Thea Falkenberg Mikkelsen, María Vera-Rodríguez, Zsofia Fedorcsák, Gareth Greggains, Péter Fedorcsák, Kirsten Hald
Reduced LIF expression may impair endometrial receptivity in women with uterine fibroids, potentially contributing to infertility. Restoration of LIF expression following myomectomy indicates a reversible molecular defect. These findings support further investigation of the relationship between fibroids, endometrial receptivity, and reproductive outcomes, which may ultimately have implications for patient selection for myomectomy prior to assisted reproduction.
OBJECTIVE: To investigate the impact of myomectomy on key endometrial receptivity genes: LIF, HOXA10, and HDAC3.
METHODS: 42 women with uterine fibroids and 25 fertile controls without fibroids. Endometrial biopsies were collected using a low-pressure suction catheter on cycle days 19-23. In the fibroid group, samples were obtained both preoperatively and postoperatively, following myomectomy. The samples were histologically dated according to Noyes' criteria, and only those in the mid- to late-secretory phase were included in the analysis. Eligible samples included 21/42 preoperative and 15/35 postoperative fibroid cases, and 9/25 controls. LIF, HOXA10, and HDAC3 expression was assessed by quantitative PCR.
RESULTS: Endometrial LIF expression was significantly reduced in women with fibroids, showing a twofold decrease compared with fertile controls. Expression levels of HOXA10 and HDAC3 did not differ between the two groups. After myomectomy, LIF expression in the fibroid group increased to levels similar to those of fertile controls. The reduction in LIF expression was primarily driven by women with FIGO type 3 fibroids, although the limited sample size precludes conclusions regarding other fibroid subtypes. LIF expression was significantly higher after complete fibroid removal compared with residual fibroids (0.017 vs. 0.0059).
CONCLUSION: Reduced LIF expression may impair endometrial receptivity in women with uterine fibroids, potentially contributing to infertility. Restoration of LIF expression following myomectomy indicates a reversible molecular defect. These findings support further investigation of the relationship between fibroids, endometrial receptivity, and reproductive outcomes, which may ultimately have implications for patient selection for myomectomy prior to assisted reproduction.