Objective: To study the effect of estradiol supplementation during the luteal phase on mouse endometrial expression of leukaemia inhibitory factor and pinopodes in controlled ovarian stimulation cycles.

Methods: Female mice were randomly divided into four groups: group A [controlled ovarian stimulation (COS) group], group B (COS group with progesterone for luteal-phase-support), group C (COS group with progesterone and estradiol for luteal-phase-support), and group D of natural cycle group. Pinopodes were investigated by scanning electronic microscopy (SEM) in the uterine endometrium of pregnant mice on pregnancy days (pd) 3 - 5. Leukaemia inhibitory factor (LIF) protein was determined by immunohistochemistry in the uterine endometrium of pregnant mice on pd 3 - 5.

Results: (1) In groups B, C, and D, there were small developed pinopodes in the endometrial surface of pregnant mouse on day 3; there were large fully developed pinopodes in endometrial surface, which was smooth with well defined borders resembling a mushroom on day 4. The regressing pinopodes were observed on day 5. In group A, there were small developed pinopodes in endometrial surface of pregnant mouse on day 3. The regressing pinopodes were seen on day 4. (2) In the pregnant mice of groups C and D, the level of LIF protein on days 3 - 5 (138.5 +/- 20.3, 143.1 +/- 19.0) was significantly higher than group A (103.2 +/- 5.0, P < 0.05), and strong immunostaining of LIF protein was found on day 4 of gestation. In group B, the level of LIF protein on days 3 - 5 (123.5 +/- 10.8) was significantly higher than group A (P < 0.05), but significantly lower than groups C and D (P < 0.05). Strong immunostaining of LIF protein was found on day 4 of gestation. In group A, weak immunostaining of LIF protein peaked on day 3 of gestation. In groups B, C, and D, the level of LIF protein on day 4 was significantly higher than group A on day 3 (F = 55.76, P < 0.01).

Conclusions: Estradiol supplementation during the luteal phase can improve the expression of LIF and pinopodes in mouse endometrium in controlled ovarian stimulation cycles and redress the harmful effect on implantation window by COS. Therefore, estradiol supplementation can improve the endometrial receptivity.