Effect of microsurgical varicocelectomy on sperm DNA integrity and association with reproductive outcomes at IVF/ICSI
Men with clinical varicoceles have been shown to have elevated levels of sperm DNA fragmentation (DFI), which is associated with adverse reproductive outcomes. We examined the effect of microsurgical subinguinal varicocele repair (VR) on sperm DFI assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and/or sperm chromatin structure assay (SCSA) and correlated these data with pregnancy and live birth outcomes at IVF/ICSI.
We performed a retrospective review of 78 men who underwent microsurgical subinguinal VR by a single surgeon for male factor infertility and had pre and postoperative measurements of sperm DFI. Sperm DFI was assessed by TUNEL and/or SCSA assay and compared with IVF/ICSI outcomes. Comparisons were assessed with t-test and McNemar&[prime]s test.
Mean patient age was 38.5 years old and mean partner age was 36.6 years old. Mean TUNEL and SCSA values both decreased significantly following VR, with the mean percentage of TUNEL positive sperm decreasing by 6.9% from 17.0±8.9% to 10.1±6.2% (n=60, p<0.001) and the mean SCSA decreasing by 6.5% from 31.2±11.5% to 24.6±10.9% (n=35, p=0.004). The percentage of patients with an abnormal TUNEL assay (defined as >7% TUNEL-positive sperm) decreased from 93% of patients (56/60) to 62% (37/60) post-operatively (p<0.001). Similarly, the percentage of patients with abnormal SCSA results (defined as >30%) decreased from 71% (25/35) to 31%(11/35) post-operatively (p<0.001). Of the 78 men, 32 patients required IVF/ICSI. Among these couples, the pregnancy rate was 63% (20/32) and live birth rate 41% (13/32), which is superior to previous outcomes for male factor. Of couples that achieved pregnancy, the mean decreases in TUNEL and SCSA following VR were 4.6% from 13.9±5.6% to 9.3±5.7% (n=16, p=0.006) and 0.36% from 28.1±8.3% to 27.7±17.4% (n=9, p=0.47), respectively. Differences in DFI amongst patients who never achieved pregnancy were not statistically significant.</p>
Treatment of varicocele using microsurgical subinguinal VR technique significantly improves sperm DFI as measured by TUNEL and SCSA. Improvements in TUNEL following VR are associated with improved pregnancy outcomes using IVF/ICSI.
Funding: The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.