Effects of a single post-ovulatory dose of RU486 on endometrial maturation in the implantation phase

Abstract

The effect of a single post-ovulatory dose of RU486 on endometrial maturation was studied in the implantation phase. A total of 11 healthy women were followed for one control and one or two treatment cycles. In treatment cycles, a dose of 200 or 400 mg RU486 was administered on day luteinizing hormone (LH)+2. In both control and treatment cycles, an endometrial biopsy was obtained on LH+6 to LH+8. These biopsies were assessed by morphometric and immunohistochemical analyses. The treatment with RU486 did not disturb the normal menstrual rhythm but caused a significant inhibition in the endometrial development. Glandular progesterone receptor staining was significantly more pronounced after RU486 treatment, while there was a reduction in the Dolichos biflorus agglutinin lectin binding, indicating inhibition of the normal secretory transformation of the endometrium. It is likely that these effects on endometrial development and secretory activity represent the basis of the contraceptive effect of post-ovulatory RU486 treatment.

PIP: The aim was to evaluate further the effect of a single, immediate, post-ovulatory dose of RU-486 on endometrial maturation at the time of implantation. A total of 11 healthy women, 21-40 years old, with regular menstrual cycles, volunteered for the study (height 167 cm; weight 66 kg). None of them had used steroidal contraceptives or an IUD for a minimum of 3 months prior to the study. The study included 1 control cycle and 1 or 2 treatment cycles, the subjects serving as their own controls. During the 1st treatment cycle, 200 mg mifepristone (RU-486) were given orally between 8 and 10 p.m. on cycle day LH+2. Four subjects participated in a 2nd treatment cycle in which the dose of RU-486 was increased to 400 mg. Blood samples were obtained 3 times weekly during the entire study period and were analyzed for estradiol and progesterone by radioimmunoassay. One endometrial tissue specimen was obtained in the control and the treatment cycle(s) from the anterior and lateral walls of the uterine cavity using a Randall curette. The secretory components of endometrial glands were detected by lectin cytochemistry using biotinylated Dolichos biflorus agglutinin (DBA) and the Vectastain Elite ABC immunoperoxidase detection system. The treatment did not disturb the menstrual cycle, but it produced profound endometrial changes in all subjects. A histological pattern corresponding to the proliferative phase was seen in 7 subjects, whereas 2 others demonstrated irregular secretory activity, and 2 biopsies showed a pattern corresponding to LH+4. Significantly decreased glandular diameter (p 0.01), as well as increased number of glandular (p 0.01) and stromal (p 0.01) mitoses, occurred in comparison with biopsies taken in the control cycle. In all endometrial specimens examined after RU-486 treatment there was a reduction in the DBA staining. The profound effects of RU-486 on endometrial development and secretory activity are most likely the underlying reason for the contraceptive effect of RU-486 when administered immediately following ovulation.