Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis

Edy Fakhrizal; Budi Santoso; Eighty Mardiyan Kurniawati; Fedik Abdul Rantam; Salmon Charles P. T. Siahaan; Jojor Sihotang; Arya Marganda Simanjuntak; Raehan Satya Deanasa; Putri Mahira Afladhanti

doi:10.12688/f1000research.157123.1

Home Browse Platelet-rich plasma as a potential therapy of cystocele: a systematic...

ALL Metrics

-

Views

-

Downloads

Get PDF

Get XML

Export

▬

✚

Systematic Review

Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis

[version 1; peer review: 1 approved with reservations]

Edy Fakhrizal^1-3, Budi Santoso^4,5, Eighty Mardiyan Kurniawati^4,6, [...] Fedik Abdul Rantam⁷, Salmon Charles P. T. Siahaan⁸, Jojor Sihotang^2,3, Arya Marganda Simanjuntak⁹, Raehan Satya Deanasa¹⁰, Putri Mahira Afladhanti¹⁰

Edy Fakhrizal^1-3, Budi Santoso^4,5, [...] Eighty Mardiyan Kurniawati^4,6, Fedik Abdul Rantam⁷, Salmon Charles P. T. Siahaan⁸, Jojor Sihotang^2,3, Arya Marganda Simanjuntak⁹, Raehan Satya Deanasa¹⁰, Putri Mahira Afladhanti¹⁰

PUBLISHED 09 Dec 2024

Author details Author details

¹ Student of Doctoral Program, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
² Dept. Obstetrics & Gynecology, Faculty of Medicine, Universitas Riau, Pekanbaru, Riau, Indonesia
³ Reconstructive Urogynecology Division, Dept. Obstetrics & Gynecology, Arifin Achmad General Hospital, Pekanbaru, Indonesia
⁴ Dept. Obstetrics & Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
⁵ Reproductive Endocrinology & Fertility Division, Dept. Obstetrics & Gynecology, Dr. Soetomo General Academic Hospital, Surabaya, East Java, Indonesia
⁶ Reconstructive Urogynecology Division, Dept. Obstetrics & Gynecology, Dr. Soetomo General Academic Hospital, Surabaya, East Java, Indonesia
⁷ Virology & Immunology Laboratory, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia
⁸ School of Medicine, Universitas Ciputra, Surabaya, East Java, Indonesia
⁹ Research Intern, Department of Internal Medicine, Faculty of Medicine, Universitas Riau, Arifin Achmad General Hospital, Pekanbaru, Indonesia
¹⁰ Faculty of Medicine, Universitas Sriwijaya, Palembang, South Sumatra, Indonesia

Edy Fakhrizal
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Budi Santoso
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing

Eighty Mardiyan Kurniawati
Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Fedik Abdul Rantam
Roles: Conceptualization, Data Curation, Investigation, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Salmon Charles P. T. Siahaan
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Jojor Sihotang
Roles: Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing

Arya Marganda Simanjuntak
Roles: Investigation, Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing

Raehan Satya Deanasa
Roles: Investigation, Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing

Putri Mahira Afladhanti
Roles: Methodology, Project Administration, Resources, Software, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background

Platelet-rich plasma (PRP) therapy, is known for its regenerative properties. PRP may be able to help with cystocele cases. This review aims to explore how it might be applied to urogynecological cases, particularly those involving cystocele.

Methods

The present systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline 2020, Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guideline. The present systematic review was registered with PROSPERO with the registered number CRD42023414366. PubMed, Science Direct, Epistemonikos, COCHRANE, Google Scholar, and ProQuest were among the databases we searched. “(PRP OR Platelet-Rich Plasma) AND (Cystocele OR Anterior Pelvic Organ Prolapse)” from January 2007 to December 2022. Based on the PICO framework (Population = Patients with Cystocele; Intervention = Reconstruction with platelet-rich plasma injection; Compare = Reconstruction only; Outcome: Recurrency of Cystocele), four investigators (AMS, PMA, EAU, RSD, and AH) independently assessed eligibility by titles and abstracts. Using the Joanna Briggs Institute Critical Appraisal tool, each author evaluated full-text articles based on the kind of articles they had received. When consensus could not be obtained, disagreements were settled by involving the supervisors (EF, EMK, and BS).

Results

A total of 8,924 studies were identified. After removing duplicates and applying eligibility criteria, two articles were included, encompassing 65 patients. In two studies, PRP injections were found and administered post-anterior colporrhaphy at the pubovesical fascia. According to these two trials, women who had anterior colporrhaphy and PRP injections required fewer reoperations.

Conclusion

PRP has the potential to be a good alternative treatment to prevent cystocele recurrence. However, it cannot be generalized to large populations due to the small number of findings. Further studies with large samples examining the efficacy and safety of the therapy are needed to prove it.

Keywords

anterior vaginal prolapse, cystocele, platelet-rich plasma, potential therapy, recurrence

Corresponding author: Budi Santoso

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2024 Fakhrizal E et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Fakhrizal E, Santoso B, Kurniawati EM et al. Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 1 approved with reservations]. F1000Research 2024, 13:1508 (https://doi.org/10.12688/f1000research.157123.1) First published: 09 Dec 2024, 13:1508 (https://doi.org/10.12688/f1000research.157123.1) Latest published: 09 Dec 2024, 13:1508 (https://doi.org/10.12688/f1000research.157123.1)

Introduction

Pelvic organ prolapse (POP) refers to the descent of pelvic organs, such as the colon, small intestine, urethra, or bladder, into or beyond the vaginal opening.¹ POP affects an estimated 40% of women globally, with a higher prevalence in low-income countries and increasing severity with age.² Cystocele, the protrusion of the bladder into the vagina, is the most common type of POP, constituting 81% of the 200,000 annual POP surgeries in the United States of America (USA).^3,4 Risk factors include previous pregnancies, physically demanding work, and genetic disorders.³ Kayondo et al found that 56.3% of recurrences occurred at the same site in 25.2% of patients, with 80% of these being cystoceles.⁵

An anterior corporal reconstruction is a treatment option for cystocele; however, it primarily reinforces the vaginal wall and does not adequately address the apical compartment.^1,3 To address these deficiencies, platelet-rich plasma (PRP) therapy, known for its regenerative properties, offers a potential solution.⁶ PRP, which contains growth factors and cytokines, is used in orthopedic and cosmetic surgery for tissue repair and regeneration.⁶ In cases of POP, the use of autologous regenerative substances may facilitate the repair of connective tissue, smooth muscle, vascularization, and innervation supporting the pelvic organs.⁶ PRP injection aims to reinforce pelvic support structures, strengthen ligaments, and restore normal anatomical function, thereby reducing the risk of POP recurrence.⁶ This systematic review aimed to explore the effect of PRP in treating cystocele, an area less frequently addressed compared to orthopedic and cosmetic applications. To the best of our knowledge, the present systematic review and meta-analysis is the first to assess platelet-rich plasma as a potential alternative for preventing cystocele recurrence.

Methods

Study design and setting

The present systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline 2020, Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guideline. The present systematic review was registered with PROSPERO with the registered number CRD42023414366.

Research question

Recurrence in pelvic organ prolapse that has been reconstructed surgically shows a high rate. So the incidence of re-operation also increases. This is certainly uncomfortable for patients, so the author has a research question whether there is a method or further therapy to reduce the recurrence rate of pelvic organ prolapse. Platelet Rich Plasma is known to have a good anti-inflammatory and tissue repair profile and has been used by various specialist fields. So our research question is whether PRP can be an adjunct therapy to reduce the recurrence of pelvic organ prolapse.

Eligibility criteria

Population, intervention, comparison, and outcome (PICO) framework was employed to evaluate the effect of PRP injections in treating cystocele. The population of interest includes patients diagnosed with cystocele, a condition where the bladder protrudes into the vaginal wall. The intervention being assessed is PRP injection, a regenerative therapy designed to enhance tissue repair and strengthen pelvic support structures. This intervention is compared to the standard treatment of surgical reconstruction alone. The primary outcome is the recurrence of cystocele, with the study comparing the effectiveness of PRP combined with reconstruction versus reconstruction alone in preventing cystocele recurrence. The included studies were full-text and in English or Indonesian. Reviews /Case Reports/Experimental Studies, unpublished data, and duplicate studies were excluded. References from included studies were screened for additional eligible papers.

Searching strategy

Articles were sourced from PubMed, Science Direct, Epistemonikos, COCHRANE, Google Scholar, and ProQuest for the period January 2007 to December 2022, using the keywords (PRP OR Platelet-Rich Plasma) AND (Cystocele OR Anterior Pelvic Organ Prolapse). Four investigators (A.M.S., P.M.A., E.A.U., R.S.D., and A.H.) independently assessed study eligibility based on titles and abstracts. Disagreements were resolved through consultation with supervisors (E.F., E.M.K., and B.S.).

Data extraction

Each study was reviewed for details including author, year, design, country, population sample, GPAH, intervention, PRP cycle, dose (mL), injection site, cystocele recurrence, and observation length.

Quality assessment

Each author assessed potential bias using the Joanna Briggs Institute’s critical appraisal tools (jbi.global/critical-appraisal-tools). Bias was quantified by calculating the percentage of affirmative responses to appraisal questions. A graph depicting each author’s evaluation for each article was then generated. Disagreements were resolved with input from supervisors (EF, BS, EMK, and FAR).

Statistical analysis

Licensed RStudio was employed for meta-analysis utilizing a random-effects model. The use of a random effects model was chosen so that the results could be interpreted generally outside the included sample population. Findings were reported as proportions, with heterogeneity measured using I², Q value, Degrees of freedom (df ), Tau-squared, and Tau and p-value. Lower I² values and p-values greater than 0.05 indicate less heterogeneity. Lower I² values and p-values greater than 0.05 indicate less heterogeneity.

Results*

Characteristics of included studies

A total of 8,924 studies were identified. After removing duplicates and applying eligibility criteria, two articles were included, encompassing 65 patients ( Figure 1). References from these studies and citations yielded no additional eligible papers. Atilgan et al compared PRP with cystocele reconstruction (colporrhaphy), while Einarsson et al focused solely on PRP in cystocele patients without a control group.

Figure 1. Flowchart for included studies based on PRISMA statement.

Atilgan et al conducted an observational study in Turkey with 56 women with cystoceles. Group 1 underwent anterior colporrhaphy alone, while Group 2 received reconstruction plus PRP injection. Over 48 months, group 2 showed a statistically significant greater reduction in prolapse symptoms (p = 0.002) and fewer women requiring surgery compared to group 1. In group 1, 21.4% had a symptomatic recurrence, and 17.8% needed surgery, whereas, in group 2, 7.1% had a symptomatic recurrence, and only 3.5% required repair (p = 0.0001).⁶ Einarsson et al conducted a pilot trial in the USA using autologous platelet gel (a PRP by-product) applied to the surgical site during anterior colporrhaphy. Among nine patients, only one (12.5%) required a second procedure after ten months.⁷ In all included studies, the follow-up after PRP injections was 48 months and 20 months ( Figure 2). There is a substantial difference between the research by Atilgan and Einarrson, namely the research arm used. Atilgan used a non-PRP comparator while Einarsson used a single-arm with PRP only. Therefore, a side-to-side comparison between PRP and Non-PRP can only be seen in the Atilgan study. Therefore, a meta-analysis comparing the two therapies could not be performed in this study but continued with a proportional meta-analysis of the incidence of reoperation in patients who had been treated with PRP. The next difference is that the follow-up of the study is longer in Atilgan (48 months) compared to Einarsson (20 months) so the incidence of effects or success can be more convincing by Atilgan because it uses a longer observation time.

Figure 2. Baseline and estimate characteristics of the included studies.

Risk of bias

All studies reviewed scored above 74.5%, indicating minimal bias in the included research ( Figure 3). This assessment was found because both studies did not include confounding factors that may be involved in the study and also strategies against confounding factors were not described. Atilgan has a higher score than Einarsson because it has a comparison group and more optimal measurements than Einarsson who only used single-arm studies, but it can still be included because it discusses the same thing, namely the use of PRP in Pelvic Organ Prolapse cases.

Figure 3. Joanna Briggs Institute's score for the included studies.

Effect of platelet-rich plasma in treating cystocele

A proportional meta-analysis was performed to evaluate the current evidence from studies that have investigated the use of PRP in cases of pelvic organ prolapse (POP). Additionally, a proportional meta-analysis was conducted to assess the incidence of reoperation following PRP therapy. The analysis revealed that reoperation occurred in 4 out of 100 patients (95% CI: 0.00-0.11, p = 0.46) who underwent reconstruction followed by PRP treatment. This suggests that while reoperation is possible, its incidence remains low. The study’s heterogeneity was minimal, as indicated by a low I² value (0%) and a low τ² value (0%), reflecting minimal variability between studies. However, this finding should be interpreted with caution, as it may be influenced by the small number of studies that have specifically tested PRP in POP patients. ( Figure 4).

Figure 4. Forest plot of the effect of PRP in treating cystocele.

Discussion

From the meta-analysis, the reoperative incidence following PRP treatment was 4%. Atilgan et al reported a significant reduction in recurrence incidence (p = 0.002) and fewer reoperations in the PRP group.⁶ Einarsson et al observed a low reoperation rate, with only 1 of 9 women requiring a second procedure after 10 months of PRP treatment.⁷ Both studies indicate a low reoperation rate with anterior colporrhaphy and PRP, although Einarsson et al did not compare it to reconstruction alone.^6,7

None of the studies reported significant adverse effects from PRP treatment.¹⁵ Minor side effects, such as transient erythema, edema, mild headache, itching, and brief discomfort, were noted but did not include serious complications such as scarring, infection, or allergic reactions. Patients generally resumed normal activities and returned to work the following day without the need for antibiotics.¹⁵ Additionally, allogeneic PRP was found to be immunologically safe, and studies on chronic wounds showed favorable outcomes with no significant side effects.^16,17

PRP enhances fibroblast migration and proliferation, promoting connective tissue regeneration.⁸ In urogynecology, PRP is used for prolapse repair with favorable functional and anatomical outcomes.⁸ The primary benefit of PRP is its low recurrence rate. Additionally, PRP injections significantly reduce prolapse symptoms as measured by the Pelvic Floor Distress Inventory scale.⁸ Therefore, PRP is a promising alternative for preventing cystocele recurrence.⁸ Previous studies also suggested that PRP acts as a growth factor, facilitating tendon and ligament healing.⁸

Platelets promote angiogenesis through endothelial cell proliferation and migration.⁹ Previous studies have predominantly focused on PRP for tissue regeneration, highlighting its growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin growth factor I (IGF-I), hepatocyte growth factor (HGF), transforming growth factor beta (TGF-b), and fibroblast growth factor (FGF), which are crucial for ligament reconstruction ( Figure 5).^10,11 Recent studies have explored PRP for vaginal mesh exposure and improved fibroblast adherence and repair in vaginal prolapse surgeries.^12,13 Although PRP has not been used for cystocele correction, it is proposed for injection into the pubovesical fascia to enhance support and prevent recurrence.

Figure 5. Mechanism of platelet-rich plasma.¹⁵

To the best of our knowledge, the present systematic review and meta-analysis is the first to assess platelet-rich plasma as a potential alternative for preventing cystocele recurrence. Considering the risks associated with mesh implants, PRP injection into the pubovesical fascia during anterior vaginal wall prolapse repair may offer a viable alternative to prevent cystocele recurrence.⁶ Currently, PRP is reported to have no recognized side effects, with no adverse events noted during the 48-month follow-up in Atilgan et al.⁶ However, the optimal frequency and number of PRP sessions remain unclear and vary across studies.¹⁴ Further large-scale randomized controlled trials are needed to confirm the safety and efficacy of PRP in urogynecological procedures.^6,14

The present systematic review’s applicability is limited due to the small sample size and lack of a placebo-controlled comparison. Despite these limitations, the evidence supports PRP as a promising alternative for reducing cystocele recurrence. Further observational studies, clinical trials, and preclinical research are recommended to confirm PRP’s efficacy and safety in this context.

Conclusion

Our findings indicate that PRP injections may serve as a promising alternative for preventing the recurrence of postoperative cystocele. Additionally, in female patients with cystocele, PRP injections have the potential to improve symptoms, enhance anatomical outcomes, and increase postoperative satisfaction. However, the current evidence supporting these outcomes is of low quality due to the limited number of published studies and small sample sizes. Consequently, further high-quality randomized controlled trials (RCTs) are necessary to determine whether PRP injections represent an optimal alternative.

Ethics and consent

Ethical approval and consent were not required.

Data availability statement

No data are associated with this article

Extended data

Figshare: Platelet-rich plasma as a potential therapy of cystocele: A systematic review and meta-analysis, https://doi.org/10.6084/m9.figshare.27187344.v1.¹⁸

This project contains the following underlying data:

• PRISMA checklist and flowchart
• the specific assessment of each included article for our Risk of Bias.
• the metaprop program code that we used to conduct the meta-analysis test using the R application, and also other data that produced this meta-analysis article.

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

Acknowledgments

We would like to thank the head chief department of Obstetrics-Gynecology at Riau University and Airlangga University.

References

1. Prawirohardjo S: Ilmu KandunganAnwar M, Baziad APR, editors. P.T. Bina Pustaka Sarwono Prawirohardjo.2011.
2. Wang B, Chen Y, Zhu X, et al.: Global burden and trends of pelvic organ prolapse associated with aging women: An observational trend study from to.
3. Fakhrizal E: Prolaps Organ Panggul. 1st ed.Pekanbaru: Taman Karya; 2021.
4. Barber MD, Maher C: Epidemiology and outcome assessment of pelvic organ prolapse. Int. Urogynecol. J. 2013 Nov; 24(11): 1783–1790. Publisher Full Text
5. Kayondo M, Geissbüehler V, Migisha R, et al.: Risk factors for recurrence of pelvic organ prolapse after vaginal surgery among Ugandan women: a prospective cohort study. Int. Urogynecol. J. 2022 Jul; 33(7): 1933–1939. PubMed Abstract | Publisher Full Text | Free Full Text
6. Atılgan AE, Aydın A: Cystocele Repair with Platelet-Rich Plasma. Indian J. Surg. 2021; 83(3): 726–730. Publisher Full Text
7. Einarsson JI, Jonsdottir K, Mandle R: Use of autologous platelet gel in female pelvic organ prolapse surgery: a feasibility study. J. Minim. Invasive Gynecol. 2009; 16(2): 204–207. PubMed Abstract | Publisher Full Text
8. Guevara-Alvarez A, Schmitt A, Russell RP, et al.: Growth factor delivery vehicles for tendon injuries: Mesenchymal stem cells and Platelet Rich Plasma. Muscles Ligaments Tendons J. 2014 Jul; 4(3): 378–385. PubMed Abstract | Publisher Full Text
9. Oklu R, Walker TG, Wicky S, et al.: Angiogenesis and current antiangiogenic strategies for the treatment of cancer. J. Vasc. Interv. Radiol. 2010 Dec; 21(12): 1791–1805. quiz 1806. Publisher Full Text
10. Martínez CE, Smith PC, Palma Alvarado VA: The influence of platelet-derived products on angiogenesis and tissue repair: a concise update. Front. Physiol. 2015; 6: 290.
11. El-Sharkawy H, Kantarci A, Deady J, et al.: Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J. Periodontol. 2007 Apr; 78(4): 661–669. PubMed Abstract | Publisher Full Text
12. Castellani D, Valloni A, Piccirilli A, et al.: An innovative approach to treating vaginal mesh exposure after abdominal sacral colpopexy: endoscopic resection of mesh and platelet-rich plasma; initial experience in three women. Int. Urogynecol. J. 2017 Jun; 28(2): 325–327. PubMed Abstract | Publisher Full Text
13. Sebastian M, May A, Hala K, et al.: Attachment of Primary Vaginal Fibroblasts to Absorbable and Nonabsorbable Implant Materials Coated With Platelet-Rich Plasma: Potential Application in Pelvic Organ Prolapse Surgery.2015; 21(4): 190–197.
14. Nikolopoulos KI, Pergialiotis V, Perrea D, et al.: Restoration of the pubourethral ligament with platelet rich plasma for the treatment of stress urinary incontinence. Med. Hypotheses. 2016 May; 90: 29–31. PubMed Abstract | Publisher Full Text
15. Paichitrojjana A, Paichitrojjana A: Platelet Rich Plasma and Its Use in Hair Regrowth: A Review. Drug Des. Devel. Ther. 2022; 16: 635–645. PubMed Abstract | Publisher Full Text | Free Full Text
16. Akbarzadeh S, McKenzie MB, Rahman MM, et al.: Allogeneic Platelet-Rich Plasma: Is It Safe and Effective for Wound Repair? Eur Surg Res Eur Chir Forschung Rech Chir Eur. 2021; 62(1): 1–9. Publisher Full Text
17. Semenič D, Cirman T, Rožman P, et al.: REGENERATION OF CHRONIC WOUNDS WITH ALLOGENEIC PLATELET GEL VERSUS HYDROGEL TREATMENT: A PROSPECTIVE STUDY. Acta Clin. Croat. 2018 Sep; 57(3): 434–442. PubMed Abstract | Publisher Full Text
18. Siahaan SCPT: Platelet-rich plasma as a potential therapy of cystocele: A systematic review and meta-analysis. figshare. [Dataset]. 2024. Publisher Full Text

Comments on this article Comments (0)

Version 1

VERSION 1 PUBLISHED 09 Dec 2024