Does intracytoplasmic sperm injection improve live birth rate when compared with conventional in vitro fertilization in non-male factor infertility? A systematic review and meta-analysis

Abstract

<h3>Objective</h3> To determine whether the use of intracytoplasmic sperm injection (ICSI), which was initially developed for sperm abnormalities but has progressively expanded beyond male factor infertility, improves live birth rate (LBR) compared with conventional in vitro fertilization (IVF) in non-male factor infertility cases. <h3>Evidence Review</h3> This prospectively registered systematic review and meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and Cochrane Library were searched for relevant literature reported between January 01, 2004, and March 15, 2020. Only articles conducted in couples without obvious male factor infertility according to the investigators were included. Live birth rate (LBR) per cycle and/or per transfer was used as the main outcome. Fertilization rate, cycles with total fertilization failure, and clinical pregnancy rate were also recorded as the secondary outcomes. Study selection, bias assessment, and data extraction were performed by two independent reviewers. The methodological quality of the selected studies was assessed by two independent reviewers using the Cochrane Handbook methods and by the adapted Newcastle–Ottawa Quality Assessment Scale for cohort studies. The risks of bias were assessed using the ROBIN-1 tools. Risk ratio (RR) and 95% confidence interval (CI) were estimated using the random-effects model. <h3>Results</h3> Among the 1,760 potentially eligible studies, 61 were fully assessed, and 21 were included in the meta-analysis, corresponding to almost 1,000,000 assisted reproductive technology cycles. Among the selected studies, 17 reported LBR per cycle, 11 reported LBR per transfer, and 7 among them reported both outcomes. One was a prospective randomized controlled trial, whereas others were either retrospective cohort (n=17) or case–control studies (n=4). Individual studies' sample size ranged from 60 to 569,605 cycles. Meta-analysis showed that IVF provided a significantly higher LBR per cycle when compared with ICSI (RR, 1.10; 95% CI, 1.02–1.18). LBR per transfer tended to be higher when IVF was used compared with ICSI, but this difference barely reached statistical significance (RR, 1.18; 95% CI, 1.00–1.38). Subgroup analysis performed in poor responders showed no significant difference between IVF and ICSI concerning LBR per cycle or LBR per transfer. The secondary analyses demonstrated a lower fertilization rate but comparable clinical pregnancy and fertilization failure rates with IVF compared with ICSI. Sensitivity analyses led to similar results and conclusions. <h3>Conclusion</h3> Despite its limitations, mainly related to the inclusion of most retrospective studies, this meta-analysis synthesizes and reinforces the existing literature and provides further evidence that ICSI does not improve LBR per cycle or per transfer compared with IVF in couples undergoing assisted reproductive technology for non-male factor infertility. <h3>Clinical Trial Registration Number</h3> CRD42019136383