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

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T. Siahaan" }, { "@type": "Person", "name": "Jojor Sihotang" }, { "@type": "Person", "name": "Arya Marganda Simanjuntak" }, { "@type": "Person", "name": "Raehan Satya Deanasa" }, { "@type": "Person", "name": "Putri Mahira Afladhanti" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "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. 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F1000Research 2024, 13 :1508 ( https://doi.org/10.12688/f1000research.157123.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] Edy Fakhrizal https://orcid.org/0000-0003-0646-7106 1-3 , Budi Santoso 4,5 , Eighty Mardiyan Kurniawati 4,6 , [...] Fedik Abdul Rantam https://orcid.org/0000-0001-8182-1465 7 , Salmon Charles P. T. Siahaan https://orcid.org/0000-0002-1127-5056 8 , Jojor Sihotang 2,3 , Arya Marganda Simanjuntak https://orcid.org/0000-0001-8680-7865 9 , Raehan Satya Deanasa 10 , Putri Mahira Afladhanti 10 Edy Fakhrizal https://orcid.org/0000-0003-0646-7106 1-3 , Budi Santoso 4,5 , [...] Eighty Mardiyan Kurniawati 4,6 , Fedik Abdul Rantam https://orcid.org/0000-0001-8182-1465 7 , Salmon Charles P. T. Siahaan https://orcid.org/0000-0002-1127-5056 8 , Jojor Sihotang 2,3 , Arya Marganda Simanjuntak https://orcid.org/0000-0001-8680-7865 9 , Raehan Satya Deanasa 10 , Putri Mahira Afladhanti 10 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 DETAILS REVIEWER STATUS Abstract 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. READ ALL READ LESS Keywords anterior vaginal prolapse, cystocele, platelet-rich plasma, potential therapy, recurrence Corresponding Author(s) Budi Santoso ( [email protected] ) Close 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: 2 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 I 2 , Q value, Degrees of freedom (df ), Tau-squared, and Tau and p-value. Lower I 2 values and p-values greater than 0.05 indicate less heterogeneity. Lower I 2 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 I 2 value (0%) and a low τ 2 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 ADD YOUR COMMENT Comment 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 Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 09 Dec 2024, 13:1508 https://doi.org/10.12688/f1000research.157123.1 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. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article 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: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.12688/f1000research.157123.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 09 Dec 2024 Views 0 Cite How to cite this report: Sartoneva R. Reviewer Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r438323 ) The direct URL for this report is: https://f1000research.com/articles/13-1508/v1#referee-response-438323 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Jan 2026 Reetta Sartoneva , Tampere University, Tampere, Finland Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.172532.r438323 Dear Editor, The manuscript “Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis” is a systematic review an meta-analysis of using PRP for cystocele repair. The subject is highly interesting and worth ... Continue reading READ ALL Dear Editor, The manuscript “Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis” is a systematic review an meta-analysis of using PRP for cystocele repair. The subject is highly interesting and worth studying. However, the power of the meta-analysis remains relatively thin due to the low amount of studies. In the meta-analyze, the researchers combined the results from two different studies. Only one of the study was RCT, where Atilgan et al. randomized 56 women to either PRP + surgery or surgery groups. The other study was a small pilot study including only 9 patients and only PRP group. Also, the follow-up time especially in the Einarsson et al. study was short, only 20 months. Therefore, the result of this meta-analyze highly leans to the results of the RCT. Even though, the number of studies is thin, the research question is interesting and relevant and based on this review, worth further clarification. Especially long-term results would be interesting in the future. Further questions: The title of the article is “Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis”. I would add more general review about use of PRP to the manuscript especially because there is only 2 studies valid for the meta-analysis part. I would like to combine more general information about the mechanism of action, benefits and risks of PRP and also reviews about previous research in other relevant fields. At the first paragraph of the discussion: “Both studies indicate a low reoperation rate…” I would not say that 1/9 reoperation rate is so low. But of course, because the number of patients was low in Einarsson et al. study, no definitive conclusion can be made related to that study. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Tissue engineering in urogynecology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Sartoneva R. Reviewer Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r438323 ) The direct URL for this report is: https://f1000research.com/articles/13-1508/v1#referee-response-438323 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Dwi Saputra AN. Reviewer Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r348123 ) The direct URL for this report is: https://f1000research.com/articles/13-1508/v1#referee-response-348123 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Dec 2024 Akbar Novan Dwi Saputra , Department of Obstetrics and Gynecology, Faculty of Medicine, Public Health and Nursing, Dr. Sardjito Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.172532.r348123 Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Explanation: The rationale regarding the importance of cystocele and its high recurrence rate is well ... Continue reading READ ALL Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Explanation: The rationale regarding the importance of cystocele and its high recurrence rate is well presented. The potential role of PRP in tissue regeneration is adequately explained. However, the specific objectives need better definition: Primary and secondary outcomes should be explicitly stated The research question could be more precisely formulated using the complete PICO framework The timing of PRP administration relative to surgery needs clearer specification 2. Are sufficient details of the methods and analysis provided to allow replication by others? No Explanation: Critical methodological details are missing: Complete search strategies for all databases are not provided The 2007 - 2022 date restriction is not justified Screening process details are insufficient Data extraction forms are not included The method for contacting authors for missing data is not described The exact statistical methods for the proportional meta-analysis need more detail. To make this replicable, authors must provide: Full search strategies for all databases Detailed screening criteria Complete data extraction templates Statistical analysis code or detailed methods 3. Is the statistical analysis and its interpretation appropriate? No Explanation: The statistical approach has several fundamental flaws: Conducting a meta-analysis with only two studies, one being a single-arm study, is inappropriate The interpretation of heterogeneity statistics with only two studies is meaningless The proportional meta-analysis methodology is not suitable for these disparate study designs Confidence intervals are extremely wide, indicating very low precision Required changes: Remove the meta-analysis Present a narrative synthesis Report individual study results with appropriate effect measures Discuss limitations of the available evidence 4. Are the conclusions drawn adequately supported by the results presented in the review? No Explanation: The conclusions overstate the evidence: Claims about PRP's potential are too strong given the limited evidence base Generalizability is severely limited by small sample sizes and study designs Safety conclusions are drawn from very limited data The conclusions need to: Acknowledge the preliminary nature of the evidence Emphasize the need for larger, well-designed studies Be more cautious about safety claims Clearly state the limitations of the current evidence 5. Is this a Living Systematic Review? Not applicable This is not presented as a Living Systematic Review, and given the current state of evidence in this field, a traditional systematic review format is appropriate. Key Recommendations for Improvement: Clearly state primary and secondary objectives using PICO framework Provide complete methodological details including full search strategies Remove meta-analysis and present narrative synthesis Revise conclusions to match the limited evidence base Add detailed limitations section The manuscript requires major revision to meet basic standards for systematic review reporting and to ensure its conclusions are appropriately aligned with the available evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? No Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: regenerative medicine, urogynecology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Dwi Saputra AN. Reviewer Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r348123 ) The direct URL for this report is: https://f1000research.com/articles/13-1508/v1#referee-response-348123 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 09 Dec 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 09 Dec 24 read read Akbar Novan Dwi Saputra , Universitas Gadjah Mada, Yogyakarta, Indonesia Reetta Sartoneva , Tampere University, Tampere, Finland Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Sartoneva R. This is an open access peer review report 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. 12 Jan 2026 | for Version 1 Reetta Sartoneva , Tampere University, Tampere, Finland 0 Views copyright © 2026 Sartoneva R. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear Editor, The manuscript “Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis” is a systematic review an meta-analysis of using PRP for cystocele repair. The subject is highly interesting and worth studying. However, the power of the meta-analysis remains relatively thin due to the low amount of studies. In the meta-analyze, the researchers combined the results from two different studies. Only one of the study was RCT, where Atilgan et al. randomized 56 women to either PRP + surgery or surgery groups. The other study was a small pilot study including only 9 patients and only PRP group. Also, the follow-up time especially in the Einarsson et al. study was short, only 20 months. Therefore, the result of this meta-analyze highly leans to the results of the RCT. Even though, the number of studies is thin, the research question is interesting and relevant and based on this review, worth further clarification. Especially long-term results would be interesting in the future. Further questions: The title of the article is “Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis”. I would add more general review about use of PRP to the manuscript especially because there is only 2 studies valid for the meta-analysis part. I would like to combine more general information about the mechanism of action, benefits and risks of PRP and also reviews about previous research in other relevant fields. At the first paragraph of the discussion: “Both studies indicate a low reoperation rate…” I would not say that 1/9 reoperation rate is so low. But of course, because the number of patients was low in Einarsson et al. study, no definitive conclusion can be made related to that study. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests No competing interests were disclosed. Reviewer Expertise Tissue engineering in urogynecology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Sartoneva R. Peer Review Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r438323) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1508/v1#referee-response-438323 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Dwi Saputra A. This is an open access peer review report 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. 18 Dec 2024 | for Version 1 Akbar Novan Dwi Saputra , Department of Obstetrics and Gynecology, Faculty of Medicine, Public Health and Nursing, Dr. Sardjito Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia 0 Views copyright © 2024 Dwi Saputra A. This is an open access peer review report 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. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Explanation: The rationale regarding the importance of cystocele and its high recurrence rate is well presented. The potential role of PRP in tissue regeneration is adequately explained. However, the specific objectives need better definition: Primary and secondary outcomes should be explicitly stated The research question could be more precisely formulated using the complete PICO framework The timing of PRP administration relative to surgery needs clearer specification 2. Are sufficient details of the methods and analysis provided to allow replication by others? No Explanation: Critical methodological details are missing: Complete search strategies for all databases are not provided The 2007 - 2022 date restriction is not justified Screening process details are insufficient Data extraction forms are not included The method for contacting authors for missing data is not described The exact statistical methods for the proportional meta-analysis need more detail. To make this replicable, authors must provide: Full search strategies for all databases Detailed screening criteria Complete data extraction templates Statistical analysis code or detailed methods 3. Is the statistical analysis and its interpretation appropriate? No Explanation: The statistical approach has several fundamental flaws: Conducting a meta-analysis with only two studies, one being a single-arm study, is inappropriate The interpretation of heterogeneity statistics with only two studies is meaningless The proportional meta-analysis methodology is not suitable for these disparate study designs Confidence intervals are extremely wide, indicating very low precision Required changes: Remove the meta-analysis Present a narrative synthesis Report individual study results with appropriate effect measures Discuss limitations of the available evidence 4. Are the conclusions drawn adequately supported by the results presented in the review? No Explanation: The conclusions overstate the evidence: Claims about PRP's potential are too strong given the limited evidence base Generalizability is severely limited by small sample sizes and study designs Safety conclusions are drawn from very limited data The conclusions need to: Acknowledge the preliminary nature of the evidence Emphasize the need for larger, well-designed studies Be more cautious about safety claims Clearly state the limitations of the current evidence 5. Is this a Living Systematic Review? Not applicable This is not presented as a Living Systematic Review, and given the current state of evidence in this field, a traditional systematic review format is appropriate. Key Recommendations for Improvement: Clearly state primary and secondary objectives using PICO framework Provide complete methodological details including full search strategies Remove meta-analysis and present narrative synthesis Revise conclusions to match the limited evidence base Add detailed limitations section The manuscript requires major revision to meet basic standards for systematic review reporting and to ensure its conclusions are appropriately aligned with the available evidence. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? No Is the statistical analysis and its interpretation appropriate? No Are the conclusions drawn adequately supported by the results presented in the review? No If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise regenerative medicine, urogynecology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Dwi Saputra AN. Peer Review Report For: Platelet-rich plasma as a potential therapy of cystocele: a systematic review and meta-analysis [version 1; peer review: 2 approved with reservations] . F1000Research 2024, 13 :1508 ( https://doi.org/10.5256/f1000research.172532.r348123) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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