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Vol 72, No 6 (2023)

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Original Research

The potential of survivin as a non-invasive diagnostic marker for endometriosis in patients with type 1 diabetes mellitus

Andreeva N.Y., Yarmolinskaya M.I., Misharina E.V., Tkachenko N.N.

Abstract

BACKGROUND: According to international data, about 5-10% of women of reproductive age suffer from this disease, while in women with chronic pelvic pain or infertility the incidence ranges from 35% to 50%. At the same time, women of reproductive age diagnosed with diabetes mellitus type 1 may also suffer from endometriosis, but asymptomatic or atypical in the initial stages of the disease, which varies considerably in duration, may be the cause of untimely diagnosis. Existing diagnostic methods in the form of bimanual examination, ultrasound, MRI, laparoscopic surgery, and even histologic verification do not allow to exclude with certainty the presence of the disease.

AIM: The aim of this study was to investigate the prevalence and characteristics of endometriosis among patients with type 1 diabetes mellitus to develop a diagnostic prognostic model.

MATERIALS AND METHODS: We carried out a retrospective analysis of medical records from the Gynecological Unit of the Second Department of Gynecology and Endocrinology and the Scientific Advisory Department of D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductive Medicine, St. Petersburg, Russia for the period of 2010–2021. The study cohort included cases of endometriosis in patients with type 1 diabetes mellitus recorded in inpatient or outpatient medical histories. Clinical characteristics of the prevalence of endometriosis in women with type 1 diabetes mellitus were based on an analysis of 2316 medical records in this patient group. The prospective cohort of the case-control study included 137 patients and involved the evaluation of survivin levels in serum on days 5–7 of the menstrual cycle in four study groups: type 1 diabetes mellitus in combination with endometriosis, endometriosis, type 1 diabetes mellitus, and healthy women of reproductive age. Additionally, we examined the gynecological history of patients. Statistical processing of the data obtained and predictive modeling were performed using a binary logistic regression analysis.

RESULTS: The prevalence of endometriosis among patients with type 1 diabetes mellitus was 1.11%. Risk indicators for the presence of endometriosis were determined based on risk factor values for patients with or without type 1 diabetes mellitus. Patient groups with a probability of having endometriosis exceeding 50% were identified, requiring diagnostic and therapeutic measures aimed at timely initiation of therapy.

CONCLUSIONS: Predicting the likelihood of endometriosis presence will enable timely preventive and therapeutic measures aimed at improving the patient’s quality of life.

Journal of obstetrics and women's diseases. 2023;72(6):5-15
pages 5-15 views

Species composition of vaginal lactobacilli in the first, second and third trimester as a marker of pregnancy outcomes

Beliaeva N.R., Budilovskaya O.V., Khusnutdinova T.A., Krysanova A.A., Shalepo K.V., Savicheva A.M., Tapilskaya N.I.

Abstract

BACKGROUND: Lactobacilli are the main and most important component of the vaginal microbiota of reproductive-age women. During pregnancy, the composition of the vaginal microbiota changes and acquires additional significance, acting as a barrier against infection for both the mother and the fetus. Furthermore, the vaginal microbiota contributes to the normal course of pregnancy, postpartum recovery, and primary colonization of the newborn. Changes in the composition and number of vaginal lactobacilli during pregnancy can lead to serious disorders. Despite much research on the role of the vaginal microbiota, the details of how changes in lactobacilli composition and diversity may affect pregnancy outcomes are poorly understood.

AIM: The aim of this study was to evaluate the vaginal lactoflora composition and stability in each trimester to predict pregnancy outcomes.

MATERIALS AND METHODS: This open prospective study involved 100 women who had been registered at the dispensary in early pregnancy (up to 12 weeks). To determine the type of microbiocenosis and the species composition of lactobacilli, the vaginal discharge was examined microscopically and by real-time polymerase chain reaction.

RESULTS: Normocenosis was identified in 86 (86%) pregnant women, the intermediate type of vaginal microbiocenosis in 4 (4%) pregnant women, and bacterial vaginosis in 10 (10%) pregnant women. The rate of negative pregnancy outcomes was 19%, of which 7% and 12% of women had premature births or miscarriages, respectively. The concentration of vaginal lactobacilli in each pregnant woman was relatively stable over the three trimesters. Among the dominant microflora, the frequency of Lactobacillus crispatus increased by the third trimester. Lactobacillus iners was associated with an increased incidence of premature birth and may be considered as a risk factor.

CONCLUSIONS: Real-time PCR test for specific detection and quantification of vaginal lactobacilli in pregnant women has prognostic value and may be recommended as a possible screening test for women with high risk of adverse pregnancy outcomes.

Journal of obstetrics and women's diseases. 2023;72(6):17-32
pages 17-32 views

Evaluation of the effectiveness of third-generation lipid emulsion therapy for early pregnancy loss

Zhernakova T.S., Bespalova O.N., Shengelia M.O., Kornyushina E.A., Pachuliia O.V., Postnikova T.B.

Abstract

BACKGROUND: Immune mechanisms play an important role in the pathogenesis of early pregnancy loss. To regulate disorders of immune homeostasis, immunoefferent therapy is used, such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and lipid emulsions, which may help to overcome infertility and recurrent miscarriage. Third-generation lipid emulsion (TGLE) is the modern “gold standard” of parenteral lipid therapy. It contains high concentrations of omega-3-polyunsaturated fatty acids, which can directly or indirectly affect the activity of natural killer (NK) cells. The literature comprises contradictory data on the efficacy of TGLE for repeated implantation failure. This may be due to the determination of biochemical parameters for its use and the selection of criteria for assessing the effectiveness of this therapy.

AIM: The aim of this study was to evaluate the effectiveness of TGLE therapy in patients with a history of early pregnancy loss.

MATERIALS AND METHODS: This prospective randomized controlled study enrolled 140 patients with early pregnancy loss (recurrent miscarriage and repeated implantation failure) at the Research Institute of Obstetrics, Gynecology and Reproducto logy named after D.O. Ott, Saint Petersburg, Russia from 2021 to 2023. Group 1 consisted of 50 women with TGLE therapy, and group 2 included 90 women without therapy. Patients of group 1 received lipid therapy according to the following regimen: TGLE 20% IV 6 ml per kilogram of body weight once a month for two months on end. Inclusion criteria: women from 18 to 45 years of age with two cases of reproductive failure – pregnancy loss up to 12 weeks of gestation and/or unsuccessful in vitro fertilization attempts (embryo transfers without effect) with normal karyotypes of the spouses. Exclusion criteria: women with miscarriage with an abnormal karyotype of the fetus, with anatomical abnormalities in the development of the reproductive apparatus, with an abnormal karyotype of any of the spouses, with hypersensitivity to omega-3 polyunsaturated fatty acids. We assessed the omega-3 index, functional characteristics of NK cells in the peripheral blood, and the effectiveness of lipid therapy based on biochemical and immunological parameters, as well as the clinical onset of pregnancy.

RESULTS: The difference in the omega-3 index before and after treatment with TGLE was significant (p = 0.0002), this parameter being increased by 1.23 times compared to the initial level. The functional activity of NK cells in the blood was significantly different after the administration of TGLE: NK (CD3CD(16+56+)) (p = 0.0041), NKT (CD3+CD(16+56+)) (p = 0.0498), and spontaneously activated NK (CD107a) (p = 0.0498). These parameters decreased by 1.63, 1.29, and 2.07 times relative to their initial levels. In group 1 of patients receiving TGLE therapy, clinical pregnancy occurred twice as often as compared to those who did not receive this therapy (56.41%, n = 22 vs. 31.25%, n = 20; p = 0.01).

CONCLUSIONS: TGLE has shown effectiveness in pregnancy rates by increasing the omega-3 index and reducing the functional activity of NK cells in women with early pregnancy loss.

Journal of obstetrics and women's diseases. 2023;72(6):33-40
pages 33-40 views

Endometrial NK cells in repeated implantation failure – quantity and functional markers

Zagaynova V.A., Bespalova O.N., Krikheli I.O., Gzgzyan A.M., Tral T.G., Tolibova G.K., Sokolov D.I., Kogan I.Y.

Abstract

BACKGROUND: Alteration in the composition and function of endometrial immune cells, in particular NK cells, are associated with implantation and placentation pathology, which is considered as one of the causes of reproductive losses. However, data regarding abnormalities in the number and activity of NK cells in repeated implantation failures, including depending on the type of infertility, remain ambiguous.

AIM: The aim of this study was to evaluate the number of CD56+ and CD16+ cells and the area of expression of CD107a and NKG2D markers in the endometrium of patients with repeated implantation failure (RIF).

MATERIALS AND METHODS: This prospective comparative study included patients with RIF (main group I, n = 47), who were divided into two subgroups: Ia, patients with primary infertility (n = 29); Ib, patients with secondary infertility (n = 18). Comparison group II included patients with a history of effective ART programs (n = 17). Control group III included healthy fertile women without a history of reproductive loss (n = 12). Endometrial biopsies were obtained on days 19–23 of the menstrual cycle. The expression of CD56+, CD16+, CD107a and NKG2D was assessed by immunohistochemistry.

RESULTS: In the endometrium of patients in groups I and II, as compared to the control group, the number of CD56+ cells was significantly increased (p < 0.001). In patients of subgroup Ia, when compared to the control group, we verified an increase in the number of CD16+ cells (p < 0.05) and a decrease in the expression of CD107a (p < 0.05). In patients in groups I and II, a negative correlation was revealed between the number of CD56+ and CD16+ cells and the number of pregnancies in history (rs = –0.30 and rs = –0.34, p < 0.05), while a positive correlation was found between the expressions of CD56+ and CD107a (rs = 0.66 and rs = 0.75, p < 0.05). In patients in group II, a positive correlation was revealed between the expressions of CD16+ and CD107a (rs = 0.75, p < 0.05). In the endometrial stroma, CD107a expression increased significantly in patients in group I (p < 0.05), while NKG2D expression increased in groups II and III (p < 0.01, p < 0.05) from the early to the middle stage of the secretion phase. In patients of group II, a positive correlation was established between the expressions of CD56+ and NKG2D (rs = 0.68, p < 0.05).

CONCLUSIONS: In the endometrium of patients with primary infertility and RIF, the number of CD56+ and CD16+ cells is increased with a decrease in the expression of their activation marker CD107a, which may be a potential mechanism for impaired implantation. Further studies of the immune profile of the endometrium may help to personalize diagnostic and therapeutic approaches to management of patients with RIF and to increase the chances of pregnancy in ART programs.

Journal of obstetrics and women's diseases. 2023;72(6):41-54
pages 41-54 views

An improved method for experimental modeling of premature ovarian insufficiency in Wistar rats

Zakurayeva K.A., Yarmolinskaya M.I., Adamenkov N.A., Potapova E.V.

Abstract

BACKGROUND: Despite an enormous progress in the field of reproductive endocrinology, the mechanisms of premature ovarian insufficiency have not been fully understood so far. Knowledge of the supposed causes and mechanisms underlying the development of premature ovarian insufficiency has expanded significantly in recent years, mainly due to advances in genetics and the creation of models for experimental research. The experimental modeling of premature ovarian insufficiency, which is as close as possible to the origin and development of the corresponding disease in humans, is effectively used to elaborate promising therapeutic approaches, in particular, to test new drugs or biologically active agents in order to study their preventive or curative effects. This article discusses the main methods of the experimental modeling of POI in laboratory animals. We have herein summarized the literature data related to the development of the clinical and morphological picture of the disease, with the advantages and disadvantages of each of the models analyzed.

AIM: The aim of this study was to modify the premature ovarian insufficiency modeling methodology to substantiate the effectiveness and to test new directions in drug therapy with subsequent implementation in clinical practice.

MATERIALS AND METHODS: The new method is based on the creation of an experimental premature ovarian insufficiency model in female Wistar rats. To obtain this model, experimental rats were randomized into two groups: 1) animals receiving cyclophosphamide at a dose of 150 mg/kg b.w. subcutaneously once (n = 10); 2) animals receiving 2 ml of saline intraperitoneally once (n = 9). On day10, the animals were removed from the experiment. After autopsy, a visual assessment of morphological changes in the ovaries was carried out, and a right-sided ovariectomy was performed.

RESULTS: When using the proposed model, the reproducibility rate of POI has reached 100%.

CONCLUSIONS: Our modification of the method ensures the creation of a highly reproducible premature ovarian insufficiency model in Wistar rats. Another significant advantage of this modeling method is its ease of implementation and economic efficiency.

Journal of obstetrics and women's diseases. 2023;72(6):55-62
pages 55-62 views

DNA-fragmented sperm ability to bind to the zona pellucida

Ishchuk M.A., Komarova E.M., Lesik E.A., Mekina I.D., Pendina A.A., Gzgzyan A.M., Tapilskaya N.I., Bespalova O.N.

Abstract

BACKGROUND: A high percentage of the infertile couples are classified as having unexplained infertility. At the same time, male partners may have both normozoospermia and high level of sperm DNA fragmentation. The investigation of the selectivity of the oocyte zona pellucida for spermatozoa with fragmented DNA is an extremely promising direction. The novel data could improve sperm selection methods, which in turn will increase the efficiency of IVF cycles.

AIM: The aim of this study was to assess the ability of spermatozoa with fragmented DNA to bind to the zona pellucida.

MATERIALS AND METHODS: The material for the study was ejaculate samples from patients with normozoospermia (n = 5) and sperm donors (n = 4), as well as the zona pellucida of immature oocytes (n = 25) from nine patients. Sperm preparation was carried out by centrifugation in a density gradient of silicone particles and the swim-up method. Sperm DNA fragmentation was assessed using the method of fluorescent labeling of single- and double-stranded DNA breaks (TUNEL assay). Manipulations with gametes and the zona pellucida were performed using micromanipulation equipment and a femtosecond laser.

RESULTS: Spermatozoa with fragmented DNA can effectively bind to the oocyte zona pellucida. However, among the zona pellucida-bound spermatozoa, the proportion of cells with fragmented DNA was significantly lower than among the unbound ones. The data obtained suggest the key role of the oocyte zona pellucida in the selection of spermatozoa with intact DNA.

CONCLUSIONS: Spermatozoa with fragmented DNA retain the ability to bind to the oocyte zona pellucida. The use of the selective binding of spermatozoa with intact DNA to the zona pellucida can serve as a method for selecting gametes for intracytoplasmic injection of spermatozoa into the oocyte. Data on the selective properties of the oocyte zona pellucida can serve to select the optimal strategy in cases of “hidden” male factor, in which men with normozoospermia experience impaired fertility, in particular, due to sperm DNA fragmentation.

Journal of obstetrics and women's diseases. 2023;72(6):63-76
pages 63-76 views

Development and testing of an endometrial status assessment test based on RNAampliSeq technology

Malysheva O.V., Vashukova E.S., Gzgzyan A.M., Dzhemlikhanova L.K., Ob'edkova K.V., Popova A.K., Tkachenko A.A., Shalina M.A., Yarmolinskaya M.I., Glotov A.S.

Abstract

BACKGROUND: Approximately two thirds of all implantation failures are due to impaired endometrial receptivity. The lack of implantation may be due to an implantation window failure found in approximately 25-30% of women with a history of failure to perform assisted reproductive technology protocols. The receptivity phase in such patients can be shifted in terms of timing, have a short duration, or not form. Currently, there are several commercial tests for determining endometrial receptivity based on transcriptomic data. However, these tests differ very significantly from each other in the set of genes studied, and the exact mechanism of endometrial receptivity is still not fully understood.

AIM: The aim of this study was to create and check our own test based on RNA AmpliSeq technology to assess the receptivity status of the endometrium and the implantation window.

MATERIALS AND METHODS: We previously created an RNAampliSeq panel containing 421 gens. With its use, the differential expression of these genes was analyzed in 38 endometrial samples taken in the proliferative and receptive phases.

RESULTS: The studied samples form clearly distinguishable clusters with the receptive and proliferative endometria. 271 genes from our panel are differentially expressed in different phases of the menstrual cycle.

CONCLUSIONS: We have created and tested a model that allows clearly distinguishing between the proliferative endometrium and the receptive one and identifying patients with disorders of the menstrual cycle.

Journal of obstetrics and women's diseases. 2023;72(6):77-88
pages 77-88 views

Impact of surgical treatment of endometriomas on ovarian reserve and reproductive outcomes

Molotkov A.S., Yarmolinskaya M.I., Tsypurdeeva A.A.

Abstract

BACKGROUND: Endometriomas are most common during the reproductive years and have an extremely negative impact on ovarian reserve and fertility. In this case, the main method of treatment remains surgery, which inevitably injures healthy ovarian tissue. Assessing the impact of surgical treatment of endometriomas on ovarian reserve and fertility will help to optimize the management of patients of reproductive age with endometrioid cysts.

AIM: The aim of this study was to evaluate the effect of surgical treatment on ovarian reserve and reproductive outcomes in patients with endometrioid cysts.

MATERIALS AND METHODS: We analyzed the course of the disease in 289 patients with endometriomas. All patients underwent processing of medical histories and surgical protocols; then, 134 patients were surveyed in the long-term postoperative period (12–24 months after surgery) to gather data on complaints and age of the patients, the size of endometriomas, previous treatment, anti-Müllerian hormone level, and features of reproductive function implementation.

RESULTS: Among patients who had pain before surgery, 52.8% of patients noted a complete absence of pain after surgery; in 26.4% of patients, pain significantly decreased. In 65.8% of patients who had dysmenorrhea before surgery, menstruation became painless. Among patients who complained of dyspareunia before surgical treatment, in 80% of patients, pain during sexual intercourse decreased or disappeared after surgery. After surgical treatment, 119 of 134 surveyed patients (88.8%) received drugs for hormonal therapy for endometriosis. After treatment, pregnancy occurred in 54 out of 82 patients interested in reproductive function. The average anti-Müllerian hormone level before treatment was 3.8 ± 1.8 ng/ml in the age group of 20–34 years and 1.9 ± 1.5 ng/ml in the age group of 35–45 years old; after treatment, 2.7 ± 2.0 ng/ml and 1.0 ± 1.8 ng/ml, respectively.

CONCLUSIONS: Determining anti-Müllerian hormone level is one of the main methods for obtaining an idea of the patient’s ovarian reserve. At a young age and with not implemented reproductive function, it is mandatory to determine the ovarian reserve and consult a reproductive specialist before starting treatment. According to our results, surgical treatment of endometriomas is the most promising for overcoming infertility in young patients with endometriosis.

Journal of obstetrics and women's diseases. 2023;72(6):89-96
pages 89-96 views

Blood oxytocin levels and the rs4686302 polymorphism of the oxytocin receptor gene in patients with adenomyosis

Netreba E.A., Yarmolinskaya M.I., Malysheva O.V., Shalina M.A., Tkachenko N.N., Koloshkina A.V.

Abstract

BACKGROUND: An in-depth study of the pathogenesis of adenomyosis and the development of new therapeutic approaches are extremely relevant. Atosiban, a competitive oxytocin receptor antagonist, may be a promising drug with a potential therapeutic effect. Oxytocin is involved in the pathogenesis of adenomyosis-associated dysmenorrhea, and there is evidence of increased expression of the oxytocin receptor (OXTR) in the myometrium in adenomyosis and the association of the OXTR gene polymorphic variant rs4686302 with oxytocin-induced myometrial contractility.

AIM: The aim of this study was to evaluate blood oxytocin levels and the frequency of the polymorphic variants of the oxytocin receptor gene (OXTR) rs4686302 polymorphism in patients with adenomyosis and in healthy women of reproductive age.

MATERIALS AND METHODS: The levels of oxytocin in the blood plasma were measured by competitive enzyme immunoassay (ELISA) in patients with adenomyosis (n = 56, with mean age of 37.5 ± 8.54 years), and in women without gynecological diseases (control group; n = 33, with mean age of 32.1 ± 5.40 years). The polymorphic variant rs4686302 of the OXTR gene was analyzed by PCR-RFLP analysis in patients with adenomyosis (n = 79, with mean age of 39.9 ± 7.74 years) and in control group patients (n = 49, with mean age of 37.0 ± 9.20 years). The chi-square (χ2) test was used to analyze the distribution of genotypes and alleles. Statistical data processing was performed using the Jamovi Software, Version 1.2.27 for Windows.

RESULTS: In patients with adenomyosis, the level of oxytocin in the blood serum was significantly higher than in control group patients: 130.0 ± 27.9 pg/ml and 95.9 ± 26.7 pg/ml, respectively. The minor allele A of the OXTR gene polymorphic variant rs4686302 was significantly more common in patients with adenomyosis (28.5%) than in women in the control group (13.3%) and in the general sample (11–15% according to the 1000 Genomes Project). The odds of developing adenomyosis in patients with the presence of the A allele (the G/A and A/A genotypes) were 2.44 times higher compared to patients with the G/G genotype (OR 2.44, 95% CI 1.13–5.28).

CONCLUSIONS: The data obtained suggest the participation of oxytocin and its receptor in the pathogenesis of adenomyosis and requires further research in this direction.

Journal of obstetrics and women's diseases. 2023;72(6):97-104
pages 97-104 views

The effect of hormone-modulating therapy during pregravid preparation on the course of pregnancy and childbirth in patients with a history of endometriosis

Seyidova C.I., Yarmolinskaya M.I.

Abstract

BACKGROUND: Endometriosis is a benign proliferation of tissue similar in morphological and functional characteristics with endometrium outside the uterine. In the structure of gynecological diseases, it ranks on the third place and its prevalence is growing steadily every year.

AIM: The aim of this study was to analyze the features of pregnancy and childbirth in patients with endometriosis who received hormone-modulating therapy during pregravid preparation.

MATERIALS AND METHODS: This retrospective analysis of the course of pregnancy and childbirth in patients with a surgically confirmed diagnosis of varying severity endometriosis (n = 140) in history was carried out at the Center for Diagnosis and Treatment of Endometriosis, The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia. The control group consisted of pregnant women without endometriosis (n = 50).

RESULTS: Before pregnancy, 82.1% (n = 115) of patients with endometriosis used hormone-modulating therapy, while 17.9% (n = 15) of patients did not comply with the given therapy. During therapy, 70% (n = 98) of patients mentioned decreasing in the severity of pain. In patients with a history of endometriosis, threatened miscarriage took the leading place and was identified in 24.3% of cases in the first and second trimesters and in 33.6% of cases in the third trimester of pregnancy, which was consistently higher than in the control group. Miscarriage was observed in 38.5% of patients and recurrent pregnancy loss in 18.6% of women. Preeclampsia was diagnosed in 23.8% (n = 33) of patients with endometriosis. The use of hormone-modulating therapy during pregravid preparation was shown to reduce the risk of developing preeclampsia among patients with endometriosis by 4.1 times, and the use of dienogest 2 mg as the therapy of endometriosis to reduce the frequency of preeclampsia by ten times in comparison with patients who did not receive any treatment. Fetal growth restriction was observed in 18.6% (n = 26) of patients with endometriosis. The presence of endometriosis increased the likelihood of developing fetal growth restriction by 3.6 times and reduced the likelihood of having a large fetus by 2.7 times. Preterm birth was observed in 20% (n = 28) of patients with endometriosis, which is four times higher than in the control group (p = 0.019). Most pregnant women with a history of endometriosis – 64.3 % (n = 90) of patients – were delivered by cesarean section, while 35.7% (n = 50) of women had vaginal birth, which was 3.34 times higher than the frequency of cesarean section in the control group.

CONCLUSIONS: Patients with a history of endometriosis are at high risk for the development of obstetric complications associated with the pathogenesis of the disease. An integrated approach to the treatment of endometriosis with the use of hormone-modulating therapy during pregravid preparation and personalized management of patients in different trimesters of pregnancy can reduce the risk of complications of pregnancy and childbirth.

Journal of obstetrics and women's diseases. 2023;72(6):105-114
pages 105-114 views

Reviews

Disorders of carbohydrate metabolism and candidate genes for the pathophysiology of polycystic ovary syndrome. A literature review

Abashova E.I., Yarmolinskaya M.I., Osinovskaya N.S.

Abstract

Polycystic ovary syndrome is a common heterogeneous disease with metabolic disorders. In the last decade, the study of polycystic ovary syndrome pathogenesis has been associated with the modern development of molecular genetics, transcriptomics, and sequencing methods. Numerous studies have shown that the study of genetic markers and epigenetic changes in metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis and etiology of the disease. The aim of this literature review was to describe candidate genes involved in the pathophysiology of polycystic ovary syndrome and associated with disorders of carbohydrate metabolism according to modern domestic and foreign literature over the past five years. The candidate gene data presented were assessed based on the main aspects of polycystic ovary syndrome pathophysiology, namely, metabolic dysfunction, androgen and gonadotropin imbalance, and inflammation. The insulin genes (variable number of tandem repeats), such as INS-VNTR, IRS-1, IRS-2, and INSR, adiponectin and calpain-10 genes, as well as CY1A1, CYP11A1, PON1, DENND1A and TCF7L2 genes are associated with metabolic disorders in polycystic ovary syndrome. Genetic variants of genes involved in regulating the expression and mechanism of action of insulin, as well as its receptors and substrates (IRS-1, IRS-2, INSR), have been suggested as possible factors involved in the development and severity of the clinical and metabolic manifestations of polycystic ovary syndrome. The presented data on PPARγ gene (and its coactivator PGC-1α) expression levels in women with polycystic ovary syndrome revealed the presence of PPARγ gene polymorphisms associated with insulin resistance. Thus, the data presented in this review from genome-wide association studies (GWAS) and the study of candidate genes showed that numerous pleiotropic effects cause carbohydrate metabolism disorders in polycystic ovary syndrome. The study of genetic markers and epigenetic changes in the development of metabolic disorders, oxidative stress, chronic inflammation, and mitochondrial dysfunction in polycystic ovary syndrome is an important direction in the pathogenesis of the disease.

Journal of obstetrics and women's diseases. 2023;72(6):115-128
pages 115-128 views

Bacterial vaginosis as a factor associated with adverse pregnancy outcomes

Oganyan K.A., Krysanova A.A., Savicheva A.M., Bespalova O.N., Kogan I.Y.

Abstract

Bacterial vaginosis is the most common disease of the genitals and affects 20–70% of women. This non-inflammatory syndrome is characterized by dysbiosis of the vaginal microbiota and is accompanied by a decrease in the number of lactobacilli. Bacterial vaginosis in 60% of pregnant women is asymptomatic, but can lead to obstetric complications such as late miscarriage, premature birth, fetal growth restriction, premature rupture of membranes, choriominionitis, postpartum endometritis, and sepsis. The clinical picture of bacterial vaginosis in pregnant women is the same as in non-pregnant women, namely homogeneous whitish-gray discharge from the genital tract, often with an unpleasant “fishy” smell, rarely itching and/or burning in the genital area and urethra, as well as soreness during urination (dysuria), with no signs of an inflammation detected in the genitals. Diagnosis of bacterial vaginosis in pregnant women, as well as in non-pregnant women, is based on the use of clinical and laboratory methods. Multiplex tests based on the nucleic acid amplification method, such as real-time polymerase chain reaction, are very popular for the diagnosis of bacterial vaginosis in this country. The Femoflor-16 Reagent Kit (DNA Technology CJSC, Moscow, Russia) is designed to detect the DNA of opportunistic microorganisms, lactobacilli DNA and human genomic DNA (as a control for taking biological material). Examination of pregnant women, especially in case of complaints of vaginal discharge, should be carried out when registering for pregnancy in order to start treatment early and prevent adverse pregnancy outcomes for the mother and fetus. Biofilms formed by microorganisms in bacterial vaginosis, especially G. vaginalis, limit the penetration of antibacterial agents to bacteria, their concentration being lower than therapeutic one, which leads to ineffective treatment. There remain many unexplored issues related to changes in the epidemiology of bacterial vaginosis, an increase in the frequency of relapses against the background of increasing resistance of microorganisms associated with bacterial vaginosis to antibiotics, and the development of agents that affect bacterial films.

Journal of obstetrics and women's diseases. 2023;72(6):129-138
pages 129-138 views

Fibroid pseudocapsule: a modern view of the problem. A literature review

Polenov N.I., Yarmolinskaya M.I.

Abstract

Uterine fibroids are a benign polyetiological, hormone-sensitive, monoclonal tumor originating from the smooth muscle cells of the myometrium. They differ in size, location, growth rate, parenchyma-stroma ratio, morphohistogenesis, and clinical manifestations. Despite the frequent occurrence of this disease, its pathogenesis is poorly understood. In particular, the role of the fibroid pseudocapsule is a topic of interest. The appropriateness of retaining the pseudocapsule during myomectomy and the association of its retention with the risk of disease recurrence also remain controversial. This article is a literature review of data ranging from 2013 to 2023, available in the PubMed and Scopus databases. The main aspects of domestic and international clinical guidelines are also presented. This review covers epidemiological features and clinical aspects of uterine fibroids, as well as intraoperative and morphological characteristics of the fibroid pseudocapsule. Current data on the role of the MED12 gene, PGP 9.5, SP, VIP, VEGFR, IGF-2, endoglin, and oxytocin in the pathogenesis of uterine fibroids are also presented. Literature on the effect of gonadotropin-releasing hormone agonists on the morphology and functions of the pseudocapsule is submitted in the text. Despite the possible regenerative properties of the fibroid pseudocapsule, there is still a lack of systematic studies in the literature regarding the molecular and biochemical characteristics of the pseudocapsule, which makes it necessary to further investigate this morphological structure.

Journal of obstetrics and women's diseases. 2023;72(6):139-147
pages 139-147 views

The role of microRNAs in preeclampsia

Postnikova T.B., Vashukova E.S., Glotov A.S., Mozgovaya E.V., Pachuliia O.V., Bespalova O.N.

Abstract

AIM: The aim of this study was to review current sources of scientific literature covering the role of miRNAs in preeclampsia.

BASIC PROVISIONS: MicroRNAs are a class of short RNA nucleotide sequences that are not involved in protein synthesis, but are capable of controlling complex processes such as cell growth, differentiation, stress response, and tissue remodeling, which under certain conditions play a key role in a variety of pathological processes, including preeclampsia. MicroRNAs regulate up to 60% of the human genome. There are three types of placental miRNAs: placenta-specific, placenta-associated and circulating ones. Three miRNA gene clusters, namely chromosome 19 cluster (C19MC), chromosome 14 cluster (C14MC), and miR-371 ~ 373 cluster, encode most placenta-specific miRNAs. C19MC encodes 58 mature miRNAs and is expressed in trophoblast cells in early pregnancy and then, in placental differentiated cells. C14MC encodes 63 mature microRNAs, which are also expressed in trophoblasts. The miR-371~373 cluster only encodes six mature microRNAs expressed in placental differentiated cells and embryonic stem cells. The functions of placenta-specific miRNAs are being actively studied now. It has been established that the action of these microRNAs is associated with proliferation, apoptosis, migration, angiogenesis of trophoblast cells and placentation in early pregnancy. Recently, special attention has been paid to identifying microRNAs as possible predictors of preeclampsia in early pregnancy.

CONCLUSIONS: Literature data indicate that miRNAs are associated with the pathogenesis of preeclampsia. It has been proven that more than a hundred types of miRNAs are expressed in placental tissues, and some of them can be isolated and detected in peripheral blood and urine in patients with preeclampsia. Studying the miRNA types will allow for determining the most significant prognostic markers for early detection of preeclampsia and developing non-invasive tests.

Journal of obstetrics and women's diseases. 2023;72(6):149-160
pages 149-160 views

The role of papillomavirus and herpesvirus infections in the origins and genesis of genital endometriosis. A literature review

Khanova A.M., Khachaturian A.R., Khusnutdinova T.A., Savicheva A.M., Yarmolinskaya M.I.

Abstract

Endometriosis is a chronic multifactorial disease that affects one in ten women of reproductive age. Genetic, endocrine and immunological factors play an important role in the pathogenesis of endometriosis. In recent years, an increasing number of studies have been devoted to the role of vaginal microbiota in the pathogenesis of endometriosis. However, the role of viral infections, such as papillomavirus and herpesvirus infections, in the development of the disease has not been sufficiently studied. The review highlights current ideas about the role of human papillomavirus and herpesvirus infections in the genesis of endometriosis. The data obtained have convinced us of the need to further search for new relationships between papillomavirus and herpesvirus infections, microbiota of reproductive organs and pathogenesis of such a complicated disease as endometriosis.

Journal of obstetrics and women's diseases. 2023;72(6):161-172
pages 161-172 views

Theory and Practice

Prospects for preconception genetic screening at the pregnancy planning stage

Glotov A.S., Nasykhova Y.A., Dvoynova N.M., Bespalova O.N., Kogan I.Y.

Abstract

To date, the active introduction of genetic technologies into practical medicine continues in the healthcare sector. The number of genetic diseases is growing, for which different gene therapy and targeted therapy options are emerging. At the same time, the genetic burden in the population is also increasing. The only way to reduce it is the universal introduction of primary preventive programs, the most significant of which is preconception screening, or carrier screening of monogenic diseases. In this review article, various options for preconception screening are considered in detail and the main categories of people for whom such a survey is indicated are identified. The latter are high school students, couples registering a marriage, couples planning a pregnancy, women in early pregnancy, relatives of family members of adolescents with established disabilities, as well as donors of sperm or eggs used in IVF cycles. A detailed historical perspective and examples of various international carrier screening programs for genetic diseases are given in this review. Our analysis shows that sequential testing for monogenic diseases is an appropriate screening strategy (the woman shall be examined first). As part of the screening, the ethnic composition of the population should be taken into account. However, in the case of a mixed population and a high frequency of migration, it is preferable to use an expanded panel that includes the most frequent diseases characteristic of the nationalities inhabiting a certain region. The best results are achieved with mandatory or almost mandatory screening. This review shows the main steps that have been taken in the Russian Federation over the past two years and describes the programs of the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott, Saint Petersburg, Russia. These include free screening programs for family members and relatives of patients with the most common diseases and couples with reproductive loss, as well as a carrier screening program for six major diseases at the expense of the patient. The summary part provides an assessment of the prospects for the practical use of carrier screening in the general population and high-risk groups, as well as for donors of reproductive material, in Russia.

Journal of obstetrics and women's diseases. 2023;72(6):173-192
pages 173-192 views

TIME-LAPSE technology in modern embryological practice

Ishchuk M.A., Lesik E.A., Sagurova Y.M., Komarova E.M.

Abstract

This article describes the basic principles of TIME-LAPSE technology. We report the use of this technology in modern embryological practice and compare it with the conventional cultivation system. Herein, we overview modern incubators equipped with the TIME-LAPSE system, including domestic ones, with their advantages and disadvantages listed. The main events of early human embryo development are described and rare events noted, such as abnormal pronucleus formation and disappearance, multinucleation of blastomeres, reverse cleavage, or “direct cleavage” into three blastomeres, which can only be visualized using TIME-LAPSE technology, but not with traditional visual assessment of embryo morphology. The use of artificial intelligence in conjunction with TIME-LAPSE technology for objective assessment and ranking of embryos based on their morphokinetic characteristics is given a thorough consideration. In conclusion, the article presents data on the impact of using technology on the effectiveness of IVF programs. Moreover, we herein describe such unobvious advantages of the TIME-LAPSE system as the ability to train and transfer video data between participants in the IVF protocol.

Journal of obstetrics and women's diseases. 2023;72(6):193-201
pages 193-201 views


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