with a decrease in the number and quality of oocytes in ART.

Background. Rectovaginal fistula (RVF) is a rare type of malformation. Rectovaginal fistulas represent 5% of all anorectal fistulas. The results of surgical treatment are disappointing, and disease recurrence is in 20-80% of cases. Aim. Assessment of the efficacy of invagination technique. Materials and methods. The study included 57 women with high RVFs aged 20-73 years. The mean age of the patients was 34years. The causes of RVFs were: inflammatory diseases in 11 women (19,3%); obstetric injury - in 29 (51%); pelvic surgery - in 12 (21%); and RVFs due to other causes - in 5 (8,8%) women. 33 (57,8%) patients previously underwent surgical tratment. Diverting stomas were previously formed in 11 cases (19,2%). Results. Surgical treatment using invagination technique was performed in all patients. The mean follow-up period was 23,2 months. Successful treatment of patients was in 63.2% of cases, and no postoperative complications were registered. Conclusion. The invagination technique is an effective and safe method for treatment of high rectovaginal fistulas. In most cases application of this technique is possible without performing preventive colostomy.

Objective. To estimate the expression level of long non-coding RNAs ROR and MALAT1 in the endometriosis-affected ovarian tissue biopsy specimens relative to the control group. Materials and methods. The endometrioid ovarian cyst and endometriosis-unaffected ovarian tissue samples from 20 reproductive-aged women were examined. The expression of long non-coding RNAs ROR and MALAT1 was analyzed by real-time PCR using primers that were specific to these genes. Results. There was a substantial decrease in the expression level of long non-coding RNA ROR and an increase in the expression of MALAT1 in the endometriosis-affected tissue samples relative to the control group. Conclusion. The investigation revealed a relationship between the decreased level of lncROR expression, the increased level of MALAT1, and the presence of ovarian endometriosis. The findings suggest that long non-coding RNAs play a possible role in the development of proliferative processes in ovarian endometriosis and correlate with the data obtained from the analysis of uterine myoma samples. Further investigations may determine the clinical potential of long non-coding RNAs in the diagnosis and treatment of proliferative diseases of the female reproductive system, in particular precancerous ovarian lesions.

The review demonstrates that endometriosis is now considered as a chronic recurrent disease that requires early diagnosis and long-term, often combination treatment. It analyzes the efficacy of drugs used in the treatment of endometriosis and the mechanism of their action. First-line hormone therapy is recognized to be the use of currently available progestogens that can be successfully used in outpatient practice not only for relief of endometriosis-associated painful symptoms, but also for anti-relapse purposes after laparoscopic surgery. Dienogest is a thoroughly studied drug as this approach. The review considers the results of hormone treatment with a progestogen (a dienogest 2 mg tablet) that causes a decidual transformation, as well as antiinflammatory and anti-angiogenic effects in the endometrioid explants, which can yield the favorable results of dienogest therapy in young patients with deep infiltrating endometriosis who have refused surgical treatment. Conclusion. It presents the importance of timely diagnosis of endometriosis and the feasibility of a combined approach to its treatment, including medical (nonsteroidal anti-inflammatory drugs, progestins, hormonal contraceptives, aromatase inhibitors, progesterone receptor modulators) and surgical methods.

Topical glucocorticosteroids (GCS) are one of the most commonly prescribed groups of drugs in dermatology. Due to the high anti-inflammatory efficacy of GCS, this group of drugs is capable of rapid elimination of skin and mucosal symptoms, such as itching and burning. These symptoms represent a significant decrease in the quality of life in patients with both non-infectious and infectious diseases affecting the vulva. The range of available topical GCS includes drugs characterized by varying degrees of activity. Unlike dermatological practice, the use of topical GCS with enhanced activity in gynecology can lead to a remarkable increase in systemic absorption and, therefore, the risk of side effects. This review includes the most relevant issues of the efficacy and safety of topical GCS in gynecology. Conclusion. The analysis of international clinical guidelines and published results of clinical studies indicate the necessity to limit the duration of the use of highly active topical GCS in gynecological practice and to choose drugs of moderate or low activity, including hydrocortisone, as a long-term therapy. The low level of systemic absorption in the vulvovaginal area and the low risk of adverse drug reactions, along with the high level of delivery of hydrocortisone to the cells of the mucous membrane, suggest that the drug has therapeutic potential for safe and effective use in gynecology.

Abdominal pregnancy (AP) is a very rare form of ectopic pregnancy. This pathology detected at different stages of pregnancy is accompanied by a large number of serious maternal and fetal complications. The clinical manifestations of AP are very diverse and nonspecific. However, only with this oval localization, the pregnancy may progress to full term. It is obvious that surgery is inevitable at early diagnosis of АР. In most cases, the diagnosis of full-term AP is made only intraoperatively; moreover, acute abdomen and hemorrhagic shock are often indications for surgery. To identify AP, a physician should display special vigilance for this pathology. The full-term AP cases described in the literature are casuistic, so each of them is sure to be of scientific and practical interest. Case report. The paper describes a clinical case of abdominal pregnancy at 37 weeks’ gestation, which ended successfully for the mother and fetus. Indications for operative delivery were urgently set due to suspected premature placental abruption. The fetus was located freely in the abdominal cavity; a live full-term girl with no visible malformations was delivered in breech presentation; she had an Apgar score of 8/8. The placenta was located in the area of the left uterine appendages and in the space of Douglas, without damaging other abdominal organs and large major vessels. Despite this, the intraoperative blood loss was 4000ml and required massive blood transfusion therapy. Conclusion. The described clinical case should once again draw the attention of clinicians and ultrasound diagnosticians to the problem of such a rare and very dangerous pathology, as AP. Since this case occurred in a remote northern region of Karelia, it was necessary to engage an air ambulance service, thanks to which highly qualified specialists were timely delivered to the operating room, which undoubtedly contributed to a favorable outcome.

Background. The ectopic ovary is a condition that is rarely encountered in gynecological practice, the description of which uses various synonymous terms, such as an accessory ovary, supernumerary ovary, and an auto-amputated ovary. The incidence of this pathology ranges from 1 to 29 000-700 000 clinical cases. Its diagnosis is difficult due to the absence of pathognomonic symptoms characteristic of this ovarian malformation. Surgical tactics remain a controversial issue. According to the results of searching in Google Scholar, Medscape, and PubMed, the authors have described only two cases of the ectopic third ovary in patients with uterine and vaginal aplasia. Case report. Patient A., aged 22 years, diagnosed with genital organ malformations and uterine and vaginal aplasia, was admitted to the Department of Operative Gynecology. She underwent surgical treatment: laparoscopy-assisted creation of an artificial vagina from the pelvic peritoneum. Revision of the abdominal cavity and pelvis revealed that from the right ovary there is a peritoneal fold that passes cranially and laterally into the accessory ovary. Given the presence of concurrent uterine malformation in the patient, it is possible to use the ectopic ovary during subsequent follicular puncture. Conclusion. This paper describes an atypical rare clinical case of a concurrence of the ectopic ovary and uterine and vaginal aplasia. Differential diagnosis is a top priority for clinicians. Various clinical and morphological variants of the ectopic ovary require that both obstetricians and gynecologists should pay precise attention and infringe on the interests of physicians of related specialties.

Congenital adrenal cortical dysfunction (CACD) is a group of diseases transmitted in an autosomal recessive pattern, which is based on a defect in steroidogenenic enzymes. In most cases, the development of pathology is caused by mutations in the CYP21 gene that encodes the enzyme 21-hydroxylase. The paper describes a clinical case of a 46,XXpatient with the salt wasting (classical) form of CACD. It discusses the course of the disease, mainly due to the consequence of parental will. The presence of prostate tissue revealed during the patient’s examination led to an erroneous interpretation of the diagnosis by a private clinic specialist and to discontinuation of replacement therapy. This situation could have ended fatally, with the development of an Addisonian crisis. The cases showing the presence of prostate tissue in patients with adrenogenital syndrome are extremely rare. Only a few articles documenting this condition have been published in the world medical literature. Unfortunately, there is always cancer alertness when detecting rudimentary prostatic tissue in women, since androgens act as a trigger for dysplastic processes. There are no case reports on the reduction of the hyperplastic paraurethral gland during intensified glucocorticoid replacement therapy and achieved compensation for CACD; however, there is a high probability that the proliferative processes in the paraurethral gland may slow down when the target levels of androgens achieved. Conclusion. The complexity of the clinical picture of the disease, as well as disorders of adrenal steroidogenesis, which require lifelong replacement therapy, determine the importance of following up patients with CACD and selecting the optimal therapy regimen, especially by taking into account the magnitude of hormonal changes, lifestyle, and the presence of complications.