Differential regulation of endometrial receptivity markers by levonorgestrel-releasing and copper intrauterine devices: A cross-sectional study.

OBJECTIVE

Copper and levonorgestrel-releasing intrauterine devices (IUDs) primarily prevent pregnancy through pre-fertilization mechanisms; however, their potential effects on endometrial receptivity remain incompletely understood. This study aimed to compare the regulation of selected adhesive and anti-adhesive endometrial receptivity markers in women using copper and levonorgestrel-releasing IUDs.

METHODS

Observational cross-sectional study was conducted at a tertiary referral center between November 2025 and January 2026. Endometrial samples were obtained from women undergoing elective IUD removal, including copper IUD users (n = 20), levonorgestrel-releasing IUD (LNG-IUD) users (n = 20), and age-matched controls (n = 15). After histological evaluation, secretory-phase samples from copper IUD users and controls were included, whereas all LNG-IUD samples were analyzed due to uniform endometrial atrophy. Quantitative real-time PCR was performed to assess mRNA expression of podocalyxin (PCX) and homeobox A10 (HOXA10).

RESULTS

PCX expression was significantly increased in copper IUD users and significantly decreased in LNG-IUD users compared with controls (both p < 0.001). HOXA10 expression was significantly reduced in both IUD groups compared with controls (p < 0.001). A significant negative correlation between PCX and HOXA10 was observed exclusively in copper IUD users (r = -0.653, p = 0.001).

CONCLUSION

Copper and levonorgestrel-releasing IUDs are associated with distinct patterns of endometrial receptivity marker regulation, suggesting different local molecular environments that may contribute to their contraceptive effects.