Molecular Human Reproduction, Vol. 6, No. 8, 726-734,
August 2000
© 2000 European Society of Human Reproduction and Embryology
Uterine physiology |
Modulation of endometrial transformation in gonadotrophin-stimulated and unstimulated pseudo-pregnant rabbits: studies with the progesterone receptor antagonist, onapristone
1 Department of Anatomy and Reproductive Biology, School of Medicine, RWTH University of Aachen, 52057 Aachen, and 2 Research Laboratories, Schering AG, 13342 Berlin, Germany
Abstract
Advanced endometrial transformation often occurs in IVF and embryo transfer therapy after ovarian stimulation with gonadotrophins. One reason is probably the early rise in peripheral progesterone concentration after ovulation induction. Consequently, we studied in a rabbit model, whether the post-ovulatory application of the progesterone receptor antagonist, onapristone, could prevent such an advancement of endometrial transformation after stimulation with different gonadotrophin preparations. The inhibitory effect of onapristone on the endometrium is dependent upon the strength of ovarian stimulation. In unstimulated animals or animals treated with recombinant LH (nine corpora lutea/animal in both groups), secretory differentiation and proliferation 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 proliferation was enhanced. After strong stimulation with either a 1:1 mixture of FSH and LH, or human menopausal gonadotrophin (HMG; >40 corpora lutea/animal), only limited inhibitory effects of onapristone on secretory transformation or proliferation could be detected. In conclusion, these graded effects of onapristone after stimulation with gonadotrophins, resemble the basic observations from which a therapeutic strategy emerges, to modulate the advanced endometrial transformation which occurs in many IVF patients after ovarian stimulation.
assisted reproduction/endometrium/luteal phase/ovarian stimulation/progesterone receptor antagonists
Notes
3 To whom correspondence should be addressed at: Department of Anatomy and Reproductive Biology, Wendlingweg 2, 52057 Aachen, Germany. E-mail: ckrusche{at}post.klinikum.rwth-aachen.de
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