Ovarian rejuvenation and PRP – process and outcomes explained

During this session, Dr Natalia Szlarb, Gynaecologist & Fertility Specialist at UR Vistahermosa discussed ovarian rejuvenation treatment options, its main indications, how it works, and outcomes.

We have to be aware that PRP has been used in medicine for quite a while. Whole blood is rich in red blood cells, white blood cells, and platelets. When centrifuged, the cells settle at the bottom of the tube, while the serum is usually in the upper area. By adding special factors to this blood, platelets release beneficial nutrients such as cell growth factors, cytokines, and vascular growth factors. PRP has been used in regenerative medicine, especially in orthopaedics for knee injuries, which are common in cold countries like Germany where skiing is popular.

The use of PRP in mesotherapy for advanced-aged women has shown improvements in skin quality. Collagen in the skin’s connective tissue becomes disorganized with age, but after PRP injections, collagen regains its organized structure, enhancing skin quality. Gynaecology has also adopted PRP in 3 specific indications: premature ovarian failure, low ovarian reserve patients, and endometrial regeneration.

PRP in reproductive medicine

The platelets in PRP, after a special centrifuge preparation, release nutrients that positively impact the uterus lining, especially in cases of thin endometrium, poor growth, implantation failure, premature ovarian failure, or low ovarian reserve due to age. Platelets release growth factors, insulin growth factors, tissue growth factors, and vascular factors, improving endometrial and ovarian responses.

For patients with ovarian failure, PRP injections have shown an increase in the number of undrafted follicles, improved cortex volume, and enhanced angiogenesis. These improvements allow hormones injected in subsequent cycles to penetrate the ovary better, leading to a better ovarian response. In cases of Asherman syndrome, PRP cannot be considered a treatment. However, for less severe cases where parts of the endometrium are still viable, PRP can be used to reduce pro-inflammatory factors, improve endometrial thickness, and target the remaining viable areas during embryo transfer.

It’s important to note that PRP is not used daily for endometrial growth, unlike estrogen. It is reserved for selected severe cases, such as Asherman syndrome, ovarian regeneration in premature ovarian failure, and patients with advanced maternal age and low ovarian reserve.
Assessing ovarian reserve is crucial before undergoing an IVF cycle.
Low ovarian reserve and premature ovarian failure are two separate conditions. Menopause occurs naturally between 45 and 55 years old when women stop producing eggs. Premature ovarian failure is the condition where women stop producing eggs before the age of 45. PRP can be used in cases of premature ovarian failure if the AMH levels are dropping.

It is important to plan pregnancies earlier due to the postponement of maternity. Freezing eggs at a younger age or considering PRP treatment in advanced maternal age with a low ovarian reserve can be beneficial. If PRP doesn’t work, egg donation is another option.

PRP may not be suitable for patients who have undergone strong chemotherapy or have AMH levels of 0.2 or 0.0. When your AMH is more than 2 nanograms per millilitre, you have a good ovarian reserve. When your AMH is between 1 and 2, you have diminished ovarian reserve. When your AMH is under 1 nanogram per millilitre, you have a low ovarian reserve. In patients with low ovarian reserve, the aim is to increase the number of untraveled follicles through ovarian rejuvenation. For them, one additional egg or follicle is a blessing, especially when they travel to Spain from another part of the world.

There are two separate entities: low ovarian reserve and premature ovarian failure. Premature ovarian failure occurs when women experience the cessation of egg production in their ovaries before the age of 45. This condition is also known as premature menopause. These patients, develop problems with infertility at an early age due to the lack of egg production. In cases of low ovarian reserve or premature ovarian failure, we offer PRP treatment. However, it’s important to note that we cannot expect miracles from PRP. For example, after strong chemotherapy, such as for breast cancer or leukaemia, PRP is not the best solution. Before chemotherapy, it is advisable to freeze eggs for future use after the oncological disease is under control. If we naturally observe a drop in AMH indicating premature ovarian failure, this is the moment when we can consider using PRP.

In Spain, there is an interesting trend in maternal age and pregnancy planning. In the northern part of Spain, maternal age is around 32–31 years old, while in the southern part, there are younger mothers. In big cities in the north, where people are more educated, and women are more independent, they tend to postpone maternity and focus on growing their careers. In such cases, it is recommended to freeze eggs before the age of 35 or consider PRP treatment if advanced maternal age with low ovarian reserve is a concern. If PRP treatment works, it can be amazing, but if it doesn’t, the only remaining option is egg donation. It is crucial not to wait too long and take action before the age of 35.

I have seen cases where patients experience recurrent implantation failure after undergoing DNC (dilation and curettage) due to restrictive legislation in countries like Germany. In such cases, the tissue of the embryo, which likely has poor genetic quality, is removed during DNC. However, frequent DNCs can lead to problems with the thickness of the uterine lining necessary for embryo transfer. PRP has shown improvement in uterine lining thickness due to its rich nutritive factors from platelets.

There have been cases where it took months to grow a good lining, but with PRP, improvement was observed. It is worth mentioning that after the delivery of the first child, trying for a second child is often less difficult as the body has been trained, and the growth of the uterine lining is smoother.

Implantation failure is another challenge in reproductive medicine. Even after transferring the best quality embryos from egg donors or patients’ eggs, sometimes it doesn’t work. Various immunological protocols are implemented to reduce the activity of NK cells, but if everything has been tried and it’s still not working, flushing the lining with PRP can be considered to improve implantation.

We always examine patients and perform a uterus scan and ovarian scan. We review the protocols used in your previous treatments in other clinics to find a solution and identify areas for improvement during your treatment with us. We also evaluate hormonal results such as AMH (anti-Müllerian hormone) and TSH (thyroid-stimulating hormone) to provide our honest opinion. It’s important to note that even with our honest opinion, success cannot be guaranteed.

Dosage Adjustment and Endometrial Regeneration

The dosage of hormonal stimulation, such as FSH and LH, is adjusted based on the patient’s AMH level. Lower AMH levels require a lower dose of medication to avoid overstimulation of the ovaries. In endometrial regeneration, we use vasodilators like Viagra (sildenafil) and adrenaline, but please note that this is not commercial Viagra and should not be taken orally. The vasodilators are taken vaginally in combination with high doses of estrogen and PRP flushing to improve the thickness of the uterine lining. However, it often takes months to see improvements in the lining thickness.

PRP Preparation Process

For endometrial rejuvenation, two syringes of blood (10 millilitres each) are needed, and from this, plasma is prepared to contain growth factors and platelets. The platelets are activated with calcium fluoride to release cytokines and growth factors. For ovarian rejuvenation, more blood is required, and four syringes of blood (10 millilitres each) are collected. Three millilitres of PRP are then injected into each ovary. These procedures are performed in the lab, and the upper part of the plasma, which contains the beneficial components, is taken for the therapy.

PRP Treatment Timing and Organization

The timing of the PRP treatment can vary depending on the complexity of the case. In some cases, it is given on the 8th or 9th day of the cycle, while in selected cases, it may be administered for the entire cycle. The scheduling can be challenging, especially for patients travelling from other parts of Europe. We strive to provide convenience by organizing the workflow efficiently. On the day of the first appointment, we send the consent, medication protocol, and prescriptions to ensure everything is in order. We understand that patients have different needs, so the medication plan can be adjusted accordingly.

Benefits of PRP

PRP offers advantages in complicated cases and is an autologous treatment, meaning it comes from the patient’s own body and reduces the risk of rejection. The PRP procedure does not typically cause allergic reactions. It can be beneficial for cases where egg donation is not yet suitable, aiming to increase the number of follicles. It can also improve the thickness of the uterine lining and potentially enhance pregnancy rates. However, in severe cases of Asherman syndrome or extensive adhesions, PRP may not be effective, and alternative treatments may be necessary.

Conclusion

PRP in reproductive medicine is still considered experimental, and more research is needed to fully understand its effects on ovarian and uterine tissue. It is not used routinely but is reserved for selected cases. While PRP has shown benefits in uterine lining growth, better protocols are required to achieve more consistent results in ovarian rejuvenation.