The impact of follicle-stimulating hormone and the sperm concentration on the success of varicocelectomy

Dear Editor, Varicocele (VC) is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord. VC is commonly observed in young adults, predominantly on the left side; it is a frequent cause of male infertility and can lead to testicular hypofunction, pain, and discomfort. Microsurgical varicocelectomy is the gold standard for treating infertility caused by VC. VC repair is strongly recommended for couple infertility, oligoasthenoteratozoospermia (OAT), Grade 2 or 3 clinical VC, partner age <37 years, patient age <40 years, or testicular hypotrophy in children and adolescents. These indications are reinforced when OAT is severe and occurs in younger patients. On the other hand, few indications exist to treat VC in patients with azoospermia. Finally, an additional indication for VC repair is an elevated sperm DNA fragmentation, particularly in partners of women who have undergone unsuccessful intracytoplasmic sperm injection or experienced repeated miscarriages. Sperm quality improves in approximately 70% of patients following varicocelectomy.1 A meta-analysis of 548 patients across 7 studies highlighted the significant improvement in progressive sperm motility following varicocelectomy.2 However, some studies have indicated that surgical intervention may have no beneficial impact on male subfertility.3 Research aimed at identifying prognostic variables for successful varicocelectomy has shown inconsistencies. Therefore, identifying patients who are likely to benefit from varicocelectomy is essential. Given that spermatogenesis is regulated by gonadotropins and androgens, this study aimed to investigate the impact of sex hormones and semen parameters on varicocelectomy success. After receiving approval from the Ethics Review Board of The Second Hospital of Dalian Medical University (Dalian, China; Approval No. PJ-KS-KY-2023-232), oral and written informed consent was obtained from all patients. Data from 71 patients diagnosed with VC on the left side via physical examination and scrotal color Doppler ultrasound between March 2022 and December 2023 were retrospectively evaluated. All patients had at least one abnormal semen parameter and underwent varicocelectomy of the left side. All patients underwent varicocelectomy via a microsurgical subinguinal approach. The exclusion criteria included azoospermia, a history of scrotal surgery, the use of hormone therapy, and vascular conditions. At least two semen samples were analyzed before varicocelectomy in patients with VC. Patients were instructed to abstain from sexual activity for 2–7 days before the semen test. All semen analyses were conducted within 1 h. Parameters such as semen volume, sperm concentration, total sperm count, progressive motility, total motility, and total motile sperm count (TMSC) were recorded. The highest TMSC, either before or after surgery, was used as the reference. Patients were categorized on the basis of the improvement in sperm analysis values. For the postoperative 3-month semen analysis, success was defined as more than a 50% increase in the TMSC for patients with a preoperative TMSC >5 × 106 per ejaculate and at least a 100% increase in the TMSC for those with a preoperative TMSC <5 × 106 per ejaculate.4 Group A included patients who showed no improvement, whereas Group B included those who did. Among the 71 patients who underwent varicocelectomy, 38 (53.5%) showed no improvement in semen parameters (Group A), whereas 33 (46.5%) showed improvement (Group B). The mean age of the patients was 32.1 (standard deviation [s.d.]: 5.4) years. The general characteristics and laboratory data of the patients are presented in Supplementary Table 1. The median follicle-stimulating hormone (FSH), luteinizing hormone (LH), preoperative sperm concentration, and preoperative TMSC were significantly greater in Group A (5.42 mIU ml−1, 4.00 mIU ml−1, 55.89 × 106 ml−1, and 101.68 × 106 per ejaculate, respectively) than in Group B (4.68 mIU ml−1, 2.87 mIU ml−1, 26.25 × 106 ml−1, and 43.40 × 106 per ejaculate, respectively), with all P < 0.05. The results of univariate and multivariate logistic regression analyses of predictive factors for varicocelectomy success are shown in Supplementary Table 2. In the multivariate analysis, the FSH level (odds ratio [OR]: 0.74; P = 0.032) and sperm concentration (OR: 0.97; P < 0.001) were identified as independent predictive factors for varicocelectomy success. Receiver operating characteristic (ROC) curve analysis was conducted to determine threshold values for predictive variables of varicocelectomy success via the Youden’s index (Supplementary Table 3). In our cohort, the threshold value for the sperm concentration was 72.98 × 106 ml−1, with an area under the curve (AUC) of 0.689 (95% confidence internal [CI]: 0.562–0.815). The highest sensitivity and specificity were 0.970 and 0.395, respectively (P = 0.006). The optimal cut-off value for the FSH level was 6.82 mIU ml−1, with an AUC of 0.645 (95% CI: 0.517–0.773). The highest sensitivity and specificity were 0.879 and 0.395, respectively (P = 0.036). The combined AUC of the FSH level and sperm concentration for predicting varicocelectomy success was 0.804 (95% CI: 0.701–0.907). The highest sensitivity and specificity were 0.939 and 0.658, respectively (P < 0.001; Figure 1).Supplementary Table 1: General characteristics, hormone profiles, and semen parameters of the patientsSupplementary Table 2: Univariate and multivariate logistic regression analyses of predictive factors for varicocelectomy successSupplementary Table 3: Receiver operating characteristic curve analysis of parameters affecting varicocelectomy successFigure 1: Receiver operating characteristic curve analysis of follicle-stimulating hormone (FSH), sperm concentration, and the combination of FSH with sperm concentration. AUC: area under the curve; TPR: true positive rate; FPR: false positive rate.In our study, the sperm concentration and FSH level were identified as independent predictors of varicocelectomy success. Our findings indicate that patients with low sperm concentrations are more likely to benefit from varicocelectomy than those with high sperm concentrations. According to the 6th edition of the World Health Organization (WHO) laboratory handbook on the testing and processing of human sperm, the sperm concentration is associated with male fertility.5 Although the sperm concentration is known to be a predictor of conception and is related to the time to pregnancy and pregnancy rates,6 further research is needed to clarify its link to reproductive outcomes. The relationship between FSH levels and recovery following VC is controversial. Evidence suggests that patients with low preoperative FSH levels have better surgical outcomes, whereas those with higher levels experience poor outcomes or show no improvement.7 In a study involving 118 patients, the percentage change in the FSH level, rather than the initial value, was found to be a predictive factor.8 A study involving 123 patients with VC reported that varicocelectomy responders had slightly lower FSH levels than nonresponders did, although this difference was not statistically significant.9 A study involving 66 patients suggested that preoperative FSH levels might predict the postoperative TMSC, with lower FSH levels associated with an improvement in TMSC categories and a strong correlation with the postoperative TMSC.10 Patients with moderate-to-severe oligozoospermia associated with VC have been reported to have elevated FSH levels.11 On the basis of our findings, preoperative FSH levels can help identify which patients with VC are likely to benefit most from microsurgical varicocelectomy. FSH levels serve as a marker for the degree of spermatogenesis. High FSH levels indicate impaired spermatogenesis, which may explain why patients with elevated FSH levels in our study did not benefit from surgery. A patient with a low FSH level (<6.82 IU l−1) and low sperm concentration (<72.98 × 106 ml−1) is considered to have a reduced likelihood of improvement. We should lower the expectations of these patients regarding VC repair and provide effective psychological counseling. AUTHOR CONTRIBUTIONS HJ and TJ conceived the study, and reviewed and revised the manuscript. LHW and LZ were responsible for conducting the publication search, drafting the manuscript, and editing the tables and figures. All authors read and approved the final manuscript. COMPETING INTERESTS All authors declare no competing interests. Supplementary Information is linked to the online version of the paper on the Asian Journal of Andrology website.