BackgroundThe use of testicular over ejaculated spermatozoa for ICSI has been presented as an alternative to overcome infertility in men with poor semen parameters or high levels of sperm DNA fragmentation.ObjectiveTo evaluate the efficacy of testicular ICSI outcomes in couples with no previous live birth and recurrent ICSI failure using ejaculated spermatozoa by comparison to the outcomes of couples with similar history of recurrent ICSI using ejaculated spermatozoa only.Materials and MethodsA total of 145 couples undergoing ejaculated or testicular ICSI cycles with no previous live births and with at least two previous failed ICSI cycles with ejaculated spermatozoa were evaluated retrospectively. ICSI was performed either with ejaculated (E‐ICSI) or with testicular (T‐ICSI) spermatozoa. Semen parameters and sperm DNA quality were assessed prior to the oocyte collection day. Primary outcomes included cumulative live birth and pregnancy rates. Secondary analysis included percentage of DNA fragmentation in ejaculated spermatozoa (SCSA® and TUNEL).ResultsPatients undergoing T‐ICSI (n = 77) had a significantly higher clinical pregnancy rate/fresh embryo transfer (ET) (27.9%; 17/61) and cumulative live birth rate (23.4%; 15/64) compared to patients using E‐ICSI (n = 68) (clinical pregnancy rate/fresh ET: 10%; 6/60 and cumulative live birth rate: 11.4%; 7/61). Further, T‐ICSI yield significantly better cumulative live birth rates than E‐ICSI for men with high TUNEL (≥36%) (T‐ICSI: 20%; 3/15 vs. E‐ICSI: 0%; 0/7, p < 0.025), high SCSA® (≥25%) scores (T‐ICSI: 21.7%; 5/23 vs. E‐ICSI: 9.1%; 1/11, p < 0.01), or abnormal semen parameters (T‐ICSI: 28%; 7/25 vs. E‐ICSI: 6.7%; 1/15, p < 0.01).ConclusionsThe use of testicular spermatozoa for ICSI in non‐azoospermic couples with no previous live births, recurrent ICSI failure, and high sperm DNA fragmentation yields significantly better live birth outcomes than a separate cohort of couples with similar history of ICSI failure entering a new ICSI cycle with ejaculated spermatozoa.

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