OVARIAN PRP – OVARIAN REJUVENATION

• Women with poor ovarian reserve, low AMH and /or low antral Follicular Count
• Women who want to try with own eggs instead of egg donation
• Women who have failed previous IVF attempts, because of poor ovarian reserve or poor quality blastocysts
• Women who are perimenopausal / menopausal
• Women in early menopause
• Women who want to restore their hormonal balance and possibly enhance sexual drive
• Women experiencing reduced ovarian reserve or unexplained infertility

When we puncture the ovary, a local inflammation cascade, takes place.
Growth factors and cytokines are naturally produced by blood platelets and white blood cells. These
factors, naturally repair the body’ s tissues, by stimulating the production of new cells, from stem cells, to replace the damage, caused by the injury.

Growth factors derived from a woman’s blood platelets, are believed to have a similar regenerative effect to the ovaries of an infertile woman.

Initially these growth factors can stop bleeding and prevent infection on the injured site. At the same time can help with the formation of blood vessels and new healthy tissue, actually rejuvenating the ovaries, increasing stem cell production and helping to generate new follicles.

The effect of PRP lasts for about 5-6 months. Maximum effect is achieved in 1-3 months after the procedure. If we have not noticed any significant improvement, after three months, is highly unlikely to see that later.

In menopausal women without their periods, PRP can be done anytime.

In women who are perimenopausal or still ovulating, is better to be performed, in the first days of the cycle, so that we can avoid the presence of big follicles.

If you decide to go ahead with Magellan PRP, you will need to plan a 2 days trip in Athens, ideally in the follicular (1st phase) of the menstrual cycle, when ovaries are usually quiet.

PRP is an invasive procedure. Like all invasive procedures, can have minor risks of bleeding, infection, injury of bowels, bladder etc, like egg collection. The rate of these complication is quite minor.

After the procedure, mild pain or vaginal spotting, might be experienced, which is usually improved very quickly with mild analgetics.

We always advise FSH, AMH levels assessment before the procedure, as well as antral follicular count assessment.
We always advise repeat assessment of the above tests 1 month and 2 months, after the procedure.
When improvement has been achieved, we go ahead with ovarian stimulation, when the indication of it is fertility.

We do have now, long experience to say, that ovarian PRP does help in majority of the cases, as far as it regards at least the follicular recruitement, number of antral follicles and finally number of eggs retrieved.

Best results are achieved in younger women less than 40 years old. As we very well know, chromosomes depend mainly on one factor and that is age. There is no conclusive evidence that PRP does help the quality or the chromosomes of the oocytes retrieved. We do know though, that when more eggs are retrieved, statistically the chances of even one of them being chromosomically normal, are increased. In that way, PRP might have a benefit even in older women that do not want to jump straight into the egg donation process.

Magellan PRP (Platelet-Rich Plasma) is an advanced regenerative therapy that uses a highly concentrated sample of the patient’s own blood. Through a specialized automated process of double centrifugation, this sample is separated to isolate plasma rich in platelets, growth factors, cytokines, and other bioactive proteins. These components are crucial for tissue repair and cellular regeneration.

In ovarian rejuvenation, the PRP is injected into the ovaries under ultrasound guidance with the goal of stimulating follicular activity, improving hormonal function, and potentially enhancing fertility.

This treatment may be considered for women experiencing reduced ovarian reserve, early menopause, or unexplained infertility.

Difference in comparison to the normal PRP has to do with the automated centrifugation process. The process includes a second spin. Thus the PPP (platelet poor plasma) is removed, while the PRP remains. This precise separation ensures a concentration of growth factors that is up to 4-6 times higher than the traditional PRP methods as an average. On some occasions even 14 times higher concentrations can be achieved.

On the other hand our data is limited in comparison to normal PRP. So far results though, are promising and show a higher improvement rate in the hormonal profile, which cannot be statistically proven yet.

Adipose-derived (fat) stem-cell ovarian “rejuvenation” is an experimental procedure where a patient’s own fat is harvested, processed mechanically to recover stromal vascular fraction (SVF) & then injected into the ovary under ultrasound guidance. In our Unit we use the SVF in combination with the PRP (Platelet Rich Plasma).

So far data shows signals of improved ovarian markers, occasional return of menses and some pregnancies, but high-quality evidence is still limited.

Compared with PRP alone, stem-cell approaches are more invasive, as they require a procedure which is called liposuction, they are more complex and costly. Theoretically may offer stronger regenerative effects — but they also carry greater practical & regulatory issues. Moreover the data behind these is more limited in comparison to PRP alone and long-term safety issues remain unknown.

HOW IT IS DONE:

In our clinic we use the SVF method. This is a same day, not cultured approach that has to do with stromal vascular fraction from a lipoaspirate.

Typical steps:

• Liposuction / fat harvest — small volume abdominal subcutaneous fat (e.g., 40–200 mL) is collected under local anaesthesia. The procedure is performed by senior experienced plastic surgeon. On very slim women adipose tissue might be taken from the thigh or other parts of the body.
• Lipoaspirate is mechanically processed and centrifuged on special machine, to yield a cellular fraction (SVF) containing ADSCs (adipose derived stem cells), endothelial progenitors, immune cells, etc. This is done within hours. Usually millions of cells are produced.
• Injection into the ovary — transvaginal, ultrasound-guided needle insertion (similar route to oocyte retrieval) with injection of the SVF into one or both ovaries. This usually happens under sedation.
• Follow up — hormonal labs (AMH, FSH, estradiol) & antral follicular count (AFC) is checked monthly after the procedure and where applicable, IVF stimulation cycles take place.

PROPOSED MECHANISMS OF ACTION:

Stem cells are not thought to directly “become eggs.” Instead they appear to help the ovarian environment, especially if these are combined with PRP, via secretion of growth factors and cytokines that reduce the granulosa cell apoptosis. Also they promote new blood vessel formation, that improves follicle perfusion. They have anti-inflammatory effects, lowering fibrosis in damaged ovaries. Finally cell free mechanisms like exosomes may mediate much of the benefit.

WHAT DOES THE EVIDENCE SHOW?

Animal studies in rodents and early human studies show improvement on ovarian reserve markers & some pregnancies.

A noteworthy randomized, double-blind, placebo-controlled study (Cassim et al., Global Reproductive Health, 2023) used autologous SVF (not cultured) in 30 women (poor responder or POI). That study reported: safety (no major adverse events), some temporary increases in AMH in low-reserve patients (not statistically significant vs placebo), a placebo effect, and a modest pregnancy signal in the small number of patients who subsequently underwent IVF (12 stimulated; 9 embryo transfers; pregnancy rate ~33% for those who did transfer). Authors concluded the approach is experimental but reasonably safe and encouraged further study. There are no randomised big clinical trials. Bottom line on data: promising but preliminary.

ADVANTAGES OF STEM CELLS IN COMPARISON TO PRP ALONE:

The advantages are actually theoretical & suggested. PRP provides a bolus of growth factors but no living cells. Stem cells provide living cells too. Stem cells can reduce fibrosis & apoptosis, alterate the immune status and mitochondrial functions in ways PRP cannot. When injected together with PRP the benefit of stem cell is combined with the benefit of PRP.

ADVANTAGES OF PRP ALONE OVER STEM-CELL APPROACHES:

• Less invasive — PRP requires only a blood draw, not liposuction.
• Cheaper and simpler — PRP prep is quick, bedside, and lower cost.
• Stronger real-world evidence for short-term ovarian marker improvements — there are many larger case series and meta-analyses suggesting PRP can increase AMH/AFC and oocyte yield in some patients.

So: stem cells = potentially more powerful but more invasive/costly and with less high-quality human outcome data; PRP = simpler, cheaper, some supportive data but also heterogeneous and not a proven cure.

Combining PRP with stem cells gives additional benefits of both, further boosting theoretically the results. Stem cell including treatments though because of their experimental nature and limited data should be performed only as a last resort treatment to women that have not reacted to PRP alone treatments.

RISKS OF THE PROCEDURE ITSELF:
Bleeding, infection, pain, anesthesia complications (from liposuction or transvaginal injection), and potential ovarian, bowel or bladder injury from needle puncture.

THEORETICAL TUMOR RISK:
MSCs have been studied widely and most clinical literature has not shown transformation/tumor formation when autologous MSCs are used, but long-term safety data specifically for ovarian injection are limited.

REGULATORY STATUS:
The Greek National Regulatory Authority considers stem cells an experimental treatment for fertility so can only be used for gynecological reasons of hormonal balancing and improvement after signing of relevant consents. The relevant consents signed mention that you use it for gynecological reasons (hormonal improvement, return of menstruation) with the hope to help you on fertility too.