LAUSR

Is the cycle outcome of day0-ICSI (day0-matured oocytes) and delayed-ICSI (day1-matured oocytes) in low responders affected by maternal age? Delayed-ICSI improves cycle outcome of low responders in all age groups by providing additional blastocysts for embryo transfer and/or pre-implantation genetic testing for aneuploidies (PGT-A). We had previously compared the fertilization, blastulation, blastocyst utilisation, and euploidy rates between day0-ICSI and delayed-ICSI (Lee, C.S.S., 2018). We believed that patients who have <7 mature oocytes (low responders) can benefit by having their concomitant immature oocytes cultured to day 1. This study evaluates the benefit of delayed-ICSI in improving the cycle outcome of such low responders from different age groups. From January 2018 to December 2020, 434 IVF cycles in Alpha IVF & Women’s Specialists were classified as low responder (being <7 oocytes injected on day 0). The immature oocytes were further cultured and delayed-ICSI was done on day1-matured oocytes. Patients were divided into 3 groups: (A) ≤35 years old (n = 137; mean maternal age=32.5; range=23.0–35.0); (B) 36–40 years old (n = 208; mean maternal age=38.2; range=36.0–40.0); and (C) >40 years old (n = 89; mean maternal age=42.7; range=41.0–49.0). Semen samples were processed by density gradient centrifugation and/or swim-up method. Day0-matured oocytes were injected at 2.5–4.5 hours post-retrieval (PIEZO, Japan). Immature oocytes were further cultured for 18–24hours and delayed-ICSI was done immediately after maturity assessment. Injected oocytes were cultured up to 7 days and trophectoderm biopsy for PGT-A screening (IonTorrent, USA) was performed on selected blastocysts prior to vitrification (Cryotec, Japan). The cycle outcomes of day0-ICSI and delayed-ICSI were analysed and compared. In Group A, the fertilisation, blastulation, blastocyst utilisation and euploidy rates of day0-ICSI and day1-ICSI were 80.0% vs. 70.9%, 74.7% vs. 33.6%, 57.1% vs. 17.9%, and 52.3% vs. 30.8% respectively. The fertilisation (p = 0.0024), blastulation (p = 0.0001), utilization (p = 0.001) and euploidy (p = 0.0205) rates of delayed-ICSI were significantly lower compared to day0-ICSI. In Group B, the fertilisation, blastulation, blastocyst utilisation and euploidy rates of day0-ICSI and day1-ICSI were 77.3% vs. 64.1%, 75.0% vs. 37.5%, 52.7% vs. 20.6% and 26.0% vs. 32.1% respectively. Delayed-ICSI showed significantly lower fertilisation (p = 0.0001), blastulation (p = 0.0001) and utilization (p = 0.0001) rates than day0-ICSI, but the euploidy rate was comparable (p = 03997). In Group C, the fertilisation, blastulation and blastocyst utilisation rates of day0-ICSI and delayed-ICSI were 76.6% vs. 56.4%, 67.1% vs. 22.8%, 34.3% vs. 7.9% respectively. Similar to Group B, the fertilization (p = 0.0001), blastulation (p = 0.0001) and utilisation (p = 0.0003) rates in day0-ICSI was significantly higher than delayed-ICSI. No significant difference was observed between the euploidy rates of day0-ICSI and delayed-ICSI (18.9% vs. 0.0%, p = 0.3452). Despite all blastocysts derived from delayed-ICSI in this group being aneuploid, it could still increase the chances of these patients obtaining an euploid blastocyst. Analysis on Group B was done on a larger sample size compared to Group A and C. A larger sample size in Group A and C is needed to further support our results. Wider implications of the findings: Delayed-ICSI generates additional blastocysts for low responders from all age groups. Therefore, delayed-ICSI could be a routine procedure in low responder IVF patients in order to optimise the cycle and clinical outcomes. Not applicable