Use of hyaluronan in the selection of sperm for intracytoplasmic sperm injection (ICSI): significant improvement in clinical outcomes—multicenter, double-blinded and randomized controlled trial

Abstract

STUDY QUESTIONDoes the selection of sperm for ICSI based on their ability to bind to hyaluronan improve the clinical pregnancy rates (CPR) (primary end-point), implantation (IR) and pregnancy loss rates (PLR)?SUMMARY ANSWERIn couples where ≤65% of sperm bound hyaluronan, the selection of hyaluronan-bound (HB) sperm for ICSI led to a statistically significant reduction in PLR.WHAT IS KNOWN AND WHAT THIS PAPER ADDSHB sperm demonstrate enhanced developmental parameters which have been associated with successful fertilization and embryogenesis. Sperm selected for ICSI using a liquid source of hyaluronan achieved an improvement in IR. A pilot study by the primary author demonstrated that the use of HB sperm in ICSI was associated with improved CPR. The current study represents the single largest prospective, multicenter, double-blinded and randomized controlled trial to evaluate the use of hyaluronan in the selection of sperm for ICSI.DESIGNUsing the hyaluronan binding assay, an HB score was determined for the fresh or initial (I-HB) and processed or final semen specimen (F-HB). Patients were classified as >65% or ≤65% I-HB and stratified accordingly. Patients with I-HB scores ≤65% were randomized into control and HB selection (HYAL) groups whereas patients with I-HB >65% were randomized to non-participatory (NP), control or HYAL groups, in a ratio of 2:1:1. The NP group was included in the >65% study arm to balance the higher prevalence of patients with I-HB scores >65%. In the control group, oocytes received sperm selected via the conventional assessment of motility and morphology. In the HYAL group, HB sperm meeting the same visual criteria were selected for injection. Patient participants and clinical care providers were blinded to group assignment.PARTICIPANTS AND SETTINGEight hundred two couples treated with ICSI in 10 private and hospital-based IVF programs were enrolled in this study. Of the 484 patients stratified to the I-HB > 65% arm, 115 participants were randomized to the control group, 122 participants were randomized to the HYAL group and 247 participants were randomized to the NP group. Of the 318 patients stratified to the I-HB ≤ 65% arm, 164 participants were randomized to the control group and 154 participants were randomized to the HYAL group.MAIN RESULTS AND THE ROLE OF CHANCEHYAL patients with an F-HB score ≤65% demonstrated an IR of 37.4% compared with 30.7% for control [n = 63, 58, P > 0.05, (95% CI of the difference −7.7 to 21.3)]. In addition, the CPR associated with patients randomized to the HYAL group was 50.8% when compared with 37.9% for those randomized to the control group (n = 63, 58, P > 0.05). The 12.9% difference was associated with a risk ratio (RR) of 1.340 (RR 95% CI 0.89–2.0). HYAL patients with I-HB and F-HB scores ≤65% revealed a statistically significant reduction in their PLR (I-HB: 3.3 versus 15.1%, n = 73, 60, P = 0.021, RR of 0.22 (RR 95% CI 0.05–0.96) (F-HB: 0.0%, 18.5%, n = 27, 32, P = 0.016, RR not applicable due to 0.0% value) over control patients. The study was ori...

Is sperm hyaluronic acid binding ability predictive for clinical success of intracytoplasmic sperm injection: PICSI vs. ICSI?

“…A similar increase in IR, CPR, and lower PLR values was found by Worrilow and colleagues [Worrilow et al 2006;Worrilow et al 2007;Worrilow et al 2012]. Others compared conventional sperm selection and the use of sperm selected from a liquid source of HA and an increased IR was found [Parmegiani et al 2010].…”

A prospective randomized study to evaluate the effect of hyaluronic acid sperm selection on the intracytoplasmic sperm injection outcome of patients with unexplained infertility having normal semen parameters

“…Recently in 2013, in a large multi-centric trial, Worrilow et al [15], reported a greater implantation rate and clinical pregnancy rate along with a statistically significant lower pregnancy loss rate when hyaluronan bound sperm was used for ICSI. However, this improvement was only attributed to patients demonstrating a compromised hyaluronan binding assay (HBA) score.…”

“…However, recently a large study comparing ICSI using HA and conventional ICSI showed no statistical difference in embryo quality and pregnancy rates [12]. Moreover, improvement in fertilization rate and pregnancy rates has been observed only in semen samples exhibiting either poor morphology [13] or compromised HA binding [14,15]. This suggests that while PICSI might prove to be a valuable tool for sperm selection in patients with male factor infertility, its role needs to be further investigated in patient populations other than male factor infertility.…”

Regulation and roles of the hyaluronan system in mammalian reproduction

“…sHABA has proved useful in selecting spermatozoa with a high DNA integrity and morphology and may sometimes be used as a screening test for sperm quality before IVF (Worrilow et al 2013). However, its use remains controversial as sHABA does not predict freeze-thawing sperm survival (Boynukalin et al 2012), and it does not predict the pregnancy rates either in intrauterine insemination (Yogev et al 2010) or IVF (Ye et al 2006, Boynukalin et al 2012.…”