Poor fertilisation plays a significant role in poor artificial reproductive technique outcomes. Male factor infertility accounts for a large portion of such cases. Several modalities have been proposed as a solution, including physiological intra-cytoplasmic sperm injection (PICSI). PICSI is a technique used to select the sperm to use in intra-cytoplasmic sperm injection (ICSI) treatment. It involves placing sperm with hyaluronic acid, a natural compound found in the body. PICSI identifies sperm that can bind to hyaluronic acid and these sperms are selected for use in treatment.

Some studies have suggested that PISCI may be advantageous to reduce miscarriage. However, the evidence is not strong and it remains unknown if PICSI is effective in a selected group of couples with a history of poor fertilisation. Based on previous medical records, we observed a higher clinical pregnancy rate (CPR) and a trend towards lower miscarriage rates with PICSI. To verify the findings and address the clinical gap, we propose a randomised controlled trial (RCT) with 234 couples (117 in each group) to evaluate the effectiveness of PICSI comparing with ICSI for improving CPR and reducing miscarriage rate in couples with a fertilisation rate of <50% in their first cycle of ICSI.

Inclusion Criteria:

• Couples with <50% fertilisation in their first ICSI cycle, and scheduled for their second ICSI/PICSI cycle

Exclusion Criteria:

• Women with diminished ovarian reserves (AMH <1.2ng/ml) or severe endometriosis (rAFS Stage III or IV)
• Male partner with severe oligoasthenoteratozoospermia (Density < 5 million, Total motility < 40) or those require surgically retrieved sperm
• Couples using donor gametes
• Couples using frozen gametes
• Couples undergoing split IVF-ICSI cycles
• Couples where a freeze all approach has been done, either clinically indicated or secondary to patient choice

Trial participants, research team collecting data outcome, and all study team members except the embryologists will be blinded to treatment allocation. It is not possible to conceal allocation to the embryologists, who will perform the intervention.