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

EBERHARD NIESCHLAG

HENRY G. BURGER

NIELS E. SKAKKEBAEK

ROBERT OCHSENKUEHN

ANNEMARIE SYSKA

ROBERT I. MCLACHLAN

From the ^* Department of Endocrinology, The Royal Free Hospital, London, United Kingdom; Institute of Reproductive Medicine of the University, Münster, Germany; Prince Henry's Institute of Medical Research, Clayton, Australia; Rikshospitalet, Copenhagen, Denmark;^|| Department of Endocrinology, Manchester Royal Infirmary, University of Manchester, United Kingdom;^¶ ANZAC Research Institute, Sydney, Australia;^# Royal Women's Hospital, Melbourne University, Melbourne, Australia; ¹ Fertility Centre, Scanian Andrology Centre, Malmö, Sweden; ² Department of Andrology, Concord Hospital, University of Sydney, Sydney, Australia; and³ NV Organon, Oss, The Netherlands.

Correspondence to: Gerrit Voortman, NV Organon, Clinical Development Department, PO Box 20, 5340 BH, Oss, The Netherlands (e-mail: gerrit.voortman{at}organon.com).

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 x 225 IU recFSH per week [group A] or 3 x 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 x 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 x 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 x 150 IU or 2 x 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.

     Key words: Follistim, gonadotrophin deficiency, male infertility, testis