C. Frapsauce1, C. Ravel1, M. Legendre2, M. Sibony3, J. Mandelbaum1, B. Donadille4, J.C. Achermann5, J.-P. Siffroi2,6 and S. Christin-Maitre4,6,*1UPMC, AP-HP, Hôpital Tenon, Service de Biologie de la Reproduction, 75020 Paris, France 2AP-HP, Hôpital Trousseau, Service de Génétique et d'Embryologie Médicales, 75012 Paris, France 3AP-HP, Hôpital Tenon, Service d'Anatomopathologie, 75020 Paris, France 4Service d'Endocrinologie, Hôpital Saint-Antoine, AP-HP, Centre de maladies endocriniennes rares de la croissance CMERC, 75012 Paris, France 5Developmental Endocrinology Research Group, Clinical & Molecular Genetics, UCL Institute of Child Health, University College London, London WC1N 1EH, UK 6ER9, génétique de la reproduction, Faculté de médecine Pierre et Marie Curie, University Paris VI, France *Correspondence address. Service d'Endocrinologie, Hôpital Saint-Antoine, AP-HP, Centre de maladies rares de la croissance (CMERC), 184 rue du faubourg Saint-Antoine, ER-9 Université Paris VI, 75012 Paris, France. Tel: +33-1-49-28-24-00; Fax: +33-1-49-28-31-95; E-mail: sophie.christin-maitre{at}sat.aphp.frReceived July 4, 2010. Revision received November 30, 2010. Accepted December 3, 2010. DAX1/NR0B1 mutations are responsible for X-linked congenital adrenal hypoplasia (AHC) associated with hypogonadotropic hypogonadism (HH). Few data are available concerning testicular function and fertility in men with DAX1 mutations. Azoospermia as well as failure of gonadotrophin treatment have been reported. We induced spermatogenesis in a patient who has a DAX1 mutation (c.1210C>T), leading to a stop codon in position 404 (p.Gln404X). His endocrine testing revealed a low testosterone level at 1.2 nmol/l (N: 12–40) with low FSH and LH levels at 2.1 IU/l (N: 1–5 IU/l) and 0.1 IU/l (N: 1–4 IU/l), respectively. Baseline semen analysis revealed azoospermia. Menotropin (Menopur®:150 IU, three times weekly) and human chorionic gonadotrophin (1500 IU, twice weekly) were used. After 20 months of treatment, as azoospermia persisted, bilateral multiple site testicular biopsies were performed. Histology revealed severe hypospermatogenesis. Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed. Four embryos were obtained and, after a frozen–thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy. We report the first case of paternity after TESE–ICSI in a patient with DAX1 mutation, giving potential hope to these patients to father non-affected children. Furthermore, this case illustrates the fact that patients with X-linked AHC have a primary testicular defect in addition to HH. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This ArticleHum. Reprod. (2011) 26 (3): 724-728. doi: 10.1093/humrep/deq372 First published online: January 11, 2011
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