Diagnostic Markers of Primary Infertility in Women of Reproductive Age with Hypothalamic Dysfunction in the Pubertal Period

The aim of the study was to assess fertility in women of reproductive age with hypothalamic dysfunction (HD) in the pubertal period and to determine the diagnostic significance of pro-inflammatory (TNF-α and IL-1β), anti-inflammatory cytokine (IL-10) and NF-kB activity in the diagnosis of primary infertility in these women. Materials and Methods: Fertility was assessed in 86 women of reproductive age with HD in the pubertal period. A comparative characteristic of fertile women (Group 1, n=46) and primary infertility women (Group 2, n=21) with HD in the pubertal period was performed. FPG and FPI were determined after 8 to 12 hours of fasting. Serum IRI concentrations were measured using an ELISA kit. The levels of TNF-α, IL-1β and IL-10 were determined in the venous blood serum after a 12-hour fasting, as well as in UA on the 21st day of the menstrual cycle using ELISA kits. The activity of NF-kB was determined in UA on the 21st day of the menstrual cycle using an enzyme immunoassay kit. Results: BMI in Group 1 was significantly lower than in Group 2: 22.63±2.68 kg/m2 versus 27.05±4.03kg/m2 (p=0.000). WC in women of Group 1 was 66.11±5.66cm versus 78.52±10.54cm in Group 2 (p = 0.000); WC >80cm was found in 2(4.4%) and 14(66.7%) women, respectively (p = 0.000). The average levels of FPG and FPI were significantly higher in Group 2. Serum levels of TNF-α and IL-1β in Group 2 were significantly higher than in Group 1. The serum level of anti-inflammatory cytokine IL-10 was significantly lower in Group 2; accordingly, the TNF-α/IL-10 ratio in Group 2 was 1.8 times higher than in Group 1. The IL-1β level in UA (P=0.000) and the TNF-α/IL-10 ratio (P=0.02) were significantly higher in women of Group 2 than Group 1, which indicated the pronounced inflammatory effects of TNF-α in the endometrium. Imbalance in the production of pro-inflammatory and anti-inflammatory factors indicated the activation of the Th-1 immune response with the formation of the inflammatory reactions at the systemic level and in the endometrium. In women of Group 2, the NF-kB level in UA was 1.4 times higher than in Group 1 (P=0.000). Conclusion: every fourth woman of reproductive age with HD in the puberty period has primary infertility. The results obtained indicate the activation of the Th-1 immune response with the formation of the inflammatory reactions at the systemic level and in the endometrium. Diagnostically significant markers of primary infertility are the serum TNF-α level and the UA levels of IL-1β and NF-kB

Interval Hypoxic Training in Rehabilitation Program for Adolescents with Overweight / Obesity and Comorbid Arterial Hypertension: Open-Label Randomized Study

Background. Searching for new strategies for the rehabilitation of adolescents with obesity and comorbid arterial hypertension (AHT) before significant pathological changes development in the cardiovascular system remains the urgent challenge. Objective. The aim of the study was to examine the effect of interval hypoxic training (IHT) on blood pressure (BP) levels in adolescents with overweight / obesity and comorbid AHT. Methods. Adolescents aged 14-17 years with body mass index SDS ≥ 1 and grade I AHT (mean level of systolic and/or diastolic BP ≥ 95th percentile for population of corresponding age, sex and height) have been randomized to the group «aerobic training» (treadmill walking) and “aerobic training + IHT” (usage of hypoxicator in intermittent operation cycles). All patients were on subcaloric diet (10% reduction in caloric intake for given age). Primary outcome measure was the difference between groups on systolic/diastolic BP levels according to 24-hour BP monitoring after completion of training program (10 classes each). The effects of IHT on body composition (bioelectrical impedance analysis), heart rate variability and psychoemotional state (Spielberger scale, assessment of health, activity and mood) were further estimated. Results. 43 patients were assigned to the index group, and 42 — to the control group. 67 patients have completed the research program. 5 patients (12%) from the IHT group and 13 patients (31%; p = 0.029) from the control group prematurely discontinued participation in the trial due to poor exercise tolerance. The groups were comparable in baseline systolic and diastolic BP. Decrease in BP occurred in both groups after 10 workouts. There were no differences in decrease value: mean difference for SBP was 2.4 mm Hg (95% CI -6.6 ... 1.8), for DBP — 0.2 mm Hg (-3.6 ... 4.0). However, the incidence of reaching the targeted SBP (< 95th percentile for the corresponding age and sex) after completion of the treatment was recorded in 66% patients in the experimental group and in 42% patients in the control group (p = 0,047). Positive dynamics in several indicators of heart rate variability and psychoemotional state were mentioned in the IHT group. Conclusion. The IHT implementation in the complex of rehabilitation program for adolescents with overweight / obesity and AHT has no additional positive effect on BP levels. However, the incidence of reaching the targeted SBP (< 95th percentile for the corresponding age and sex) after completion of the treatment was recorded in 66% patients in the experimental group and in 42% patients in the control group (p = 0,054)

Polycystic Ovary Syndrome and Gut Microbiota: Phenotype Matters

Abnormalities in gut microbiota diversity are considered important mechanisms in metabolic disorders in polycystic ovarian syndrome (PCOS). However, the data on the association of these disorders with the PCOS phenotype remain controversial. The objectives of this study were to estimate the alpha diversity of the gut microbiota of healthy women and PCOS patients depending on phenotype. The study participants (184 premenopausal women: 63 with PCOS, 121 without PCOS) were recruited during the annual employment assessment in the Irkutsk Region and the Buryat Republic (Russia) in 2016–2019. For PCOS diagnosis, we used the Rotterdam (2003) criteria and definitions of PCOS phenotypes. Five indexes of alpha diversity (ASV, Shannon, Simpson, Chao, and ACE) were estimated for the gut microbiota in all participants using amplicon metasequencing. As a result, two out of five alpha diversity indexes showed a statistical difference between the non-PCOS and PCOS groups. We did not find a significant difference in the alpha diversity of gut microbiota in the subgroups of women with hyperandrogenic PCOS phenotypes vs non-androgenic phenotype D and the group of women with the presence of only one of the PCOS criteria. Nevertheless, “classic” PCOS phenotypes demonstrated the most significant decrease in alpha diversity compared with healthy women without any signs of PCOS

Establishing Normative Values to Determine the Prevalence of Biochemical Hyperandrogenism in Premenopausal Women of Different Ethnicities from Eastern Siberia

Androgen assessment is a key element for diagnosing polycystic ovary syndrome (PCOS), and defining a “normal” level of circulating androgens is critical for epidemiological studies. We determined the upper normal limits (UNLs) for androgens in a population-based group of premenopausal “healthy control” women, overall and by ethnicity (Caucasian and Asian), in the cross-sectional Eastern Siberia PCOS Epidemiology and Phenotype (ESPEP) Study (ClinicalTrials.gov ID: NCT05194384) conducted in 2016–2019. Overall, we identified a “healthy control” group consisting of 143 healthy premenopausal women without menstrual dysfunction, hirsutism, polycystic ovaries, or medical disorders. We analyzed serum total testosterone (TT) by using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and DHEAS, sex-hormone-binding globulin (SHBG), TSH, prolactin, and 17-hydroxyprogesterone (17OHP) were assessed with an enzyme-linked immunosorbent assay (ELISA). The UNLs for the entire population for the TT, free androgen index (FAI), and DHEAS were determined as the 98th percentiles in healthy controls as follows: 67.3 (95% confidence interval (CI): 48.1, 76.5) ng/dl, 5.4 (3.5, 14.0), and 355 (289, 371) μg/dl, respectively. The study results demonstrated that the UNLs for TT and FAI varied by ethnicity, whereas the DHEAS UNLs were comparable in the ethnicities studied