What Is and What Is Not PRP (Platelet-Rich Plasma) Application in Low Ovarian Reserve?
Despite the progress in assisted reproductive techniques today, medicine still seems helpless—at least for now—when it comes to decreased ovarian reserve. Especially delayed childbearing age and environmental factors are considered the two major causes of ovarian insufficiency.
Menopause is the last menstrual bleeding. It is the name given to the last menstrual period after one year has passed due to decreased estrogen caused by the ovaries no longer functioning (more precisely, the few remaining eggs no longer responding to the stimulation of activating hormones). The average menopause age is 51 (between 45–55 years). Research has shown that even during menopause, there are at least 1,000 eggs remaining. However, these eggs do not respond to developmental stimulation. In blood tests, an FSH value of 40 IU/L (provided that the estrogen value is <80 pg/ml) is accepted as a menopausal value. 5% of women experience ovarian depletion between the ages of 40–45, and 1% before the age of 40.
The desire to become a mother is perhaps an instinctive feeling for women regardless of age. Therefore, the condition of ovaries no longer functioning is an important issue that medicine tries to find solutions for. In countries like ours, where egg donation (using someone else’s egg) is illegal, medicine is in serious search of alternatives. In a study conducted at Harvard University in 2012, it was shown that stem cells exist beneath the ovarian cortex (shell), and stimulating these with growth factors can develop mature eggs (1). After this, research shifted toward stimulating stem cells in the ovaries and transforming them into eggs. The first report regarding PRP use was presented in 2016 (2).
In this article, I will try to shed light on the application of PRP to the ovaries, which has become a popular term in recent years.
What Does “Diminished Ovarian Reserve” Mean?
It means a decrease in the number of eggs and therefore a reduction in the chance of reproduction. The presence of at least 2 of the Bologna criteria proposed in 2011 medically establishes the diagnosis of “diminished ovarian reserve” (ovarian insufficiency).
Bologna Criteria (3);
- Advanced age (40 years and older)
- Formation of 3 or fewer eggs despite previous normal ovarian stimulation (treatment)
- Abnormal ovarian reserve tests (ovarian function tests) (for example: during menstruation, having 5–7 or fewer follicles called egg sacs; AMH value being less than 1.1)
What Is Autologous PRP (from the person’s own blood)?
Platelet-rich plasma (PRP) is a blood product obtained by taking a sample of the person’s whole blood (20–60 ml), centrifuging it at room temperature for a certain period of time (10–15 minutes) at a certain speed (1200 rpm), sterile collection of the uppermost part of the three layers formed, centrifuging it again, and separating the bottom part to make it ready for use. Approximately 30 ml of blood sample provides 3–5 ml of PRP.
PRP is a blood product enriched with many important substances such as cytokines and growth factors (TGF-beta, epidermal growth factor, vascular endothelial growth factor, platelet-derived vascular growth factor, connective tissue growth factors, etc.). It is thought that delivering these substances to the ovaries may stimulate stem cells in that area and enable egg production. The growth factors in the PRP-prepared sample are concentrated 5–10 times more than in whole blood.
For Whom Can PRP Be Recommended for the Ovaries?
It can be performed in individuals with diminished ovarian reserve (reduced egg count). However, in people with “sclerotic,” meaning very small ovaries, the procedure seems to be more difficult and less successful.
How and When Is PRP Applied to the Ovary?
PRP is applied vaginally with a needle under ultrasound guidance under light anesthesia (sedation). Basically, it is similar to egg retrieval during IVF treatment. However, the small size of the ovaries may create technical difficulties.
PRP fluid is applied by injecting approximately 2–3 ml into each ovary, under the outermost covering of the ovary (cortex).
Although PRP can be performed at any time when there is no vaginal bleeding, in our unit we generally prefer to apply it immediately after the egg retrieval procedure. Thus, the need for additional anesthesia is eliminated.
What Do We Expect from PRP Applied to the Ovary?
Within approximately 1–3 months, we expect an increase in egg count and development—which we can detect as follicles (egg sacs) on vaginal ultrasound. However, this does not occur at the widely promoted rate of 70%. Although studies are promising, it is not true that PRP is a miraculous method that can develop eggs in everyone. WE STILL DO NOT HAVE FULLY SUFFICIENT DATA regarding PRP applied to the ovaries. Studies in this direction are ongoing.
I would also like to share another claim on this subject with you; there is also the opinion that perhaps it is not PRP itself, but rather the stimulation of the ovaries by the needle that triggers egg formation. Most likely, even if the needle has an effect, it seems to be temporary.
Can PRP Applied to the Ovary Have Any Negative Effects?
After all, even though the procedure is performed under ultrasound guidance, it involves blindly injecting a fluid into the ovary with a needle. Therefore, it should certainly not be presented as a completely harmless procedure. Risks that may also be encountered during egg retrieval—such as bleeding, injury to surrounding organs like the bowel, or infection—may be expected to be even higher because the procedure is performed on a small ovary.
The latest thing that can be said about PRP for the ovaries is this; “With CORRECT PATIENT SELECTION, proper technique, and sterile conditions, PRP application to the ovary—provided that the risks are not ignored—may be seen as a source of hope.”
I wish you all days full of health and happiness.
Prof. Dr. Ümit İNCEBOZ
Gynecology and Obstetrics Specialist
References
- White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med, 2012; 18:413-421.
- Pantos K, Nitsos N, Kokkali G, Vaxevanoglou T, Markomichali C, Pantou A et al. Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment. Proceedings of 32nd Annual Meeting of ESHRE, 2016 July 3-6, Helsinki, Finland.
- Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L. ESHRE Working Group on Poor Ovarian Response Definition. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: The Bologna criteria. Hum Reprod. 2011;26:1616–24.