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

• Published in: Molecular human reproduction Vol. 6; no. 8; pp. 726 - 734
• Main Authors: Krusche, Claudia A., Herrler, Andreas, Classen-Linke, Irmgard, Hegele-Hartung, Christa, von Rango, Ulrike, Beier, Henning M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2000; Oxford Publishing Limited (England)
• Subjects: Animals; Apoptosis - drug effects; assisted reproduction; Biological and medical sciences; Birth control; CD13 Antigens - drug effects; CD13 Antigens - genetics; Corpus Luteum - drug effects; Corpus Luteum - metabolism; endometrium; Endometrium - cytology; Endometrium - drug effects; Endometrium - physiology; Female; Follicle Stimulating Hormone - pharmacology; Gonanes - pharmacology; Gynecology. Andrology. Obstetrics; Hormone Antagonists - pharmacology; Ki-67 Antigen - metabolism; luteal phase; Luteinizing Hormone - pharmacology; Medical sciences; Menotropins - pharmacology; Ovarian Follicle - drug effects; Ovarian Follicle - physiology; ovarian stimulation; Ovulation Induction - methods; Progesterone - metabolism; progesterone receptor antagonists; Prolactin - blood; Pseudopregnancy; Rabbits; Receptors, Progesterone - antagonists & inhibitors; Sterility. Assisted procreation; Testosterone - blood; Uteroglobin - drug effects; Uteroglobin - genetics; Ovulation inducer; Assisted procreation; Rabbit; Gonadotropin; Lagomorpha; Ovarian hormone; In vitro fertilization embryo transfer; Onapristone; Vertebrata; Mammalia; Uterus; Animal; Female genital system; Female; Antagonist; Progesterone; Sex steroid hormone; Endometrium; Hormonal receptor
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/6.8.726

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.