Action of a midcycle contraceptive (R 2323) on the human endometrium

Over 2,148 cycles of midcycle oral administration of R 2323 (50 mg. per day on Days 15, 16, and 17), the authors recorded a drug-failure pregnancy rate of 5 per cent and an unusually regular cycle length of 28 ± 2 days. During this trial, endometrial biopsies obtained in the luteal phase were examined by light and electron microscopy and compared to pretreatment biopsies. Light microscopy indicated a weakly secretory endometrium suggestive of some, albeit low, progesterone impregnation. Ultrastructural examination revealed deleterious changes in the development of the nucleolar channel system and giant mitochondria and a delay in the migration of glycogen granules. This low progesterone impregnation could be explained either by a direct effect of R 2323 on cell ultrastructure or by interference with progesterone availability. It would appear that R 2323 acts as a temporary substitute for progesterone at the receptor level but that it does not induce all the biological manifestations of this hormone, in particular, the endometrial changes required for implantation.