THE EFFECT OF VARIOUS DOSES OF MIFEPRISTONE ON ENDOMETRIAL LEUKEMIA INHIBITORY FACTOR EXPRESSION IN THE MIDLUTEAL PHASE - AN IMMUNOHISTOCHEMICAL STUDY

Leukaemia inhibitory factor (LIF) is a cytokine which plays an obligat ory role in mouse blastocyst implantation. In human endometrium, LIF e xpression is significantly increased in the mid-luteal phase indicatin g that LIF may also play an important role in the human. We have previ ously shown that a single dose of 200 mg of mifepristone immediately p ost-ovulation is an effective contraceptive method, probably due to in hibition of endometrial development and function. The purpose of this study was to investigate the effect of various doses of mifepristone o n endometrial LIF expression. A total of 22 fertile, regularly-menstru ating women were studied during control and treatment cycles. The subj ects were divided into four groups: group I received a single dose of 200 mg of mifepristone on cycle day LH + 2 (n = 7). The subjects in gr oups II and III were treated with either 5 mg (n = 5) or 2.5 mg (n = 5 ) once a week for 2 months. Group IV subjects received 0.5 mg per day (n = 5) of mifepristone for 3 months. LIF was measured immunohistochem ically in endometrial tissue specimens taken on the corresponding day (cycle day LH + 6 to LH + 8) in hormonally-characterized control and t reatment cycles. LIF immunostaining was observed in all controls and l ocated to the cytoplasm of the luminal and glandular epithelial cells and stromal cells. In the treatment cycles the staining of luminal epi thelium and stroma was similar to controls, while the glandular staini ng was reduced in all treatment groups. This study reveals that early luteal phase treatment as well as intermittent or daily low dose treat ment with mifepristone reduces endometrial glandular LIF expression at the expected time of implantation. The results further support the co ntraceptive potential of mifepristone in low doses.