Impaired endometrial function and unexplained recurrent pregnancy loss

Abstract

Couples with unexplained recurrent pregnancy loss (RPL) cannot achieve a live birth due to repeated sporadic abortions or undetected causes of RPL on routine examinations. Adverse intrauterine circumstances and endometrial decidualization are candidate risk factors for unexplained RPL. During peri-implantation and decidualization, endometrial stromal cells are transformed into decidual cells through acute inflammatory reactions, followed by an anti-inflammatory state, via reprogramming of the corticosteroid and retinoid signaling pathways. Inappropriate inflammation in mid-luteal endometrial stromal cells, such as chronic endometritis, is associated with aberrantly elevated uNK cell density, abnormal angiogenesis, and impaired endometrial decidualization, leading to repeated reproductive failure and complications of pregnancy such as hypertensive disorders. To the best of our knowledge, no efficient treatment for unexplained RPL has yet been established. The optimization of intrauterine circumstances and endometrial decidualization may be key to treating unexplained RPL.