Thin endometrium is defined as an endometrial thickness of less than 7 mm in the midluteal phase of the menstrual cycle, a condition often seen in women of childbearing age with a history of uterine trauma, such as dilation and curettage or intrauterine adhesion separation. This inadequate thickness poses a substantial threat to endometrial receptivity and subsequent pregnancy, particularly during infertility treatments. Despite efforts to stimulate endometrial growth through agents such as high doses of estrogen, improvements in both endometrial thickness and pregnancy rates have been marginal. Consequently, it is referred to as “unresponsive endometrium or refractory thin endometrium.” To explore novel therapeutic avenues, a deeper understanding of the underlying mechanisms is urgently needed.

In this review, we examine recent single-cell sequencing studies that have identified key alterations in cell populations, signaling pathways, and cell-cell communication in the endometrium during the late proliferative phase, comparing normal endometrium and thin endometrium following uterine injuries. Evidence suggests that endometrial injury acted as a primary contributor, initiating an accelerated aging process across diverse cell types and establishing an environment characterized by immune incompetence and dysfunction. Senescence, a consequence of this injury, may impede endometrial proliferation, disrupt vascular development, and lead to fibrosis, creating a milieu of abnormal receptivity—a critical downstream event associated with implantation failure and infertility. Addressing these identified challenges necessitates advancing research to comprehend and target the key factors contributing to thin endometrium, a crucial step for clinical translation.

(10.01 Mo)