Abstract
The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58–3.00; p < 0.00001; OR 2.03; 95% CI 1.22–3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40–4.16; p = 0.002; OR 3.73; 95% CI 1.13–12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58–3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55–3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.
Highlights
The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent in vitro fertilization (IVF) cycle outcome
According to Simon and Laufer, RIF can be defined as the failure to obtain a clinical pregnancy after three consecutive IVF attempts, in which one to two embryos of high-grade quality are transferred in each c ycle[5]
Meta-analysis of studies investigating the possible impact of intrauterine G-CSF infusion, LMWH, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome
Summary
The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. A minority but not negligible proportion of authors prefer a broader definition and diagnoses RIF after only two previous IVF-ET failed attempts[1] Another school of thought suggests that the focus should be on the number and quality of transferred embryos. Most of the previous meta-analyzes aimed at determining the efficacy of single therapeutic intervention for RIF included patients with at least two previous failed ET attempts By applying these criteria, the rate of false positive RIF diagnosis is estimated to be considerable [at least 46%]7 and, as a consequence, the studied population probably included a significant proportion of patients without a real obstacle to conception but who had not yet succeeded just because of statistical misfortune. Evidence about efficacy of therapeutic interventions deriving from meta-analyzes conducted with these assumptions cannot be considered completely reliable
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