Intraovarian platelet-rich plasma injection for ovarian rejuvenation

Dear Editors,

I have read with careful attention and interest the randomized study published by Herlihy et al. (2024) in Human Reproduction, and I have found it important to highlight two notable findings and compare them with a randomized controlled trial (RCT) published in the same journal a few months earlier (Barrenetxea et al., 2024).

First, the authors report that platelet-rich plasma (PRP) administration was not associated with an increase in the percentage of euploid blastocysts or with a higher pregnancy rate. Second, the authors reported that PRP administration was also not associated with an increase in the number of oocytes retrieved.

Regarding the first point, both RCTs published in 2024 (Barrenetxea et al., 2024; Herlihy et al., 2024) reached similar conclusions: PRP treatment does not improve the percentage of euploid embryos or pregnancy rates per oocyte retrieved.

However, a difference between the two RCTs emerged concerning the increase in the number of oocytes following PRP administration. A possible reason for this discrepancy lies in the timing between PRP administration and oocyte retrieval. In Herlihy et al., the average interval was 28 days (26–29), while in Barrenetxea et al., each patient underwent two egg retrievals after PRP. The first retrieval (P2), at 24 days post-PRP, showed no significant increase, whereas the second retrieval (P3), at 49 days post-PRP, did show a significant increase in oocyte count. This extended interval could potentially explain the observed difference.

Recently, the term ovarian rejuvenation has become very popular regarding reproduction. Indeed, it is very appealing. Given the advanced age of many of our patients and the limited success rate of assisted reproduction procedures for these women, many women prefer to hear the words ‘ovarian rejuvenation’ rather than to consider the need or advisability of resorting to egg donation. However, it is crucial to evaluate the evidence behind intraovarian PRP injections purported to ‘rejuvenate’ the ovaries critically.

Scientific evidence varies widely, from case reports to retrospective and prospective studies, RCTs, and meta-analyses, each with differing levels of rigor and impact on clinical practice. For example, the meta-analyses published in 2024 (Adiga et al., 2024; Éliás et al., 2024; Li et al., 2024; Maged et al., 2024; Vahabi Dastjerdi et al., 2024; Wu et al., 2024) on this topic have a major limitation: they rely on pre–post comparisons of outcomes like oocyte or embryo numbers without the robust control of an RCT, introducing potential bias.

In conclusion, while there may be an ongoing debate about whether PRP can stimulate the ovaries to produce more oocytes, it seems obvious that oocyte or embryo quality is not enhanced, indicating that true ovarian ‘rejuvenation’ remains unproven.

So, it is time to eliminate the term ‘ovarian rejuvenation’ implying quality improvement. A term like ‘reactivation’, suggesting increased oocyte yield from quiescent follicles, may be more accurate. This distinction is crucial for managing patient expectations and improving pregnancy outcomes without misleading terminology.

Obviously, patients may prefer terms like ‘rejuvenation’, yet the current data do not substantiate such a claim. Thus, while further well-designed studies, particularly RCTs, are warranted, avoiding misleading language is even more critical.

Clinical decisions based on flawed evidence risk ineffective or even harmful treatments, underscoring the need for scientific rigor and ethical responsibility in research and clinical practice.

Conflict of interest

None declared.