Pre-eclampsia (PE) is one of the severe complications of pregnancy in 2–8% of all cases and is one of the leading causes of maternal and perinatal mortality. The fundamental role in the pathogenesis of PE is assigned to maternal and/or placental factors, whereby the combination and manifestation of which determines the time of onset of the clinical symptoms of PE (before or after 34 weeks of gestation) and their severity. It is known that the expression level of miRNAs, the regulators of signaling cascades in the cell, depends on gestational age. In the present study, we focused on the identification of the placenta-specific miRNAs that differentiate between early- and late-onset pre-eclampsia (ePE and lPE) throughout pregnancy, from the first to the third trimester. A total of 67 patients were analyzed using small RNA deep sequencing and real-time quantitative PCR, which resulted in a core list of miRNAs (let-7b-5p, let-7d-3p, let-7f-5p, let-7i-5p, miR-22-5p, miR-451a, miR-1246, miR-30e-5p, miR-20a-5p, miR-1307-3p, and miR-320e), which in certain combinations can predict ePE or lPE with 100% sensitivity and 84–100% specificity in the 1st trimester of pregnancy. According to the literature data, these miRNA predictors of PE control trophoblast proliferation, invasion, migration, syncytialization, the endoplasmic reticulum unfolded protein response, immune tolerance, angiogenesis, and vascular integrity. The simultaneous detection of let-7d-3p, miR-451a, and miR-1307-3p, resistant to the repeated freezing/thawing of blood serum samples, in combination with biochemical (b-hCG and PAPP-A) and ultrasound (UAPI) parameters, allowed us to develop a universal model for the prediction of ePE and lPE onset (FPR = 15.7% and FNR = 9.5%), which was validated using a test cohort of 48 patients and demonstrated false-positive results in 26.7% of cases and false negatives in 5.6% of cases. For comparison, the use of the generally accepted Astraia program in the analysis of the test cohort of patients led to worse results: FPR = 62.1% and FNR = 33.3%.

The identification of the earliest diagnostic markers for infections in newborns remains one of the priorities in neonatology. In our study, we aimed to assess the diagnostic value of presepsin (P-SEP) as a marker for congenital infections in newborn children. The study was prospective in design and took place from January 2020 to February 2021. We enrolled a total of 64 children with a gestational age of 24 to 40 weeks. The study was approved by the Biomedical Research Ethics Committee (Minutes No.12 of 17 November 2016) and the Scientific Council (Minutes No.19 of 29 November 2016) of the V.I. Kulakov NMRC OGP of Ministry of Healthcare of the Russian Federation. Written voluntary consent to the patients’ participation in the study was obtained from their legal representatives. The patients were divided into 2 groups: a group of interest consisting of newborn children with congenital infections (n = 30), and a control group comprising newborns without signs of infection (n = 34). The group of interest included children with congenital pneumonia (n = 25), urinary tract infections (n = 3), and infections specific to the perinatal period, without a focus of infection (n = 2). Gestational age and birth weight were comparable between the groups. No statistically significant differences in CRP levels, neutrophil counts, immature-to-total neutrophil ratios and lactate concentrations on days 1 and 3 of life were found between the two groups. In the group of interest, P-SEP on day 1 of life was significantly higher than in the control group (р = 0.015). Our findings suggested that P-SEP levels ≥ 481 pg/mL could predict a high risk of congenital infections in newborns. The sensitivity and specificity were 91.0% and 60.0% respectively. P-SEP levels determined in capillary blood were similar to those obtained from venous blood samples suggesting that either can be used for P-SEP measurement with equal success. P-SEP levels were shown to decrease by day 3 of life in the children with congenital infections who had been treated with antibiotics.

Aim. To assess the possibility of using androstenedione levels in blood serum and follicular fluid to predict ovarian response in assisted reproductive technology programs and to conduct a comparative analysis of the results obtained by 2 methods chemiluminescent immunoassay (CLIA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Materials and methods. A prospective study included 55 couples who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer program therapy. The patients were divided into 3 groups depending on the ovarian response to stimulation: 1st (13 oocytes, n=4), 2nd (49 oocytes, n=27), 3rd (over 10 oocytes, n=24). Androstenedione levels were measured in blood serum obtained on the day of transvaginal ovarian puncture and in follicular fluid samples with CLIA and HPLC-MS/ MS methods at the laboratories of Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology. Results. On the day of transvaginal ovarian puncture, the serum androstenedione levels, which were measured by HPLC-MS/MS, were increasing with an increase of the number of oocytes obtained. The CLIA method revealed a difference in the androstenedione levels between the groups with the number of oocytes obtained of less than 3 and more than 10. Moreover, the androstenedione levels measured by CLIA were significantly different between the patient groups (p0.05). Comparison of serum androstenedione levels measured by CLIA and HPLC-MS/MS, showed high correlations between the values [=0.73 (p0.001)], which makes it possible to use both methods equally, given the existing equipment of the clinical base. Conclusion. Prediction of ovarian response to stimulation is an important step in assisted reproductive technology programs. Measuring androstenedione concentration in blood serum on the day of transvaginal ovarian puncture with highly specific methods (CLIA and HPLC-MS/MS) can be used to predict the degree of ovarian response along with the traditional assessment of the ovarian reserve based on determining anti-Mullerian hormone levels in the early follicular phase of the menstrual cycle.

The review presents data on metabolites in the follicular fluid (FF) from the perspective of reproductive medicine and their use in order to predict outcomes of assisted reproductive technology (ART) programs. It considers various components of this biological medium (hormones, lipids, melatonin, etc.) with an assessment of their predictive value in prognosis of the effectiveness of in vitro fertilization (IVF) programs. The data on experimental directions in this field and the prospects for their use in clinical practice are presented. The article emphasizes that the growing clinical need and the unsolved problem of increasing the effectiveness of ART programs determine the need for further studies of the FF composition. Materials and methods. The review includes data related to this topic from foreign and Russian articles found in PubMed which were published in recent years. Results. Given the established fact of a direct effect of FF composition on growth and maturation of oocytes, and further, on the fertilization process, various FF metabolites are actively investigated as non-invasive markers of quality of oocytes/embryos. The article provides data on the experimental directions in this field and the prospects for their use in clinical practice. However, clinical studies of a relation between various FF metabolites levels and outcomes of IVF programs are contradictory. Conclusion. Owing large economic cost for treatment of infertility with IVF, there is need for expansion and intensification of studies to identify and use reliable predictors in prognosis of ART programs outcomes.