Uterine PRP: Potential Tissue Regeneration and Healing

Platelet-rich plasma (PRP) therapy is emerging as a potential treatment for uterine conditions involving tissue damage or poor endometrial receptivity. By concentrating platelets from a patient’s blood, PRP delivers growth factors that may aid healing and regeneration. Researchers are investigating its use for conditions such as thin endometrium, recurrent implantation failure, and Asherman’s syndrome.

Platelet Collection And Preparation

PRP preparation begins with a controlled blood draw, typically 30 to 60 mL, depending on the protocol. The blood is immediately transferred into anticoagulant-containing tubes to prevent premature clotting. The choice of anticoagulant, such as acid citrate dextrose (ACD) or sodium citrate, helps maintain platelet integrity.

Centrifugation separates blood components by density. A two-step process is common: an initial low-speed spin (100–200 × g for 10–15 minutes) isolates plasma from red blood cells, followed by a higher-speed spin (400–1000 × g for 5–10 minutes) to concentrate platelets. The resulting PRP is extracted, often leaving behind platelet-poor plasma (PPP), which may be discarded or used in specific protocols.

Platelet concentration in PRP varies by preparation method, with optimal therapeutic ranges between 3 to 5 times the baseline platelet count. Higher concentrations do not necessarily improve efficacy and may even inhibit tissue regeneration. To activate platelets before administration, calcium chloride, thrombin, or autologous serum can be added, triggering the release of growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF). Activation ensures the rapid availability of bioactive molecules upon injection.

Growth Factor Composition

PRP’s regenerative potential comes from its concentrated growth factors, which drive cellular processes essential for tissue repair. Platelet-derived growth factor (PDGF) stimulates fibroblast proliferation and extracellular matrix synthesis, both crucial for endometrial thickening and structural integrity. It also enhances angiogenesis by recruiting pericytes and smooth muscle cells to developing blood vessels, improving tissue perfusion.

Transforming growth factor-beta (TGF-β) regulates epithelial-mesenchymal interactions in the uterine lining, promoting collagen deposition and maintaining a balanced microenvironment for implantation. It also plays a role in reducing fibrosis in intrauterine adhesions, suggesting potential benefits for Asherman’s syndrome.

Vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation and capillary formation, essential for restoring a functional endometrium. PRP-derived VEGF has been shown to increase microvascular density, counteracting ischemic damage. Fibroblast growth factor (FGF) complements this process by accelerating epithelial cell migration and proliferation, supporting endometrial regeneration.

Biological Pathways Involved

PRP’s regenerative effects in uterine tissue are mediated by signaling pathways that regulate cellular proliferation, differentiation, and vascular remodeling. The phosphoinositide 3-kinase (PI3K)/Akt pathway plays a central role in cell survival and tissue regeneration. Growth factors like PDGF and VEGF stimulate PI3K, leading to Akt phosphorylation, which enhances endothelial cell migration and blood vessel formation. Dysregulation of this pathway has been linked to recurrent implantation failure.

PRP also activates the mitogen-activated protein kinase (MAPK) cascade, a regulator of cellular growth and differentiation. Fibroblast growth factor (FGF) and epidermal growth factor (EGF) in PRP activate extracellular signal-regulated kinases (ERK1/2), driving stromal cell proliferation and extracellular matrix synthesis. c-Jun N-terminal kinase (JNK) and p38 MAPK further modulate fibroblast function and collagen deposition, ensuring structural integrity.

The hypoxia-inducible factor 1-alpha (HIF-1α) pathway responds to oxygen deprivation by stimulating angiogenesis. VEGF from PRP stabilizes HIF-1α, promoting endothelial cell recruitment and capillary formation. This pathway is particularly relevant in cases of uterine hypoxia, where poor blood flow leads to endometrial thinning and suboptimal implantation conditions.

Injection Approach

PRP is administered into the uterus during the proliferative phase of the menstrual cycle, when estrogen promotes endometrial growth. Transcervical injection, guided by ultrasound, ensures precise delivery while minimizing invasiveness. A thin catheter is inserted through the cervix to evenly distribute PRP within the endometrial cavity.

The volume of PRP administered varies based on the uterine condition being treated. Clinical protocols typically recommend 0.5 to 1 mL per injection, with multiple applications over several cycles if necessary. Freshly prepared and activated PRP is essential for maximizing bioactive molecule availability.

Tissue Response Considerations

PRP’s effects on uterine tissue depend on endometrial receptivity and the extent of pre-existing damage. One key response is increased cellular proliferation within the stromal and epithelial layers. Histological analysis has shown enhanced mitotic activity in endometrial cells after PRP treatment, supporting tissue expansion. This is particularly beneficial for patients with thin endometrium. PRP also upregulates genes associated with tissue remodeling, such as matrix metalloproteinases (MMPs), which aid extracellular matrix turnover.

PRP improves vascularization, enhancing oxygen and nutrient delivery. Doppler ultrasound studies have reported increased subendometrial blood flow after PRP administration, correlating with higher implantation success rates. VEGF-driven angiogenesis promotes microcapillary formation, counteracting ischemic damage and improving endometrial receptivity. While PRP shows promise as a regenerative therapy, further clinical trials are needed to refine treatment protocols and assess long-term efficacy.