Introduction: Sperm DNA fragmentation index (SDF) has been associated with impaired spermatogenesis and infertility, with negative consequences on biological events such as fertilization and embryonic development. Clomiphene citrate (CC) and FSH treatment (either highly purified FSH (uhFSH) and recombinant human FSH (rhFSH)) have been used to empirically improved sperm quality, but their effect on SDF is relatively relatively poorly studied. We cross-sectionally analyzed the effect of CC and FSH treatment on SDF in men presenting for primary couple’s infertility
Methods: Semen analysis, SDF (according to SCSA) and serum hormones were measured in every patient; health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Data from 433 men treated with either CC (n=370, 85.5%) or FSH (n=63, 14.5%) for pathologic SDF were analyzed. Pre vs. post treatment Semen analysis, SDF were evaluated with paired t-test. Logistic regression analysis was used to test potential predictors of DFI improvement after treatment.
Results: Overall, median (IQR) age, FSH and SDF were 37.5 (24, 64) years, 4.8 (2.8, 5.0) mUI/mL and 43.5% (33.2, 61.4), respectively. At first post-treatment (any) assessment, an improvement in terms of SDF, sperm concentration, percentage of progressive motility and of normal morphology was observed in 36 (60%), 167 (52.5%), 152 (54.9%), and 154 (57%) men, respectively. SDF rate was significantly reduced after treatment (any) (44.9 vs. 52.5%; mean post vs. pre change -7.6; p=0.001). Conversely, sperm concentration (12.3 vs. 15.0x10^6/mL) and progressive motility (18.6 vs. 19.1%) were slightly but not significantly improved after treatment (any). Normal morphology (10.8 vs. 6.5%) was significantly reduced after treatment (any) (p<0.001), particularly after CC treatment (10.9 vs. 6.9%, p<0.001). Both CC (p=0.001) and FSH (p=0.04) therapy significantly improved SDF levels, with a higher improvement after CC compared to FSH treatment (-12.5 vs. -2.5; p=0.01). ROC curves revealed that baseline SDF>35% could predict SDF improvement after treatment, with 97% sensitivity and 71% specificity. At multivariable logistic regression analysis, only a baseline SDF>35% was associated with SDF improvement after treatment, after accounting for age, BMI, serum FSH and smoking status.
Conclusions: Both CC or FSH treatment improved SDF in primary infertile men. Patients who benefit most are those with higher baseline SDF, with SDF>35% as a possible clinical cut-off. Source of
