Role of platelet-rich plasma in pelvic floor disorders: A systematic review

Abstract Background Management for pelvic floor disorders needs to be improved. Platelet-rich plasma (PRP) offers an innovative treatment in general medical care to promote cell regeneration. Objective This review aims to investigate the role of PRP in pelvic floor disorders. Materials and Methods 6 international databases were accessed using several keywords namely PubMed, Science Direct, Cochrane Library, ProQuest, Google Scholar, and Scopus. The inclusion criteria were articles written in English, published in 10-yr period from 2012 until 2022, and investigated the relevant topic. This systematic review followed PRISMA guideline. Results 644 articles were found in several databases and 15 articles met the criteria. Management for pelvic floor disorders needs to be improved, but there are still many challenges, such as less effective treatments, risk of recurrence, and postoperative wound healing. PRP offers an innovative treatment in general medical care to promote cell regeneration. A total of 644 articles from the database were found, but 15 studies met the criteria. A total of 600 women with various pelvic floor disorders treated with PRP were analyzed. PRP positively impacts female sexual dysfunction, perineal trauma, vulvovaginal atrophy, stress urinary incontinence, vesicovaginal fistula, perineal rupture, and pelvic organ prolapse. Dosages, preparation techniques, injection techniques, and additive materials are varied. Most studies do not report side effects from the therapy, but the urinary disorder complaints must be paid attention to. Conclusion PRP can be used to manage pelvic floor disorders. Future studies should clarify and standardize the dose in each case and how to make PRP produce the best results.


Introduction
Women in developed and developing countries can experience pelvic floor disorders during their reproductive cycle.The risk of developing the disease increases with age.Older women complain of pelvic floor disorders more frequently than younger women, resulting in increased visits to health facilities (1).A cross-sectional study of the female population in the United States found that 23.7% of women may have pelvic floor disorders, and this prevalence doubles in women aged 80 yr (2).Greater discomfort due to symptoms of pelvic floor disorders correlates with poorer quality of life (3).Treatment of pelvic floor dysfunction has evolved for better management (4).Unfortunately, better treatment must be done because the existing treatment is not fully satisfactory.Recurrence and surgery can be repeated (5).In cases of fistula, postoperative wound healing is a challenge (6).Patient outcomes will improve as the quality of service improves (7).
Harmonious relationships among muscles, nerves, connective tissue, and bones establish the structure and function of the pelvic floor.If this relationship is disrupted, women will complain of pelvic floor disorders (8).Musculoskeletal health is related to pelvic floor physiological functions (9).Chronic pelvic pain can appear as a form of disruption of this system (10).
Platelet-rich plasma (PRP) is frequently discussed in literature.PRP is a derivative of whole blood containing a supraphysiological concentration of platelets (11).PRP can help regenerate damaged tissue.The resulting cytokines can serve as an alternative treatment.
Previous research used studies with rats as experimental animals.PRP administration impacts tendon healing in the initial phase and produces greater mechanical resistance (8).
The inflammatory, regeneration, and remodeling phases are assisted by the presence of PRP (9).The use of PRP has increased in the last 10 yr.This is because PRP is a part that comes from the human body itself and contains growth substances 3-5 times greater than plasma.In gynecology, the problem of Lichen sclerosis or cervical ectopia is treated with PRP and has shown promise.In addition, PRP is a simple substance, side effects are small and easy to find (12).
This study aims to explore the role of PRP in pelvic floor disorders through a systematic review study, specifically to evaluate the effectiveness and safety of PRP in women with pelvic floor disorders.

Study design and search strategy
The preparation of the review follows the PRISMA guidelines.The international databases, namely PubMed, Science Direct, Cochrane Library, ProQuest, Google Scholar, and Scopus were accessed to search for peer-reviewed papers relevant to the topic.Pelvic floor disorders were conditions that affect the proper function of the female pelvic organs.
The search used several relevant keywords that match the medical subject heading terms and word synonyms.Articles were searched using the following keywords: "urogynecology", "pelvic floor disorders", "platelet-rich plasma" and Table I shows the terms, keywords, and outcomes.
Articles not found in the database but found through the bibliography of other articles were also selected in the review.

Vulvovaginal atrophy
"vulvovaginal atrophy" OR "Genitourinary syndrome of menopause" OR "vaginal atrophy" OR "urogenital atrophy" OR "atrophic vaginitis" AND "platelet-rich plasma"   (15).The quality of article was presented in tables III, IV, and V.In this manuscript, no meta-analysis could be carried out due to the different types of cases, the limited number of articles, and the heterogeneous population.

Study selection and study characteristics
644 articles were found in several databases.There were 27 duplicate articles.594 articles were excluded because they were not relevant to the topics discussed, review articles, not studies on humans, not written in the English language, not open access, male studies, letters to the editor, and abstract conference.

Quality assessment
The quality assessment results of the manuscripts are shown in tables III, IV, and V.The results of the quality of the cohort manuscripts using CASP indicate that the 5 studies are in the moderate category.
The results of the PEDro assessment showed that 5 articles were in the medium category, and 1 article was in the good category.The results of the case report assessment showed that the manuscript is worthy of being included in the review.

Production technique
The production technique starts by taking blood.
4 studies mention the location in the human body for collecting blood samples.Peripheral blood was collected from superficial saphenous vein in the cubital area of the arm.The centrifugation procedure is known to differ from one study to another.There is a one-spin centrifugation speed, namely 3200 rpm for 8 min, 6000 rpm for 6 min, 1500 rpm for 8 min, 5000 rpm for 5 min, 1500 g for 5 min, and 3400 rpm for 15 min.In addition to one spin, the centrifugation process can be carried out using 2 spin methods, namely, the first spin was at 2500 rpm for 3 min,  however, the technique is not mentioned.Also, the dose given varies.The injection technique and additives are listed in table VI.

Outcome
The outcome seen refers to each case.The administration of PRP was associated with an increase in female sexual function index (FSFI) scores, subdomain orgasm scores, and genital perception.
The female genital self-image scale (FGSIS) scores (p < 0.001 and p < 0.05) but was not related to the results of the Rosenberg scale.The female sexual distress scale-revised (FSDS-R) score showed a minimal increase in stress score observed at the 4 th administration (p < 0.001).In the case of vulvovaginal atrophy, the total vaginal health index (VHI) increased significantly (p < 0.0001) at 6 months.The female sexual distress (FSD) score decreased significantly (p < 0.0001, respectively).
In the case of SUI, the mean VAS of SUI scores decreased significantly after treatment (p < 0.001, and p < 0.05).Bladder function variables were significantly improved (p < 0.002).Some studies found that symptoms of SUI at 1 month and 6 months experienced a trend of recovery after being given PRP.The younger group showed a better trend but it did not reach statistical significance (p = 0.07).The results of the incontinence questionnaire (ICIQ) study indicates the effect of this method in the treatment of SUI.The results of the incontinence quality of life (I-QOL) assessment after the treatment observed a significant increase (p < 0.01).
Positive results were also found in case reports and case series research.The data were seen from the patient's responses and complaints after being given PRP therapy.In the case of female sexual satisfaction, improved treatment of secondary sexual dysfunction was seen from the use of PRP for pelvic radiotherapy in a cancer patient.In the case of perineal trauma, PRP impacts ending the patient's complaints of severe pain.In the case of a vesicovaginal fistula, the vaginal wall heals without scarring.In addition, the patient did not complain of difficulty urinating or urinary tract disorders.On the Stabbatsberg scale, an increasing modification was found.In the vulva-perineum, rejuvenation occurs by improving vaginal trophics and rehabilitate normal vaginal caliber.

Adverse effect
Some studies do not discuss the adverse effects experienced.In cases of SUI, adverse effects can occur in a patient (3.8%) (16,17).Mild hematuria and painful urination were reported in 10 patients (28.6%) (18).
International Journal of Reproductive BioMedicine PRP plasma in pelvic disorders     PRP preparation.There is no evidence that ideal concentrations are required (37).In addition, PRP activation is not required when injected into soft tissue (38).
Some studies add HA.In many tissues and fluids, HA (also known as hyaluronan) is found naturally but is more abundant in articular cartilage and synovial fluid.Although easy to find, HA content varies greatly across joints and species (37).HA is involved in angiogenesis, reactive oxygen species, chondrocytes, cancer, lung injury, and immune and skin regulation (39).In This type cannot be injected (34).
Most studies show that there are no side effects.However, 2 studies reported side effects or disorders related to urination.PRP has few side effects because it comes from the patient's blood.In addition, PRP is a relatively inexpensive biological material that is easy to produce.This makes PRP superior to synthetic materials (33).
The use of PRP needs to be uniform to find a pattern of administration for the management of pelvic floor disorders.This study could not The content will also depend on the levels of platelets, leukocytes, and growth factors (40).
Different centrifugation guidelines, and the wide variation in platelet concentrations, make it difficult for clinicians to choose among the available PRP. Nonetheless, PRP is commercially available with the advantages of ready-to-use, sterile but high cost and limited volume (34).19 articles were not open access, so that can cause bias in concluding.In addition, this research is still limited to several databases.

Conclusion
The available evidence suggests positive therapeutic effects of PRP for various pelvic floor disorders.However, a clinical trial with a standardized PRP preparation, route of administration, and regime/dosage are required to establish its clinical efficacy.PRP is shown to be safe except for a few urinary symptoms, however, the evidence is limited.

International
Journal of Reproductive BioMedicine PRP plasma in pelvic disorders their synonyms.In addition, pelvic floor disorders were searched in detail based on the name of the disease.The term pelvic floor disorders in this study covered 6 problems including pelvic organ prolapse (POP), stress urinary incontinence (SUI), female sexual satisfaction, perineal trauma, vulvovaginal atrophy, and vesicovaginal fistula.
Study characteristics are shown in table VI.This systematic review involved 15 studies on PRP use in various cases of pelvic floor disorder, including female sexual dysfunction, perineal trauma, vulvovaginal atrophy, SUI, vesicovaginal fistula, perineal rupture, and POP.A total of 600 women were included in this systematic review.The number of study participants was broken down into 164 patients with sexual dysfunction and orgasmic disorder, 1 patient with pain during urination, defecation, coitus, during menstruation, walking and sitting, 20 patients with vulvovaginal atrophy, 179 SUI patients, 16 patients with recurrent vesicovaginal fistula, 210 postpartum patients with perineal rupture, and 10 patients with POP.
https://doi.org/10.18502/ijrm.v21i12.15034International Journal of Reproductive BioMedicine Kurniawati et al. and the second spin was at 4000 rpm for 15 min, or by first 800 rpm for 10 min, then 15 min at 3500 rpm.

2
studies added activating ingredients such as calcium chloride.Another 2 studies added hyaluronic acid (HA).PRP-HA injection appears to be a promising method to increase vaginal mucosa trophic and hydration for the treatment of vesicovaginal fistula in postmenopausal breast cancer patients with contraindications to hormone therapy.The combined injection technique of PRP and HA aids in enhancing the modified Stabbatsberg scale and vulva-perineal rejuvenation.The injection technique depends on the problem at hand.In cases of sexual dysfunction, injections are performed on the anterior vaginal wall and the clitoris.In perineal trauma, it is injected into the perineum.In SUI, it is injected into the urethral meatus, external sphincter, anterior lower one-third of the vagina and periurethral area, or anterior vaginal mucosa.In a vesicovaginal fistula, the injection is done transvaginally.The injection is administered subcutaneously, subvaginally, or via intramucosal; , C: Cannot tell, N: No, M: Moderate overall quality https://doi.org/10.18502/ijrm.v21i12.15034International Journal of Reproductive BioMedicine Kurniawati et al.Table IV.Physiotherapy evidence databases (PEDro) scale assessment reviewed randomized controlled trials and experimental study /doi.org/10.18502/ijrm.v21i12.15034International Journal of Reproductive BioMedicine PRP plasma in pelvic disorders , N: No https://doi.org/10.18502/ijrm.v21i12.15034International Journal of Reproductive BioMedicine Kurniawati et al.
this study, HA and PRP were used to support each other in increasing positive outcomes, although the administration technique was different.The technique of administration is subcutaneous, subvaginal, and intramucosal injection.PRP has certain types, one of which is platelet-rich fibrin.
be meta-analyzed due to the limited number of studies and variations between cases, different outcome measurement techniques, and varied types of research.The preparation method, sample content, and the proposed application are the guidelines for classifying PRP preparations.Centrifugation speed, centrifugation time, and use of anticoagulants cause variations in preparations.
Table I presented the terms, keywords, and outcomes.

Table I .
The terms, keywords, and outcomes

2. Study selection and outcome measure
VHI, VAS, FSD score POP: Pelvic organ prolapse, SUI: Stress urinary incontinence, P-QOL: Prolapse quality of life, GRA: Global response assessment, VAS: Visual analog scale, ICIQ: Incontinence questionnaire, I-QOL: Incontinence quality of life, UDI-6: Urogenital distress inventory, FSFI: Female sexual function index, FGSIS: Female genital self-image scale, FSDS-R: Female sexual distress scale-revised, VHI: Vaginal health index, FSD: Female sexual distress2.relevanttopicswere included in the review.All studies, observational designs such as case reports, case-series, cross-sectional, cohort, experimental designs, and randomized controlled trials, were considered for inclusion in the review.The exclusion criteria in this study

Table II .
PICO framework

Table III .
Critical appraisal skills program checklist for cohort study

Table V .
Quality assessment for case report/case series using the Joanna Briggs Institute Critical Appraisal tools ( JBI)

Table VI .
Effect of platelet rich plasma (PRP) in urogynecological disorders