Platelet-rich Plasma in Gynecological Cases and Female Infertility

Ruchika Garg¹, Neharika Malhotra², Anushree Rawat³

^1,3Department of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh, India
²Department of Obstetrics and Gynecology, Rainbow Hospital, Agra, Uttar Pradesh, India

Corresponding Author: Anushree Rawat, Department of Obstetrics and Gynecology, SN Medical College, Agra, Uttar Pradesh, India, Phone: +91 9826702138, e-mail: anushree.jain10@gmail.com

How to cite this article Garg R, Malhotra N, Rawat A. Platelet-rich Plasma in Gynecological Cases and Female Infertility. J South Asian Feder Obst Gynae 2020;12(3):119–121.

Source of support: Nil

Conflict of interest: None

INTRODUCTION

Platelet-rich plasma (PRP) is an innovative treatment designed to stimulate cellular regeneration, neovascularization, and healthy cell formation.

Autologous PRP is derived from an individual’s whole blood and then centrifuged to remove red blood cells. The remaining plasma has a 5- to 10-fold higher concentration of growth factors than whole blood. These growth factors have been found to promote natural healing responses by researchers across multiple specialties, such as dentistry, dermatology, urology, and gynecology.^1,2

The theory underlying this treatment modality was derived from natural healing processes, as the body’s first response to tissue injury is to deliver platelets to the injured area. Platelets promote healing and attract stem cells to the site of the injury.

PHYSIOLOGICAL ROLE OF PRP

Platelets contain high concentrations of cytokines and growth factors stored within α-granules.³ These growth factors include platelet-derived growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived angiogenic factor, transforming growth factor β, fibroblast growth factor, epidermal growth factor, connective tissue growth factor, and interleukin 8. In addition to growth factors, platelets contain other substances, such as fibronectin, vitronectin, and sphingosine 1-phosphate, that initiate wound healing⁴ (Flowchart 1 and Fig. 1).

Growth factors promote wound healing by initiating the following stages:

Tissue necrosis resolution
Chemotaxis
Cell regeneration
Cell proliferation and migration
Extracellular matrix synthesis
Remodeling
Angiogenesis
Epithelialization⁵

PREPARATION

The following steps present a representative method of preparing PRP:

Venous blood (15–50 mL) is drawn from the patient’s arm in anticoagulant-containing tubes.
The recommended temperature during processing is 21°C to 24°C to prevent platelet activation during centrifugation of the blood.
The blood is centrifuged at 1,200 rpm for 12 minutes.
The blood separates into three layers: an upper layer that contains platelets and white blood cells, an intermediate thin layer (the buffy coat) that is rich in white blood cells, and a bottom layer that contains red blood cells (Fig. 2).
The upper and intermediate buffy layers are transferred to an empty sterile tube. The plasma is centrifuged again at 3,300 rpm for 7 minutes to help with the formation of soft pellets (erythrocytes and platelets) at the bottom of the tube.
The upper two-thirds of the plasma is discarded because it is platelet-poor plasma.
Pellets are homogenized in the lower third (5 mL) of the plasma to create the PRP.
The PRP is now ready for injection.

The stages of this process can be outlined in the following order:

Step 1–Collection of blood from the patient
Step 2–Separation of platelet-rich plasma
Step 3–Processing the separated autologous plasma
Step 4–Injecting the patient with PRP

Fig. 1: Mechanism of action of PRP in the body

Fig. 2: Stepwise preparation of PRP

Flowchart 1: Physiological role of PRP

TYPES OF PRP

PRP preparations can be classified according to the preparation method, the content of the sample, and the proposed application. Preparations vary in terms of centrifugation speed, centrifugation time, and anticoagulant use, while the content varies depending on the predominant constituent (e.g., platelets, leukocytes, or growth factors).⁶

After centrifugation of whole blood, four types of preparations can be obtained as shown in Table 1. This classification was proposed by Dohan Ehrenfest et al.,⁷ and is based on cell content and fibrin density. This classification was recommended by a multidisciplinary consensus committee.⁸

PRP in Gynecology and Reproductology

Platelet-rich plasma therapy has slowly started to replace antibiotics as a main form of treatment in these two fields. The reason for this is that antibiotics can only block infection triggers, while PRP can also eliminate the consequences that were brought upon a patient by an infection. Because of that, PRP can be used for the treatment of chronic gynecological and reproductive diseases. Also, the results of the therapy kick in quicker and last longer. Platelets can have a positive effect on patients suffering from the following conditions:

**Table 1**: PRP classification was proposed by Dohan Ehrenfest et al.⁷
Preparation	Acronym	Leukocytes	Fibrin density
Pure platelet-rich plasma	P-PRP	Poor	Low
Leukocyte- and platelet-rich plasma	L-PRP	Rich	Low
Pure platelet-rich fibrin	P-PRP	Poor	High
Leukocyte- and platelet-rich fibrin	L-PRP	Rich	High

Lichen sclerosus
Vulvodynia
Vaginismus
Chronic endometritis
Vaginal dryness
Lichen planus
Vestibulitis
Leukoplakia of the cervix
Kraurosis vulvae
Gynecologic inflammations
Chronic endocervicitis and exocervicitis
Cervical erosion
As an alternative therapeutic method in the cases of chronic endometritis and endometriosis. These diseases can initiate inflammation processes that can make embryo implantation difficult in both natural pregnancy and in vitro fertilization (IVF) cycles. Application of the PRP injections helps to eliminate inflammation processes in the uterus as well as enhance the activity of the progesterone receptors that stimulates proper growth of the endometrium and, in turn, help to the implantation of the embryos. After this therapy, it is possible to continue IVF treatment with better results.
In the cases of ovarian failure syndrome, PRP treatment fosters ovarian rejuvenation. If to inject PRP into the ovaries of menopausal and perimenopausal women, it is possible to restart menstrual cycle, which makes it possible to receive and then fertilize the eggs that produced women’s ovaries.
Role in infertility–PRP is used in a number of fertility treatments including intrauterine injection and IVF to assist with and improve egg quantity/quality and improve uterine lining thickness/enhance endometrial receptivity during an embryo transfer. It is most often used in those who have undergone multiple IVF cycles with a history of recurrent implantation failure (RIF), a condition in which multiple IVF transfers do not result in pregnancy, despite high-quality embryos being transferred on multiple occasions. PRP is usually tried before turning to donor egg IVF but may be used alongside donor egg cycles along with other supporting treatments focusing on reproductive immunology.
Innovative PRP treatment of the testicles helps those men who are diagnosed with infertility to have their own children.Indications:
Oligozoospermia %3C;10 million/mL
FSH %3E; 10, normal or low testosterone level
Testicular ultrasound—normal or diffusely altered echogenicity, not including patients with local formations or diffuse microcalcinosis.
Negative tumor markers (LDH), alpha-fetoprotein, free HCG
Normal karyotype, negative microdeletions of the Y chromosome (oligozoospermia <5 million/mL).

PRP in Cervical Ectopy

Hua et al.⁹ conducted a randomized clinical study to compare the effectiveness of autologous PRP application to that of laser treatment for benign cervical ectopy. They applied PRP twice on the area of cervical erosion with a 1-week interval in 60 patients, while laser treatment was used in the other 60 patients. They found that the complete cure rate was 93.7% in the PRP group and 92.4% in the laser group (p value > 0.05). The mean time to re-epithelialization was significantly shorter in the PRP group (p value < 0.01). The rate of adverse treatment effects (i.e., vaginal discharge or vaginal bleeding) was much lower in the PRP group than in the laser group (p value < 0.01). They concluded that autologous PRP application appeared promising for the treatment of cervical ectopy in symptomatic women, as it yielded a shorter tissue healing time and milder adverse effects than laser treatment.

CONCLUSION

Platelets are foundational in many of the body’s functions, especially where the mucosa or skin is concerned. PRP is the ultimate “body’s own” physiological product because it comes from the patient herself, it is safer, and more natural than animal-derived or human donated products.

REFERENCES

1. Everts PA, Hoogbergen MM, Weber TA, et al. Is the use of autologous platelet-rich plasma gels in gynecologic, cardiac, and general, reconstructive surgery beneficial? Curr Pharm Biotechnol 2012;13(7):1163–1172. DOI: 10.2174/138920112800624346.

2. Lai LP, Stitik TP, Foye PM, et al. Use of platelet-rich plasma in intra-articular knee injections for osteoarthritis: a systematic review. PM R 2015;7(6):637–648. DOI: 10.1016/j.pmrj.2015.02.003.

3. Jo CH, Roh YH, Kim JE, et al. Optimizing platelet-rich plasma gel formation by varying time and gravitational forces during centrifugation. J Oral Implantol 2013;39(5):525–532. DOI: 10.1563/AAID-JOI-D-10-00155.

4. International Cellular Medicine Society. Platelet Rich plasma (PRP) guidelines [Internet] Las Vegas: International Cellular Medicine Society; 2011. [cited 2018 Jun 18]. Available from: http://www.cellmedicinesociety.org/icms-guidelines/guidelines.

5. Sundman EA, Cole BJ, Karas V, et al. The anti-inflammatory and matrix restorative mechanisms of platelet-rich plasma in osteoarthritis. Am J Sports Med 2014;42(1):35–41. DOI: 10.1177/0363546513507766.

6. Anitua E, Sanchez M, Orive G. The importance of understanding what is platelet-rich growth factor (PRGF) and what is not. J Shoulder Elbow Surg 2011;20(1):e23–e24. DOI: 10.1016/j.jse.2010.07.005.

7. Dohan Ehrenfest DM, Andia I, Zumstein MA, et al. Classification of platelet concentrates (platelet-rich plasma-PRP, platelet-rich fibrin-PRF) for topical and infiltrative use in orthopedic and sports medicine: current consensus, clinical implications and perspectives. Muscles Ligaments Tendons J 2014;4(1):3–9. DOI: 10.32098/mltj.01.2014.02.

8. Ehrenfest DMD, Bielecki T, Mishra A, et al. In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes. Curr Pharm Biotechnol 2012;13(7):1131–1137. DOI: 10.2174/138920112800624328.

9. Hua X, Zeng Y, Zhang R, et al. Using platelet rich plasma for the treatment of symptomatic cervical ectopy. Int J Gynaecol Obstet 2012;119(1):26–29. DOI: 10.1016/j.ijgo.2012.05.029.

________________________
© The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.