Impact of Intra-fascial Platelet-Rich Plasma Injection on PDGF Expression, UDI and POP-Q Scores, and Recurrence Risk in Cystocele Patients: A Randomised Controlled Trial

Introduction

Pelvic Organ Prolapse (POP) is a common medical condition among women that can significantly impact quality of life, particularly in terms of sexual function and overall health.¹ The prevalence of POP is estimated at around 11.1%, with cystocele being the most common form, accounting for approximately 80% of all prolapse surgery cases.^2,3 Cystocele occurs when the bladder protrudes into the anterior vaginal wall due to weakness or damage to the pubovesical fascia. Despite reconstructive surgery to repair this condition, the risk of recurrence remains high, with retrospective studies such as Fialkow et al. (2008) reporting that 72% of POP recurrence incidents were caused by cystocele.³ Therefore, there is an urgent need to explore therapeutic approaches that can reduce the likelihood of recurrence and improve patients' quality of life.

Although reconstructive procedures using prosthetics such as meshes, implants, and tapes are common choices for prolapse repair, the use of these materials is often followed by serious complications, including infections and tissue erosion, leading to warnings from the U.S. Food and Drug Administration (FDA).^4,5 These complications have prompted surgeons to seek safer and more effective alternatives for pelvic organ prolapse care, including biologic therapies that are minimally invasive.

One biologic therapy that has gained increasing attention is Platelet-Rich Plasma (PRP), an autologous blood product containing high concentrations of platelets. PRP is known to contain various biological growth factors, including Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), and Transforming Growth Factor Beta (TGF-β), which play vital roles in tissue healing and injury repair.^6,7 One of PRP's primary benefits is its ability to enhance cell proliferation and collagen secretion in tenocytes, as well as accelerate tissue repair processes, which can speed up recovery following tendon or muscle injuries. Further research has shown that PRP injections stimulate angiogenesis (the formation of new blood vessels) and collagen synthesis during the early stages of tissue healing.⁶

With its rapid and effective healing properties, PRP has started being applied in various medical fields, including urogynecology, for pelvic tissue repair. While PRP has been used in orthopedics and other regenerative medicine fields, its application in cystocele repair remains under-researched. The use of PRP to repair damaged pubovesical fascia could enhance vaginal wall strength and reduce cystocele recurrence risk.⁸

In 2010, the World Anti-Doping Agency (WADA) banned PRP use due to concerns about its potential performance-enhancing effects on athletes. However, this ban was lifted in 2011 after further research demonstrated that PRP does not have systemic effects that could provide an unfair competitive advantage. As a result, PRP has become more widely accepted in the medical field, including for pelvic organ prolapse treatment.⁹

This study aims to evaluate the effects of autologous PRP injection into the pubovesical fascia during cystocele repair surgery, focusing on tissue repair and reducing recurrence risk. We also aim to identify molecular markers that can differentiate patients who receive PRP injections from those who do not, as well as assess its impact on healing and post-operative quality of life. We hope that the results of this study will provide new insights into developing safer and more effective therapeutic alternatives for patients with cystocele and help reduce the social and financial morbidity associated with more invasive pelvic reconstructive procedures.^10,11

Methods

This was a parallel-group, randomized controlled trial involving 44 patients with cystocele. This study was conducted at the Urogynecology Clinic and operating theatre of RSUD Arifin Achmad Pekanbaru, involving patients presenting with vaginal bulging clinically diagnosed as cystocele. Cystocele diagnosis was confirmed using the International Pelvic Organ Prolapse Quantification (POP-Q) system, an objective method for describing and determining the degree of pelvic organ prolapse.^12,13 In the POP-Q system, cystocele degree is determined based on the position of two points on the anterior vaginal wall: point Aa, located 3 cm proximal from the hymen, and point Ba, the most prominent part of the anterior vaginal wall.^12,13 In women without prolapse, both points are at the same anatomical position, 3 cm proximal to the hymen (–3), which is considered the zero point in the POP-Q system.¹² In cases of prolapse, the position of these points is compared to the hymen and assigned values ranging from –1, –2, or –3 if they are more proximal to the hymen or values from 0, +1, +2, +3 to +10 if they are at or more distal from the hymen.^13–15 Patients with cystocele grades 3 or 4 according to the POP-Q system were selected for the study and underwent cystocele repair surgery (anterior colporrhaphy).

Before surgery, patients were given full information about the procedure and asked to provide written consent. Baseline data such as age, parity, body mass index (BMI), and cystocele grade were recorded. Platelet levels were checked to ensure compatibility with the research protocol. Subjects were randomized into two homogeneous groups using computer randomization: group 1 (Control group) undergoing cystocele repair only (n = 21), and group 2 (PRP group) undergoing cystocele repair with PRP injection into the pubocervical fascia (n = 23). Participants were blinded to the group assignment, and care providers performing assessments were also blinded to the group allocation. The randomization process was concealed, and outcome assessors were unaware of the patient’s group to minimize bias. Written informed consent was obtained from all patients participating in this study.

Anterior colporrhaphy with PRP injection was performed with the patient in a sterile dorsolithotomy position under spinal anesthesia. A 16F Foley catheter was inserted. After the anterior vaginal wall mucosa was retracted, and the damaged pubocervical fascia was fully exposed, 10 ml of prepared PRP was injected into the pubocervical fascia at five sites (distal, proximal, central, left and right lateral) using a 30 G ½ needle. The pubocervical fascia was then sutured with PGA sutures. Excess vaginal epithelium was trimmed and sutured continuously with 2.0 PGA sutures. All surgical procedures were performed by a single surgeon (EF) using uniform techniques.

Activated autologous PRP (aaPRP) was prepared using a method developed by Karina et al.¹⁶ The preparation involved standard equipment such as 23 G butterfly needles (Nipro, Cat# SSB23G), Vacutainer blood collection tubes with gel separator (BD, Cat# 367989), and 10% calcium chloride solution (Otsuka, Cat# OTS-CaCl2-10, 0.15 ml per preparation). Thirty-two ml of peripheral blood was collected into the Vacutainer tubes, followed by two centrifugation steps. The first centrifugation at 1000 rpm for 10 minutes separated erythrocytes and leukocytes, while the second centrifugation at 3000 rpm for 10 minutes generated soft pellets. The soft pellets were activated with the addition of calcium chloride to form a clot, which was then separated to isolate autologous activated PRP (aaPRP). AaPRP was then mixed with 0.9% NaCl (B Braun, Cat# 07543937) to reach a final volume of 10 ml before injection into the pubocervical fascia at five designated sites: proximal, distal, left and right lateral, and central areas during cystocele repair surgery by the same operator.¹⁶

Systemic PDGF levels were measured using a human Platelet-Derived Growth Factor (PDGF) ELISA Kit (FINETEST, Cat# EH3531-96well, 96 wells), supplied by Kairos. The assay was conducted according to the manufacturer’s instructions to ensure optimal sensitivity and specificity for detecting serum PDGF levels.

Data collection involved measuring Platelet-Derived Growth Factor (PDGF) levels and performing POP-Q examinations at several predefined time points. Blood samples were collected on day 0 (pre-operation), day 3, day 28, and day 90 post-operation to measure systemic PDGF levels. This measurement aimed to assess changes in PDGF expression related to cystocele repair procedures and PRP injection use. Cystocele degree was measured using the POP-Q system on days 0, 3, 28, and 90 post-operation to assess changes in pelvic organ prolapse degree after cystocele repair.⁶

Symptoms and quality of life were assessed using the Urinary Distress Inventory (UDI), which evaluates urinary symptoms, including frequency, urgency, incontinence, and their impact on daily activities.¹⁷ The UDI is a valid instrument for assessing urinary tract disturbances in pelvic organ prolapse and response to therapy.^18,19 In this study, UDI was measured on days 0, 3, 28, and 90 post-operation to assess symptom and quality of life changes. Each UDI question was scored, and the total score was calculated to reflect the severity of symptoms and the impact on quality of life. Lower scores indicate symptom improvement and better post-operative quality of life.

Patients who met any of the following criteria were excluded from the study: platelet disorders or severe thrombocytopenia, use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours before surgery, corticosteroid use within the last month, receiving anti-cystocele therapy other than the intervention studied, a history of pelvic organ prolapse (POP) surgery, or inability or unwillingness to follow the study protocol.

Statistical analysis was performed using IBM SPSS Statistics for Windows, version 29.0.2.0 (IBM Corp., Armonk, NY, USA). Demographic characteristics of patients were compared between the control and PRP groups using the Student’s t-test for parametric data and the Mann-Whitney U test for non-parametric data. Differences in proportions between groups for categorical variables were analyzed using Pearson's Chi-square test. A p-value < 0.05 was considered statistically significant for all analyses.

Results

A total of 44 patients participated in this study, divided into two groups: the control group, which underwent cystocele repair alone (21 subjects), and the PRP group, which underwent cystocele repair combined with intrafascial pubocervical PRP injection (23 subjects). All surgical procedures were performed by a single surgeon (EF) using a standardized technique.

Comparison of Platelet-Derived Growth Factor (PDGF)

Table 2 and Figure 1 show the comparison of PDGF levels between the two groups at different time points. At pretest (before surgery), PDGF levels showed no significant difference between the control and PRP groups (P = 0.770). On day 3 postoperatively, although PDGF levels in both groups varied, no significant difference was found (P = 0.435), indicating that the PRP effect was not yet visible at this early time point. However, on day 28, the PRP group exhibited significantly higher PDGF levels compared to the control group (2135.53 ± 197.16 vs. 1415.29 ± 766.58), with a statistically significant difference (P = 0.001), suggesting that PRP may stimulate an increase in PDGF levels during the later healing phase. On day 90, the difference in PDGF levels became more pronounced between the PRP and control groups, with the PRP group showing much higher levels (1810.59 ± 622.79 vs. 805.69 ± 530.73), and this difference was highly significant statistically (P < 0.001). Furthermore, a decrease in PDGF levels was observed in both groups on day 90, though the PRP group still showed higher PDGF levels compared to the control group (1810.59 ± 622.79 vs. 805.69 ± 530.73), with a highly significant statistical difference (P < 0.001). This reduction in PDGF levels reflects the ongoing healing process, with decreasing need for further stimulation as tissue matures.²⁰

Table 2. Comparison of PDGF levels between control and PRP groups.

Time	Control	PRP	P-value
Pretest	43.3 ± 42.5	44 ± 37.6	.770
Day 3	34.7 ± 27.3	48.8 ± 47.5	.435
Day 28	1415.29 ± 766.58	2135.53 ± 197.16	.001
Day 90	805.69 ± 530.73	1810.59 ± 622.79	<.001

Figure 1. Platelet-Derived Growth Factor (PDGF) levels before and after cystocele repair in control and PRP groups.

Comparison of UDI scores

Table 3 and Figure 2 present the comparison of Urinary Distress Inventory (UDI) scores between the control and PRP groups at different time points. Before surgery (pretest), there was no significant difference in UDI scores between the two groups (P = 0.972), indicating that the symptoms measured were similar between the control and PRP groups before the intervention. On day 3 postoperatively, although UDI scores showed variation in both groups, the difference was not significant (P = 0.328), indicating that the effect of PRP injections had not yet led to visible changes in symptoms at this early postoperative stage. However, on day 28, the PRP group demonstrated a significantly greater improvement in UDI scores compared to the control group (6.31 ± 6.93 vs. 13.93 ± 10.35), with a statistically significant difference (P = 0.01). This finding confirms that PRP plays a role in accelerating tissue healing and reducing symptoms related to cystocele, thus contributing to improved quality of life in the later healing phase. On day 90, the difference in UDI scores between the two groups became even more evident, with the PRP group showing much lower (better) scores compared to the control group (2.66 ± 5.45 vs. 7.70 ± 8.33), and this difference was highly significant (P < 0.002). This indicates that the benefits of PRP in improving quality of life by reducing cystocele-related symptoms persist into the later healing phases.²⁰

Table 3. Comparison of UDI scores between control and PRP groups.

Time	Control	PRP	P-value
Pretest	31.39 ± 8.31	31.45 ± 12.38	.972
Day 3	21.61 ± 15.81	17.14 ± 11.92	.328
Day 28	13.93 ± 10.35	6.31 ± 6.93	.011
Day 90	7.70 ± 8.33	2.66 ± 5.45	.002

Figure 2. UDI scores before and after cystocele repair in the control and case (PRP) groups.

Comparison of POP-Q scores

Table 4 and Figure 3 show the comparison of POP-Q scores between the two groups. At pretest, there was no significant difference between the control and PRP groups (P = 0.792). On day 3 postoperatively, both groups showed uniform POP-Q values (-3.00 ± 0.0), with no significant difference between the control and PRP groups (P = 1.000), suggesting similar early effects in both groups. On day 28, the control group showed a POP-Q value of -2.24 ± 0.5, while the PRP group had a value of -2.30 ± 0.5 (P = 0.717), showing no significant difference. On day 90, although there was a numerical difference in POP-Q values (-1.95 ± 0.8 for the control group vs. -2.13 ± 0.6 for the PRP group), this difference was not statistically significant (P = 0.472).²⁰

Table 4. Comparison of POP-Q scores between control and PRP groups.

Time	Control	PRP	P-value
Pretest	4.23 ± 1.51	4.39 ± 1.9	.792
Day 3	-3.00 ± 0.0	-3.00 ± 0.0	1.000
Day 28	-2.24 ± 0.5	-2.30 ± 0.5	.717
Day 90	-1.95 ± 0.8	-2.13 ± 0.6	.472

Figure 3. POP-Q scores before and after cystocele repair in control and PRP groups.

Discussion

Cystocele is the most common condition (80%) among pelvic organ prolapse surgeries,²¹ Approximately 40% of cases will experience recurrence within two years post-surgery,^22,23 with about 30% requiring reoperation for the same issue during their lifetime.¹ The risk of cystocele recurrence increases with the severity of the prolapse according to POP-Q staging.²⁴ From 2012 to 2019, reports from Indonesia indicated an anatomical recurrence rate of 24.2% and a symptomatic recurrence rate of 12.1% after cystocele surgery.²⁵ This highlights the need for more effective approaches to reduce prolapse recurrence, including the use of Platelet-Rich Plasma (PRP) as a postoperative healing adjunct.

PRP initially activates pluripotent cells, which then stimulate tissue remodeling and angiogenesis at the injection site.²⁶ Given the high incidence of anterior vaginal wall prolapse and the high risk of recurrence post-surgery, PRP serves as a potential adjunct for addressing these issues.²⁷ Additionally, PRP has no proven side effects to date,^26,28 and no side effects were noted in this study for either group. Another important point in this study is that PRP injection was administered only once, as there is no conclusive evidence supporting the benefits of repeated PRP injections.²⁹ The frequency and quantity of PRP injections vary across studies.^26,28,29

The results of this study indicate that PRP administration in cystocele repair significantly increases PDGF levels on days 28 and 90 post-surgery, reflecting enhanced tissue healing in pelvic organ prolapse. These findings align with previous studies showing that PRP can elevate growth factors involved in tissue repair.³⁰ However, despite the trend of improvement in the PRP group, clinical improvements measured by POP-Q scores and recurrence rates did not show significant differences compared to the control group. This is consistent with findings from Smith et al. (2020), which noted that although PRP increased PDGF levels, there was no significant difference in clinical outcomes during short-term follow-up.³¹

Our findings, which show increased PDGF levels in the PRP group but no significant difference in POP-Q scores, are consistent with Johnson et al. (2021), who evaluated PRP effects on pelvic organ prolapse and found that PRP significantly improved POP-Q scores, particularly in patients with milder to moderate prolapse.³¹ The more severe prolapse stages in our study might influence the response to PRP therapy, potentially affecting improvements in POP-Q scores. Furthermore, factors such as differences in PRP protocols and smaller sample sizes may have contributed to these results.

In the recurrence risk analysis, although the PRP group demonstrated a lower recurrence rate compared to the control group, this difference was not statistically significant (P > 0.05). However, it is important to note that on day 28, only 1 recurrence event (with BA values ranging from -1 to +1) occurred in the control group (4.8%), while no recurrence was observed in the PRP group. On day 90, the control group had a higher recurrence rate (3 out of 21, or 14.3%) compared to the PRP group, which showed only 1 recurrence (4.3%) out of 23 subjects. Despite the lack of statistical significance (P = 0.252), these findings suggest a clear trend toward reduced recurrence in the PRP group.²⁰ This finding is consistent with a study by Turner et al. (2019), which noted that although PRP has the potential to accelerate tissue healing, clinical benefits such as reduced recurrence of prolapse may only become detectable after more than one year of follow-up.³² With a limited follow-up period of 90 days, no significant differences in recurrence rates were observed, suggesting that the effect of PRP on prolapse recurrence requires a longer time to manifest.

While no significant changes were observed in POP-Q scores or recurrence rates, a more intriguing finding was the significant improvement in symptoms related to cystocele, as measured by the Urinary Distress Inventory (UDI) scores. On day 28 postoperatively, the PRP group showed a significantly greater improvement in UDI scores compared to the control group (6.31 ± 6.93 vs 13.93 ± 10.35; P = 0.01),²⁰ illustrating the role of PRP in accelerating tissue healing and reducing cystocele-related symptoms. This improvement aligns with findings from Vasquez et al. (2018), who reported that PRP contributed to symptom relief, such as urinary incontinence, despite no significant changes in POP-Q scores, which measure the anatomical position of pelvic organs.³⁰ This suggests that while anatomical changes may not directly reflect in POP-Q scores, symptomatic improvements, such as reduced urinary incontinence and vaginal fullness, can occur with PRP administration.

At a later time point, on day 90, the PRP group exhibited significantly lower (better) UDI scores compared to the control group, further confirming that the benefits of PRP in improving quality of life are not just temporary but may persist into the longer healing phase. The sustained improvement in symptoms supports the role of PRP in providing long-term benefits for reducing cystocele-related symptoms, even though improvements in POP-Q scores or recurrence rates still require further investigation with longer follow-up. This study concludes that while PRP may stimulate the healing process at the molecular level, its long-term clinical effects still need further evaluation.

Overall, while the analysis of POP-Q scores and recurrence rates did not reveal statistically significant changes that would confirm the effectiveness of PRP, the substantial improvement in UDI scores provides compelling evidence that PRP has the potential to improve the quality of life by reducing symptoms related to cystocele. The increase in PDGF levels plays a crucial role in enhancing tissue repair and function, which may help reduce symptoms like urinary incontinence, as highlighted by Vasquez et al. (2018).³⁰ This finding emphasizes the need to assess clinical symptoms more comprehensively, as anatomical changes, measured through POP-Q, may take a longer period to manifest after PRP administration.

Despite the limitations of this study, including a small sample size and a relatively short follow-up period (90 days), these results offer a solid foundation for future investigations into the potential benefits of PRP for improving long-term clinical outcomes in cystocele patients. Although no definitive conclusions regarding the long-term impact of PRP on recurrence or POP-Q outcomes can be made at this stage, the study suggests that PRP may have a role in reducing recurrence risk, potentially becoming evident over a longer observation period. Further studies with larger sample sizes, extended follow-up periods, and randomized controlled designs are needed to confirm these findings and evaluate the long-term safety and efficacy of PRP. Additionally, future research should explore factors such as the PRP injection technique, platelet concentration, and the influence of other risk factors to better understand the therapeutic potential of PRP.

Reporting guidelines

This study adheres to the CONSORT reporting guidelines for randomized controlled trials. A completed CONSORT checklist and participant flowchart have been uploaded to an open-access repository and are available at: Fakhrizal E. CONSORT Checklist and Flowchart for ‘Impact of Intra-fascial Platelet-Rich Plasma Injection on PDGF Expression, UDI and POP-Q Scores, and Recurrence Risk in Cystocele Patients: A Randomised Controlled Trial’ [dataset]. Zenodo; 2025. Available from: https://doi.org/10.5281/zenodo.15161640³³

All data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).