Endometrial hypoperfusion: the missing link in refractory thin endometrium

Persistently thin endometrium remains one of the hardest challenges in reproductive medicine, often linked to implantation failure and poor pregnancy outcome. Growing evidence implicates deficient uterine blood supply in the pathogenesis of an inadequately thin endometrial lining. This narrative review synthesizes current knowledge on how endometrial vascularization influences endometrial thickness (EMT) and receptivity. We outline the normal endometrial structure and vascular physiology, then examine the pathophysiological features of thin endometrium, highlighting mechanistic studies that demonstrate impaired angiogenesis, reduced microvessel density, and tissue hypoxia in thin endometrial tissue. Doppler ultrasound studies consistently show that women with thin endometrium have reduced endometrial and subendometrial blood flow and higher resistance indices. Clinical correlations indicate that poor endometrial perfusion is associated with lower implantation and pregnancy rates in assisted reproduction. We review diagnostic tools for assessing endometrial perfusion, including two-dimensional (2D) and three-dimensional (3D) Doppler ultrasound measures of uterine and subendometrial blood flow. Therapeutic strategies aiming to improve uterine blood supply, such as vasoactive medications, intrauterine infusion of platelet-rich plasma (PRP), stem cell therapies, and other angiogenic treatments, often result in a marginal improvement of EMT and pregnancy outcomes. While these interventions show promise, limitations include small sample sizes and heterogeneous study designs. We discuss future directions, emphasizing the need for larger trials and a deeper understanding of angiogenic signaling in the endometrium. In conclusion, converging evidence supports poor endometrial blood supply as a key contributor to persistently thin endometrium. Future therapies that specifically target enhancement of endometrial blood supply may prove to be effective tools for improving endometrial growth and fertility outcomes.