Comprehensive Chromosome Screening Improves Embryo Selection: a Meta-analysis

Objective: To study whether preimplantation genetic screening with comprehensive chromosome screening (PGS-CCS) improves clinical implantation rates (IR) and sustained IR (beyond 20 weeks) compared with routine care for embryo selection in IVF cycles.

Design: Meta-analysis of randomized controlled trials (RCTs) and observational studies (OSs).

Setting: University-affiliated teaching hospital.

Patient(s): Infertile couples undergoing IVF.

Intervention(s): PGS-CCS with the use of different genetic platforms performed on polar body (PB), cleavage embryo, or blastocyst following embryo biopsy.

Main Outcomes Measure(s): Clinical IR and sustained IR in RCTs as well as OSs comparing PGS-CCS and routine care were determined after a complete review of the literature. Pooled estimates of risk ratios (RRs) with their 95% confidence intervals (CIs) according to a fixed-effects model with the use of the Mantel-Haenszel method were calculated after the meta-analysis. Forest plots are provided for comparative purposes.

Result(s): Out of 763 citations identified, 29 articles met initial eligibility criteria and were further analyzed. Of these, only three RCTs and eight OSs met full inclusion criteria, allowing direct comparison of PGS-CCS and routine IVF care based on embryo morphology selection. In the RCTs, all embryo biopsies were performed on day 5-6 of embryo development. In the OSs, biopsies were performed on different stages of embryo development, including PB, day 3, or day 5-6. Meta-analysis of the RCTs (3 studies; n = 659) showed that PGS-CCS was associated with a significantly higher clinical IR, with a pooled RR of 1.29 (95% CI 1.15-1.45), as well as a significantly higher sustained IR, with a pooled RR of 1.39 (95% CI 1.21-1.60). Similar findings were shown in the OSs, where the pooled RR for clinical IR was 1.78 (95% CI 1.60-1.99; 7 studies; n = 2,993) and for sustained IR was 1.75 (95% CI 1.48-2.07; 4 studies; n = 1,124). Statistical heterogeneity (I(2)) was minimal for RCTs and substantial among OSs.

Conclusion(s): PGS with the use of CCS technology increases clinical and sustained IRs, thus improving embryo selection, particularly in patients with normal ovarian reserve. Results from ongoing RCTs conducted on different patient populations (e.g., decreased ovarian reserve) and different embryo stage biopsy (e.g., PB, day 3) may further clarify the role of this technology.