Tatyana S. Zhernakova’s scientific contributions

A modern approach to predicting the quality of embryos in ART programs is the search for promising biomarkers in follicular fluid. Objective. To determine the composition of follicular fluid and blood serum in women with infertility and evaluate its effect on the quality of embryos. Material and methods. A pilot prospective cohort study was conducted on 26 patients aged 27 to 44 years who were undergoing infertility treatment at the ART department of the D.O. Ott Research Institute from June 2023 to September 2023. Inclusion criteria: primary and secondary infertility. Exclusion criteria: contraindications to the use of ART methods. Samples of follicular fluid (FF) and blood serum obtained on the day of follicle puncture were examined for 26 indicators: vitamins B12, B9, vitamin D, magnesium, phosphorus, iron, copper, zinc, total calcium, homocysteine, glucose, total protein, albumin, urea, uric acid, creatinine, cholesterol, LDL, ferritin, transferrin, latent iron-binding capacity, total iron-binding capacity, transferrin iron saturation coefficient, cystatin C, C-reactive protein, albumin-globulin ratio. The patients were divided into two groups depending on the obtained embryos: group 1 — with optimal embryo quality; group 2 — with embryos of suboptimal quality. Results. The levels of homocysteine, vitamin B12, glucose, creatinine, total protein, albumin, LDL, cholesterol, transferrin, ferritin, iron, total iron-binding capacity, transferrin saturation coefficient with iron, magnesium, copper, zinc, total calcium between FF and blood serum are statistically significantly different (p<0.0001). In serum, the median of the listed substances is higher than in FF. Also, a statistically significant difference was observed between the levels in the FF and in the blood: vitamin D, cystatin C, CRP, albumin-globulin ratio, urea (p< 0.0001) and phosphorus (p=0.04). In the FF, the median of the listed substances is higher than in the blood. As a result of the analysis of FF and serum parameters in women with infertility, depending on the quality of the embryos, a statistically significant difference was obtained in the follicular fluid for homocysteine (p=0.004), uric acid (p=0.015), comparing the serum/FF ratio for folic acid (p=0.004), vitamin D (p=0.007), glucose (p=0.009), phosphorus (p=0.016), cystatin C (p=0.036). Conclusion. The composition of the studied biochemical parameters in the FF was determined. Levels of homocysteine, uric acid in FF and assessment of the serum/FF ratio for folic acid, vitamin D, glucose, phosphorus, cystatin C can serve as biomarkers for predicting the quality of embryos.

In the conditions of rapid development of computer technologies, the field of application of artificial intelligence (AI) systems is continuously expanding. During the last ten years AI programs have been actively developed and integrated into various spheres of healthcare with increasing number and complexity of the tasks they solve. Due to the ability to analyze a large set of data and high performance, AI is a promising direction in improving the accuracy and speed of diagnosis, the choice of treatment tactics and its objectification, and the possibility of individual prognosis. The programs of assisted reproductive technologies (ART) represent a sequence of stages, the effectiveness of each of which is influenced by a combination of many factors. In this regard, the application of AI systems in overcoming infertility, described for various aspects of treatment, including individual selection of stimulation schemes and monitoring of ovarian response, selection of gametes, embryos and their cryopreservation, non-invasive diagnosis of the genetic status of the embryo, and prognosis of the effectiveness of ART cycles, is relevant. This literature review was prepared on the basis of the analysis of PubMed, MedLine, eLibrary databases publications for the period 1972—2022 on the keywords Artificial Intelligence, Machine Learning in the field of reproductive medicine and embryology, and describes the main AI methods used at all stages of ART programs. Conclusion. AI technologies are a promising direction for improving the quality of medical care in infertility, transition to personalized medicine and increasing the effectiveness of ART programs. The development of AI systems requires the participation of a medical specialist in the selection and preparation of data, determination of algorithm tasks, its approbation and implementation in clinical practice. It should be noted that AI systems can also be applied in the field of medical research. However, before AI algorithms are integrated, large-scale randomized controlled trials and their standardization are required, which involves solving a number of ethical, legislative and organizational issues.

Aim: To describe the tools for determining the nutritional status of patients, possible methods for its correction, the main components (vitamins, macro- and micronutrients, and antioxidants) for oral and intravenous administration, involved in the implementation of the reproductive function. Key points. The correct combination of enteral and parenteral forms of vitamins, macro- and microelements makes it possible to adequately, personalized and quickly compensate for the deficient conditions of patients at the pregravid stage, to ensure a favorable start of pregnancy, taking into account personal risks. The optimal nutritional status maintains normal immunological reactivity of the organism, influencing the processes of implantation and placentation, which is extremely important for overcoming miscarriage, especially in the early stages. Conclusion. Intravenous nutritional support is an additional tool in the practitioners' arsenal to improve reproductive outcomes and improve patients' quality of life. Keywords: vitamins, macro- and micronutrients, preconception preparation, antioxidants, intravenous nutritional therapy.

BACKGROUND: Currently, more than a hundred immunological biomarkers are known that are important for fertilization, implantation and placentation. AIM: The aim of this study was to assess the immunological profile for the main allo- and autoantibodies in women with reproductive loss and infertility in the North-West region of the Russian Federation. MATERIALS AND METHODS: This prospective cohort study was conducted at the stage of pregnancy planning in 325 women with reproductive disorders (spontaneous miscarriages, missed abortions, infertility, IVF failures) on the premises of the D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductive Medicine (St. Petersburg, Russia) from 2015 to 2022. The study assessed the immune interface of women with a history of reproductive disorders and matching loci of the HLA class II system (DQA1, DQB1, DRB1) among 100 married couples. RESULTS: In couples with reproductive disorders, coincidences of HLA class II allele (DQA1, DQB1, DRB1) loci were diagnosed in 14% (at 2 loci), 31% (at 3 loci), 14% (at 4 loci), 3% (at 5 loci) and 10% (at 6 loci) of couples. In 34.4% of women, we found an elevated number of spontaneously activated NK cells (CD107a). As many as 31.15% of women had a high level of antibodies to human chorionic gonadotropin. We found that 22.34% of women were carriers of at least one criteria antiphospholipid antibody, and 3.16% of women of two antiphospholipid antibodies. The diagnosis of antiphospholipid syndrome was not established in any patient. Non-criteria antiphospholipid antibodies were found in 6.15% of women. In 12.2% of women, we diagnosed a high level of antibodies to thyroperoxidase, while the average antibody value was 30.76 IU/ml. Only one patient had a high level of antisperm antibodies in the blood serum. CONCLUSIONS: In 59% of patients with a history of reproductive disorders, we identified some features of the immunological profile, which can lead to this pathology. Thus, 32% of women had a deviation in one immunological parameter, while 20% of patients had it in two parameters, and 7% in three or more parameters.

BACKGROUND: Immune mechanisms play a leading role in the pathogenesis of early reproductive loss. Modern methods of regulating disorders of immune homeostasis to overcome infertility and recurrent miscarriage include immune-efferent therapies such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and fat emulsions. Intralipid is the gold standard of the first generation parenteral fat emulsion that reduces the cytotoxicity of NK cells. In the literature, there are opposite data on the effectiveness of Intralipid fat emulsion in repeated implantation failure. This may be due to indications for its appointment and the choice of criteria for evaluating the effectiveness of this therapy. AIM: The aim of this study was to evaluate the effect of Intralipid therapy on the onset of pregnancy in patients with a history of early reproductive loss. MATERIALS AND METHODS: This prospective cohort study was conducted in Saint Petersburg, Russia in 20182021 and included 97 patients with a history of early reproductive loss (recurrent pregnancy loss or repeated In Vitro Fertilization failures). Patients were randomized into two study groups. The first group consisted of 41 women with Intralipid therapy, and the second group comprised 56 women without this therapy. Patients of the first group received 200 ml of Intralipid 20% (intravenous fat emulsion) once a month for three consecutive months before pregnancy. Inclusion criteria were ages 18 to 40 years, two cases of reproductive failure (pregnancy loss up to 12 weeks and / or unsuccessful In Vitro Fertilization attempts), and normal spouse karyotypes. Exclusion criteria were miscarriage due to fetal chromosomal abnormalities diagnosed by curettage and histopathological examination of products of conception from miscarriages, anatomical anomalies in the development of the genital apparatus, abnormal spouse karyotypes, and soy protein allergy. We evaluated anamnesis data and immunological parameters (functional activity of NK cells in peripheral blood before and after treatment). The efficacy of therapy was judged by the onset of pregnancy. RESULTS: The Mann Whitney U-test showed the difference in the levels of NKT cells before and after treatment with fat emulsions (p = 0.0076), this parameter decreasing 1.846 times compared to control. Clinical pregnancy in patients treated with Intralipid occurred twice as often compared to patients who did not receive fat emulsion therapy: 59.3% (n = 19) vs. 27.6% (n = 13), respectively (p = 0.0048). CONCLUSIONS: Intralipid fat emulsion increases pregnancy rates by decreasing NKT cells in women with early reproductive loss.

Omega-3 and omega-6 polyunsaturated fatty acids are among the nutrients essential for the vital functions of the human body. Fundamental cellular functions of omega-3 and omega-6 polyunsaturated fatty acids affect both physical and reproductive health. Based on the principles of personalized medicine, early detection of polyunsaturated fatty acid deficiency is necessary for its prompt correction and prevention of further diseases. We present a literature review on the effects of polyunsaturated fatty acids on female and male fertility. The brief information on biochemical aspects, current data on diagnosis, and possible methods for correction of polyunsaturated fatty acid deficiency are described in this article.