Intraovarian injection of platelet-rich plasma in assisted reproduction: too much too soon?

Abstract

The prospect of ovarian rejuvenation offers the tantalising prospect of treating age-related declines in fertility or in pathological conditions such as premature ovarian failure. The concept of ovarian rejuvenation was invigorated by the indication of the existence of oogonial stem cells (OSCs), which have been shown experimentally to have the ability to differentiate into functional follicles and generate oocytes; however, their clinical potential remains unknown. Furthermore, there is now growing interest in performing ovarian rejuvenation in situ. One proposed approach involves injecting the ovary with platelet rich plasma (PRP). PRP is a component of blood that remains after the in vitro removal of red and white blood cells. It contains blood platelets, tiny anucleate cells of the blood, which are responsible for forming a thrombus to prevent bleeding. In addition, PRP contains an array of cytokines and growth factors, as well as a number of small molecules. The utility of PRP has been investigated in a range of regenerative medicine approaches and has been shown to induce differentiation of a range of cell types, presumably through the action of cytokines. A handful of case reports have described the use of PRP injections into the ovary in the human, and while these clinical data report promising results, knowledge on the mechanisms and safety of PRP injections into the ovary remain limited. In this article, we summarise some of the physiological detail of platelets and PRP, before reviewing the existing emerging literature in this area. We then propose potential mechanisms by which PRP may be eliciting any effects before reflecting on some considerations for future studies in the area. Importantly, on the basis of our existing knowledge, we suggest that immediate use of PRP in clinical applications is perhaps premature and further fundamental and clinical research on the nature of ovarian insufficiency, as well as the mechanism by which PRP may act on the ovary, is needed to fully understand this promising development.

Preliminary report of intraovarian injections of autologous platelet-rich plasma (PRP) in extremely poor prognosis patients with only oocyte donation as alternative: a prospective cohort study

“…Even in previous studies, there was no long-lasting effect that could be called ‘rejuvenation’. While the promise of attempting to restore some ovarian reserve for even a short time warrants serious investigation ( Atkinson et al , 2021 ), it is premature to accept such treatment as part of general fertility practice outside of a research setting. Findings, in this study, moreover, once again highlight the need for controlled trials.…”

“…PRP use was initiated in sports medicine in the 1970s ( Peerbooms et al ., 2010 ; Thanasas et al ., 2011 ) and has since expanded into many medical specialty fields: to regenerate skin ( Fabi and Sundaram, 2014 ) and cartilage ( Xie et al ., 2014 ), to treat autoimmune conditions ( Lippross et al ., 2011 ; Tong et al ., 2017 ) and even to treat hair loss ( Gentile and Garcovich, 2020 ). In most medical disciplines, the efficacy of PRP is, however, still under debate ( Wolf et al ., 2011 ; Cai et al ., 2020 ; Guida et al ., 2020 ; Zhao et al ., 2020 ; Atkinson et al ., 2021 ; Yao et al ., 2021 ).…”

“…The location and volume of PRP injected into ovaries also greatly varies between studies, as do techniques of PRP administration. Efficacy comparisons between the few published reports, therefore, are currently impossible and PRP treatment clearly requires additional well-controlled investigations described in more detail ( Atkinson et al , 2021 ; Rinaudo and Albertini, 2021 ).…”

Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age

“…For example, adipose-derived stem cells can rescue the ovarian function via secretion of HGF and bFGF from stem cells ( 16 , 17 ). Many growth factors were vital for maintaining the balance of ovarian microenvironment and further affecting the functions of ovary, however, the low of cytokines production and expensive treatment costs are not conducive to their wide application ( 18 , 19 ). Despite the growing attention in ovarian antiaging research, there are no clinically feasible strategies to either preserve or rejuvenate reproductive functions during aging ( 20 , 21 ).…”

An audit of clinical outcomes following ovarian administration of platelet‐rich plasma (PRP) in women with severe diminished ovarian reserve

“…However, to date none of these therapies have been proven to be of absolute benefit. [5][6][7][8] While recognising that oocyte donation from a young donor is of proven benefit, the use of donor oocytes is generally considered a last resort treatment due to most women's strong preference for having their own genetic child, plus very limited availability of donor oocytes. Therefore, there is presently a clear unmet need for new 'ovarian rejuvenation' therapies.…”