Sequential ejaculated- and testicular-sperm ICSI cycles in couples with prior ICSI failure: a within-pair analysis of embryo quality, euploidy, and live birth

Introduction Persistent poor outcomes after intracytoplasmic sperm injection (ICSI) occur in a clinically significant subset of couples despite reassuring conventional semen analysis. In such couples, testicular sperm aspiration (TESA) may be undertaken in a subsequent cycle on clinical and embryological grounds. We assessed whether TESA-ICSI improves embryo-quality indicators and live birth rates compared with EJAC-ICSI in couples whose initial EJAC-ICSI cycle did not result in a live birth. Methods This retrospective paired cohort study included 58 sequential ICSI cycle pairs at a single tertiary IVF center. Each pair comprised an initial ICSI cycle with ejaculated sperm (EJAC-ICSI) that had not resulted in a live birth, followed by a subsequent TESA-ICSI cycle in the same couple; the cycle pair was the unit of analysis. The primary outcome was live birth rate per cycle; secondary outcomes included fertilization, blastulation, Grade A blastocyst formation, PGT-A, clinical pregnancy, miscarriage, and live birth per embryo transfer. Paired comparisons used McNemar exact and Wilcoxon signed-rank tests. Results Total oocyte, mature oocyte, 2PN, and blastocyst counts were similar between paired cycles (all p > 0.05), while the fertilization rate was lower in TESA-ICSI cycles at the oocyte level (71.3% vs. 79.7%; p = 0.001). By contrast, the blastulation rate per 2PN was higher in TESA-ICSI cycles ( p = 0.008), as was the Grade A blastocyst rate both at the per-embryo level (EJAC: 2.4% vs. TESA: 8.9%; p = 0.0006) and at the per-patient level ( p = 0.0032). PGT-A euploidy increased from 27.9% to 65.0% ( p = 0.0009), the clinical pregnancy rate from 6.9% to 31.0% ( p = 0.0026), and the live birth rate from 0% to 29.3% (absolute risk difference 29.3%; number needed to treat 3.4) ( p = 1.5 × 10 −5 ), while the miscarriage rate per clinical pregnancy fell from 4/4 to 1/18 ( p = 0.0007). Conclusions In couples whose prior EJAC-ICSI cycle had not resulted in a live birth, a subsequent TESA-ICSI cycle in the same couple was associated with significant improvements in embryo quality, euploidy, and live birth without change in embryo numbers. These findings support TESA-ICSI as a reasonable therapeutic option in this clinical scenario.