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

Abstract

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.

Keywords

• hypothalamic dysfunction
• primary infertility
• endometrium
• cytokines