Technical Questions

Okay I'm Interested. What do I do Next?

If you’ve read everything on this page, you will probably know more than most people do (including doctors) about ovarian PRP, Enriched Platelet Factors (like EnPLAF), ULTRA and ULTIMATE. Nevertheless, you likely still have some questions about these procedures. We are always available to help address your questions by telephone well in advance of any personal consult. Just call our office at +1 858-267-4365 and one of our Ovarian Rejuvenation specialists will be happy to speak with you.

What Will I Experience?

First, we draw blood from you. We then process that blood to isolate the platelets. Prior to each procedure, your vagina is prepared for the injections. In the case of the Ovarian Rejuvenation with PRP, the platelets are “activated” which causes them to begin releasing several growth factors. Using a vaginal ultrasound, the ovaries are identified, and activated PRP is injected into each accessible ovary in a special way. In the case of the Ovarian Rejuvenation with EnPLAF (EPF) procedure, the platelets are held in an incubator while they release the growth factors into the fluid around them. This fluid, now filled with growth factors, is then injected into each accessible ovary, again using a special technique. With ULTRA, a proprietary method is used to combine activated platelets (PRP) along with the growth factors obtained from EnPLAF (EPF) to create a powerful combination of these two procedures. This combined solution is injected simultaneously in a near painless procedure.
Specimen processing and ovarian injection requires about 45-60 minutes to complete for PRP, around 2.5 hours for EnPLAF (EPF) and 3 hours for ULTRA. As noted above, it is almost always performed without anesthesia. The goal of treatment with PRP, with EnPLAF and with ULTRA is to improve (“rejuvenate”) ovarian function, primarily by fostering the development of more high-quality oocytes. When this succeeds, your hormonal profile will change and additional follicles will appear to be developing in ovaries previously considered dormant.

Who are the ideal patients for this procedure?

Any infertile woman that is concerned that she does not have enough eggs or will have eggs that are not of sufficient high quality should consider Ovarian Rejuvenation (OR). This includes both those that plan to do IVF (in Vitro Fertilization) and those that plan to use other methods. A recent scientific study we published indicates that OR may also be useful for women that do not have fertility concerns. Look below to learn much more about that.
As noted above, at G5F we offer four options for Ovarian Rejuvenation. One is “Platelet Rich Plasma (PRP),” another is a related procedure called EPF (Enriched Platelet Factors or “EnPLAF”), as well as a hybrid procedure called ULTRA, and an Anti-Ovarian Aging procedure called the ULTIMATE. All of these are designed to further increase the concentration of growth factors you will receive from your activated platelets. Each of these these procedures are designed for specific patients, but in some cases you may have more than one option. We will discuss this important topic with you directly.

What are the goals of PRP, EPF (EnPLAF) and ULTRA treatments?

We offer activated PRP, EPF (EnPLAF) and ULTRA as enhancements of the original clinical trial. Although not all patients respond, our goal is to modify ovarian function to enable a subsequent successful IVF (oocyte retrieval) using the patient’s own eggs. After the Ovarian Rejuvenation procedure is completed, periodic blood testing will be done to monitor one or more of the hormones that reflect ovarian function. These blood tests do not need to be done at Gen 5 Fertility and can be completed at specified intervals at a commercial laboratory near the patient’s home. Some women respond very quickly, while with others, the response is delayed. If a beneficial effect is achieved, it could require approximately three months after Ovarian Rejuvenation for this to be observed. Because another unknown is the expected duration of ovarian ‘rejuvenation’ following this procedure, we encourage patients with a satisfactory response to undergo treatment, usually with IVF (either with us or elsewhere), with a minimal delay once an improvement is seen. For patients seeking this procedure for non-reproductive reasons, early results have also been encouraging.

Can you tell me more about EPF (EnPLAF)?

In February 2018, a procedure known as Enriched Platelet Factors (EPF), like EnPLAF, became available for those who did not respond to standard PRP treatment. As with ovarian PRP, ENPLAF has an established record of safe clinical use in other medical fields; here it is being used for a reproductive application: infertility. With ENPLAF, the ultrasound-guided ovarian injection technique is identical to PRP. But what is inserted into ovarian tissue is highly enriched (and platelet-free) autologous growth factors instead. Studies indicate that the concentration of growth factors may be as much as 10-15 times higher than with PRP alone. Working with associates at Neokine, G5F 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,” many patients now request and we recommend ENPLAF as the optimal first-line therapy.

How is “Ovarian Rejuvenation” thought to work?

PRP, EPF (EnPLAF), and ULTRA treatments all involve carefully inserting cytokines, chemokines, and other growth factors into ovarian tissue. These can be thought of as molecular signals that activate cell growth, angiogenesis (blood vessel growth), and improved blood flow. These changes are thought to improve oocyte number and quality.
At G5F, we have already published findings describing improvements in ovarian function after insertion of PRP — a result that may occur for at least two reasons. One possibility is that the oocytes (eggs) we recovered within several weeks of treatment were really just there all along, but simply awakened from “sleep” by our intervention. Another explanation is that the growth factors from platelets communicated with ovarian stem cells to provide the proper setting to build new eggs.
More information about the scientific basis for these procedures is given at the bottom of this page.

If I decide to do Ovarian Rejuvenation, how long will it take?

PRP, EPF (EnPLAF), and ULTRA are all completed in less than one day. Because EnPLAF requires platelet incubation, this procedure does take longer than standard PRP. ULTRA required additional time as well since it involves both PRP and EnPLAF. Our Ovarian Rejuvenation patients arrive in the office before 9 am in the morning, have their platelet sample(s) obtained (by blood draw), and then return within 1-4 hours for their procedure. Our nursing team will inform all patients about when to return for the remainder of the treatment.

How can I know if either EnPLAF, PRP or ULTRA is right for me?

Studies on ovarian response after PRP are only now beginning to appear in medical journals with the majority of publications coming from our staff and facility. Ours is the only fertility center in the world able to provide all three of these techniques using formal, standardized protocols.
The only way to determine which treatment is best is by matching a patient’s situation with ongoing research here. When we speak with you, we discuss all three options with you and offer PRP, EnPLAF or ULTRA on a case by case basis after reviewing your medical history.

What is the scientific basis of Ovarian Rejuvenation?

For over a century, the accepted paradigm of the “biological clock” has shaped the understanding of how the ovary changes over time. It is believed by many that a woman is born with all the eggs she will ever have. We also know that a woman’s supply of eggs (her “ovarian reserve”) diminishes with time—this results in a decline in both number and genetic quality of oocytes as she grows older and approaches menopause.
The human ovary is covered by a a layer of tissue that undergoes rupture and repair with each ovulation. This causes considerable wear and tear on the ovary. While stem cells are thought to be crucial for the regeneration, the full role of ovarian stem cells is still unknown. Although recent research has advanced our understanding of ovarian stem cells, treatments based on that understanding are still being developed. The work we perform at Gen 5 Fertility is generating essential data on this important topic.
PRP is perhaps best known for as a remedy for low platelets to improve blood clotting. But PRP also contains factors that orchestrate immune responses and tissue regeneration. Closely associated with inflammation, PRP is important in wound repair and coordinates the complex interplay of several critical related processes (cellular migration, extracellular matrix remodeling, cell proliferation, apoptosis, differentiation, and angiogenesis).
In addition to the now well-established surgical role of PRP in wound healing and tissue repair, scientific data have also suggested that platelets can contribute to overall organ function. Because the main problem in many cases of infertility is ovarian aging and the presumably unstoppable decline in the number of eggs, it seems plausible to consider PRP in a reproductive context as a way to address this challenge. Particularly since the concept of lost ovarian reserve is being challenged by current research here and elsewhere, the possibility of PRP improving the ovarian environment, and even interacting with possible ovarian germline stem cells (GSC) to create new eggs, warrants consideration.

What things predict if Ovarian Rejuvenation will work for me?

Women who are not fully menopausal and have at least some AMH (anti-mullerian hormone) and antral follicles are more likely to respond. Women with premature ovarian insufficiency (POI) / premature ovarian failure (POF) are more likely to respond if they have not had it for a long period of time.
The good news is that even if only one ovary can be injected with platelet derived growth factors, there does not appear to any reduction in the improvement in ovarian reserve that is seen. Although not yet published, it appears that the much higher concentrations of many growth factors with EnPLAF yields a generally superior response. We plan to publish data on this question soon.
At G5F, we recently found many things, including age and weight, were not highly predictive of response after growth factor injection into ovarian tissue. However, baseline platelet counts were different. Women with higher platelet levels were more likely to show significant improvements in ovarian reserve. This is why blood tests are recommended before your consult here, so that that information can help guide the decision on which pathway may be best in each situation.

What other benefits are seen after this treatment?

This is a key question, because you may have already completed your family. In 2018, we completed a study based on data from 80 women who had received ovarian PRP. The goal of this research was to find out more about ‘quality of life’ changes they experienced after PRP. In brief, we learned that even when making new eggs is not the goal, important improvements are still possible for many women, including improved sexual function, sleep quality, cervical mucus production, energy level, scalp hair growth, and skin appearance.

Will Insurance cover this?

It is difficult to generalize about individual health plan coverage, but because Ovarian Rejuvenation is a novel, new procedure, most insurance will not cover it. Please review the terms & conditions of your particular health plan for coverage limits in your situation. If your health insurance plan does not recognize Ovarian Rejuvenation as a covered procedure/service, please contact us for full financial information.

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