Intraovarian Injection of Platelet-rich Plasma in Assisted Reproduction: Too Much too Soon?

Lloyd Atkinson; Francesca Martin; Roger G. Sturmey

Disclosures

Hum Reprod. 2021;36(7):1737-1750. 

In This Article

PRP and Ovarian Rejuvenation: The Evidence so far

Over the past decade, there have been a growing number of studies that have reported that injection of PRP directly into the ovary can increase folliculogenesis and egg harvest. One of the earliest studies reporting this approach was from Callejo et al. (2013), who implanted cryopreserved ovarian tissue within the peritoneum. PRP was used as a pro-angiogenic and proliferative agent, and the approach supported a successful live birth. The proangiogenic effect of PRP was further highlighted in a study by Bakacak et al. (2015), who used a rat model of ovarian ischaemia induced by torsion. In that study, PRP treatment in all conditions significantly increased peritoneal vascular endothelial growth factor (VEGF) and provided protection from ROS-induced oxidative damage during reperfusion.

More recently, direct injection of PRP into ovaries has been reported. In 2016, a short communication at the ESHRE Annual Meeting indicated that infusion of PRP into the ovary of perimenopausal women led to resumption of menstrual cycles (Pantos et al., 2016). The study included only eight women but was the first reported use of PRP for rejuvenation of the perimenopausal ovary. Since then, there have been several limited investigations into the utility of PRP injection into the ovaries of perimenopausal women which are summarised in Table I. Sills et al. (2018) reported that for healthy women with a history of infertility, ovarian PRP infusion produced several MII oocytes for cryopreservation, with one individual proceeding to successful embryo transfer at time of publication. Other studies have reported similar cases; commonly ovarian PRP therapy has caused AMH to increase and FSH levels to fall in previous non-responders, leading to folliculogenesis, significant levels of oocyte retrieval, and in a handful of cases, spontaneous pregnancy (Sfakianoudis et al., 2018; Farimani et al., 2019; Pantos et al., 2019; Hsu et al., 2020).

In the only preclinical study on the effect of PRP injection into human ovaries, Hosseini et al. (2017) obtained healthy donated ovaries from deceased donors. PRP injection led to an increase in follicle size and their viability at 10 days compared to treatment with foetal calf serum (FCS) alone. Surprisingly, a combination of FCS and PRP did induce follicular growth, which is an interesting observation worthy of further investigation.

While these case studies appear encouraging, it is important to reflect on the experimental designs. A common feature of the first studies of the effect of PRP infusion is the absence of a sham injection group. It is conceivable that the mechanical stretching and/or mild injury to the ovary resulting from the procedure is sufficient to elicit an inflammatory response leading to temporary resumption of ovarian function. For example, laparoscopic ovarian 'drilling' is a therapeutic option for the treatment of clomiphene-resistant PCOS (Lebbi et al., 2015) and, thus, a comparable ovarian needle stick injury may be a causative factor in the success of PRP therapy. Importantly, the recent study of Ahmadian et al. (2020) used a sham injection group, which showed no morphologically normal follicles, and the same result was observed in the 'no injection' group. This demonstrated that injection with saline is not sufficient to reverse the effects of premature ovarian insufficiency in this animal model, nor can it elicit a comparable response to the two groups with different concentrations of PRP, which show reduced follicular atresia and increased follicular quality. It is vital that future studies control for this component of the intervention.

An important study was published by Melo et al. (2020) who reported findings from a non-randomised interventional study involving 83 subfertile women, 46 of whom opted for several infusions of 200 μl of autologous PRP into each ovary, and 37 who opted for no treatment. These two arms were further subdivided into groups who opted for IVF, and those who continued with unassisted conception. Overall, significantly higher antral follicle counts were observed in women who received PRP infusion compared to those women who received no treatment. In addition, embryo quality was scored higher from those obtained through PRP therapy, although there was no difference in the fertilisation rate of oocytes from either group. The authors concluded that ovarian injection of PRP did lead to increased egg yield in subfertile women and prompted changes within the oocyte which may lead to increased 'quality' of subsequent embryos. In both the IVF and spontaneous conception groups, those receiving PRP therapy developed 13 clinical pregnancies, compared to 2 in the control group although there were insufficient data on live births to draw any definitive conclusions. Although these data are encouraging, the absence of randomisation may have led to a socioeconomic selection bias, since PRP intervention was adopted only by couples able to pay for the treatment. Examples such as this illustrate the necessity that case studies are scrutinised in detail. Ideally, a properly controlled randomised clinical trial will be necessary to confirm the efficacy of ovarian PRP therapy.

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