Ovarian hyperstimulation inhibits embryo implantation in the mouse

Embryo implantation is dependent on the synchronous development of the embryo and of the endometrium. Pharmacologic doses of estrogens change endometrial histology and are known to inhibit implantation. During controlled ovarian hyperstimulation, such as occurs during an in vitro fertilization cycle, serum estradiol levels may be elevated to as much as three to six times those found during spontaneous cycles. Serum progesterone levels are also increased and may counteract the elevated estradiol levels. The overall effect of ovarian stimulation on implantation is therefore not known. To study this question, we developed a mouse embryo donation model. Donor embryos were obtained in the late morula to early blastocyst stage from hyperstimulated mated mice. The donated embryos were then transferred to the uteri of two groups of recipient mice. The study group underwent ovarian hyperstimulation with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) (OHR group), while the controls were allowed to cycle spontaneously (SR group). All recipient mice underwent cervical stimulation to induce a pseudopregnant state. Five embryos were transferred to the left uterine horn of each of nine OHR mice and seven SR mice. A higher implantation rate was noted in the SR group than in the OHR group (50 +/- 12 vs 8 +/- 4%, P less than 0.001). Our data suggest that, in the mouse, ovarian hyperstimulation impedes implantation by causing adverse changes in uterine receptivity.