Certain cytokine profiles in follicular fluid are associated with successful assisted reproductive technology (ART) outcomes (interleukins (IL)-1, IL-1a, IL-1b, IL-12/23 (p40) and vascular endothelial growth factor (VEGF)) while others are associated with poor ART outcomes (historically, IL-12, IL-15). What are cytokines and why are they present in follicular fluid?
Cytokines are proteins which are produced and secreted into the follicular fluid by the immune system after an immune response is activated. Follicular fluid was previously presumed to be sterile, but Pelzer et al. show that microorganisms are present in the follicular fluids of women undergoing IVF who are fertile (male factor infertility) and infertile (due to endometriosis, PCOS, genital tract infections or currently unexplainable reasons “idiopathic”). These bacteria and yeast could be responsible for activating the immune response which results in the presence of beneficial or detrimental cytokines in the follicular fluid.
There is no adverse outcome for having bacteria/yeast in follicular fluid. According to the study, the fertilization rates and clinical pregnancy rates after IVF are actually significantly higher in fertile and infertile women who have the same bacteria and yeast in their vagina and follicular fluid compared to fertile and infertile women who have the flora in their follicular fluid only. That is, when bacteria colonize the follicular fluid only, there may well be an adverse ART outcome.
Pelzer et al. found that all 16 cytokines were detectable in follicular fluid, most probably in response to bacterial colonization. IL-6, IL-8, IL-12, IL-18, IL-10 and VEGF were associated with endometriosis, PCOS, genital tract infection or idiopathic infertility. Women with idiopathic infertility had significantly higher levels of IL-18 in their follicular fluid compared to all other women in the study. IL-18 may be an important candidate for further research into the causes of unexplained infertility.
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