PRP in Gynaecology Presenter – Dr Sakshi Sharma Moderator – Dr Tapasya Dhar
INTRODUCTION Platelet-rich plasma (PRP) is a non - operative treatment option for a spectrum of medical disorders. It is being widely used in orthopedic and sports medicine to relieve pain in musculoskeletal diseases such as tendonitis, arthritis, ligament sprains, and tears. Resulting in exceptional healing, a rapid return to regular activities, and complete pain relief It is also widely used in Dermatology But there are limited experiences for the use of PRP to treat gynecological disorders.
WHAT IS PRP ? Autologous - derived from an individual's whole blood, then centrifuged to remove RBCs. The remaining plasma has a 5 – 10 folds higher concentration of growth factors than whole blood. These growth factors promote natural healing responses. The theory is derived from natural healing processes, as the body's first response to tissue injury is to deliver platelets to the injured area. Platelets attract stem cells to the site of the injury and promote healing .
SCIENCE OF PRP PRP preparation Types of PRP preparations PRP composition and activation Mechanisms of action of PRP
PRP PREPARATION Multiple methods developed, with variation in the speed and timing of centrifugation The preparation of PRP is an outpatient procedure that involves a Approximately 30 mL of venous blood yields 3 – 5 mL of PRP PRP stimulates a series of biological responses, and the injection site may become swollen, painful and scarred for roughly 3 days. blood draw preparation of PRP injection of PRP into the diseased area.
STEPS 1) venous blood ( 15–50 mL ) taken in anticoagulant-containing tubes ; 2) the blood is centrifuged at 1,200 rpm for 12 min, recommended temp is 21℃ – 24℃ to prevent platelet activation
3) the blood separates into three layers : Upper - Platelets, WBCs intermediate, thin - Buffy coat - WBCs bottom - RBCs 4) the upper and intermediate buffy layers are transferred to an empty sterile tube
5) The plasma is centrifuged again at 3,300 rpm - 7 minutes leads to formation of soft pellets (erythrocytes and platelets) at the bottom of the tube
6) The upper two-thirds of the plasma is discarded because it is platelet-poor plasma 7) pellets are homogenized in the lower third (5 mL) of the plasma to create the PRP 8) The PRP is now ready for injection
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Types of PRP preparations 1) This classification is based on cell content and fibrin density. After centrifugation of whole blood, four types of preparations can be obtained
2) DEPA - dose of injected platelets, efficiency of production, purity of the PRP, activation of the PRP
PRP composition and activation Platelets contain high concentrations of cytokines and growth factors stored within α-granules . Platelets contain other substances, such as, that initiate wound healing GROWTH FACTORS PDGF, insulin-like growth factor, VEGF, platelet-derived angiogenic factor, transforming growth factor beta, fibroblast growth factor, epidermal growth factor, connective tissue growth factor, and interleukin-8 OTHERS fibronectin, vitronectin, and sphingosine 1-phosphate
Platelet activation triggers the release of these growth factors by a variety of substances or stimuli such as thrombin, calcium chloride, and collagen.
MECHANISM The mechanisms of PRP have not been completely elucidated Growth factors promote wound healing by initiating the following stages tissue necrosis cell proliferation angiogenesis migration cell regeneration chemotaxis extracellular matrix synthesis remodeling epithelialization.
PRP is superior to recombinant human growth factor As platelet activation leads to the release of multiple growth factors and differentiation factors.
PRP in Gynaecological disorders
GYNAECOLOGICAL CONDITIONS Cervical ectopy Vulvar dystrophy Reconstructive surgery for vulvar cancer Skin lesions and wound healing Urogenital disorders genital fistulae genital prolapse and urinary incontinence Reproductive medicine premature ovarian failure ovarian torsion refractory endometrium repeated implantation failure PPROM Aesthetic gynaecology breast reconstruction female sexual dysfunction 1) O-Shot therapy 2) Vaginal rejuvenation
PRP in Cervical Ectopy . Hua et al. conducted a randomized clinical study to compare the effectiveness of PRP application PRP was applied twice on the area of cervical erosion within a week interval complete cure rate was higher re-epithelialization mean time shorter The rate of adverse treatment effects (i.e., vaginal discharge or vaginal bleeding) was much lower Laser treatment complete cure rate was lesser mean time longer concluded that PRP application is promising in cervical ectopy, as it yielded a shorter tissue healing time and milder adverse effects than laser treatment.
PRP in Vulvar Dystrophy extensive scarring progressive loss of the labia minora sealing of the clitoral hood burying of the clitoris Lichen Sclerosis affects the vulva pruritus disturbing physical activity, sexual pleasure, emotional and psychological problems dyspareunia genital bleeding . treated by topical and systemic corticosteroids.
Behnia-Willison et al. injected PRP into the vulva in a fanning pattern in cases of LS resistant to steroid therapy . Patients received three PRP treatments 4 weeks apart. Nearly ALL patients exhibited clinical improvements in the size of their lesions , and in 28.6% of the patients, the lesions disappeared completely after PRP treatment. Minimal pain and no complications were reported. concluded that PRP injections could be considered an effective therapy for LS.
PRP in reconstructive surgery for vulvar cancer . Morelli et al. conducted a study of patients who underwent surgery for vulvar cancer (radical vulvectomy) to evaluate the efficacy Platelet gel application Platelet gel placed after radical surgery on the vaginal breach during reconstructive surgery lower rates of wound infection, necrosis of vaginal wounds, and wound breakdown postoperative fever rate a shorter hospital stay, faster wound healing Only radical surgery Underwent only surgical treatment higher rates of adverse effects a longer hospital stay, Slower wound healing They concluded that platelet gel application during vulvar reconstruction represented an effective strategy for preventing wound breakdown after surgery to treat locally advanced vulvar cancer
PRP in skin lesions and wound healing Due to the ability of PRP to promote angiogenesis and wound healing , PRP was tested in wound healing in high-risk women undergoing cesarean sections . A greater reduction in the redness, edema, ecchymosis, discharge was found and was effective for pain reduction They concluded that PRP was an effective approach for wound healing
PRP in UROGENITAL DISORDERS
PRP in Genital Fistulae PRP has been tried in the treatment of VVF as a minimally invasive approach for the closure of genital fistulae . Shirvan et al. injected PRP around the edges of fistula into the tissue, and platelet-rich fibrin (PRF) glue was interpositioned in the tract. Cystography Physical examination
After 6 months 11/12 patients were clinically cured , with normal findings on transvaginal physical examinations and cystography. concluded that PRP injection and PRF glue interposition offered a safe, effective, and novel minimally invasive approach for the treatment of vesicovaginal fistulae that obviated the need for open surgery.
PRP in genital prolapse Both absorbable and non - absorbable vaginal implants used in pelvic floor reconstructive procedures have numerous adverse effects.
PRF is a mixture of Gorlero et al. in a study of 10 women requiring surgery for prolapse recurrence (stage II or higher ) injected PRF after operating platelets Leukocytes, cytokines, stem cells optimal for stimulating fibroblast migration and proliferation. causes rapid remodeling and connective tissue growth after vaginal surgery
Success rate was 80% with complete symptom relief. Sexual activity increased by 20% without dyspareunia. PRP restores the anatomy and function of pelvic ligaments They concluded that the use of PRF for site-specific prolapse repair was associated with good functional outcomes.
PRP in REPRODUCTIVE MEDICINE
PRP in premature ovarian failure Premature ovarian failure (POF) refers to loss of normal function of the ovaries < 40 years loss of fertility. Treatment with PRP is referred to as OVARIAN REJUVENATION ; in this, PRP is injected into the ovary under USG guidance , similarly to ovum retrieval in IVF.
This modality of treatment is still being investigated in trials. Pantos et al. injected PRP in 8 POF women with poor ovarian reserve. They found successful ovarian rejuvenation 1–3 months after PRP treatment with follicles of 15.20 ± 2.05 mm in diameter.
PRP in ovarian torsion In an animal model , subjected to bilateral adnexal torsion and ischemia for 3 hours. Intraperitoneal PRP was administered 30 min prior to ischemia in one group, while the other group was not injected with PRP. Detorsion was then done, and oxidative stress levels, histopathological changes, and reperfusion injuries were lower in the PRP group than in the other group. The researchers concluded that PRP was effective for the prevention of ischemia and reperfusion damage in rat ovary
PRP in refractory endometrium The endometrium plays an important role in achieving optimal outcomes of ARTs. Endometrial growth following inadequate ovarian stimulation may be insufficient, leading to poor results of IVF/ICSI cycles. PRP is a novel therapy to improve ET , especially in resistant cases. Colombo et al. injected PRP in 8 patients, the ET was satisfactory in 7 cases. A positive test for beta- HCG was found in 6 women. They concluded that the multiple implantation failures were caused by inefficient expression of adhesion molecules, which could potentially be improved by PRP application .
PRP in repeated implantation failure Repeated implantation failure (RIF) - failure to conceive following several embryo transfers in IVF cycles. Numerous factors are involved in implantation process, including embryo quality, endometrial receptivity, and immunological factors Several methods have been suggested for RIF management Recently, the intrauterine infusion of PRP has been described as a way to promote endometrial growth and receptivity Nazari et al. enrolled 20 participants with a H/O RIF and reported that 18/20 participants (90%) became pregnant. They concluded that PRP was effective in improving pregnancy outcomes in RIF patients.
PRP in aesthetic gynecology
PRP in breast reconstruction PRP together with adipose tissue has been used in breast reconstruction. Gentile et al. ,. 100 patients , aged 19 - 60 years affected by breast soft-tissue defects Study group Control group treated with fat grafting and PRP fat grafting injections only 69% 39% maintenance rate restored contour and of three-dimensional volume after 1 year concluded that PRP mixed with fat grafts led to improvements in the maintenance of breast volume in patients affected by breast soft-tissue defects.
PRP in female sexual dysfunction ( 1 ) O-SHOT THERAPY PRP use in sexual dysfunction is a revolutionary new non-surgical outpatient treatment improve both urinary incontinence and sexual dysfunction through using a woman's own growth factors . The PRP is injected into specific areas of the vagina with the aid of local anesthetic cream. This modality of treatment is called the “O-shot.” PRP immediately activates tissue regeneration , and the enhancement in sexual response . The desired response includes improved arousal, stronger orgasm, decreased dyspareunia, and increased natural lubrication.
2 ) VAGINAL REJUVENATION Aesthetic practitioners have used PRP for the regeneration o f vaginal mucosa, muscles, and skin. After PRP injection, vaginal vascularity is increased , with a subsequent dramatic increase in sensitivity. The skin becomes thicker and firmer , making the vagina look much more youthful. Also, the ligaments and muscles supporting the urethra become stronger, alleviating urinary incontinence . concluded that the application of autologous lipofilling mixed with PRP in a patient with vaginal atrophy produced relief of symptoms and contour restoration.
PRP in premature rupture of membranes PPROM occurs due to damage and tears in the fetal membrane PRP was tried in an in vitro model The PRP plug was stable and attached firmly to the amnion tear. Experimental evidence that a PRP plug persisted for nearly 2 months in an amniotic fluid environment. It provided waterproof sealing of iatrogenic defects in the amnion and chorion. Moreover, PRP stimulates cell growth and proliferation , and may thereby enhance the membrane-healing response.
PROCEDURE After counselling the patient, tell her to empty the bladder Preferably local numbing cream is used (Benzocaine, Lidocaine) Then the PRP injection is given at the desired site The procedure takes less than 5 minutes A course of 2- 4 procedures is recommended which varies according to the patient.
CONTRAINDICATIONS Acute Infectious Diseases Viral Hepatitis B and C Systemic Diseases H/O oncology Allergic reactions to anticoagulants Blood clotting disorders Immun o-suppressive conditions Pregnancy Lactation Age < 18 years
SIDE EFFECTS PRPs rarely have side effects, even if the patient has drug allergies can safely opt the procedure COMMON SIDE EFFECTS Pain or discomfort at the injection site Swelling and inflammation Dizziness or lightheadednes
RECOMMENDATIONS Sexual Abstinence for 3 days Abstrain from regular bathing, can take steam baths Use cotton undergarments till 5 days after PRP Avoid NSAIDs like Ibuprofen, Naproxen; can use acetaminophen for pain relief Avoid Corticosteroids
BENEFITS OF PRP Minimum contraindications as the PRP uses the own blood Risk of Allergy and rejection is excluded Outpatient Procedure Can be performed immediately, takes ~ 30 minutes Doesn’t require FDA approval as it is not a medicine or device, comes from patient’s own body
CONCLUSION PRP is an innovative, non-invasive therapeutic modality It is affordable, simple, easily performed, and effective with minimal side effects. The main issue is not preparation or performance but a woman’s own particular body’s capability to heal using it’s own blood components. In the field of gynecology, the few studies have been conducted Large randomized controlled studies are required to confirm its efficacy and safety in various gynecological disorders.