Busnelli Andrea, Somigliana Edgardo, Cirillo Federico, Baggiani Annamaria, Levi-Setti Paolo Emanuele
Department of Gynecology, Division of Gynecology and Reproductive Medicine, Fertility Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090, Pieve Emanuele, Milan, Italy.
Sci Rep. 2021 Jan 18;11(1):1747. doi: 10.1038/s41598-021-81439-6.
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.
本系统评价和荟萃分析的目的是评估反复胚胎植入失败（RIF）的不同治疗方案对后续体外受精（IVF）周期结局的影响。纳入了22项随机对照试验（RCT）和19项观察性研究。结果汇总显示，宫腔内输注外周血单个核细胞（PBMC）对临床妊娠率（CPR）（风险比[RR] 2.18；95%置信区间[CI] 1.58 - 3.00；p < 0.00001；优势比[OR] 2.03；95% CI 1.22 - 3.36；p = 0.006）和活产率（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）均有有益影响，皮下注射粒细胞集落刺激因子（G - CSF）对CPR（RR 2.29；95% CI 1.58 - 3.31；p < 0.0001）有有益影响，宫腔内输注富血小板血浆（PRP）对CPR（RR 2.45；95% CI 1.55 - 3.86；p = 0.0001）有有益影响。观察性研究还表明，静脉注射免疫球蛋白（IVIG）和宫腔内注射人绒毛膜促性腺激素（hCG）对CPR和LBR均有积极影响，阿托西班对CPR有积极影响。研究宫腔内注射G - CSF、低分子肝素（LMWH）、静脉注射脂肪乳、宫腔镜检查、囊胚期胚胎移植（ET）、输卵管内胚胎移植（ZIFT）、植入前遗传学检测A（PGT - A）和辅助孵化（AH）对IVF结局未观察到影响。聚焦于宫腔内输注PBMC和皮下注射G - CSF的RCT所产生的证据质量为中等。对于所有其他治疗/干预措施，证据质量从低到极低不等。总之，宫腔内输注PBMC和皮下注射G - CSF是RIF最有前景的治疗方案。然而，在将其引入临床实践之前，还需要进一步开展高质量的RCT。
