Intrauterine Infusion of Human Platelet-Rich Plasma Improves Endometrial Regeneration and Pregnancy Outcomes in a Murine Model of Asherman’s Syndrome

Abstract

Asherman's syndrome (AS) is characterized by intrauterine adhesion or fibrosis resulting from damage to the endometrium, often leading to amenorrhea, infertility, or recurrent pregnancy loss. Although various therapeutic strategies for AS have been proposed, the options remain limited. New strategies such as bone marrow-derived mesenchymal stem cell (BM-MSC) therapy aim to potentiate the intrinsic capacity of endometrial regeneration. However, BM-MSC therapy has not been widely adopted mainly because it involves invasive and expensive procedures such as bone marrow biopsy and cell storing. On the other hand, platelet-rich plasma (PRP) is considered safe and affordable because it involves the less invasive procedure of blood collection from peripheral veins to produce PRP. To assess the effectiveness of human PRP infusion for endometrial regeneration, we established a murine model of injury-induced AS and evaluated endometrial morphology, expression of fibrosis-related factors, implantation sites (IS), and pregnancy outcomes associated with human PRP treatment. We found that treatment with human PRP was associated with improved endometrial morphology, reduced degree of fibrosis, and down-regulated expression of fibrosis-related factors in murine model of AS. Furthermore, human PRP treatment was associated with a higher number of IS and live-births. Our results suggest that human PRP treatment may become a valuable strategy to promote the regeneration of damaged endometrium and thus improve fertility and pregnancy outcomes in clinical practice.

Effects of platelet-rich plasma on mesenchymal stem cells isolated from rat uterus

“…In a study by Kim et al (2020) , therapeutic effects from PRP treatment in a mouse model of Asherman’s syndrome were demonstrated. Asherman’s syndrome is characterized by formation of adhesions and fibrotic lesions inside the uterus.…”

Strategies for managing Asherman's syndrome and endometrial atrophy: Since the classical experimental models to the new bioengineering approach

“…In vivo rodent models with injured endometrium also show promising results after intrauterine administration of autologous PRP, decreasing fibrosis and increasing expression of several markers of proliferation (Ki-67), angiogenesis (VEGF), and normal endometrial function (cytokeratin, homeobox A10 -HOXA10-) (Jang et al, 2017). Further, PRP administration improves endometrial morphology, reduces the degree of fibrosis, and produces a higher number of implantation sites and live-births (Kim et al, 2020). PRP was also described as a promotor of the regenerative action of BMDSCs (Zhou et al, 2020).…”

Platelet-Rich Plasma as a Potential New Strategy in the Endometrium Treatment in Assisted Reproductive Technology

“…Last but not least, PRP treatment may have succeeded in reducing the degree of fibrosis via down-regulating expression of fibrosis-related factors including collagen type 1A (COL1A1), transforming growth factor β1 (TGFβ1), tissue inhibitor of metalloproteinase-1 (TIMP1), and finally enhanced implantation sites and live birth rate ensued ( 6 , 71 ). Matrix metalloproteinase(MMP)1, MMP3, MMP7, and MMP26, members of MMP gene family, involved in tissue regeneration and wound healing via degradation of extracellular matrix (ECM) and wound remodeling ( 74 ), are activated by a wide range of cytokines and GFs present in PRP and then are elevated ( 62 ).…”

“…Matrix metalloproteinase(MMP)1, MMP3, MMP7, and MMP26, members of MMP gene family, involved in tissue regeneration and wound healing via degradation of extracellular matrix (ECM) and wound remodeling ( 74 ), are activated by a wide range of cytokines and GFs present in PRP and then are elevated ( 62 ). Hence, in terms of intrauterine adhesions, where factors stimulating the formation of fibrotic tissue into the intrauterine environment are released, PRP may be a potential ideal cure due to the mechanism above ( 6 ).…”

“…As an autologous biologic material, PRP minimizes the risk of immune reactions and contagious diseases ( 5 ). In addition, the application of PRP is considered less invasive since it is produced from peripheral blood ( 6 ).…”