The influence of continuous intrauterine infusion of enzyme-inhibitors of the arachidonic acid cascade on ovulation and tubal ovum transport in the hyperstimulated rabbit.

Cyclo-oxygenase and prostaglandin-15-hydroxydehydrogenase are rate-limiting steps in the arachidonic acid cascade. These enzymes were affected by indomethacin and lonazolac treatment in hyperstimulated rabbits through continuous intrauterine or single vaginal applications in three different experiments. In terms of the ovulation-index, there was no difference between animals treated via the intrauterine or the vaginal routes. Compared with controls (83 to 89%), there was a significant reduction in the ovulation index to 32% with indomethacin and to 51 or 55% with lonazolac, 28 h after induction of ovulation (experiment 1). The values turned almost back to normal 52 h after induction of ovulation 72% (experiment 3). The treatment with lonazolac resulted in a higher sum of corpora lutea and unruptured follicles (experiment 1: control-group = 90.9 vs lonazolac-group = 110.5). The recovered ova showed a shift from the 4 and 8 cell stages to the 16 or more cell stages under lonazolac treatment when compared with controls (experiment 3). The histologic examinations showed advanced luteinization of unruptured follicles in the indomethacin-treated groups. Hyperplasia of the theca interna was also noted. Our data indicate that indomethacin was capable of inducing premature luteinization resulting in arrested or delayed ovulation. Lonazolac, in contrast, did not impair ovulation. Moreover, it induced the growth of more follicles, probably through a second wave at the time of ovulation initiated by hCG. For the clinical practice these experiments point towards the possibility of the treatment of the luteinized unruptured follicle syndrome and towards the application of lonazolac for ovarian stimulation.