Clomiphene citrate directly impairs endometrial receptivity in the mouse

Clomiphene citrate (CC) has known antifecundity effects in animal models. To help define the site of action of this effect, we studied the direct effect of CC on endometrial receptivity by transferring embryos to hormonally prepared prepubertal mice. Prepubertal mice were begun on one of four blinded hormonal preparations consisting of two consecutive 3-day periods of daily injections: oil vehicle, oil-progesterone (P), estradiol (E2)-P, or CC-P. Blastocysts, which had not been exposed to CC, were then surgically transferred to these prepubertal recipients. Fourteen days after embryo transfer, implantations and term pregnancies were counted at necropsy. In this model, CC demonstrated no estrogen agonist effect, and had a significant adverse effect on endometrial receptivity. CC appeared to lower fecundity by a direct endometrial effect.