Impact of Exogenous Gonadotropin Stimulation on Circulatory and Follicular Fluid Cytokine Profiles

Abstract

Background. The natural cycle is the prototype to which we aspire to emulate in assisted reproduction techniques. Increasing evidence is emerging that controlled ovarian hyperstimulation (COH) with exogenous gonadotropins may be detrimental to oogenesis, embryo quality, and endometrial receptivity. This research aimed at assessing the impact of COH on the intrafollicular milieu by comparing follicular fluid (FF) cytokine profiles during stimulated in vitro fertilization (IVF) and modified natural cycle (MNC) IVF. Methods. Ten women undergoing COH IVF and 10 matched women undergoing MNC IVF were recruited for this pilot study. 40 FF cytokine concentrations from individual follicles and plasma were measured by fluid-phase multiplex immunoassay. Demographic/cycle/cytokine data were compared and correlations between cytokines were computed. Results. No significant differences were found between COH and MNC groups for patient and cycle demographics, including outcome. Overall mean FF cytokine levels were higher in the MNC group for 29/40 cytokines, significantly so for leukaemia inhibitory factor and stromal cell-derived factor-1α. Furthermore, FF MNC cytokine correlations were significantly stronger than for COH data. Conclusions. These findings suggest that COH perturbs intrafollicular cytokine networks, in terms of both cytokine levels and their interrelationships. This may impact oocyte maturation/fertilization and embryo developmental competence.

Effect of exogenous gonadotropin on the transcriptome of human granulosa cells and follicular fluid hormone profiles

“…Cytokine-cytokine receptor interactions and the TNF signaling pathway were all functionally enriched among up-regulated DEGs. Inconsistent with the results obtained from a previous study, Baskindet al [22], reported that the majority of circulatory cytokines, such as IL8, were present at higher concentrations in the modified natural-cycle cohort than in the COH group. Kollmann et al [20] also reported that FF contained a marginally lower concentration of IL8 under a stimulated cycle than a natural cycle.…”

Description of the Follicular Fluid Cytokine and Hormone Profiles in Human Physiological Natural Cycles

“…Nevertheless, in stimulated ICSI cycles the FF IL-15 concentrations are negatively correlated with the follicle size and with the maturity of the corresponding retrieved oocytes, suggesting that in stimulated ICSI cycles FF IL-15 could be a possible negative predictor for oocyte maturity ( 66 ). Again, we could hypothesize that stimulation with exogenous gonadotrophins could significantly perturb the intrafollicular cytokine network, impacting oocyte maturation/fertilization and embryo developmental competence ( 67 ).…”

Fresh versus Frozen Embryo Transfer in PCOS: Arguments for and Against

“…15 Ovarian stimulation results in more oocytes as well as supraphysiological estradiol, progesterone, and cytokines. 22,23 The endometrium and implanting embryo in the fresh transfer cycles immediately after ovarian stimulation are subject to altered internal environment. 24 Laboratory studies have suggested that endometrium in the fresh cycles was different from that in natural ovulation cycles in terms of histological development, gene expression, and immunological responses, which may denote impaired endometrial receptivity.…”