Evaluating the Effect of Induced Immunosuppression on possible IVF Outcomes

Abstract

In vitro fertilization (IVF) is one of the assisted reproductive technologies (ARTs) used to treat infertility. One in six couples worldwide experiences infertility, which leads to an increased utilization of assisted reproductive technologies. While the success of IVF depends on numerous factors, increasing attention has recently been focused on the role of the immune system. On the one hand, a certain level of immunosuppression is required for successful implantation, on the other hand, excessive immunosuppression may increase susceptibility to infections and inflammation, as well as the proliferation of opportunistic pathogens, which adversely affect embryo implantation and pregnancy progression. In clinical practice, low doses of the glucocorticoid dexamethasone are sometimes used to modulate the immune response; however, data regarding its direct effect on the embryo and reproductive potential are limited. Understanding the potential risks of dexamethasone use in IVF programs requires preclinical studies. The aim of this work was to evaluate the effect of low-dose dexamethasone on the reproductive tract microbiota and oocyte morphological characteristics using a laboratory animal model, and to correlate these changes with the dynamics of immunological parameters to assess the safety of drug utilization in IVF programs. Wistar rats of both sexes were used to create the biological model. Immunosuppression was induced via intraperitoneal administration of dexamethasone (Ellara, Russia) to female rats for three consecutive days. All animals in both the control and experimental groups underwent hormonal stimulation with Follimag and human chorionic gonadotropin (hCG) concurrently with dexamethasone administration. Biological samples were collected from the vagina and gut of the animals before and on the fourth day after dexamethasone administration. The obtained data demonstrated that against the background of immunosuppression, no statistically significant changes were detected in the abundance of most isolated microorganisms (Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Staphylococcus spp., Streptococcus spp., Morganella morganii, Escherichia coli). The immune status of rats was assessed based on the relative and absolute lymphocyte counts in peripheral blood, as well as the phagocytic index of peripheral blood neutrophils. Consequently, the administration of a reasonable dose of dexamethasone to the animals resulted in a decrease in the absolute T-lymphocyte count, driven by a reduction in T-helper lymphocytes, as well as a decline in the phagocytic index. The potential outcome of in vitro fertilization in Wistar rats following dexamethasone administration was assessed based on ovarian reserve and reproductive capacity. The results showed that while administration of dexamethasone did not significantly affect oocyte quantitative characteristics, prominent morphological abnormalities were observed in these cells. Evaluation of the reproductive capacity of immunosuppressed female rats through mating with males demonstrated a 1.5-fold decrease in the number of offspring compared to animals without immunosuppression. The findings suggest that low-dose dexamethasone may exert a direct embryotoxic effect that is not mediated solely by immunosuppression, as manifested by impaired germ cell morphology and reduced reproductive capacity.  The results of the study underscore the need for monitoring immunological parameters, controlling the reproductive tract microbiota, and substantiating the use of glucocorticoids in clinical IVF protocols, as well as the necessity for further preclinical studies to assess the risks of the drug's embryotoxic effect on oocytes.