Ovarian Rejuvenation: PRP and EnPLAF
Gen 5 Fertility (G5F) is the first IVF clinic in the United States to focus on therapeutic and research applications for platelet enriched plasma (PRP) and EnPLAF for the human ovary. We offer this as a extension of the original PRP protocol pioneered in Greece. It is a safe but relatively new elective procedure in which platelet-derived growth factors are placed inside the ovaries near eggs and potential eggs. This is achieved by a near-painless injection through the top of the vagina under direct ultrasound guidance. No anesthesia is required.
In addition to other ways these techniques might be helpful, it may recruit stem cells so that they develop into eggs. If the number and/or quality of the eggs available for IVF is increased, the chance of pregnancy may be improved and the need for donor eggs reduced.
Members of our team worked on the first registered “ovarian rejuvenation” human research study in the United States, as listed with ClinicalTrials.gov. To date, our group has safely completed nearly 300 ovarian PRP procedures using an established methodology with precision laboratory support from RegenLab (Lausanne) and Neokine.
Because ovarian PRP involves the use of a patient’s own platelets rather than donor platelets, there is no risk of cell rejection or graft-versus-host reaction. The procedure is almost always well tolerated and there have been no adverse events or complications associated with PRP as performed by our proprietary method.
Below we answer many of the questions we have received about this revolutionary technology from patients throughout the World.
Ok, i’m interested…what do i do next?
If you read this full page, you will probably know more than most people do (including doctors) about ovarian PRP and ENPLAF. Nevertheless, you may 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 +1 858-267-5342 and one of our Ovarian Rejuvenation specialist 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 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.
Specimen processing and ovarian injection requires about 45-60 min to complete for PRP and around 2.5 hours for EnPLAF. As noted above, it is almost always performed without anesthesia. The goal of treatment with PRP and with EnPLAF 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.
what are the goals of PRP and EnPLAF treatment?
We offer activated PRP and EnPLAF as an extension 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 PRP procedure is completed, periodic blood testing will be done to monitor a variety of hormones that reflect ovarian function. These blood tests do not need to be done at this clinic and can be completed at specified intervals at a commercial laboratory near the patient’s home. Some women respond very quickly, while for others, the response is delayed. If a beneficial effect is achieved, it could require approximately three months after ovarian PRP 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 IVF (either with us or elsewhere) with 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 EnPLAf?
In February 2018, a procedure known as ENPLAF (Enriched/Enhanced Platelet Activating Factors) 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’s inserted into ovarian tissue is very highly enriched (and platelet-free) autologous growth factors instead. Studies indicate that the concentration of growth factors is approximately 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,” some patients have requested ENPLAF as their first-line therapy.
Who is the ideal patient for this procedure?
Any patient that is concerned that she will do In Vitro Fertilization (IVF) and not have enough eggs or will have eggs that are not high quality should consider Ovarian Rejuvenation (OR). 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 two options for Ovarian Rejuvenation. One is “Platelet Rich Plasma (PRP)” and the other is a related procedure called “EnPLAF,” which is designed to further increase the concentration of growth factors you will receive from your activated platelets.
How can I know if either EnPLAF or PRP is right for me?
Studies on ovarian response after PRP are only now beginning to appear in medical journals, and there is only one scientific report on healthy pregnancies with IVF following EnPLAF—based on clinical success at G5F. Ours is the only IVF unit in the world able to provide both of these techniques according to 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 both options with you and offer PRP or EnPLAF on a case by case basis after reviewing your medical history.
What data exist on how to select PRP or EnPLAF?
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. While it is likely that the much higher concentrations of many growth factors with EnPLAF could yield a superior response, we are still studying this to be certain.
At G5F, our work recently found that age, weight, and AMH level were not highly predictive of response after growth factor injection into ovarian tissue. However, baseline platelet count was 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 this information can help guide the decision on which pathway may be best in each situation.
Besides fertility enhancement, what other benefits could be expected 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.
How is “rejuvenation” of the ovaries thought to work?
Both EnPLAF and PRP treatment involves carefully inserting cytokines, chemokines, and other growth factors into ovarian tissue. These can be thought of as molecular signals which 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 which could have occurred 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.
Okay if I want to do this, how long does it take?
Both EnPLAF and PRP can be completed here in less than one day. Because EnPLAF requires platelet incubation, this procedure does take longer than standard PRP. Our EnPLAF patients arrive in the morning, have their platelet sample obtained (by blood draw), then return in a few hours for their procedure. Our nursing team will inform all patients about when to return for the remainder of the treatment.
For “ovarian rejuvenation” do I need to be on a certain day of my cycle?
Not necessarily. In the registered clinical trial for ovarian PRP in over 180 women here, many patients were already menopausal so they had no ‘cycle day’. Interestingly, some women started having periods again after treatment—a very good sign. For women who are still having regular cycles, we ask that they schedule their procedure during the first half of their cycle. One of our Ovarian Rejuvenation specialists will give you complete details.
Before coming to G5F for this procedure, is there any special preparation required?
The only medical advice to follow is to get baseline lab tests before you arrive, and more importantly, to avoid aspirin compounds for at least two weeks before your appointment. This applies to both PRP and EnPLAF, because both treatments depend on platelet health and aspirin has a harmful effect on platelets.
What can I expect after treatment…will I feel any different?
Both PRP and EnPLAF are very well tolerated. Some patients go back to the airport later the same evening as their procedure here, and there has not been any problem with such travel. On a pain scale of 1 to 10, most PRP and EnPLAF patients say this is about a two or three. Many patients have no discomfort at all. This low level of discomfort is why anesthesia is not necessary. Hopefully, after “ovarian rejuvenation” there will be an improvement across several “female” issues like cervical mucus production, energy level, scalp hair growth, and of course, egg production.
Is it possible to have more than one ovarian PRP attempt? What about ENPLAF?
Yes. Although limited data exist to answer this question specifically, some of our patients have undergone a second ovarian PRP treatment or have had EnPLAF after an unsuccessful ovarian PRP. In general, these patients are older and may require more than one “dose” to achieve a satisfactory response.
will my insurance cover this?
It is difficult to generalize about individual health plan coverage, but most insurance will exclude any treatment classified as investigational. 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 PRP or ENPLAF as a covered procedure/service, contact G5F for financial information.
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. 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.