Advances In Semen Analysis, Automation, and Point Of Care Testing
Semen quality is an important determinant of male fertility, however, defining clear thresholds for normal ranges has proven difficult. One approach is to look at time to pregnancy studies which show that fecundity starts to decline when sperm concentrations fall below 30-55 × 106/ml. Yet, the WHO criterion for normal is currently 15 × 106/ml. Since multiple studies over the past 15 years report median sperm concentration of 41-55 × 106/ml in young men from the general population (mean age 18-21 years) this suggests that many of these young men have suboptimal semen quality.
Automation of semen analysis
Semen analysis is the corner stone of male infertility workup. Conventional microscopic examination of semen is prone to high variability and lack of standardization. Reporting an accurate manual semen analysis is fraught with difficulty due to a variety of factors. Human errors or inconsistencies influencing the accuracy of semen analysis are most often associated with counting, statistical errors, poor sample handling, lack of consistent adherence to protocols, and technician stress. This is further compounded by instrument variation and deterioration, varying protocols, and the nature of a time sensitive biologic sample.
It is a challenge to perform a single accurate assessment of the basic semen parameters such as sperm concentration, motility, and morphology. Because of the factors listed previously and the subjective nature of manual analysis, repeatability is poor and inter-operator variability is high. The World Health Organization (WHO) manual (5) has attempted to standardize semen analysis and promote consistency and accuracy by recommending that 200 spermatozoa be counted in duplicate to enhance the repeatability by increasing the sample size. Even if this recommendation is followed for manual semen analysis, WHO permits a 20 percent difference between duplicate sperm counts. Scoring of motility manually is prone to overestimation. This may be attributed to the well-documented fact that manual assessment of motility is subjective and generally overestimated because of the attraction of the eye to movement. Accuracy and precision can only be achieved by eliminating human error, adhering to an effective and standardized protocol, and assessing a very large sample size. It is evident that automation is a key factor to address all of these objectives.
The results of the American Association of Bioanalyists national proficiency testing program showed that CVs in sperm counts ranged from 24 percent to 138 percent, with computer-assisted sperm analysis (CASA) displaying a lower overall CV (53% 8%) compared with manual methods (80% 9%). A wide variation in normal morphology results was reported in the same publication. The study concluded that an urgent need to improve the quality of semen analysis was in order. Furthermore, the accuracy of reporting concentration is dependent on the number of frames analyzed and impacted by the presence or absence of debris in the specimen. Additionally, the study found that the ability to standardize semen analysis using CASA is impacted by the varying algorithms resident in different CASA systems. Based on the publications reviewed it is evident that precision, accuracy, and standardization are still issues impacting manual and CASA.
There is a debate about the best technology to automate semen analysis: signal processing vs. image processing. The signal processing technology, utilized by sperm quality analyzers such as the newly introduced SQA Vision shows better motility statistics when compared to manual motility results. In addition, compared with the manual method, the results are objective and rapid (a few minutes versus over 30 minutes). This technology also provides percent normal morphology results without quantifying specific abnormalities. As such, it is limited when compared with manual methodology where morphological defects need to be identified and quantified but as a morphology qualitative screen, it can be useful.
