Infertility is a fairly common condition and it is estimated that about 12 to 15% of all healthy couples are unable to conceive after one year of unprotected sex. 1 This large figure of infertility has led to the development of many alternative methods for conception. Some common ones include in vitro fertilization (IVF), intrauterine insemination (IUI), and zygote intrafallopian transfer, to name a few. The appropriate procedure for a couple is selected based on multiple factors, such as the partner’s fertility status, patency of the sexual organ’s anatomical structure, and the complications that can possibly arise. Each of these assisted fertilization techniques come with their own set of limitations.
Factors Responsible for Infertility
Female factors leading to infertility status include hormonal imbalances and associated disorders, structural abnormalities, implantation failure, and systematic disorders. In males, there can be multiple conditions, such as oligozoospermia, that prevent normal fertilization. When conventional therapy fails in these patients, they opt for assisted reproductive technologies. Despite the active efforts of the couple and multiple attempts of assisted reproductive technologies, sometimes results are not achieved, leaving the couple feeling disheartened and hopeless.
PRP is a Non-operative Option
Platelets-Rich Plasma (PRP) therapy is a novel tool in the field of therapeutic science, used to treat many chronic debilitating conditions that adversely affect the sufferer’s quality of life. It has been effectively used as a standalone therapy to treat several gynecological conditions interfering with conception and male infertility issues as well as an adjunct to assisted reproductive techniques in order to increase the success rate.
What is Platelet-Rich Plasma (PRP) Therapy?
PRP is an effective and promising therapy for the treatment of a multitude of medical conditions in a non-operative outpatient setting. It involves drawing blood, no more than what is required for a routine blood test, followed by PRP preparation and its subsequent injection into the diseased area. The following steps are involved in the preparation of PRP. 2
• Form the patient’s arm, 15-50 ml of venous blood is drawn and collected in an anticoagulant tube.
• The blood is centrifuged for an average of 12 minutes at a speed of 1200 rpm with the temperature ranging between 21℃–24℃, so that platelets are inactivated.
• The blood separates into three layers, an upper layer containing platelets and white blood cells; while, the lower two layers consist of other constituents of blood.
• The upper layer is transferred to a sterile tube and further centrifuged for 7 minutes to form soft pellets, comprising of a collection of erythrocytes (RBCs) and platelets. The upper two-third of this tube is discarded, so that, the only platelet-rich portion is left behind.
• The PRP is ready and can be injected into the site of treatment.
How does PRP work?
PRP is rich in cytokines and growth factors that are stored within α-granules of platelets. Among these, the most important ones are platelet-derived growth factor, insulin-like growth factor, vascular endothelial growth factor, transforming growth factor-beta, platelet-derived angiogenic factor, connective tissue growth factor, epidermal growth factor, and fibroblast growth factor. The presence of these compounds in the PRP makes it potentially beneficial for damaged and destructive tissue. A higher concentration of growth factors in a wounded tissue initiates the following reactions:
• Tissue necrosis resolution
• Chemotaxis
• Cell regeneration, proliferation, and migration
• Extracellular matrix synthesis
• Tissue remodeling
• Angiogenesis
• Epithelization
All these steps are an integral part of tissue repair and recovery. The ability of PRP to activate multiple platelets derived growth factors makes it superior to recombinant human growth factor preparation (laboratory preparation of natural growth factors). 2
Infertility Issues That can be Treated using PRP Therapy
Female Infertility Issues
Physiologically, tissue repair begins with clot formation, followed by platelet degranulation. The growth factors in the platelet granules then speed up the process of healing. The wound-healing properties of PRP are found to be useful in the following gynecological conditions: 2
• Vulvar dystrophy
• Urogenital disorders
• Genital fistulae
• Genital prolapse and urinary incontinence
• Premature ovarian failure
• Ovarian torsion
• Refractory endometriosis
• Repeated implantation failure
• Breast reconstruction
• Female sexual dysfunction
• Premature rupture of membranes
• Ovarian failure syndrome
• Menopausal and perimenopausal disorders
• Endometrial hyperplasia
• Asherman’s syndrome
Male Infertility Issues
PRP can be used successfully to treat multiple male fertility disorders. 3,4 The innovative approach to increase the chance of pregnancy is testicular PRP therapy. The purpose is to activate and enhances the process of spermatogenesis (sperm production). Platelets-derived growth factors initiate the healing process and cell regeneration when injected into the testicular tissue, thereby, activating the spermatogenesis. The indications for PRP in male infertility conditions are:
• Oligozoospermia i.e. sperm concentration is <10 million/ml • Hormonal therapy is not a suitable option • Hormonal therapy has failed to produce any remarkable outcome The Role of PRP in Assisted Reproductive Technologies In addition to being a standalone treatment, PRP is also used to increase the success rate of assisted reproductive technologies. 5 It works by improving egg quality and quantity, increasing uterine lining thickness, and enhancing the receptivity of endometrium (uterine lining), during the transfer of an embryo. The ideal candidates for PRP therapy can be: • Couples with a history of multiple failures with IVF and IUI cycles. • Females who have a history of recurrent implantation failure. 5 • Females who have decreased egg quality or quantity, keeping effective fertilization from happening. At the molecular level, the growth factors increase the endometrial proliferation until it reaches a significant thickness (>7mm); subsequently, the embryo is transferred for successful implantation. PRP is, therefore, injected before embryo transfer, ideally 48 hours prior, to prepare the uterus for implantation. 5
PRP offers a Promising Solution
PRP is gaining increasing popularity in the field of regenerative medicine. It effectively treats many chronic ailments, alleviating the symptoms, and restoring the function. The purpose of the selection of platelets in large quantities is to reap the benefits of high concentrations of natural growth factors that they contain. PRP, basically, works by supporting the body’s natural defense system. The idea is to utilize the body’s ability – its response to tissue injury – in an effective way, so that healing is promoted and stems cells are attracted to the site of injury, for a speedy recovery.
In a similar technique, that is plasma transfer therapy, there are strong immune responses that mask the actual benefits of the injected components. In PRP, the usage of an individual’s own blood prevents the immunologic reaction against the platelets. Hence, PRP therapy is an extremely safe treatment modality with little to no side effects and most of the existing ones being related to injection or anesthesia.
Douglas Ginter
References:
1. How common is infertility? Available from [https://www.nichd.nih.gov/health/topics/infertility/conditioninfo/common], Last Accessed 10th August, 2020)
2. Dawood, A. S., & Salem, H. A. (2018). Current clinical applications of platelet-rich plasma in various gynecological disorders: An appraisal of theory and practice. Clinical and experimental reproductive medicine, 45(2), 67–74.
3. Colombo, G., Fanton, V., Sosa, D., Criado Scholz, E., Lotti, J., Aragona, S. E., & Lotti, T. (2017). Use of platelet rich plasma in human infertility. Journal of biological regulators and homeostatic agents, 31(2 Suppl. 2), 179–182.
4. Bos-Mikich, A., de Oliveira, R., & Frantz, N. (2018). Platelet-rich plasma therapy and reproductive medicine. Journal of assisted reproduction and genetics, 35(5), 753–756.
5. Coksuer, H., Akdemir, Y., & Ulas Barut, M. (2019). Improved in vitro fertilization success and pregnancy outcome with autologous platelet-rich plasma treatment in unexplained infertility patients that had repeated implantation failure history. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 35(9), 815–818.
6. Zadehmodarres, S., Salehpour, S., Saharkhiz, N., & Nazari, L. (2017). Treatment of thin endometrium with autologous platelet-rich plasma: a pilot study. JBRA assisted reproduction, 21(1), 54–56.