Comparison of outcomes between pulsatile gonadotropin releasing hormone and combined gonadotropin therapy of spermatogenesis in patients with congenital hypogonadotropic hypogonadism.

backgroundTo evaluate whether there was a difference in outcome between pulsatile gonadotropin releasing hormone (GnRH) therapy and human chorionic gonadotropin/human menopausal gonadotropin (hCG/HMG) therapy for induction of spermatogenesis in post-pubertal male patients with congenital hypogonadotropic hypogonadism (CHH).

methodsThis was a single-center retrospective cohort study conducted at the Andrology Center of a university hospital. A total of 155 postpubertal CHH patients who met the inclusion criteria underwent spermatogenic induction at the same andrology center. All patients used pulsatile GnRH therapy or hCG/HMG therapy for at least 6 months. The effects of spermatogenic induction therapy and testicular growth were evaluated. Logistic regression analysis was used to identify statistically significant factors which could predict the outcome of treatment.

resultsThere was no difference in the efficiency of successfully inducing spermatogenesis between pulsatile GnRH therapy and hCG/HMG therapy (82.1% vs. 75.8%, P: 0.356), nor was there a difference in sperm concentration category (SCC) (P: 0.284). However, the mean time required for pulsatile GnRH therapy was shorter (12.34 vs. 14.74 months, P: 0.038). At the treatment endpoint, total testicular volume (TTV) was greater with pulsatile GnRH therapy compared with hCG/HMG therapy (15 vs. 12 ml, P: 0.010), and there was still no difference in SCC (P: 0.310). Multivariate logistic regression analysis showed that only baseline TTV was statistically significant predictor of induced spermatogenic success (odds ratio, OR: 1.156, 95% confidence interval, CI: 1.013, 1.319). The area under receiver operating characteristic curve was 0.635, a sensitivity of 0.661, and a specificity of 0.588. In addition, multiple linear regression analysis demonstrated that younger age at treatment initiation and higher baseline TTV were significantly associated with increased sperm concentration at the end of treatment.

conclusionPulsatile GnRH therapy was similar to hCG/HMG therapy in inducing spermatogenesis in post-pubertal CHH patients, but it took less time and was more beneficial to testicular development. Larger baseline TTV may mean a better spermatogenic outcome. It was necessary for patients to have more information about spermatogenesis therapy in order to make reasonable medical decisions. CLINICAL TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry. ChiCTR2400086876. Retrospectively registered on July 5, 2024.