Ovarian Rejuvenation: Facts, myths and evidence

One of the most recent scientific advances in the field of assisted reproduction has been the development of new ovarian rejuvenation techniques. The purpose of these techniques is to improve and restore ovarian function by activating inactive follicles in women with diminished ovarian reserve or early ovarian failure. However, scientific evidence is still limited and raises questions about the effectiveness and applicability of these techniques in different patient groups. In this article, we review the main techniques, proven facts and myths surrounding this procedure.

What is ovarian rejuvenation?

Rather than ‘rejuvenating’ the ovaries, these techniques seek to reactivate dormant or silent ovarian follicles in women with low ovarian reserve or premature ovarian failure. 

These patients have a supply of follicles or eggs that are present in the ovary but are dormant or in a latent state and are resistant to the drugs commonly used in assisted reproduction treatments. 

Therefore, different ovarian rejuvenation techniques are available to try to reactivate these silent ovarian follicles (preantral follicles) to make them mature and develop, and to rescue very small primordial follicles, allowing them to grow. All of these techniques are still very new and are being studied, and we therefore lack specific data on their effectiveness.

Currently available ovarian rejuvenation techniques

Currently, the ovarian rejuvenation techniques being developed are:

● Platelet-Rich Plasma (PRP): This involves taking a blood sample, just like a routine blood test. The platelets, which are cell fragments capable of producing growth factors and tissue regeneration, are separated. Then they are injected into the ovarian cortex through an ovarian puncture under sedation. The purpose of this treatment is to rescue very small primordial follicles and promote their growth, with better results in assisted reproduction cycles, as it increases the number of eggs obtained.

● ASCOT technique (Autologous Stem Cell Ovarian Transplantation): This involves activating stem cells from the bone marrow, which are then infused into the ovary to reactivate it.

● OFFA technique (Ovarian Fragmentation for Follicular Activation): This involves removing ovarian tissue via laparoscopy. The cortex extracted from the ovary is activated in the laboratory and then reimplanted.

Ultimately, the aim of the various ovarian rejuvenation treatments is to stimulate ovarian function in order to improve the response to subsequent assisted reproduction treatments.

Tambre’s commitment to Platelet-Rich Plasma. What is the scientific evidence?

At Tambre, we perform ovarian reactivation using the Platelet-Rich Plasma (PRP) technique. As mentioned above, the plasma is obtained from the woman’s own blood, which is centrifuged to obtain cells that promote tissue growth and regeneration. These cells are then introduced into the ovaries under sedation, without the need for hospitalisation. 

This is a very simple and minimally invasive procedure that allows us to obtain several doses that can be frozen and used multiple times. As the plasma is autologous, that is, from the patient herself, the risk of rejection or disease transmission is reduced.

But why is PRP effective in ovarian rejuvenation?

Keep in mind that PRP has been used and studied since the 1970s. The most notable healing properties of platelets have led to the use of platelet-rich plasma in many aspects of regenerative medicine. This is why PRP has been implemented in routine clinical practice as a rejuvenating agent or to promote healing in dermatology, plastic surgery, dentistry, and orthopaedics (Foster TE et al., 2009)¹. 

In the field of obstetrics and gynaecology, several studies have recently been conducted, but with a small sample size, to investigate the effects of platelet-rich plasma injection on the uterus and ovaries. In particular, intraovarian injection was studied in conjunction with in vitro fertilisation for women with poor ovarian reserve, premature ovarian failure or even menopause (Sills ES et al., 2019)². Studies have shown that women who underwent PRP experienced a significant increase in the mean antral follicular count. 

Another study by Cakiroglu et al. 2020³, provides further relevant information. On the one hand, among women who developed at least one antral follicle after PRP injection and were able to undergo IVF in their study, 64% started within the first three cycles and another 21% in the fourth cycle. It is estimated that the progression of human follicles from a primary follicle to ovulation takes approximately 85 days. Their findings suggest that any type of follicle present in the ovary may be directly affected by PRP.

On the other hand, another interesting finding from this study was that women who did not have an antral follicle at the time of PRP injection were less likely to respond to treatment compared to those who had one or two antral follicles. Similarly, women with the lowest serum AMH levels and the highest serum FSH levels were less likely to respond. Taken together, these findings suggest that PRP helps activate existing preantral and/or early antral follicles, and that the number of remaining follicles in the ovaries of women with primary ovarian insufficiency likely determines the extent of their response to this treatment.

Research into ovarian rejuvenation with PRP is advancing rapidly, but it is still in the experimental stage. However, we have seen the promising results that PRP is achieving in the field of fertility, as well as its properties and the fact that it is a very simple and minimally invasive treatment. In recent years, the results in obtaining oocyte numbers have improved, leading to pregnancies that result in healthy babies. 

At Tambre, we know that more research and studies on a larger population are needed, but so far the results have been encouraging for both healthcare professionals and our patients.

Myths and facts about ovarian rejuvenation

Ovarian rejuvenation is a concept that has generated a lot of excitement among women seeking to improve their fertility, especially those with low ovarian reserve or early menopause. However, it is important to differentiate between what this technique can actually achieve and what is merely a myth. Below, we explore some of the most common beliefs and the scientific evidence behind them.

Myth 1: ‘There is true ovarian rejuvenation’

Fact: As we have already explained, this is not rejuvenation in the literal sense, but rather a reactivation of dormant ovarian follicles. The techniques used seek to stimulate ovarian function to improve response to fertility treatments, but they do not reverse the ageing of ovarian tissue.

Myth 2: ‘Ovarian rejuvenation is effective in all women’

Fact: The effectiveness of these treatments appears to be limited to women with some degree of residual ovarian function. In women with advanced menopause, results are poor. However, it is essential to evaluate each case individually to determine whether the patient is a candidate for this technique and whether she can benefit from it.

Myth 3: ‘Ovarian rejuvenation guarantees pregnancy’

Fact: Although studies suggest improvements in response to stimulation, there are no guarantees of pregnancy. Fertility also depends on many other factors, such as embryo quality and endometrial receptivity.

Myth 4: ‘Ovarian rejuvenation improves egg quality’

Fact: No available treatment will improve egg quality, which depends mainly on the patient’s age. Ovarian reactivation techniques can increase the number of available oocytes, but not their inherent quality. In short, ovarian rejuvenation does not improve egg quality or stop the biological clock, and it will not improve the prognosis associated with the age of the patient.

Myth 5: ‘PRP is a complex technique’

Fact: PRP is a relatively simple, minimally invasive and safe process. Basically, it consists of a blood sample, just like a conventional blood test, followed by centrifugation (to obtain platelet-rich plasma) and activation (so that the platelets release growth factors). Furthermore, as it is the patient’s own plasma, there is no risk of rejection. And, as PRP can be frozen, it is possible to give the patient several injections from a single blood sample.

At Tambre, we perform ovarian rejuvenation techniques using PRP with the aim of optimising the chances of success in fertility treatments. However, there is currently insufficient scientific evidence to prove its absolute effectiveness. Studies suggest that its effectiveness is linked to very specific profiles of women with a certain reproductive prognosis, so it is essential to carry out an individualised study to assess whether this technique is right for you. In addition, ovarian rejuvenation can be combined with other advanced assisted reproduction treatments that we develop at Tambre, thus offering a comprehensive and personalised approach. 

For more information, contact us or call us on 91 411 61 11 to request your first consultation.

Bibliographical references

1- Soy J Deportes Med. 2009;37(11):2259-72. Foster THE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Available at: https://pubmed.ncbi.nlm.nih.gov/19875361/ 

2-Sills ES, Wood SH: Autologous injection of activated platelet-rich plasma into adult human ovarian tissue: molecular mechanism, analysis and discussion of the reproductive response. Representative Biosci 2019. Available at: https://pubmed.ncbi.nlm.nih.gov/31092698/ 

3-Aging (Albany NY). 2020 Jun 5;12(11):10211–10222. Yigit Cakiroglu, et al. Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7346073/ 

4- Universidad Europea de Madrid. Rainia D. Sánchez Jorge. Estrategia para la restauración de la fertilidad en mujeres con baja reserva ovárica mediante el método de rejuvenecimiento ovárico. Available at: https://titula.universidadeuropea.es/bitstream/handle/20.500.12880/6450/Rainia%20Dolores%20SANCHEZ%20JORGE.pdf?sequence=1&isAllowed=y 

Other references consulted

Reproducción asistida ORG. Usos del plasma rico en factores de crecimiento en reproducción asistida. Available at: https://www.reproduccionasistida.org/usos-del-plasma-rico-en-factores-de-crecimiento-en-reproduccion-asistida/ 

Reproducción asistida ORG. ¿Qué es el rejuvenecimiento ovárico? Available at: https://www.reproduccionasistida.org/rejuvenecimiento-ovarico/ 

Instituto Bernabéu. Técnicas de rejuvenecimiento ovárico. Available at: https://www.youtube.com/watch?v=Ad9rOyWdQvM