Ovarian rejuvenation – the new hope for infertile women?
Human fertility Reproductive Health Ovarian rejuvenation

Ovarian rejuvenation – the new hope for infertile women?

Dr. Ralph Papas
Endre Szvetnik
Dr. Ralph Papas, Endre Szvetnik

In 10 seconds? A new technique offers new hope to infertile couples by “turning back the fertility clock” in women. It’s cheap and it helps naturally achieve a pregnancy – but it needs more research.

Why is it such a big deal? For so many infertile couples – including women who went through menopause early –, egg donation seems to be the only viable option to have a child, specifically when ovarian aging of the would-be mother is an issue. But ideally, most women would like to be their child’s genetic mother, not just their birth mother, which is not possible with donated eggs (although research suggests that the birth mother still passes on some of her DNA to the child). The pregnancy rate – according to this study - is about 30% from donated eggs, and the successful pregnancy rate is even lower, around 19%. Plus, evidence points to a higher risk of morbidity (illnesses) associated with pregnancies resulting from donor eggs. Ovarian rejuvenation gives women a chance to avoid the donation route.

OK, so what is ovarian rejuvenation then? To be more precise: we are talking about Ovarian rejuvenation by injection of Platelet-Rich Plasma (PRP) directly into the ovaries. Mounting evidence from several studies on the new technique is showing pregnancies using autologous oocytes (i.e. the woman’s own cells that would grow into mature eggs), giving much hope to many patients. (Find some case studies in this paper.) Researchers have also compared the women receiving PRP with those receiving PRP and IVF and those who did not. PRP injection resulted in an increased number of eggs and better quality embryos in subfertile women and six times more women became pregnant compared to the group that did not receive any help.  However, the authors highlighted that more research was needed to assess the impact of PRP on live births.

Wait, but what is this plasma-PRP thing again? OK, the proper name is Platelet-rich plasma (PRP), it’s conditioned plasma using the patient’s own platelets (these are parts of bone marrow cells that form blood clots or stop bleeding). PRP is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to remove red blood cells. PRP therapy is a form of regenerative medicine that can potentially harness the body’s own abilities and amplify the natural growth factors it uses to heal or rejuvenate tissue. For example, golf legend Tiger Woods used PRP to repair his damaged Achilles tendon in 2010.

And how would PRP counter ovarian aging? The mechanism through which PRP would help in rejuvenating the ovaries is mostly hypothetical at this stage. The idea is based on the fact that the growth factors and the many identified bioactive factors present in PRP play a role in the production of ovarian follicles(the small sacs that house the oocytes, which could become mature eggs later); and the injection of PRP is supposed to improve follicular growth. Furthermore, PRP helps with angiogenesis (the development of new blood vessels), which is thought to play an important rejuvenating role as well.

So, you said PRP is injected into the ovaries? Yes, the technique involves direct injection of PRP into each of the ovaries with a long needle that is inserted through the vagina under light sedation/anesthesia, in a similar fashion to the egg retrieval procedure which is currently standard and safe for every IVF cycle. Indeed, the risks and side effects of the procedure are minimal.

The procedure of PRP preparation and intraovarian injection.
The procedure of PRP preparation and intraovarian injection. Firstly, peripheral blood is harvested from an arm of the patient. The collected blood is centrifugated to separate the PRP. Then, the platelets in PRP are activated for releasing the growth factors, before being injected into the ovaries. Source: Cat Vo, Tanaka, Kawamura, 2021.

And what about the efficiency of the procedure? The initial reports showed improved hormonal profiles and increased numbers of retrieved oocytes in patients that had diminished ovarian reserves. Subsequently, several studies with larger sample sizes have reported that this approach resulted in several healthy live birthswith no apparent complications.

Would you say the evidence in favor of PRP for Ovarian Rejuvenation is strong? In reality, the literature published so far has demonstrated safety as well as only a potentially beneficial effect. However, the current understanding of the PRP actions in the ovaries, as well as the long-term effectiveness of this approach is still at an “incipient stage". Researchers have highlighted that the mechanism of the RPR method works in the ovaries needs research “at the cellular level”. The above paper, published in 2021, for example, highlights that no randomized controlled trial – the gold standard in medical evidence – had taken place before that date. That would be needed, to extend this novel intervention to routine standard practice in the clinic.


Premature ovarian failure – infertility way too early

For 1 percent of women, ovaries stop working normally before they turn 40. For some it’s not just the ovaries – they stop menstruating altogether. This state is also called “primary ovarian insufficiency” (POI).

A warning sign before POI sets in can be irregular periods and reduced fertility. Eventually getting pregnant will become almost the exception with the condition.

A method to counter this is the use of stem cells from the bone marrow. Stem cells can divide and turn into any other cell in the body which is great for regenerative medicine. Researchers experimenting with ovarian rejuvenation with stem cells are currently comparing if injecting them directly into the ovaries or just into the patient and letting them find their way to the ovaries works better.

This technique also aims to rescue inactive or degenerating 'primordial follicles', the little sacs where eggs grow and mature, improving the patient’s fertility.

Ralph and Endre have distilled 13 research papers saving your 45.5 of reading time.


The Science Integrity Check of this 3-min Science Digest was performed by Dr. Mónica Faut.



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