ENDOMETRIAL RECEPTIVITY AS THE KEY TO THE SUCCESS OF ART PROGRAMS: A LITERATURE REVIEW

Relevance: To date, the success of in vitro fertilization (IVF) programs in Kazakhstan is 38%. The purpose of the study was to evaluate the mechanisms of influence of various risk factors on endometrial receptivity in women in IVF programs. Materials and Methods: This review was based on a search conducted for domestic and foreign publications available in Russian and international search systems (PubMed, eLibrary) for the past 25 years. Results: Chronic endometritis is a verified cause of impaired receptivity. Many studies have proven the beneficial effect of complex empirical treatment using antibacterial, anti-inflammatory, hormonal therapy with transdermal forms of estrogens and vitamin therapy on the outcome of IVF. Conclusion: The problem of recurrent implantation disorders in IVF programs is multifactorial. Women with unrealized reproductive function require rehabilitation after an unsuccessful fertilization attempt to prevent disorders of homeostasis and ensure adequate pain relief during transvaginal puncture of ovarian follicles. In addition to hormone therapy with transdermal forms of estradiol, complex rehabilitation measures shall include immunomodulatory therapy, psychotherapy, and vitamin therapy.

«VULNERABLE» ENDOMETRIUM: A MODERN VIEW ON THE PATHOGENESIS AND PATHOGENETIC THERAPY OF ENDOMETRIAL HYPERPLASTIC PROCESSES

Relevance: Endometrium is a unique human tissue with a strong regenerative potential which is implemented after desquamation during each menstrual cycle. At that, regeneration in the endometrium is not accompanied by scarring. Endometrial hyperplasia as a variant of defect transformation is a widespread disease which remains an urgent problem of modern medicine. In recent years, endometrial hyperplasia is becoming more common among patients of reproductive age. This problem is even more significant due to the spread of endometrial cancer in developed countries, and endometrial hyperplasia being its precursor. Purpose: The article describes modern views on the pathogenesis and pathogenetic therapy of endometrial hyperplastic processes. Materials and Methods: Sources available in the Pubmed, Embase, Cochrane databases were analyzed and international reviews of randomized controlled studies in that area were selected for the last few years using the keywords «endometrial hyperplasia,» «atypical hyperplasia,» «endometrial cancer,» «progestins,» and «hysterectomy.» Results: The article discusses the modern ideas about etiopathogenesis and the tactics of management of patients, according to the data of foreign literature. Conclusion: Early diagnostics and timely treatment of endometrial hyperplasiaare an important preventive factor due to the high risk of malignancy. The patient management algorithm depends on many factors: the type of hyperplastic conditions, the patient’s age, unrealized reproductive function, and etc. Progestin therapy is more preferable for young patients wishing to preserve reproductive function. If cellular atypia is present, panhysterectomy is the first line of treatment for women who have realized their reproductive function and have endometrial hyperplasia with atypia.

THE CAPACITY OF PHYSICAL THERAPY FOR REPEATED IMPLANTATION FAILURES IN IVF PROGRAMS: A LITERATURE REVIEW

Relevance: Studies of the etiology and pathogenesis of implantation failures, both repeated and primary, as well as the possibilities of therapy today carry many contraversions. However, in recent years, numerous studies have demonstrated the high effectiveness of various physiotherapy methods in improving reproductive outcomes, including therapy and overcoming repeated implantation failures in in-vitro fertilization programs. The purpose of the study was to study the capacity of physical therapy for repeated implantation failures in in-vitro fertilization programs. Materials and Methods: The capacity of physical therapy for repeated implantation failures in in-vitro fertilization programs were studied through the search and analysis of the scientific sources for 1995-2021, available in the Scopus and Pubmed databases, using the keywords “in-vitro fertilization,” “repeated implantation failure,” “assisted reproductive technology,” and «physiotherapy.» Results: Electrical impulse therapy has established itself as the most studied method in the treatment of disorders of endometrial receptivity with proven efficacy. Physical methods of exposure can improve reproductive outcomes through a beneficial effect on the angiogenesis and architectonics of the endometrium, improving its receptivity, and normalizing physiology. Further detailed study of the etiology, pathogenetic mechanisms, as well as the effectiveness of overcoming repeated implantation failures by various methods is needed to develop treatment protocols.

MODERN APPROACHES TO CULTIVATION AND AUTOANALYSIS OF HUMAN EMBRYO MORPHODYNAMICS IN VIVO

Relevance: Currently, it is extremely important to identify predictors of the development of a competent embryo that determine its implantation potential. In this case, the predictors are predictive parameters that should be assessed together to rank and select human embryos. We introduced the concept of «human embryo morphodynamic profile» to standardize the description of the development of human embryos cultured in vitro. We identified a set of morphokinetic states that are included in the profile and located on the time scale depending on the moment of their registration. All timing cutoffs (points) are given in chronological order relative to the moment of fertilization. The purpose of the study was to implement an information system utilizing artificial intelligence technologies for an automated formation of the morphodynamic profile of a human embryo based on time-lapse photography of the process of human embryo cultivating to the blastocyst stage. Materials and methods: Visual information about the pre-implantation development of human embryos to the blastocyst stage (0 - 6 days from insemination) was collected using an «Embryovisor» incubator for IVF laboratories with a time-lapse (hyperlapse) video fixation system (LLC «WESTTRADE LTD,” Russia). The embryos were cultivated individually in special microwells of WOW dishes (Vitrolife, Sweden). Visual information about cultured human embryos was collected, marked, and prepared at the Laboratory of assisted reproductive technologies (ART) of the Clinical Hospital IDK CJSC “Medical Company IDK” (Group of Companies “Mother and Child,” Samara, Russia) and the medical center “Semya” (Ufa, Russia). The morphodynamic profile was marked using the EmbryoVisor software (customized version). Graphics and markup information was uploaded to the SberCloud cluster. A convolutional neural network for solving the multiclass classification task was implemented on the Christofari supercomputer of the SberCloud cluster. Results: Based on the available database, we have developed a system for forming the morphodynamic profile of a human embryo, taking into account the placement of markers of fixed morphokinetic states. Conclusion: The ability to record major morphodynamic events and assess them allows a more comprehensive approach to evaluating and ranking developing embryos and selecting the most promising embryo for implantation.

DYSMORPHISMS OF OOCYTES IN ART PROCEDURES: A LITERATURE REVIEW

Relevance: Assisted reproductive technologies (ART) are rapidly developing and in recent decades have become increasingly important due to the growing number of infertile couples around the world. Human oocytes are the main objects used in ART procedures. Consequently, the quality of oocytes can determine the key parameters of ART. The purpose of this review was to analyze the literature and the results of studies in the field of ART devoted to extracytoplasmic dysmorphisms of human oocytes – morphological changes outside the cytoplasmic structure of oocytes, their effect on fertilization, cleavage, implantation frequency, clinical pregnancy rate, as well as the possibility of their use as biomarkers for predicting the quality of embryos, blastocysts, and their further implantation potential. Materials and Methods: This literature review was based on a search conducted among domestic and foreign publications for 2000-2020 available in Russian and international search systems (PubMed, eLibrary) using the keywords «infertility,” “IVF,” «oocyte,” “morphological assessment of oocytes,” “dysmorphisms of oocytes ,” and “ assisted reproductive technologies.” Results: This literature review contains literature data and the analysis of research results in the field of ART devoted to the morphological qualities and abnormalities (dysmorphisms) of human oocytes. It describes the types of extracytoplasmic abnormalities encountered in the clinical practice of in-vitro fertilization, their effect on fertilization, cleavage, implantation rate, and clinical pregnancy rate, as well as the possibility of their use as biomarkers to predict the quality of embryos and blastocysts and their further implantation potential.

ANALYSIS OF THE PLATELET HEMOSTASIS AMONG PREGNANT WOMEN WITH IMMUNE THROMBOCYTOPENIA

Relevance: Thrombocytopenia is a common hematological problem that accompanies pregnancy. From 5% to 12% of pregnancies are complicated by thrombocytopenia. Gestational thrombocytopenia is the leading cause of complications (70-85%). Immune thrombocytopenia (ITP) is the most frequent reason among pre-pregnancy causes of thrombocytopenia and is responsible for 1-4% of all thrombocytopenia cases during pregnancy. Investigation of the functional potential of the thrombocyte link of hemostasis in conditions of a reduced number of thrombocytes is relevant. The purpose of the study was to analyze the platelet link of hemostasis in pregnant women with ITP of varying severity by the method of light aggregometry. Materials and Methods: Eighty-eight women with gestational and 28 with immune thrombocytopenia were undergoing treatment and delivery at the Institute of Pediatrics, Obstetrics and Gynecology of NAMS of Ukraine (Kyiv, Ukraine) from September 2018 to February 2021. The platelet link of hemostasis was studied in a group of women with immune thrombocytopenia; six (21.4%) of them had severe thrombocytopenia. Results: In mild and moderate immune thrombocytopenia, we noted a decrease in spontaneous and induced platelet aggregation; in severe immune thrombocytopenia, there was no spontaneous and a decreased induced platelet aggregation. This indicated a reduced potential of platelets to perform their direct function – the formation of a thrombus. Conclusion: Immune thrombocytopenia accounts for most pre-pregnancy conditions causing thrombocytopenia in pregnant women. Light aggregometry is a relevant and indicative way to analyze the aggregative ability of platelets. A multidisciplinary team consisting of an obstetrician-gynecologist, hematologist, anesthesiologist, and neonatologist should be involved in the management of such cases to provide effective obstetric care for this category of pregnant women. Risks for the mother and the fetus/newborn should be assessed throughout the pregnancy, considering clinical and laboratory aspects. Delivery of pregnant women with severe thrombocytopenia should be managed at institutions providing the highest level of obstetric and gynecological care.

PREGNANCY DURING A PANDEMIC: PERINATAL EFFECTS OF PROLONGED STRESS AND WAYS OF CORRECTION (LITERATURE REVIEW)

Relevance: The article presents current evidence on the perinatal effects of prolonged stress on pregnancy during the COVID-19 pandemic.The currently known features of the post-covidsyndrome in general and in the female population in particular are indicated. The purposewas to determine the perinatal effects of prolonged stress during a pandemic and ways to correct them. Materials and method sincludedan analysis of the scientific literature on the topic available in the public domain. Results: The article reviews the peculiarities of the course of pregnancy and perinatal outcomes after suffering a coronavirus infection, as well as the manifestations of post-covid syndrome in this cohort of women. An increase in the frequency of anxiety-depressive disorders in pregnant women and women in labor during a pandemic and their effect on the further mental state of the fetus and the development of its brain has been noted. The specific consequences of prolonged stress were determined.It became known that pregnant women during a pandemic are exposed to prolonged stress, which affects the course of their gestational period. One should note an increase in the frequency of the threat of termination of pregnancy, premature birth and delivery in 17-28% cases; exacerbation of chronic somatic diseases during pregnancy; an increase in BMI on the eve of pregnancy and a pathological increase in body weight during pregnancy. The article also discusses the timely detection and possible ways to correct these conditions despite a transition to remote monitoring of pregnant women in quarantine; offers organizational, treatment, and preventive measures with the use of preparations of micronized progesterone, magnesium citrate, folates (metafoline) and vitamin D, as well as psychoprophylaxis and psychotherapy methods. Particular attention is paid to the role of magnesium in pregnancy and its neuroprotective and metabolic effects, in particular when used in the form of citrate in a soluble form. The authors state the main directions of rehabilitation for pregnant women and women in labor after suffering COVID-19. Conclusion: So, our current knowledge about the course and consequences of COVID-19 in pregnant women and women in childbirth is not yet perfect and not final, but it allows determining the directions of scientific and practical research for the next period.

INFLUENCE ON THE OUTCOME OF ART PROGRAMS OF FROZEN-THAWED BLASTOCYSTS EXPANDED ON FIVE OR SIX DAY

In order to increase the effectiveness of assisted reproductive technologies (ART) programs, it is essential to improve and develop conditions of embryo culture prior its transfer or cryopreservation of expanded blastocysts on the day 5 or 6. The aim of the study was to assess the effect of human blastocysts’ expansion timing on clinical pregnancy rate (CPR), miscarriage rate (MR) and take-home baby rate (THBR) in frozen-thawed cycles during ART programs. The study involved 2275 frozen embryo transfers (FET) of blastocysts expanded on the day 5 (group A) and 170 FET of blastocysts expanded on the day 6 (group B). The pregnancy rates in both groups were 50.8% and 46.5% respectively. There were no statistically significant differences in clinical pregnancy rate 37.4% and 37.0%, miscarriage rate 26.0% and 21.5% in both groups, respectively. THBR, as the main indicator of efficiency in the programs with transfer of post thawed expanded blastocysts on the day 5 (group A) or 6 (group B) were 36.5% and 35.2%, respectively (the difference is insignificant). In conclusion, in cryoprotocols the day of blastocyst expansion (day 5 or 6 of development) does not statistically affect PR, MR and THBR. In FET programs the quality of blastocyst (excellent and good) should be prioritized regardless of the day of cryopreservation.

PERINATAL RISKS, GENDER CHARACTERISTICS AND POSSIBLE WAYS TO PREVENT COMPLICATIONS IN COVID-19

The article presents modern data on the features of the development, course and influence on the health of a pregnant, a woman in labor, a fetus and a newborn of SARS-COV-2 virus. Some of the protocols for the prevention of infection and treatment of COVID-19 that exist today in the world have been analyzed and a modification adapted for pregnant has been proposed. A method is proposed for the prevention of one of the most frequent and dangerous complications of COVID-19 in pregnant women - miscarriage and correction of nutritional deficiencies.

INFLUENCE OF OBSTETRIC GEL ON THE PROCESS AND DURATION OF LABOR

The article discusses the problems of weak labor, obstetric injuries, an increase in the number of surgical interventions. A study of the efficacy and safety of Dianatal obstetric gel when used in childbirth has been carried out.