A Pilot Study Efectiveness of Local APRP in SUI
A Pilot Study Efectiveness of Local APRP in SUI
A Pilot Study Efectiveness of Local APRP in SUI
com/scientificreports
The study aims to evaluate the effectiveness of local injection of autologous platelet rich plasma
(A-PRP) as a treatment for women suffering from stress urinary incontinence (SUI). In a prospective
intervention study, twenty consecutive women suffering from SUI were treated with A-PRP injection
at anterior vaginal wall where mid-urethra locates. Self-reported questionnaires were used to measure
pre-treatment, 1 month and 6 months post-treatment symptom severity. Secondary outcomes of
sexual function and treatment effect sorted by age were analyzed with valid statistical methods.
A-PRP is effective in relieving SUI symptoms at both 1 month and 6 months post-treatment without
significant adverse reactions reported. It seems to have a trend that treatment success rate with cured
and improved symptoms was slightly higher in the younger group, although it did not reach statistical
significance (P = 0.07). No significant changes in sexual function before and after the treatment
were reported by the patients. This pilot study is the first to report A-PRP treatment effect for SUI in
women. The result suggested that A-PRP is a considerable treatment option for mild to moderate SUI
cases. It also opens up further research opportunities for A-PRP’s clinical applications.
Platelet is rich in various kinds of growth factors and cytokines that promote soft tissue healing. Insulin-like
growth factor (IGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet-derived
growth factor (PDGF), transforming growth factors-beta (TGF-β), vascular endothelial growth factors (VEGF),
connective tissue growth factor (CTGF) hepatocyte growth factor (HGF) and interleukin 8 (IL-8) are only a few
to name1. Each has its role in enhancing cell migration, cell recruitment, cell replication, extracellular matrix
scaffolding, tissue regeneration and neo-angiogenesis. These processes are activated upon stimulation by expo-
sure to thrombin, calcium or collagen in vivo2. Collectively, they repair damaged tissues and rejuvenate aged
cells. Autologous platelet-rich plasma (A-PRP) is synthesized from patients’ own blood after concentration via
centrifugation. The autologous nature meant satisfying safety profile for reduced immune reactions, as long as
the preparation is handled with care and good sterile techniques.
A-PRP has long-standing history and good outcomes in sports medicine, particularly in treating tendonitis,
arthritis, ligament sprains and tears. It is effective in reducing injury pain, fast healing and quick return to regu-
lar activities. Other fields with evidence-based applications include dentistry, d ermatology2, sports m
edicine3,
cardiac surgery, pediatric surgery, urology4, plastic surgery and ophthalmology5. Utilization of A-PRP in the
1
Department of Obstetrics and Gynecology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical
University, Kaohsiung, Taiwan. 2Department of Obstetrics and Gynecology, Kaohsiung Medical University
Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 3Graduate Institutes of Clinical Medicine,
College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4Department of Internal Medicine,
Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 5Department
of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, 482 Shan‑ming Road,
Kaohsiung 812, Taiwan. 6Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung,
Taiwan. 7Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 8Regenerative
Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. 9These authors
contributed equally: Cheng-Yu Long and Kun-Ling Lin. *email: [email protected]
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Table 1. Demographic data (n = 20) are given as mean ± standard deviation or n(%). BMI, body mass index,
Values are expressed as mean ± standard deviation or numbers; SUI grade according to ICIQ-SF: slight (1–5),
moderate (6–12), severe (13–18) and very severe (19–21).
P value*
N = 20 Baseline 1 months post-Tx 6 months post-Tx 1 month 6 months
ICIQ-SF 11 (6–18) 6 (0–17) 4 (0–16) 0.012* 0.002*
UDI-6 33.3 (17–72) 22.2 (0–78) 17 (6–72) 0.005* 0.004*
IIQ-7 23.8 (5–90) 4.8 (0–86) 4.8 (0–86) 0.001* 0.016*
OABSS 6 (0–12) 3 (0–12) 4 (0–12) 0.034* 0.229
POPDI-6 4 (0–13) 2 (0–15) 2 (0–14) 0.254 0.232
field of obstetrics and gynecology dated back as early as 2007 by the Fanning J et al., who investigated direct
application to operated wounds in total abdominal hysterectomy, laparoscopy-assisted vaginal hysterectomy and
urogynecology surgeries. They found significantly reduced procedure related pain as early as post-operation day
16. However, no available literatures published so far have demonstrated potential therapeutic effect of A-PRP
in treating women with stress urinary incontinence (SUI).
SUI is a bothersome gynecology problem all around the world, with an estimated prevalence of 40% in adult
women7. Birth trauma, aging, obesity and estrogen deprivation are well-known risk factors. Kunkle and colleague
reported approximately 13.12 billion US dollars were spent on SUI, including disposable diapers, laundry, dry
cleaning, and sanitary p ads8. A variety of treatment modalities is currently available: lifestyle modification and
pelvic floor muscle exercise might be effective for mild degree of SUI symptom; electrostimulation, biofeedback,
and extracorporeal magnetic innervation are non-invasive symptom-control methods.
Anti-incontinence surgeries, such as mid-urethral tapes and colposuspension are effective and d urable9. Each
method has its strengths and limitations that should be adopted according to individual condition, character-
istics, disease severity, and economic considerations to reach a shared decision making between the healthcare
provider and patients. This study aims to assess A-PRP as an alternative treatment option for the treatment of
SUI. Reviewing the literature, this is the first report that demonstrates clinical outcomes of A-PRP application
in stress-incontinent women.
Results
Among the 20 patients enrolled, the average age was 44.5 years old with averaged parity of 1.6 times, body mass
index 22.7 mg/m2. Five or 25% of them are menopause. Prior to the PRP treatment, the average pad test was
5.8 g; one (5%) reported mild symptom while 12 (60%) and 7 (35%) reported moderate and severe to very severe
diseases, respectively by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score.
All patients followed for at least 6 months (Table 1). Treatment efficacy assessed by ICIQ-SF, Urogenital Dis-
tress Inventory (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and Overactive Bladder Symptom Scores
(OABSS) showed significant incontinence improvement at both 1 month and 6 months post treatment, but not
by Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6) (Table 2).
Changes in grades of SUI following treatment of PRP injection were shown in Fig. 1. These women were
then sorted by age, with the cut-off value at 40 years old to investigate age as a factor for treatment efficacy. The
result showed no significance between the characteristics of the two groups in terms of mean body mass index,
underlying diabetes mellitus, hypertension, history of hysterectomy or history of mid-urethral sling. Only parity
number was significantly higher for the older group. However, it seems to have a trend that treatment success
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25
20 1
4
15 no SUI
5
12 mild SUI
10 moderate SUI
8
severe SUI
5
7
3
0
Pre-PRP Post-PRP
Figure 1. Changes in grades of stress urinary incontinence following treatment of PRP injection.
Post-op
Pre-op Cure Mild Moderate Severe Improved Unchanged/worse Efficacy
Mild (n = 1) 1 0 0 0 1 0 1/1 (100%)
Moderate (n = 12) 3 3 5 1 6 6 6/12 (50%)
Severe (n = 7) 0 2 3 2 5 2 5/7 (71.4%)
All (n = 20) 4 5 8 3 12 8 12/20 (60%)
95% CI 95% CI
95% CI
[3.89, 9.01] [− 2.59, 0.15]
Table 3. Treatment efficacy of PRP injection. PRP, platelet-rich plasma; Pre-op, preoperative; Post-op,
postoperative; CI, confidence interval.
Table 4. Urodynamic changes before and 6 months after PRP treatment. Data are given as n(%) or
mean ± standard deviation. PRP, platelet-rich plasma; DO, detrusor overactivity; Qmax, maximum flow rate;
RU, residual urine; FS, first sensation to void; MCC, maximum cystometric capacity; Pdet, detrusor pressure
at peak flow; FUL, functional urethral length; MUCP, maximum urethral closure pressure. # Paired t-test; §
significant significance.
rate with cured and improved symptoms was slightly higher in the younger group (75%) compared to that of the
older group (50%), although it did not reach statistical significance (P = 0.07). The treatment efficacy is also dem-
onstrated by disease severity distribution pre-PRP and 6 months post-PRP (Table 3), with a shift of the majority
reporting moderate and severe diseases to moderate and milder diseases. No adverse reactions were reported.
Only 8 women completed the urodynmaic studies before and 6 months after intervention. Residual urine
and bladder volume at first sensation to void increased significantly after injection of PRP. All other urodynamic
parameters showed no significant differences following treatment (Table 4). The influence of PRP injection on
sexual function was investigated by Female Sexual Function Index (FSFI) questionnaire. No significant changes
before and after the treatment were reported by the patients, neither for the total score or for each component
(i.e. desire, arousal, lubrication, orgasm, satisfaction and dyspareunia) (Table 5). Further analysis by the factor
of age revealed there were no in-between group differences (Table 6).
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Table 5. Changes Female Sexual Function Index (FSFI) scores at baseline and 6 months post-treatment with
PRP injection. Data are given as median (range) or mean ± standard deviation. Paired’s t-test.
Table 6. Changes in scores of Female Sexual Function Index in both groups before and 6 months after
treatment. Data are given as mean ± standard deviation. Pre-op, preoperatively; Post-op, postoperatively.
*Paired t-test; ^Student’s t-test; **Statistical significance. Pa = 0.72, Pb = 0.59, Pc = 0.48, Pd = 0.13, Pe = 0.20,
Pf = 0.22, Pg = 0.59.
Discussion
The current study demonstrates A-PRP is effective in treating women with SUI for as long as 6 months post
treatment. The outcome is evidenced by multiple self-reported questionnaires before, 1 month and 6 months
after the treatment. ICIQ-SF, UDI-6, IIQ-7 and OABSS questions all revealed significant and lasting effective-
ness, while POPDI-6 showed a trend of improved symptom scores although not reaching statistical significance
(Table 2). Figure 1 further illustrated a shift of disease severity distribution to milder diseases after PRP treatment.
According to the integral theory, the most important factor in cases of female SUI is a pubourethral ligament
defect10. Nikolopoulos and colleagues have advocated the plausibility of A-PRP in restoring pubourethral liga-
ment integrity to treat SUI in as early as 201611. He promoted his hypothesis by laying out various animal models
that proved the rejuvenating abilities of A-PRP compositions, such as VEGF, IGF-1, PGDF, HGF, TGF-β and
FGF. Injecting bulking agents to provide mechanical support of urethral, thereby storing normal pelvic anatomy
and reducing urethral hypermobility, is not new in treating SUI. A-PRP serves a superior agent than previously
employed paraffin, bovine collagen, polydimethylsiloxane, polyacrylamide gel, and hyaluronic a cids1, for its
autologous nature and minimal, if any, allergic reactions. A-PRP is not only biocompatible, durable and non-
migratory; its reparative ability can repair damaged ligaments and potentially prolong treatment effectiveness.
A secondary analysis of this study observed a superior treatment outcome in the patient group younger
than 40 years old. It is postulated that being younger might pose better rejuvenating abilities, and thus better
treatment effect of A-PRP. Also, aged patients are likely to be impacted with additional variables such as more
parity number, menopausal state, more severe SUI symptoms and more underlying systemic conditions such as
diabetes mellitus and hypertension, history of hysterectomy, abdominal surgeries and previous anti-continence
treatments. The reparative ability in aged people’s plasma might be reduced is another hypothesis to be tested.
These potential confounding factors are demonstrated by a trend in our small study groups, although not reach-
ing statistical significance. Further study with greater patient number and variable-adjusted analysis is required
to validate the assertion. If proven, these factors would be very helpful for patient selection that will benefit the
most from PRP treatment.
Sexual function is intimately related to urinary incontinence, thus warranting a secondary analysis in the
treatment of SUI with A-PRP. The current study utilizes FSFI questionnaires pre- and post-PRP treatment but
failed to reveal significantly improved composite sexual function score, regardless of length of follow up (Table 2).
However, when examining each domain of FSFI, an improved sexual desire was noted in both age groups
(Table 3). This signifies how stress urinary incontinence impacts the patient’s self-image, confidence and fear of
embarrassment when it comes to sexual functions. Therefore, an improvement in SUI symptoms readily enhances
sexual desire. Interestingly, our finding is in contrary to Runels and colleagues’ 2014 report, which demonstrated
significantly improved FSFI performance in total scores, desire, arousal, lubrication and orgasm domains in 11
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women receiving PRP for sexual d isorders12. The authors also reported prolonged prolong arousal, ejaculatory
orgasm, spontaneous orgasm in younger women as side effects that resolve in 2 weeks without treatment. The
observation is not revealed by our study, which is mainly attributed to disparity in injection sites. Runels’ group,
who specifically aimed at treating sexual dysfunctions, injected A-PRP at both clitoris and a spot of anterior
vaginal wall most distal from the urinary bladder. Our study that aimed at treating urinary incontinence had a
different injection site. Cultural difference where sexual topics are not as openly discussed in Asian populations
might also contribute to the differential results.
PRP it has only gained more attention in the field of obstetrics and gynecology in recent years. Targeted
conditions encompass symptomatic ectopic cervix13, lichen sclerosis at vulvovaginal14, vesicovaginal fistula15,
pelvic organ p rolapse16,17, ovarian function r ejuvenation18, endometrial r eceptivity19, female sexual d
ysfunction12,
membrane sealant in preterm pre-labor ruptured membrane and cesarean section wound aesthetics21. We ever
20
reported that the treatment efficacy for the vaginal Er:YAG laser for SUI at 6-month follow-up was 75.5%22.
Promising impact of PRP and carbon dioxide laser for SUI was also noted r ecently23.
However, the effect of PRP alone on SUI was rarely reported.
The current study is the first report of A-PRP application on women with SUI, with treatment outcomes
demonstrated by before and after treatment questionnaires scores. The results are analyzed objectively with valid
statistical methods. An intermediate follow-up time of 6 months was investigated. Secondary analysis of impacts
of age and sexual functions were also reported. Limitations of the work included small sample size and lack of a
controlled group. Future work is encouraged to incorporate a randomized controlled trials with longer follow-up
period. Comparative study with head-to-head comparisons to other bulking agents is plausible. Other potential
areas to investigate may include A-PRP as a preventative role at the time of pelvic floor structure insult, as an
adjuvant modality in combination with corrective surgery or other conservative treatments, determination of
its lowest effective dose, repeat treatment intervals if necessary and long-term efficacy.
Conclusion
Local injection of autologous platelet rich plasma seems safe with somewhat satisfactory response in treating
female SUI both at 1 month and 6 months post treatment. It appears to have a trend that younger women have
better treatment outcome, and larger sample sizes might shed more light upon this effect. Yet how long the treat-
ment effect could sustain remains unknown. This innovated intervention could be an alternative treatment for
SUI but awaits further explorations.
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Figure 3. Diagram of the injection site and depth over anterior vaginal mucosa.
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questionnaire. The cut-off values were 1–5, 6–12, 13–18 and 19–21 points for slight, moderate, severe and very
severe, respectively24. Women were deemed for cure if they felt no complaint of SUI after procedure. Symptom
improvement was recognized with downgrading of the ICIQ-SF results. Data were collected before, 1 month and
6 months post-treatment. Statistical analysis was performed using Student’s t test and paired t-test. A difference
was considered statistically significant when P < 0.05.
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Acknowledgements
This research is supported by the Grant from Kaohsiung Municipal Siao-gang Hospital (Kmhk-107-024 and
Kmhk-108-05), Kaohsiung Medical University Regenerative Medicine and Cell Therapy Research Center (KMU-
TC108A02-07), Kaohsiung Medical University Hospital (KMUH109-9M37) and Kaohsiung Municipal Ta-Tung
Hospital (KMTTH-108-04).
Author contributions
C.-Y.L. and K.-L.L. have contributed equally for patient recruitment, manuscript writing, project development;
C.-R.K., Y.-Y.L. assisted in data acquisition, C.-R.S. and H.-H.H. is responsible for manuscript editing, Z.-X.L.
assisted in statistical analysis and while Y.-C.L. conducted the statistical analysis and project development.
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Competing interests
The authors declare no competing interests.
Additional information
Correspondence and requests for materials should be addressed to Y.-C.L.
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