Day 5 useable blastocyst rate is an early indicator of clinically significant shifts in the embryo culture system

Abstract

The ability to track performance of an IVF laboratory using statistical process controls has not been validated and remains an important goal for an early warning signal of shifts in laboratory conditions. The Vienna consensus report recently defined Key Performance Indicators (KPIs) for monitoring fresh IVF and ICSI cycles, but the effectiveness of these KPIs for detecting clinically relevant shifts following changes in laboratory processes is unknown1. The aim of this study was to assess whether embryology KPIs detect shifts in laboratory performance that result in changes in clinical outcomes. Retrospective, multicentre, analysis of KPIs for fresh IVF and ICSI cycles. Three consecutive 5-month periods of embryo culture media were investigated 1) embryo culture in Continuous Single Culture Complete (CSCM-C) (Irvine Scientific) 2) embryo culture in G-TL (Vitrolife) 3) embryo culture returned to CSCM-C (Irvine Scientific). Six primary embryology KPIs were tracked for 1523 cycles from June 2016 to August 2017; ICSI fertilization rate, IVF fertilization rate, useable day 5 blastocyst rate, overall useable blastocyst rate, clinical pregnancy rate and cumulative clinical pregnancy rate. Meaningful KPI shifts were identified by upper and lower warning (2-sigma) and control (3-sigma) limits. KPI shifts were analyzed by ANOVA and multivariate regression. During the 15 months analyzed, the novel KPI, useable day 5 blastocyst rate, fell below the 3-sigma lower control limit for 5 months. The decrease in useable day 5 blastocyst rate, from 43% to 32%, occurred following a change from CSCM-C (Irvine Scientific) to G-TL (Vitrolife) and was detected one week after the change (p < 0.0001). Useable day 5 blastocyst rate subsequently recovered after a change back to CSCM-C (p < 0.0001). A decrease in clinical pregnancy rate (54% to 41%) was also observed, but this was not detected until 3 months after the useable day 5 blastocyst rate shift (p = 0.01). Although culture media type independently effected useable day 5 blastocyst rate and clinical pregnancy rate, the cumulative clinical pregnancy rate was similar among the three time periods. Importantly, overall useable blastocyst rate (day 5-7) remained within control limits (52%) for all three periods, indicating that the overall rate alone may not sufficiently monitor embryology laboratory performance. This study validates a statistical KPI monitoring system to provide systematic, early detection of culture condition shifts in ART laboratories. Useable day 5 blastocyst rate is identified as an important KPI, which complements overall useable blastocyst rate (day 5-7).