Induction of Spermatogenesis by Recombinant Follicle-Stimulating Hormone (Puregon) in Hypogonadotropic Azoospermic Men Who Failed to Respond to Human Chorionic Gonadotropin Alone

Pierre Marc G Bouloux, Eberhard Nieschlag, Henry G. Burger, Niels E. Skakkebaek, Frederick C W Wu, David J. Handelsman, Gordon H W Baker, Robert Ochsenkuehn, Annemarie Syska, Robert I. McLachlan, Aleksander Giwercman, Ann J. Conway, Leo Turner, Jacqueline H M Van Kuijk, Gerrit Voortman

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A multicenter, open-label, randomized efficacy and safety study was performed with combined human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) (Puregon®) treatment to induce spermatogenesis in hypogonadotropic hypogonadal male patients. Patients were pretreated for 16 weeks with hCG to normalize testosterone levels. A total of 30 of 49 (61%) subjects had normalized testosterone levels but were still azoospermic after the hCG-alone phase. These patients were randomized into 2 treatment schemes with recFSH (2 × 225 IU recFSH per week [group A] or 3 × 150 IU recFSH per week [group B]), in combination with hCG for a period of 48 weeks. Total testosterone increased during the hCG-alone period from 1.08 and 1.22 ng/mL to 6.26 and 4.52 ng/mL for groups A and B, respectively. Combined gonadotropin treatment was effective in inducing spermatogenesis (sperm count ≥1 × 106/mL) in 14 of 30 subjects (47%) and this was achieved after a median duration of treatment of approximately 5.5 months. Treatment time necessary for first sperm cells to appear in the ejaculate was related to the initial testicular volume. Subjects with a history of maldescended testes (11 of 30 subjects, 37%) showed a lower mean response to treatment as indicated by the relatively lower number of subjects reaching levels of at least 1 × 106 sperm cells per milliliter. Combined testicular volume increased during combined gonadotropin treatment from 11.4 to 24.0 mL. Although subjects with a history of maldescended testes had a lower starting testicular volume, subjects with and without a history of maldescended testes showed approximately the same relative increase in testicular volume. Total testosterone levels showed only a minor further increase during the combined gonadotropin treatment period. In conclusion, a weekly dose of 450 IU (3 × 150 IU or 2 × 225 IU) recFSH, in addition to hCG, was able to induce spermatogenesis in many hypogonadotropic azoospermic men who failed to respond to treatment with hCG alone.

Original languageEnglish
Pages (from-to)604-611
Number of pages8
JournalJournal of Andrology
Issue number4
Publication statusPublished - Jul 2003
Externally publishedYes


  • Follistim
  • Gonadotrophin deficiency
  • Male infertility
  • Testis

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