精液分析預測不孕症男性基因異常的最佳閾值討論
黃烱焜1、黃奕燊1,2、黃志賢1,2
台北榮民總醫院 泌尿部1
國立陽明大學醫學院 泌尿學科 書田泌尿科學研究中心1
Incorporating various thresholds of semen parameters
for clinical suggestion of infertile men undergo genetic testing
Chiung-Kun Huang1, I-shen Huang1,2, William J.S. Huang1,2
Department of Urology, Taipei Veterans General Hospital1
Department of Urology, School of Medicine and Shu-Tien Urological Institute, National Yang-Ming University, Taipei, Taiwan2
Purpose: To investigate the prevalence of chromosomal abnormalities, AZF microdeletions and partial AZFc deletions in male infertility patients. We also aim to determine a clinical threshold for genetic testing in infertile men by using semen analysis data.
Materials and Methods: We retrospectively analyzed infertile men between August 2006 and September 2017 who received karyotype and Y chromosome microdeletion analysis. Initial semen analysis data from these infertile men, including sperm count, motility and morphology were analyzed for their association with abnormal genetic testing. Univariate logistic regression analysis was conducted to compare the semen parameters of those with or without genetic abnormalities (chromosome abnormalities, AZF microdeletions and partial AZFc deletions). Various different thresholds of seminal parameters were set (sperm concentrations: 0.1, 0.5, 1, 5 million/ml and motility:10%, 20%, 30%, 40%) to evaluate the odds ratio for detection of genetic anomaly in infertile men.
Results: A total of 1222 infertile men were analyzed, including 767 azoospermic, 264 severe oligospermic, 85 oligospermic and 106 normozoospermic men. Of them, 206 (16.85%) were diagnosed chromosomal abnormalities; AZF microdeletions and partial AZFc deletions were noticed in 104 (8.51%) and 276 (22.58%) in our cohort.Chromosome abnormalities, AZF microdeletions and partial AZFc deletions were detected in 22.6%, 10.8% and 24.1% in azoospermic men. Sperm concentration and motility were significant predictors for the identification of genetic abnormalities. Sperm concentration set at various specific level, 0.5, 1 and 5 million/ml, have the higher odds ratio to detect chromosome abnormalities (OR= 3.436, 95% CI 2.232~5.290, p<0.001), AZF microdeletions (OR=13.324, 95% CI 4.195~42.316, p<0.001), and partial AZFc deletions (OR=1.675, 95% CI 1.09~2.553, p=0.016). Sperm motility cut-off value at 20% have an odds ratio of 2.506 (95% CI 1.623~3.868, p=0.001) for prediction of chromosome abnormalities; cut-off value at 10% can predict the possibility of AZF microdeletions with an odds ratio of 5.356 (95% CI 2.575~11.14, p<0.001).
Conclusions: Infertile men with sperm concentration less than 0.5 million/ml or 1 million/ml should strongly be adviced to undergo karyotype or AZF microdeletions analysis. Sperm motility less than 20% or 10% is associated with higher probability of chromosome abnormalities or AZF microdeletions detection in our cohort.