Ovarian Rejuvenation (PRP)
CAG & Ovarian PRP – Background information
CAG is the first IVF clinic in the United States to focus on therapeutic and research applications for platelet enriched plasma (PRP) and related augmentations for the human ovary. We offer this as a continuation of the original PRP protocol pioneered in Greece . It is a safe but relatively new elective procedure which puts platelet-derived growth factors inside the ovaries and near potential eggs. This is achieved by injection under direct ultrasound guidance. If ovarian stem cells are present, then these could also be recruited to develop into eggs—thus reducing reliance on donor oocytes for IVF.
Specimen processing and ovarian injection requires about 45-60min to complete here, and is performed without anesthesia. The goal of ovarian PRP is to improve (“rejuvenate”) ovarian function and foster development of oocytes. When this succeeds, the hormonal profile changes and additional eggs appear to be developing in ovaries previously considered dormant.
E. Scott Sills, MD PhD served as Principal Investigator for the first registered “ovarian rejuvenation” human research study in the United States, as listed with ClinicalTrials.gov . To date, Dr. Sills has safely completed nearly 200 ovarian PRP procedures at CAG using an established methodology with precision laboratory support from RegenLab (Lausanne) . Because ovarian PRP entails use of the patient’s own (autologous) tissue rather than donor platelets, there is no risk of cell rejection or graft-versus-host reaction. The procedure is generally well tolerated and there have been no adverse events, complications, or hospitalizations associated with PRP as performed by Dr. Sills.
What is the scientific basis of PRP?
For over a century, the accepted paradigm of the “biological clock” has shaped the understanding of how the ovary changes over time. Because of ovarian senescence (aging), new oocytes do not develop in the ovaries and a woman will have an endowment of all the eggs she will ever have on the day she is born. We also know that a woman’s supply of eggs (ovarian reserve ) diminishes with time—this results in a decline in both number and genetic quality of oocytes as she grows older.
The human ovary is covered by an epithelial monolayer which undergoes cyclic rupture and tissue repair with each ovulation. This represents considerable wear and tear on the ovary. While resident stem cells are presumed to be crucial for the regeneration needed for hemostasis and repair, the identity and mode of action for this remains incompletely characterized. Although recent research has advanced the understanding of ovarian stem cell biology, clinical applications are still being developed. The work performed at CAG is generating original data on this important topic.
Use of PRP is perhaps best known for as a remedy for low platelets to improve hemostasis. But PRP also emits soluble mediators which orchestrate immune responses and tissue regeneration. Closely associated with inflammation and its many mediators, PRP figures prominently in wound repair and coordinates a complex regulatory interplay of cellular migration, extracellular matrix remodeling, cell proliferation, apoptosis, differentiation, and angiogenesis. This means signal transmissions from PRP are substantial and these factors are known to influence neighboring cells.
Notwithstanding the now well-established surgical role of PRP in wound healing and tissue repair, clinical data have suggested that platelets can contribute to overall organ function as well. Because the main problem in many cases of infertility is ovarian senescence and a presumably unstoppable decline in the oocyte endowment, it seems plausible to consider PRP in a reproductive context to address this challenge. Particularly since the concept of lost ovarian reserve as inexorably linked to organ (ovarian) failure is being challenged by current research here and elsewhere, the possibility of PRP improving the ovarian microenvironment, and even interacting with putative ovarian germline stem cells (GSC), warrants consideration.
What is the goal of ovarian PRP?
We offer activated PRP as an extension of the original clinical trial which ideally will modify ovarian function, with a view to enable subsequent IVF (oocyte retrieval) using the patient’s own eggs. After the ovarian PRP procedure at CAG, periodic blood testing will be done to monitor a variety of parameters expected to give insight regarding ovarian function. These blood tests do not need to be done at CAG, and can be completed at specified intervals at a commercial laboratory near the patient’s home. If a beneficial effect is achieved, it could require approximately three months after ovarian PRP for this to be observed. We still do not know if there are any clinical characteristics which may help predict which patients are more likely to respond to ovarian PRP. Because another unknown is the expected duration of ovarian ‘rejuvenation’ following this procedure, we encourage patients with a satisfactory response to undergo IVF (either here or elsewhere) with minimal delay.
Is it possible to have more than one ovarian PRP attempt? What about ENPLAF?
Yes. Although limited data exist to answer this question specifically, a number of CAG patients have undergone a second ovarian PRP treatment here without difficulty. In general, these patients are older and may require more than one “dose” to achieve a satisfactory response.
In February 2018, a related procedure known as ENPLAF (Enriched/Enhanced Platelet Activating Factors) became available for those who were refractory to injection of standard PRP treatment. As with ovarian PRP, ENPLAF has an established record of safe clinical use in other medical fields; at CAG it is likewise being repurposed for a reproductive application. With ENPLAF, the ultrasound guided ovarian injection technique is identical to PRP but the substrate inserted into ovarian tissue is comprised of very highly enriched (but platelet free) autologous growth factors instead. Working with associates at Neokine, CAG is currently the only reproductive medicine unit in USA studying this approach to modify ovarian responsiveness as a precursor to IVF. Although this intervention was initially developed as a higher-potency secondary treatment reserved for “PRP failures”, some patients have requested ENPLAF as their first-line therapy.
OK, I’m interested…what do I need to do next?
If you’ve read this far, you probably already know more than most people do about ovarian PRP and ENPLAF. Nevertheless, you may still have some questions about these procedures. Dr. Sills is usually available to help address your questions by telephone well in advance of any formal consult. Moreover PRP and ENPLAF patients may now enroll directly at CAG, so you can register with our research team in Carlsbad to begin the process by calling 760-994-0156. Dr. Sills performs all PRP and ENPLAF procedures at CAG on Mondays, Tuesdays and Fridays.
Will my insurance cover this? If not, what are the approximate costs of ovarian PRP or ENPLAF?
It is difficult to generalize about individual health plan coverage, but most insurance will exclude any treatment classified as experimental or investigational. Please review the terms & conditions of your particular health plan to better understand coverage limits in your situation. In the event that your health insurance plan does not recognize ovarian PRP or ENPLAF as a covered procedure/service, contact CAG for detailed remittance advice. For international patients or for those with no insurance eligibility, total out of pocket cost for either ENPLAF or PRP should be less than $5000 for most cases.
 the original PRP protocal pioneered in Greece
 Dr. Sills is the Principal Investigator as listed with ClinicalTrials.gov
 RegenLab (Lausanne)
 about ovarian reserve
 First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma, by E. Scott Sills, Natalie S. Rickers, Xiang Li, and Gianpiero D. Palermo, March 2018