Healthy birth after testicular extraction of sperm and ICSI from an azoospermic man with mild androgen insensitivity syndrome caused by an androgen receptor partial loss-of-function mutation

Context The androgen receptor (AR) is essential for the development and maintenance of the male phenotype, and for spermatogenesis. Mutations in the AR gene cause a wide variety of androgen insensitivity syndromes (AIS), ranging from complete feminization to phenotypic males with infertility. Objective We report the first birth achieved after intracytoplasmic sperm injection (ICSI) with sperm from an azoospermic man with an AR mutation associated with mild AIS (MAIS). Patients and methods A couple with primary infertility was referred to our centre. The man had azoospermia with testicular hypotrophy and an undervirilized phenotype despite a normal plasma testosterone level. His androgen sensitivity index and serum anti-mullerian hormone (AMH) levels were elevated, pointing to AIS. Molecular analysis of the AR gene revealed a point mutation resulting in an F754S substitution (renumbered F755S in the 2012 McGill University AR gene database), in the ligand-binding domain of the protein, and further analysis indicated impaired receptor function. Results After genetic counselling of the couple, oocytes were retrieved after controlled ovarian hyperstimulation, and sperm were obtained simultaneously by testicular extraction for ICSI. Nine embryos were obtained. Two were transferred and two were suitable for cryopreservation. A pregnancy was obtained and a healthy girl, carrying the F754S AR mutation, was born at 37 similar to weeks of gestation. AR and AMH were detected by immunohistochemistry in the patient's testicular specimens. AMH immuno-staining was intense in tubules without spermatogenesis and weak in those with ongoing spermatogenesis. Conclusion A healthy child can be obtained by testicular extraction and ICSI despite azoospermia in MAIS. The parents must be informed of the X-linked transmission of the mutation to their descendants. The relationship between AR signalling, testicular AMH expression and spermatogenesis in this patient is discussed.