Abstract
BackgroundAmong recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients.MethodThe PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis.ResultsA total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27–2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14–1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33–2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09–1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28–2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25–5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86–2.36; I2 = 52.5%; n = 372) when a random-effects model was employed.ConclusionThe administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.
Highlights
Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors
Subgroup analysis indicated that granulocyte colony-stimulating factor (G-CSF) improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles, and for both subcutaneous injection and intrauterine infusion, but the biochemical pregnancy rate of the RIF group was higher than that of the control group (RR: 1.85, 95% confidence intervals (CIs): 1.28–2.68; I2 = 20.1%, n = 469)
When subgrouped by administration route (497 with subcutaneous injection and 479 with intrauterine infusion), the results indicated that G-CSF treatment improved the clinical pregnancy rate for RIF patients for both routes; see Fig. 3 for details
Summary
Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Recurrent implantation failure has consistently been a bottleneck preventing infertile patients from achieving a better pregnancy during in vitro fertilization and embryo transplantation (IVF-ET). Many researchers consider RIF patients to be women under the age of 40 years who have failed to achieve a clinical pregnancy after the transfer of at least four good-quality embryos in a minimum of three IVF fresh or frozen cycles [3]. One cause of RIF is maternal factors, such as immune rejection and problems with endometrial receptivity and the intrauterine environment. Another cause of RIF is embryonic factors, such as poor developmental potential and chromosome aneuploidy [4]. Some research has focused on improving endometrial receptivity by using G-CSF to address the self-immune problem
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