P-635 Effect of intrauterine autologous platelet-rich plasma on women with repeated implantation failure undergoing IVF: a systematic review
Authors: Katsika E , Venetis C , Kolibianakis E 
Published: July 2024

Abstract

Study question
In women with repeated implantation failure(RIF), according to the ESHRE definition, does intrauterine autologous platelet-rich plasma(PRP) increase the probability of pregnancy after IVF?

Summary answer
Using the ESHRE definition of RIF, no RCTs exist to accept or refute a beneficial role of intrauterine PRP on the probability of pregnancy.

What is known already
Ten meta-analyses of RCTs evaluating intrauterine infusion of PRP in patients reported as being RIF have been published until today, suggesting an increase in pregnancy rates. However, due to the significant heterogeneity and low quality of the included studies, no solid conclusions can be drawn. Importantly, the variability in the definition of RIF in the literature renders extrapolation of research results problematic. In this respect, ESHRE has recently published a RIF definition to facilitate evaluation of interventions in these patients. A systematic review on the effect PRP in patients meeting the ESHRE criteria for RIF has not yet been performed.

Study design, size, duration
A literature search (according to a predefined search protocol) in MEDLINE, Embase and CENTRAL was performed until 12/2023 aiming to identify eligible RCTs. Subsequently, the search results were scrutinized independently by two reviewers and demographic, methodological and clinical data from eligible RCTs were extracted. The main outcome measure was achievement of live birth. Secondary outcomes measures included clinical pregnancy, ongoing pregnancy, implantation and miscarriage rates. Study quality was assessed using the RoB2 tool by Cochrane.

Participants/materials, setting, methods
Data from the identified RCTs were extracted to examine whether the ESHRE definition of RIF was met. Specifically, whether RCTs were performed in patients &lt;35 years of age with three unsuccessful embryo transfers(ETs) or in patients between 35 and 39 years of age with four unsuccessful ETs, or in patients aged 40 and above with six unsuccessful ETs, when embryos of unknown euploidy were used or in patients with &gt;2 failed ETs of euploid embryos.

Main results and the role of chance
Systematic review: Twelve RCTs published between 2019 and 2022 were identified, evaluating the effect of intrauterine infusion of PRP in women with RIF, undergoing IVF, transferring embryos of unknown euploidy(1596 women).
Although, the majority of the RCTs identified suggested a positive effect of intrauterine PRP infusion on the probability of pregnancy in patients with RIF, a great heterogeneity was present regarding the definition of RIF, especially considering the number of previous failed ETs, that range from at least one to more than three. Moreover, the number of failed ETs used to define RIF did not take into consideration female age, as suggested in the ESHRE definition of RIF. In two out of the twelve RCTs, patients evaluated were less than 35 years of age, which is one the age groups used by ESHRE for the definition of RIF. However, in these studies, patient with less than three failed ETs were included (1-5). Overall, in none of the RCTs identified, the ESHRE definition of RIF was met and thus, a meta-analysis to accept or refute a beneficial role of intrauterine infusion of PRP was not possible.

Limitations, reasons for caution
Although it is expected that RCTs published prior to the ESHRE definition of RIF are unlikely to meet the criteria proposed, it should be clear that currently no RCTs exist to accept or refute the beneficial role of intrauterine PRP on the probability of pregnancy in these patients.

Wider implications of the findings
It is likely that the beneficial role of intrauterine PRP infusion on the probability of pregnancy, observed in the relevant RCTs, included in previously published meta-analyses, does not apply to patients with RIF, according to the definition criteria proposed by ESHRE. Therefore, additional RCTs conforming to this definition are required.

Trial registration number
Under process in Prospero