AB22. Role of varicocele repair for male infertility in the era of assisted reproductive technologies

INTRODUCTION: Although infertile couples may include men with a varicocele, IVF/ICSI as primary treatment for male-factor infertility has greatly increased and can potentially decrease direct medical intervention for infertile men when they seek treatment from a urologist specializing in male infertility. Such series of treatment strategy might increase the risk of unnecessary interventions for the female partner, which could lead to potentially serious complications of ART, such as multiple pregnancies and ovarian hyperstimulation syndrome. In addition, repeat IVF/ICSI can be a considerable economic burden for infertile couples. However, using the internet, patients now have greater access to information on feasible treatment options for male infertility. This knowledge might motivate infertile couples to visit a male infertility clinic. In such cases, physicians and patients must choose the most appropriate treatment from the variety of treatments available for male-factor infertility. TREATMENT INDICATIONS AND VARICOCELE MANAGEMENT: Clinical varicoceles are classified into three grades: grade 1, palpable only during the Valsalva maneuver; grade 2, palpable distension while the patient is standing; and grade 3, visible distension. The 2013 European Association of Urology (EAU) guideline, as well as 2012 EAU guideline recommends that varicocele repair should be considered in cases of clinical varicocele, oligospermia, duration of infertility greater than 2 years, and otherwise unexplained infertility in a couple, which is classified as evidence level A. The WHO reported that physical examination had a sensitivity of only about 50% in detecting varicoceles. Jarow et al. used ultrasound to examine vein diameters. Men who had spermatic veins with a diameter greater than 3.0 mm had significantly better semen characteristics after varicocele repair than did men with veins less than 3.0 mm in diameter. The most widely accepted criterion is presence of multiple veins with a diameter greater than 3.0-3.5 mm in conjunction with reversal of flow on color Doppler ultrasound. There are a number of unresolved issues in the management and treatment of varicoceles in adolescents. The 2013 EAU guideline recommends varicocele treatment for adolescents with progressive failure of testicular development, as documented by serial clinical examinations. APPROACHES TO VARICOCELE REPAIR: Most recent reviews concluded that microsurgical varicocele repair has clear advantages over the other techniques, namely, better pregnancy outcomes, lower complication rates, and lower recurrence rates, although this technique requires specific training in microsurgery. Several reports mentioned that laparoscopic surgery under general anesthesia was more invasive than subinguinal microsurgical repair with local anesthesia. EFFECTIVENESS OF VARICOCELE REPAIR IN TREATING MALE INFERTILITY: A number of studies reported that varicocele repair improves semen parameters such as sperm concentration, sperm motility, and progressive sperm motility. The recent meta-analysis and review from Baazeem et al. summarized the effectiveness of varicocele repair in improving semen parameters. In that analysis, the authors selected 22 prospective studies of men with abnormal semen parameters and clinical varicoceles, and observed sperm concentration before and after surgery. The mean improvement in sperm concentration for the 22 studies was 12.3 million sperm/mL (95% CI, 7.07-14.65; P<0.001). Similarly, after varicocele repair, improvement in sperm total motility in 17 prospective studies and progressive sperm motility in 5 prospective studies was 10.86% (95% CI, 7.07-14.65; P<0.001) and 9.69% (95% CI, 4.86-14.52; P=0.003), respectively, which were statistically significant increases. In summary, current evidence indicates that varicocele repair improves semen parameters; however, evidence regarding spontaneous pregnancy rates is equivocal. NEW ROLE OF VARICOCELE REPAIR IN THE ART ERA: Varicocele repair for couples who undergo IVF/ICSI. Esteves et al. studied 242 men with infertility and evaluated clinical outcomes of ICSI in patients with abnormal semen parameters stratified by clinical varicocele treatment status (treated vs untreated). Total number of motile sperm (6.7×10 vs. 15.4×10, P<0.001) and normal 2PN fertilization rate (78% vs. 66%, P=0.04) were significantly higher in treated men than in untreated men. Notably, as compared with untreated men, the probability of achieving clinical pregnancy in couples with treated men increased by 1.82 fold, and the rate of live births increased by 1.87 fold; the rate of miscarriage rate decreased by 0.43 fold. All differences were statistically significant. There have been several reports and discussions regarding varicocele repair for men with nonobstructive azoospermia. Without testicular sperm extraction (TESE), only 3 of the 31 (9.6%) men after varicocele repair had sufficient motile sperm in ejaculate for ICSI. After varicocele repair, men with clinical varicoceles associated with nonobstructive azoospermia rarely have sufficient sperm in ejaculate to avoid TESE. A recent study by Inci et al. showed that varicocele repair had significant effectiveness for men with clinical varicoceles and nonobstructive azoospermia who had undergone micro-TESE/ICSI. In an analysis of treated and untreated men, the sperm retrieval rate (53% vs. 30%) was significantly higher in the treated group, although the clinical pregnancy rate (31.4% vs. 22.2%) did not significantly differ. These results suggest that varicocele repair may be an option for infertile men who are undergoing ICSI. Cost-effectiveness of varicocele repair with ART: Most of the several cost-effectiveness analyses of couples with infertility undergoing ART found that varicocele repair was more cost-effective than primary treatment with assisted reproduction alone, if the male has a clinical varicocele. CONCLUSIONS: Despite the necessity for specific training in microsurgery, microsurgical varicocele repair, is the most promising treatment option and is expected to become the gold standard for treating infertility in men with varicoceles. Evidence on varicocele repair is rapidly accumulating, and future research should evaluate current and new diagnostic methods, management plans, and repair techniques in studies with unified reporting methods and sufficient patient enrollment.