Serum Inhibin B and Follicle-Stimulating Hormone Levels as Tools in the Evaluation of Infertile Men: Significance of Adequate Reference Values from Proven Fertile Men

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Abstract
Inhibin B and FSH levels in 289 idiopathic infertile men were compared with reference materials consisting of 303 proven fertile men (reference group 1) and 307 healthy men from the general population with unknown fertility status (reference group 2). The diagnostic power of these two serum markers of spermatogenesis was evaluated by the use of receiver operating characteristic plot analysis, and an example of how both markers can be used simultaneously in a bivariate reference chart is presented. Inhibin B levels were significantly lower and FSH levels were significantly higher in the infertile men, compared with either reference group, but with significant overlap, especially with reference group 2. Nevertheless, approximately 50% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, whereas only approximately 25% of the infertile men had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 2. Fourteen and 11% of reference group 2 had an inhibin B or FSH, respectively, below the 2.5 percentile or above the 97.5 percentile of reference group 1, suggesting that a significant number of individuals from the general population with unknown fertility but otherwise healthy may actually be subfertile. In conclusion, 1) proven fertile men constitute the most appropriate reference group in the evaluation of the FSH-inhibin B axis; the sensitivity of these markers to identify infertility increased by approximately 20% when fertile men rather than men from the general population were used as control group; 2) FSH alone had a slightly higher positive predictive value than inhibin B alone, but the positive predictive value were highest when both markers of spermatogenesis were used in an inhibin B/FSH ratio; and 3) a bivariate reference chart is a valuable objective tool in the simultaneous evaluation of FSH and inhibin B as two interrelated markers.