A Pilot Study Efectiveness of Local APRP in SUI

Download as pdf or txt
Download as pdf or txt
You are on page 1of 8

www.nature.

com/scientificreports

OPEN A pilot study: effectiveness


of local injection of autologous
platelet‑rich plasma in treating
women with stress urinary
incontinence
Cheng‑Yu Long1,2,8,9, Kun‑Ling Lin2,3,9, Chin‑Ru Shen2, Chin‑Ru Ker2, Yi‑Yin Liu1,8, Zi‑Xi Loo2,
Hui‑Hua Hsiao4 & Yung‑Chin Lee5,6,7,8*

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]

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 1

Vol.:(0123456789)
www.nature.com/scientificreports/

Mean age (years) 44.5 ± 9.1


Mean parity 1.6 ± 0.5
Mean BMI (kg/m2) 22.7 ± 6.3
Pad test 5.8 ± 3.6
Menopause 5 (25.0)
SUI grade (ICIQ-SF)
Mild 1 (5.0)
Modetate 12 (60.0)
Severe and very severe 7 (35.0)
Follow up (months) 6

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

Table 2.  Questionnaire results at baseline and 1, 6 months post-treatment. Tx treatment, ICIQ-SF


International Consultation on Incontinence Questionnaire-Short Form, UDI-6 Urogenital Distress Inventory,
IIQ-7 Incontinence Impact Questionnaire, OABSS Overactive Bladder Symptom Scores, POPDI-6 Pelvic
Organ Prolapse Distress Inventory 6. Values are expressed as median (range). *Statistical significance;
Wilcoxon signed rank test.

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

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 2

Vol:.(1234567890)
www.nature.com/scientificreports/

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

SUI, stress urinary inconnence; PRP, platelet-rich plasma.

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.

Parameters Pre-op (n = 8) Post-op (n = 8) P value #


Qmax (ml/s) 29.8 ± 5.4 33.7 ± 4.1 0.08
RU (ml) 9.7 ± 5.1 46.7 ± 13.4 0.028 §
FS (ml) 135.8 ± 42.5 163.8 ± 17.0 0.001 §
MCC(ml) 428.0 + 21.5 408.8 ± 41.1 0.17
Pdet ­(cmH2O) 24.5 ± 5.4 23.8 ± 5.8 0.52
FUL (mm) 24.8 ± 6.2 25.4 ± 6.8 0.22
MUCP ­(cmH2O) 65.5 ± 9.8 54.1 ± 21.5 0.14

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).

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 3

Vol.:(0123456789)
www.nature.com/scientificreports/

Pre-treatment 6 months post-treatment P value


FSFI total scores 17.9 ± 10.2 20.3 ± 11.0 0.25
Desire (1, 2) 2.7 ± 1.3 2.7 ± 1.2 0.79
Arousal (3–6) 2.6 ± 1.8 2.9 ± 0.9 0.46
Lubrication (7–10) 3.2 ± 2.1 3.5 ± 2.1 0.34
Orgasm (11–13) 3.0 ± 1.9 3.4 ± 2.1 0.35
Satisfaction (14–16) 3.2 ± 2.0 3.8 ± 2.3 0.13
Pain (17–19) 3.2 ± 2.0 3.9 ± 2.4 0.11

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.

Age < 40 (n = 8) Age > 40 (n = 12)


Domains Pre-op Post-op P value* Pre-op Post-op P value* Intergroup P value^
Sexual desire 2.6 ± 1.4 2.9 ± 1.2^ 0.03** 2.8 ± 1.3 2.3 ± 1.1^ 0.014** Pa
Sexual arousal 2.5 ± 1.7 3.2 ± 1.2^ 0.19 3.7 ± 1.0 3.0 ± 1.3^ 0.029** Pb
Lubrication 3.5 ± 1.8 4.3 ± 1.1^ 0.30 4.0 ± 1.5 3.6 ± 2.0^ 0.23 Pc
Orgasm 2.8 ± 1.5 3.6 ± 1.6^ 0.27 4.2 ± 1.3 4.1 ± 1.7^ 0.71 Pd
Satisfaction 3.1 ± 1.7 4.2 ± 1.7^ 0.22 4.4 ± 1.3 4.5 ± 1.9^ 0.77 Pe
Dyspareunia 3.8 ± 1.7 4.7 ± 1.2^ 0.24 3.4 ± 1.6 3.7 ± 2.3^ 0.39 Pf
Total scores 18.3 ± 8.5 22.8 ± 6.7^ 0.21 24.3 ± 6.1 24.1 ± 6.7^ 0.89 Pg

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

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 4

Vol:.(1234567890)
www.nature.com/scientificreports/

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.

Material and methods


From June 2018 to November 2018, females with SUI (involuntary loss of urine on effort or physical exertion or
on sneezing or coughing), age over 20 years old, the platelet counts within normal limit (150 k–450 k/uL) and
Prothrombin Time (PT) was normal, were offered the innovative treatment of autologous platelet-rich plasma
(A-PRP) injections. The study employed a prospective interventional design. A total number of 20 consecutive
patients consented to enter the trial with full awareness of the experimental nature and treatment process without
compensations in any form. The treatment utilizes autologous material that poses minimal adverse reactions
to the patients.
The Institutional Review Board (IRB) Committee of Kaohsiung Medical niversity Hospital approved this
research (IRB Number: KMUHIRB-F (I)-20170048) and confirmed that all methods were performed in accord-
ance with the relevant guidelines and regulations. This clinical trial was registered in a publically accessible
primary register that participates in the WHO International Clinical Trial Registry Platform with Clinical trial
registration number ID: NCT04279210) and date of registration (21/02/2020). All procedures involving human
participants were in accordance with the ethical standards of Institutional Review Board of Kaohsiung Medi-
cal University Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical
standards. Patients with the following conditions were excluded from the study: known platelet dysfunction,
critical thrombocytopenia, hypofibrinogenemia, hemodynamic instability, sepsis, acute or chronic infections,
chronic liver disease, anti-coagulant users and known malignancy (Fig. 2). They did not receive concurrent
treatment for SUI during the study period.
The study employed commercialized PRP kit from RegenKit (Regenlab, Le Mont-sur-Lausanne, Switzerland).
PRP was prepared according to the standardized procedures instructed by the kit. Two tubes preloaded with
anticoagulant additive were used to collect individual patient’s whole blood, 10 mL each. The content was mixed
by inverting the tubes gently 4–5 times. The tubes were centrifuged at 3400 rpm for 15 min. After centrifugation,
three-layered content was noted with platelet pellet, separating gel and red blood cells from top to bottom in
order. Platelet pellet was remixed with the supernatant by inverting the tubes gently for 5–10 times. The super-
natant then was collected in a 5-mL Luer-Lock syringe. The yielded volume was approximately 5 mL from each
tube. The Regen system was specifically designed to produce APRP with a platelet concentration of 1.6X. With
a 27-gauge needle, PRP was injected into the anterior vaginal mucosa around the patient’s mid-urethra, which
was approximately 1 cm below the urethra meatus with a depth about 1.5 cm. Two mL underneath mid-urethra
and 1.5 mL for each side of urethra (Fig. 3). No anesthesia was used in this procedure. Monthly treatment was
given for 3 consecutive months.
Before enrollment, the patients signed informed consent for participation. The primary outcome was the
degree of SUI relief, while the secondary outcome assesses sexual function. Urodynmaic studies were scheduled
for them before and 6 months after treatment. Questionnaires that assess the severity of their urinary inconti-
nence and sexual dysfunction were distributed. Specifically, they were asked to fill out OABSS, UDI-6, IIQ-7,
ICIQ-SF, POPDI-6 and FSFI questionnaires. ICIQ-SF was the primary tool for assessing SUI severity, which was
categorized into slight, moderate, severe and very severe according to the total points obtained after answering the

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 5

Vol.:(0123456789)
www.nature.com/scientificreports/

Enrollment Females with stress urinary inconnence,

Age over 20 years old,

Normal platelet counts (150k~450k/μL) Normal


Excluded
prothrombin me.
 Platelet dysfuncon
 Thrombocytopenia
 Hypofibrinogenemia
 Hemodynamic instability
 Sepsis
 Acute or chronic infecons
 Chronic liver disease
 Ancoagulant users
 Malignancy

Allocaon 20 consecuve paents were


allocated to platelet-rich plasma
injecon. (n=20)

Follow-up Complete follow-up at 1 month and Complete follow-up at 6 months


6 months
 FSFI (n=20)
 ICI-Q SF, UDI-6, IIQ-7, and  Urodynamic study (n=8)
OABSS (n=20)

Figure 2.  The clinical trial flowchart for platelet-rich plasma injection.

Figure 3.  Diagram of the injection site and depth over anterior vaginal mucosa.

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 6

Vol:.(1234567890)
www.nature.com/scientificreports/

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.

Received: 1 February 2020; Accepted: 22 December 2020

References
1. Andia, E., Rubio-Azpeitia, J., Martin, I. & Abate, M: Current concepts and translational uses of platelet rich plasma biotechnology.
In Biotechnology (ed. Ekinci, D.) (InTech, 2015). https​://doi.org/10.5772/59954​. https​://www.intec​hopen​.com/books​/biote​chnol​
ogy/curre​nt-conce​pts-and-trans​latio​nal-uses-of-plate​letri​ch-plasm​a-biote​chnol​ogy.
2. Alves, R. & Grimalt, R. A review of platelet-rich plasma: history, biology, mechanism of action, and classification. Skin Appendage
disord. 4, 18–24. https​://doi.org/10.1159/00047​7353 (2018).
3. Guevara-Alvarez, A., Schmitt, A., Russell, R. P., Imhoff, A. B. & Buchmann, S. Growth factor delivery vehicles for tendon injuries:
mesenchymal stem cells and platelet rich plasma. Muscles Ligaments Tendons J. 4, 378–385 (2014).
4. Matz, E. L., Pearlman, A. M. & Terlecki, R. P. Safety and feasibility of platelet rich fibrin matrix injections for treatment of common
urologic conditions. Investig. Clin. Urol. 59, 61–65. https​://doi.org/10.4111/icu.2018.59.1.61 (2018).
5. Moutray, T. et al. Different lasers and techniques for proliferative diabetic retinopathy. Cochrane Database Syst. Rev. 3, CD012314.
https​://doi.org/10.1002/14651​858.CD012​314.pub2 (2018).
6. Fanning, J. et al. Phase I/II prospective trial of autologous platelet tissue graft in gynecologic surgery. J. Min. Invas. Gynecol. 14,
633–637. https​://doi.org/10.1016/j.jmig.2007.05.014 (2007).
7. Hunskaar, S., Burigio, K., Diokno, A. C., Herzog, A. R., Hjalmas, K. & Lapitan, M. C. Epidemiology and natural history of urinary
incontinence. In Incontinence: 2nd International Consultation on Incontinence. Recommendations of the International Scientific
Committee: The Evaluation and Treatment of Urinary Incontinence. Paris, 1–3 July 2001 (ed. Abrams, P., Cardozo, L., Khoury, S. &
Wein, A.) Medline: 20304 (Health Publication Ltd, Plymouth, UK, 2002).
8. Kunkle, C. M. et al. Cost utility analysis of urethral bulking agents versus midurethral sling in stress urinary incontinence. Female
Pelvic Med. Reconstr. Surg. 21, 154–159. https​://doi.org/10.1097/spv.00000​00000​00017​3 (2015).
9. Capobianco, G. et al. Management of female stress urinary incontinence: a care pathway and update. Maturitas 109, 32–38. https​
://doi.org/10.1016/j.matur​itas.2017.12.008 (2018).
10. Petros, P. E. & Ulmsten, U. I. An integral theory of female urinary incontinence, experimental and clinical considerations. Acta
Obstet. Gynecol. Scand. Suppl. 153, 7–31 (1990).
11. Nikolopoulos, K. I., Pergialiotis, V., Perrea, D. & Doumouchtsis, S. K. Restoration of the pubourethral ligament with platelet rich
plasma for the treatment of stress urinary incontinence. Med. Hypotheses 90, 29–31. https​://doi.org/10.1016/j.mehy.2016.02.019
(2016).
12. Runels, C., Melnick, H., Debourbon, E. & Roy, L. A pilot study of the effect of localized injections of autologous platelet rich plasma
(PRP) for the treatment of female sexual dysfunction. J. Women’s Health Care 3, 169 (2014).
13. Hua, X. et al. Using platelet-rich plasma for the treatment of symptomatic cervical ectopy. Int. J. Gynaecol. Obstet. Off. Organ Int.
Fed. Gynaecol. Obstet. 119, 26–29. https​://doi.org/10.1016/j.ijgo.2012.05.029 (2012).
14. Behnia-Willison, F. et al. Use of platelet-rich plasma for vulvovaginal autoimmune conditions like lichen sclerosus. Plast. Reconstr.
Surg. Glob. Open 4, e1124. https​://doi.org/10.1097/gox.00000​00000​00112​4 (2016).
15. Bodner-Adler, B., Hanzal, E., Pablik, E., Koelbl, H. & Bodner, K. Management of vesicovaginal fistulas (VVFs) in women follow-
ing benign gynaecologic surgery: a systematic review and meta-analysis. PLoS ONE 12, e0171554. https​://doi.org/10.1371/journ​
al.pone.01715​54 (2017).
16. Chrysanthopoulou, E. L. et al. Platelet rich plasma as a minimally invasive approach to uterine prolapse. Med. Hypotheses 104,
97–100. https​://doi.org/10.1016/j.mehy.2017.05.018 (2017).
17. Einarsson, J. I., Jonsdottir, K. & Mandle, R. Use of autologous platelet gel in female pelvic organ prolapse surgery: a feasibility study.
J. Min. Invas. Gynecol. 16, 204–207. https​://doi.org/10.1016/j.jmig.2008.12.012 (2009).
18. White, Y. A. et al. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat. Med.
18, 413–421. https​://doi.org/10.1038/nm.2669 (2012).
19. Colombo, G. V. L. et al. Use of platelet rich plasma in human infertility. J. Biol. Regul. Homeost. Agents 31, 179–182 (2017).
20. Lewi, L. et al. In vitro evaluation of the ability of platelet-rich plasma to seal an iatrogenic fetal membrane defect. Prenat. Diagn.
29, 620–625. https​://doi.org/10.1002/pd.2249 (2009).
21. Tehranian, A. et al. Application of autologous platelet-rich plasma (PRP) on wound healing after caesarean section in high-risk
patients. Iran. Red Crescent Med. J. 18, e34449. https​://doi.org/10.5812/ircmj​.34449​ (2016).
22. Lin, K. L., Chou, S. H. & Long, C. Y. Effect of Er:YAG laser for women with stress urinary incontinence. Biomed. Res. Int. 15,
7915813 (2019).
23. Behnia-Willison, F. et al. Promising impact of platelet rich plasma and carbon dioxide laser for stress urinary incontinence. Eur.
J. Obstet. Gynecol. Reprod. Biol. X 5, 100099 (2019).
24. Klovning, A., Avery, K., Sandvik, H. & Hunskaar, S. Comparison of two questionnaires for assessing the severity of urinary
incontinence: the ICIQ-UI SF versus the incontinence severity index. Neurourol. Urodyn. 28, 411–415. https​://doi.org/10.1002/
nau.20674​(2009).

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.

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 7

Vol.:(0123456789)
www.nature.com/scientificreports/

Competing interests
The authors declare no competing interests.

Additional information
Correspondence and requests for materials should be addressed to Y.-C.L.
Reprints and permissions information is available at www.nature.com/reprints.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and
institutional affiliations.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International
License, which permits use, sharing, adaptation, distribution and reproduction in any medium or
format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons licence, and indicate if changes were made. The images or other third party material in this
article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this licence, visit http://creat​iveco​mmons​.org/licen​ses/by/4.0/.

© The Author(s) 2021

Scientific Reports | (2021) 11:1584 | https://doi.org/10.1038/s41598-020-80598-2 8

Vol:.(1234567890)

You might also like