Interleukin-1 beta (IL-1 beta) is increased in the follicular fluids of patients with premature luteinization.

Abstract

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. 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 3 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. 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. 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.