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Abstract Study question How do severely altered parameters in both ejaculated and surgically retrieved testicular sperm affect preimplantation embryo morphokinetics, blastocyst quality and cumulative clinical outcomes? Summary answer Severely altered semen parameters impaired fertilization, embryo morphokinetics, and blastocyst quality, but only the use of testicular sperm reduced cumulative outcomes, including live birth rates. What is known already Semen quality is a significant determinant of reproductive success. Sperm play a crucial role in embryonic genome activation and facilitate embryo progression to the blastocyst stage. Yet, comprehensive analyses of embryo developmental outcomes in cases of male factor infertility remain scarce. Limited by small study cohorts, inconsistent findings and a lack of cumulative outcomes, existing studies have failed to provide a clear understanding of the differential impacts of altered semen parameters on embryo development. Uncertainty about outcomes following the use of poor-quality or testicular sperm complicates clinical management, ultimately leaving patients without comprehensive information to make informed treatment decisions. Study design, size, duration This retrospective study evaluated 10,622 embryos derived from 1,680 patients, across 1,837 ICSI cycles. We included both autologous (n = 429) and donor oocyte (n = 1,407) cycles, performed at a single IVF center between January 2019 and August 2023. To assess differences in critical aspects of reproductive success, we compared various embryo developmental and clinical outcomes across cycles using sperm with severely altered parameters (either ejaculated or obtained through testicular sperm extraction, TESE) to those using normospermic samples. Participants/materials, setting, methods Embryos were distributed into four groups according to sperm quality and origin, as per WHO guidelines: normospermia (n = 8,798), severe oligospermia (5 million/ml; n = 567), severe oligoastenospermia (5 million/ml and progressive motility 32%; n = 716) and TESE (n = 541). We assessed differences in embryo morphokinetics using adjusted Cox survival curves. We used multivariate analyses to evaluate associations between sperm groups and clinical outcomes, adjusting for relevant confounders pertaining to patient demographics and treatment characteristics. P-values 0.05 were considered significant. Main results and the role of chance Compared to normospermia, altered semen parameters resulted in lower mean fertilization rates (74.5% normospermia versus 69.7% severe oligospermia, 69.1% severe oligoastenospermia and 60.6% TESE). While oligospermia and oligoastenospermia showed a negative correlation with fertilization rates (R2=-0.05, p = 0.02 and R2=-0.07, p 0.0001, respectively), this trend was more pronounced for TESE (R2= -0.12, p 0.0001). Embryo morphokinetics were comparable for normospermia, oligospermia and oligoastenospermia. However, TESE resulted in faster early morphokinetic patterns (tPNf, t2, t3, t4 and t5; p 0.05), and similar t8, tsB, tB, with comparable cell cycle durations (s2, s3, cc2 and cc3; p 0.05). Compared to normospermia, severe oligospermia had no effect on inner cell mass (ICM) (OR = 0.93, 95%CI: 0.72-1.21) nor trophectoderm (TE) quality (OR = 0.79, 95%CI: 0.58-1.06), while oligoastenospermia reduced the odds of having a good quality ICM (OR = 0.75, 95%CI: 0.58-0.97) but showed no effect on TE (OR = 0.94, 95%CI: 0.71-1.23). Notably, TESE had the most profound effect on blastocyst quality (ICM, OR = 0.68, 95%CI: 0.49-0.92; TE, OR = 0.68, 95%CI: 0.46-0.98). Following the first embryo transfer, ongoing pregnancy rates were similar across all groups, apart from TESE (R2=-0.217, p = 0.0160). Unlike the other groups (p 0.05), TESE also led to decreased cumulative implantation, ongoing pregnancy, and live birth rates compared to normospermia (R2=-0.19, p = 0.03; R2=-0.23, p = 0.009; R2=-0.22, p = 0.019, respectively). Limitations, reasons for caution The primary limitation of this study is its retrospective design, which may not account for all confounders. Moreover, lifestyle factors, such as smoking or alcohol consumption were not considered. The reliance on data from a single IVF center may also restrict the generalizability of the results to a broader population. Wider implications of the findings Our findings underscore the imperative need for careful consideration of sperm quality for ICSI, highlighting the distinct challenges presented by TESE sperm for achieving reproductive success. While altered semen parameters compromised fertilization rates and embryo quality, TESE cycles were markedly less efficient, ultimately leading to reduced cumulative live birth rates. Trial registration number not applicable
Quintana-Vehí et al. (Mon,) studied this question.