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, 44% and <60% CMA₃ (n = 39, IVF); group C, 60% CMA₃ (n = 45 IVF); and group D, 60% CMA₃(n = 41 ICSI). During receiver operator characteristic analyses the estimated cutoff value for CMA₃ staining, to distinguish between <4% and 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.