Effect of two antiprogestins (mifepristone and onapristone) on endometrial factors of potential importance for implantation.
OBJECTIVE
To investigate the effects of postovulatory administration of antiprogestins on endometrial factors that may be of importance for successful implantation.


METHODS
Ten women were given 200 mg mifepristone and an additional 10 women 400 mg of onapristone 48 hours after the LH surge in urine (LH + 2).


METHODS
Biopsies were assessed for histologic dating and the immunolocalization of [1] leukemia inhibitory factor, [2] 15-hydroxyprostaglandin dehydrogenase, and [3] the cell proliferation marker Ki 67. Hormonal measurements in blood and urine were used to monitor the effects on the ovarian cycle. Glycodelin (placental protein 14) concentrations were measured in blood taken on LH + 12.


RESULTS
Treatment with antiprogestins retarded the development of secretory changes without affecting the length of the luteal phase. In addition, there was reduced immunostaining for 15-hydroxyprostaglandin dehydrogenase within glands and a significant reduction in serum levels of glycodelin. Reduced immunostaining for leukemia inhibitory factor also was apparent within glands in biopsies taken on LH + 6 of the treatment cycle. Increased Ki 67 immunostaining was observed on both cycle days after treatment, consistent with P antagonism.


CONCLUSIONS
Administration of mifepristone and onapristone adversely affects uterine receptivity. This adds further evidence to support their potential as a method of postovulatory fertility control.
Cameron
S T
ST
Department of Obstetrics and Gynecology, University of Edinburgh, United Kingdom.
Critchley
H O
HO
Buckley
C H
CH
Kelly
R W
RW
Baird
D T
DT
D000021:Abortifacient Agents, Steroidal / Q000494:pharmacology*; D015415:Biomarkers; D001706:Biopsy; D002455:Cell Division; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D000071816:Glycodelin; D006023:Glycoproteins / Q000097:blood; D006067:Gonanes / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000032:analysis; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis; D015850:Interleukin-6; D019394:Ki-67 Antigen / Q000032:analysis; D053605:Leukemia Inhibitory Factor; D007986:Luteinizing Hormone / Q000378:metabolism / Q000652:urine; D008222:Lymphokines / Q000032:analysis; D008597:Menstrual Cycle; D015735:Mifepristone / Q000494:pharmacology*; D011257:Pregnancy Proteins / Q000097:blood
D000021:Abortifacient Agents, Steroidal; D015415:Biomarkers; D005300:Fertility Agents, Female; D000071816:Glycodelin; D006023:Glycoproteins; D006067:Gonanes; D006131:Growth Inhibitors; D006727:Hormone Antagonists; D015850:Interleukin-6; D019394:Ki-67 Antigen; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D015735:Mifepristone; D007986:Luteinizing Hormone; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; C053238:onapristone