EFFECTS OF DAILY LOW-DOSE MIFEPRISTONE ON ENDOMETRIAL MATURATION AND PROLIFERATION

Following an ovulatory control cycle, six women took 2 mg of mifeprist one daily for 30 days. Endometrial biopsies were collected in the cont rol cycle between 7 and 11 days after the plasma luteinizing hormone ( LH) surge and on the corresponding day of the treatment cycle (days 19 -28). In order to investigate the effects of unopposed oestrogen on th e endometrium, persistent proliferative endometrium was obtained from six women with anovulatory infertility due to polycystic ovarian syndr ome (PCOS) on a similar cycle day (days 21-23) following a progestogen -induced withdrawal bleed. Endometrium was evaluated for histology and immunolocalization of oestrogen receptors (ER), progesterone receptor s (PR) and the cell proliferation markers [proliferating cell nuclear antigen (PCNA) and Ki67]. Treatment with mifepristone inhibited ovulat ion in four of the six subjects. In the two subjects in whom ovulation did occur, secretory transformation was delayed, suggesting that succ essful implantation of a blastocyst would be unlikely. In subjects who remained anovulatory during treatment, the histology and pattern of s teroid receptor expression was similar to proliferative phase endometr ium. In women with PCOS, mitoses and intense immunostaining for ER, PR and cell proliferation markers were observed in both glands and strom a. Although PCNA and Ki67 immunostaining were also present in mifepris tone-treated endometrium from subjects who did not ovulate, there were no mitoses and significantly less ER immunostaining in spite of expos ure to unopposed oestrogen for a similar duration. Since PCNA and Ki67 detect cells throughout all stages of the cell cycle this would sugge st that mifepristone might affect the entry of cells into the mitotic phase of the cell cycle and, therefore, might prevent endometrial hype rplasia. These findings add further evidence to support the contracept ive potential and antiproliferative activity of daily low dose mifepri stone.