Principal findings
The data generated by the present study provide strong evidence that sperm quality is associated with embryonic development and final clinical outcomes.
Strengths of the study
The primary strength of our study is that we focused on sibling oocytes, thus eliminating any potential bias relating to female factors. To our knowledge, this is the first study to explore the effect of paternal factors on embryonic development and the clinical outcomes with sibling oocytes. In this study, we observed a significant improvement in clinical outcomes following the first ET with embryos derived from donor sperm in cases where previous ETs, involving embryos derived from the partner’s sperm, failed to achieve pregnancy. This split IVF/ICSI strategy might be helpful for patients with no embryos to transfer in the first few cycles. There are several advantages to this strategy. First, this method provides patients with one or more alternative options for treatment, thus relieving psychological pressure. Second, this method can alleviate economic stress incurred by the patients by increasing the utilization rate of the oocytes acquired. Third, this method may help to define reasons for patients with impaired embryo quality in the first few cycles.
Limitation of the data
However, several limitations need to be considered in interpreting our findings. First, the sample size of the study was relatively small. Second, we did not evaluate sperm DNA fragmentation in semen samples because this is not a routine form of analysis in our center. Finally, the study was limited by the nature of retrospective study.
Interpretation
Our results are in agreement with a number of previous studies showing that abnormalities in sperm morphology and DNA integrity can exert negative effects on embryo quality and development (5-8). Our findings also concur with a recently published review article that provided significant evidence to support the fact that sperm with an abnormal structure of chromatin fragmented DNA, Y chromosome microdeletion, an abnormal number of chromosomes, or an altered genetic imprint, may be correlated to poor fertilization rates, and the impairment of embryogenesis and development (14). However, our results do not support a number of previous publications that found no association between the maturity of sperm chromatin or sperm DNA fragmentation with embryonic development and pregnancy outcomes (30, 31). We believe that these discrepancies are related to inconsistencies in the methods used to determine sperm DNA; it is highly evident that we do not have a gold standard for determining sperm DNA fragmentation at present.
In this study, we observed that the proportion of high quality embryos on day 2 in the group derived from the partner’s sperm was significantly lower than that in the group derived from the donor sperm. The results of our experiments fail to support the hypothesis that zygotic genome activation only occurs after the 4-cell stage in humans (32). However, our results are in accordance with the study previously reported by Simon which showed that increased levels of sperm DNA damage can exert negative impact on embryo quality, beginning on day 2 of early embryonic development and continuing after embryo transfer, thus leading to lower implantation rates and pregnancy outcomes (8). In addition, our current data concurred with those generated by Harrouk et al., who previously demonstrated that sperm DNA damage might be translated into chromosome aberration as early as the first metaphase (33). Further studies are now needed to confirm these results.
Apart from paternal factors, a range of female factors are known to be involved in the creation of high quality embryos with the competence to implant, including a number of factors associated with cytoplasmic maturation and nuclear maturation. In the present study, we found an interesting phenomenon in that, for some of the included couples, the proportion of utilized oocytes did not differ when compared between the group of oocytes fertilized by the partner’s sperm and those fertilized by a donor’s sperm. Our explanation for this phenomenon is that the delayed embryonic development in these patients might be attributed to the maturity and quality of the oocytes. These results are consistent with the results published previously by Ziegler et al., and others, which reported that a number of female and environmental factors can exert significant influence on embryonic development and implantation (26).