Sperm DNA integrity does play a crucial role for embryo development after ICSI, notably when good-quality oocytes from young donors are used

Abstract

Based on the inconsistent literature published thus far involving infertile patients, whether intracytoplasmic sperm injection (ICSI) allows overcoming total fertilization failure due to sperm DNA fragmentation is still unclear. Related to this, female factors, which may have a significant impact on assisted reproduction outcomes, can mask male infertility. In this scenario, evaluating ICSI outcomes following cycles using healthy donor gametes could shed light on this realm, as it would avoid the influence of (un)known confounding factors present in infertile individuals. The present work, therefore, aimed to address whether single- and double-stranded sperm DNA fragmentation leads to impaired ICSI outcomes in double gamete donation cycles. The study also compared these double-gamete donation cycles to cycles in which only sperm were donated and oocytes were obtained from infertile patients. Two cohorts were included: (a) the Donor-Donor (DD) cohort, which included 27 semen donor samples used in 49 ICSI cycles with young healthy oocyte donors; and (b) the Donor-Infertile (DI) cohort, which involved 34 semen donor samples used in 57 ICSI cycles with oocytes from patients. Single- and double-stranded sperm DNA breaks were determined with alkaline and neutral Comet assays, respectively; ICSI was conducted following standard protocols and embryos were monitored through time-lapse microscopy. In the DD cohort, the percentage of sperm with high overall DNA damage correlated with fertilization rates (Rs = − 0.666; P < 0.001) and with the percentage of blastocysts per injected oocyte (Rs = − 0.414; P = 0.040). In addition, sperm DNA damage delayed the first embryo division (Rs = 0.421; P = 0.036), and development from the 8-cell to the morula stage (Rs = 0.424; P = 0.034). In contrast, double-stranded DNA breaks had no effect in this cohort. As far as the DI cohort is concerned, while overall sperm DNA damage was not found to be correlated to fertilization or blastocyst rates, pronuclei formation following ICSI was delayed when the incidence of double-stranded DNA breaks was high (Rs = 0.485; P = 0.005). In conclusion, this study, which is the first involving double donation cycles (i.e., a donor-donor cohort), supports that sperm DNA damage has a detrimental impact on fertilization rates after ICSI, and delays embryo development. Moreover, the use of oocytes from infertile individuals is suggested to hide the male-factor effect.

Ultra-Rapid Freezing and Rapid Freezing Methods in Clinical ICSI Program: Effects on Sperm Biological Characteristics, DNA Methylation Stability, DNA Methyltransferase Activity, and Embryo Morphokinetics

“…Esbert et al [60] stated that high sperm DNA fragmentation can lead to a delay in early embryo kinetics, which is related to the increase in the time required before the first cell division to activate DNA repair mechanisms in oocyte. Also, Ribas-Maynou et al [61] observed that the overall DNA damage in sperm was associated with a delay in tPNa, tPNf, and t2 which led to an increase in the time of transition from eight cells to the morula stage.…”

Short-interval second ejaculation improves sperm quality, blastocyst formation in oligoasthenozoospermic males in ICSI cycles: a time-lapse sibling oocytes study

“…However, the paternal genome also affects the developmental speed of the embryo. As stated in a recent study, poor DNA integrity in sperm can cause delayed embryo development, which may be related to the extended time required for oocytes to repair paternal genetic material ( 33 ). Furthermore, from a more microscopic perspective of molecular biology, after the maternal genome controls are transformed during the 8-16 cell stage of human embryos, transcriptional activation of the paternal genome begins to participate in regulating the process of embryonic development ( 35 , 36 ).…”

Checkpoint Kinase 1 Is a Key Signal Transducer of DNA Damage in the Early Mammalian Cleavage Embryo

“…Additionally, a significant portion of the resulting embryos may become arrested in G2/M-stage transition. The cause is the high proportion of aneuploidy of mitotic origin and subsequent disorders in chromosome segregation, resulting in 20 to 30 percent of blastocysts having the so-called mosaic phenotype [ 54 , 55 , 56 ]. Considering these facts and the still incomplete knowledge about the effectiveness or activity and control points of the cell cycle in maturing oocytes as well as in very early embryos, further research in this area is important, but it must be in connection with exogenous environmental factors that have the potential to damage DNA.…”