The impact of different WHO reference criteria for semen analysis in clinical practice: Who will benefit from the new 2021 thresholds for normal semen parameters?

Background In 2021, the World Health Organization (WHO) has provided the latest update on processing and evaluating semen analysis. Objectives To assess (i) the rate of discordance in semen parameters categorization across three different WHO reference values (namely WHO21, 2010 and 1999) and (ii) the clinical differences among discordant semen analyses from a cohort of primary infertile men. Materials and methods Data from 788 infertile men were analyzed. Semen parameters were interpreted based on WHO21, WHO10, and WHO99 reference criteria. Pregnancy outcomes with assisted reproductive techniques (ART) were available for 110 (14%) patients. Descriptive statistics was applied to describe potential differences among the three consecutive WHO references criteria. Results Semen parameters categorizations were highly different across the three groups (p < 0.001). Of all, 271 (42.2%) patients had normal semen parameters according to WHO10 but were pathologic when considered with WHO21 reference criteria (namely, men with increased semen abnormalities). Infertile men with increased semen abnormalities had lower testicular volume (p < 0.001) but higher FSH (p < 0.01) and LH (p < 0.001) values than those who had no change in terms of semen parameters categorization. Negative ART outcomes were more frequently reported in men with worsening semen parameters compared with those with confirmed semen parameters at WHO21 versus WHO10 (26.8% vs. 49%, p = 0.03). Conversely, infertile men with worsening semen parameters at WHO21 versus WHO99 were similar in terms of clinical and hormonal characteristics compared with those with the same rate of semen abnormalities. Conclusions One out of three infertile men showed worsened semen categorization according to WHO21 versus WHO10. Infertile men with worsening of semen parameters had worse clinical and hormonal characteristics than those with confirmed numbers of semen abnormalities. Moreover, live birth rates were lower in men with worsening semen abnormalities as for WHO21.