Chromatin packaging as an indicator of human sperm dysfunction.

Purpose: Understanding the causes of fertilization failure is an important research field in assisted reproductive programs. The present study aimed to evaluated the possible relationship between chromatin packaging quality (CMA3 staining) and (i) normal morphology and (ii) its ability to predict the functional integrity of spermatozoa in both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment programs.

Methods: Semen of 140 men from IVF and ICSI couples were analyzed for sperm concentration, motility, morphology, and chromatin packaging (CMA3). For CMA3 classification, two cutoff values were used, namely, 44.5% +/- 13 and 1 SD above the mean, i.e., 57.5% (rounded off to 60%). IVF and ICSI data were stratified using three basic cutoff values for CMA3 staining, namely, < 44%, > 44-60%, and > 60%.

Results: Based on CMA3 results patients were divided into four groups, namely, group A, < 44% CMA3 (n = 15, IVF); group B, > or = 44% and < 60% CMA3 (n = 39, IVF); group C, > or = 60% CMA3 (n = 45 IVF); and group D, > or = 60% CMA3 (n = 41 ICSI). During receiver operator characteristic analyses the estimated cutoff value for CMA3 staining, to distinguish between < 4% and > or = 4% morphology groups, was 60%. The area under the curve was 0.89, sensitivity of 75%, and specificity of 100%. When IVF rates of > 60% and < 60% were used, the optimal CMA3 value for prediction of fertilization success again was recorded at 60%. The area under the curve was 0.76, sensitivity of 81.5%, and specificity of 63.6%.

Conclusions: Chromatin packaging assessments should be included as a complementary assay to the sequential diagnostic approach of the male-factor patients.