Modulation of endometrial transformation in gonadotrophin-stimulated and unstimulated pseudo-pregnant rabbits: studies with the progesterone receptorantagonist, onapristone

Advanced endometrial transformation often occurs in IVF and embryo transfer therapy after ovarian stimulation with gonadotrophins. One reason is proba bly the early rise in peripheral progesterone concentration after ovulation induction. Consequently, we studied in a rabbit model, whether the post-ov ulatory application of the progesterone receptor antagonist, onapristone, c ould prevent such an advancement of endometrial transformation after stimul ation with different gonadotrophin preparations. The inhibitory effect of o napristone on the endometrium is dependent upon the strength of ovarian sti mulation. In unstimulated animals or animals treated with recombinant LH (n ine corpora lutea/animal in both groups), secretory differentiation and pro liferation of the endometrium was strongly inhibited by onapristone. After weak ovarian stimulation with a 3:1 mixture of FSH and LH (22 corpora lutea /animal), secretory differentiation was strongly inhibited, while prolifera tion was enhanced. After strong stimulation with either a 1:1 mixture of FS H and LH, or human menopausal gonadotrophin (HMG; >40 corpora lutea/animal) , only limited inhibitory effects of onapristone on secretory transformatio n or proliferation could be detected. In conclusion, these graded effects o f onapristone after stimulation with gonadotrophins, resemble the basic obs ervations from which a therapeutic strategy emerges, to modulate the advanc ed endometrial transformation which occurs in many IVF patients after ovari an stimulation.