Gonadotropin releasing hormon agonists versus antagonists for controlled ovarien hyperstimulatipon in assisted reproductive cycles and comparing serum and follicule fluid levels of cytokines between the two groups.

OBJECTİVE : Cytokines which have many functions, play a role in all physiologic events. It has been recognized that cytokines have many important functions in reproductive system such as ovulation, fertilization, and embryo devleopment. The aim of this study, for the first time in literature to compare the six cytokine levels ( IFN-?, IL-4,IL-2,IL-6, IL-5, TNF-?) in serum and follicule fluid in women treated with gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian hyperstimulation.DESİGN: Prospective Randomized StudySETTİNG: Tertiary care medical centerMETHOD: A total of 66 patients were included in the study. Between these patients; 32 women underwent long gonadotropin releasing hormone agonist protocol and 34 women underwent gonadotropin releasing hormone antagonist protocol for controlled ovarian hyperstimulation. Serum, follicul fluid and oocytes were evaluated for these patients. In addition, before starting the gonadotropin treatment (pre-ovarian hyperstimulation) and on the day of the oocyte retrieval (OPU) serum were taken for cytokines levels. Serum and follicul fluid cytokine levels were compared between gonadotropin-releasing hormone agonists versus antagonists.RESULTS: Basal cytokine serum levels (pre-ovarian hyperstimulation) showed no difference between gonadotropin-releasing hormone agonist group and gonadotropin antagonist group. (p<0.05) On the day of oocyte retriveal (OPU), level of IFN? in serum and follicule fluid were significantly lower in the antagonist group. On the day of oocyte retriveal, when long agonist and antagonist groups were compared seperately, serum and follicule fluid level of TNF and IL-6 level were found to be lower than basal serum cytokine levels in the agonist group and on the other hand IFN? levels were significantly lower only in the agonist group. (p<0.05) In the same group, follicule fluid levels and serum levels of the cytokines showed that IFN ? levels were lower in basal serum when compared with follicule fluid level. (p<0.05). In the agonist group, on the day of oocyte retriveal, serum IFN?, IL-4 and IL-6 levels were lower than the follicule fluid level.(p<0.05) On the day of oocyte retriveal, in the antagonist group, basal serum IFN? level was significantly lower than serum and follicule fluid level (p<0.05).On the day of oocyte retriveal, in the antagonist group, serum IL-4, IL-6 and IFN? levels were lower compared to follicule fluid levels (p<0.05). When two hyperstimulation techniques were compared IFN-?, IL-4, IL2, IL-6, IL-5, TNF-? levels did not show any significant difference in pregnancy rates, oocyte maturation, embryo development and fertilization rates. In the antagonist group, serum IL-4 level was higher in women who got pregnant compared to cycles which did not resut with pregnancy.CONCLUSİON: As a result for controlled ovarian hyperstimulation when gonadotropin-releasing hormone agonist and antagonist protocols are compared serum and follicular fluid levels of cytokines are similar. The low level of IFN-? in the antagonist group did not affect the pregnancy, oocyte maturation fertilization, or embryo development.