INTERLEUKIN-1-BETA (IL-1-BETA) IS INCREASED IN THE FOLLICULAR FLUIDS OF PATIENTS WITH PREMATURE LUTEINIZATION

PROBLEM: Most, but not all, studies indicate that premature luteinization correlates with poor pregnancy outcome in in-vitro fertilization (IVF) programs. It remains unclear whether cytokines (IL-1 beta, TNF alpha), the established immune mediators, play a role in regulation or initiation of an abnormal follicular or embryo development in patients with premature luteinization. METHODS: Levels of cytokines (IL-1 beta, TNF alpha), estradiol (E2), progesterone (P4), and androstenedione (A'ione) were examined in 18 preovulatory follicular fluid (FF) samples from patients with premature luteinization (group 1) and 37 FF samples from patients without premature luteinization (group 2). The number of oocytes recovered, fertilization rate, and pregnancy outcome were evaluated in these two groups. RESULTS: IL-1 beta (25.4+/-11.9 pg/ml, mean +/-SD) and TNF alpha (13.4+/-10.7 pg/ml) were present in these FF samples. The mean level of IL-1 beta in group 1 was significantly higher than that in group 2 (37.3+/-12.3 vs. 20.0+/-7.6 pg/ml; P<0.00001) and the mean level of E2 was significantly lower in group 1 than that in group 2 (1064+/-686 vs. 1570+/-641 ng/ml; P=0.02). The levels of TNF alpha, P4, and A'ione showed no distinction between these two groups. There was no correlation between the levels of either IL-1 beta or TNF alpha and P4, E2 or A'ione. The fertilization rate in group 1 (62/77; 80%) was Similar to that in group 2 (124/160; 78%). Five of 7 patients in group 1 and seven of 20 patients in group 2 achieved pregnancy following embryo transfer. One of five pregnancies in group 1 aborted. CONCLUSION: The exaggerated levels of IL-1 beta in patients with premature luteinization may arise from accumulation of this cytokine owing to sustained high LH stimulation, and this may be a protective response to the abnormal LH surge and function to inhibit prematurely increased secretion of P4. These data indicate the important role of LH in the induction of IL-1 beta secretion and the possible regulatory action of IL-1 beta in luteinization. According to the diminution of E2 in group 1, there may be a subtle atretic process progressing in follicles primed with prematurely elevated LH. However, the detrimental effect of premature luteinization, if it exists, may work at the stage during or after implantation.