IMBALANCE IN CYTOKINE NETWORK/REGULATORY TRANSPORT PROTEIN SYSTEM IN VARIOUS TYPES OF INFERTILITY DURING IN VITRO FERTILIZATION PROGRAMS

Treatment efficiency of chronic infertility does not exceed 40% when using in vitro fertilization (IVF) programs. Therefore, sufficient attention should be given to studies of pathogenetic mechanisms, identification and correction of the factors that adversely affect onset and outcomes of pregnancy. It is known that hypersecretion of cytokines interferes with implantation, but their relationship with immunoregulatory proteins is poorly understood for various types of infertility. The aim of present study was to investigate changes in cytokine contents (IL-8, IL-6, TNFα, IFNγ), lactoferrin and α2-macroglobulin concentration in follicular fluid and venous blood of women with infertility of various genesis, and to evaluate their effects upon results of the IVF programs. The studied proteins were determined in the samples obtained on the day of transvaginal puncture of follicles in 28 infertile women with external genital endometriosis, 38 cases of chronic endometritis, 31 women with polycystic ovary syndrome, 25 patients with adenomyosis, and in 37 women with pure tubal infertility factor (comparison group). According to IVF outcomes, the patients were retrospectively divided into those who became gravid, and women with pregnancy failure. In cases of external genital endometriosis, we have found reduced contents of chemoattractant IL-8 in follicular fluid and blood, as well decreased levels of lactoferrin, which modulates its synthesis and shows antiproliferative activity. In blood of non-pregnant women with tubal infertility associated with chronic endometritis, increased concentrations of pro-inflammatory TNFα and lactoferrin were revealed, thus suggesting presence of latent inflammation. Among women with polycystic ovary syndrome, the TNFα concentration in follicular fluid and blood was reduced, along with increased content of IFNγ. In cases of adenomyosis, the IFNγ levels in follicular fluid were increased, accompanied by reduced content of regulatory-transport α2-macroglobulin in blood samples. The revealed changes in cytokine concentrations and proteins which regulate their synthesis, in biological samples from infertile women may explain the ineffectiveness of IVF programs in a number of cases. Such an imbalance has a negative impact upon development of oocytes, growth of embryos, and their ability for implantation. It is important to continue further investigations of such pathogenetic factors in order to improve approaches providing better efficiency of IVF in chronic infertility treatment.