Spermatogenesis of Male Patients with Congenital Hypogonadotropic Hypogonadism Receiving Pulsatile Gonadotropin-Releasing Hormone Therapy Versus Gonadotropin Therapy: A Systematic Review and Meta-Analysis

Purpose: Pulsatile gonadotropin-releasing hormone (GnRH) therapy and gonadotropin therapy (GT) were widely used for male patients with congenital hypogonadotropic hypogonadism (CHH), but their efficacy was not well compared before. We conducted this meta-analysis to compare the efficacy of restoring fertility using these two therapies. Materials and Methods: PubMed, Web of Science, and Scopus were systematically searched for comparative studies evaluating the efficiency of GnRH therapy and GT for male patients with CHH. For continuous outcomes, the weighted mean difference (WMD) was used to measure the difference, whereas the risk ratio with 95% confidence interval was calculated for binary variables. Results: Overall, eight articles from seven studies with 420 patients enrolled were included in the analysis. Patients from the two different groups were determined to be comparable in age, proportion with Kallmann syndrome, percentage of cryptorchidism and pretreatment hormones (follicular-stimulating hormone, luteinizing hormone, and testosterone). GnRH therapy was related to a larger testicular volume (standardized mean difference=-1.43; p=0.01) and earlier spermatogenesis (WMD=- 5.30 months; p=0.004) compared to GT. However, the difference in the rate of positive sperm detection (p=0.08), sperm concentration (p=0.37), and pregnancy rate (p=0.11) were not significant. Allergic reactions mostly occurred during GnRH therapy, while GT was related to a higher incidence of gynecomastia and acne. Conclusions: Compared to GT, GnRH was related to earlier spermatogenesis and less estradiol-related adverse reactions, although there were no significant differences in spermatogenesis rate, sperm concentration, and pregnancy rate. High-quality randomized controlled trials are needed for future research.