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Induction of Spermatogenesis and Fertility during Gonadotropin Treatment of Gonadotropin-Deficient Infertile Men: Predictors of Fertility Outcome

Department of Andrology (P.Y.L., V.J., A.J.C., D.J.H.), Concord Hospital and ANZAC Research Institute, University of Sydney, Concord, New South Wales 2139, Australia; Department of Obstetrics and Gynaecology (H.W.G.B.), The Royal Women’s Hospital and University of Melbourne, Parkville, Victoria 3053, Australia; Department of Endocrinology and Diabetes (M.Z.), Royal Children’s Hospital and University of Melbourne, Parkville, Victoria 3052, Australia; and Endocrine and Metabolic Research, Woolcock Institute, University of Sydney, Glebe, New South Wales 2037, Australia

Address all correspondence and requests for reprints to: Associate Professor Peter Y. Liu, F.R.A.C.P., Ph.D., Department of Andrology, Concord Hospital and ANZAC Research Institute, University of Sydney, Sydney, New South Wales 2139, Australia. E-mail: pliu{at}mail.usyd.edu.au.

Background: The induction of spermatogenesis and fertility with gonadotropin therapy in gonadotropin-deficient men varies in rate and extent. Understanding the predictors of response would inform clinical practice but requires multivariate analyses in sufficiently large clinical cohorts that are suitably detailed and frequently assessed.

Design, Setting, and Participants: A total of 75 men, with 72 desiring fertility, was treated at two academic andrology centers for a total of 116 courses of therapy from 1981–2008.

Outcomes: Semen analysis and testicular examination were performed every 3 months.

Results: A total of 38 men became fathers, including five through assisted reproduction. The median time to achieve first sperm was 7.1 months [95% confidence interval (CI) 6.3–10.1]) and for conception was 28.2 months (95% CI 21.6–38.5). The median sperm concentration at conception for unassisted pregnancies was 8.0 M/ml (95% CI 0.2–59.5). Multivariate correlated time-to-event analyses show that larger testis volume, previous treatment with gonadotropins, and no previous androgen use each independently predicts faster induction of spermatogenesis and unassisted pregnancy.

Conclusions: Larger testis volume is a useful prognostic indicator of response. The association of slower responses after prior androgen therapy suggests that faster pregnancy rates might be achieved by substituting gonadotropin for androgen therapy for pubertal induction, although a prospective randomized trial will be required to prove this.