Intracytoplasmic sperm injection (ICSI) is a commonly used in vitro fertilization technique. Selection of sperm for injection is currently done using subjective assessment of morphology, which may not accurately identify the best-quality sperm. Hyaluronic acid receptors on sperm plasma membranes are a marker of maturity, and sperms which are capable of binding immobilized hyaluronic acid in vitro are of higher quality. This can be used as an advanced sperm selection technique to choose sperm for ICSI, termed physiological ICSI (PICSI). Several studies reported improved fertility treatment outcomes when using PICSI compared with conventional ICSI; however, the majority of studies are underpowered. Recently, a large, multicenter, randomized controlled trial, known as the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial, found a significant reduction in miscarriage rates with PICSI, but no significant effect on live birth rate. There are still many avenues through which PICSI may provide an advantage, subject to confirmation by future research, such as improved long-term health of offspring. Other advanced sperm selection techniques include intracytoplasmic morphologically selected sperm injection, magnetic-activated cell sorting, and Zeta potential sperm selection; however, the most recent Cochrane review concluded that there is currently insufficient evidence to ascertain whether these techniques improve clinical outcomes, such as live birth rates.

EmbryoGlue is available to patients at many in vitro fertilization clinics, usually at an additional cost. The efficacy of hyaluronan-enriched transfer medium (HETM) is supported by moderate quality evidence that indicates a significant improvement in clinical outcomes such as live birth rates for patients, including poorer prognosis women (i.e., maternal age factor [>35 years] and recurrent implantation failure). An increased multiple pregnancy rate has been reported with the use of HETM; therefore, a single embryo transfer policy should be considered in conjunction with the use of EmbryoGlue. There is no evidence to suggest that HETM has any detrimental impact, and therefore the use of HETM in clinics may be justified for a specific demographic of patients. Further robust evidence, in the form of meta-analyses or large-scale randomized controlled trials, is needed to build a sufficient consensus regarding the benefit of hyaluronan supplementation in embryo transfer media.

A fertility clinic observed a reduction in its fresh intracytoplasmic sperm injection (ICSI) implantation rate key performance indicator (KPI) below benchmark threshold which was further monitored but did not improve. The clinic had been performing ICSI successfully for >16 years with good ICSI implantation rates meeting benchmark level. A root cause analysis (RCA) was conducted, including the input from an external observer, reviewing all systems and processes. A bundle of recommended changes was implemented as part of an improvement cycle with the aim to increase fresh ICSI implantation rates back to benchmark. Quality improvement (QI) methodology and tools were used including Statistical-Process-Control charts (BaseLine SAASoft). Measurements included standard clinical outcome data. KPIs were tracked following defined and controlled clinical and laboratory changes. Fresh ICSI implantation rates improved significantly (p=0.013, ChiSq). The improvement work was limited by its design of a plan-do-study-act (PDSA) cycle ‘intervention bundle’ as opposed to small PDSA cycles of single changes. Therefore, the improvement could not be attributed to any singular intervention within the bundle. It took longer than anticipated to see improvement due to the impact of the pandemic. The QI project highlighted the difficulty for clinics with low cycle volumes to sensitively monitor KPI’s in a timely and responsive way. The need to accumulate sufficient data to be confident of any trends/concerns means small clinics could be less responsive to any problems or too reactive to false positives. It is important to disseminate the learning from this improvement work because there is currently no agreed standardised optimal protocol for ICSI, resulting in clinics using slightly different approaches, and there are limited published reports where embryology KPI’s are tracked following defined and controlled laboratory/clinical changes. This project provides useful knowledge about ICSI improvement interventions and could be more effective within a larger clinic with higher cycle volumes.