A teenage boy with a rare genetic mutation (NR5A1) that affects testicle development was given triptorelin to treat early puberty, but later attempts to collect sperm for future use failed, showing that this drug didn’t improve his fertility prospects.

Steroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 (<i>NR5A1</i>) gene, is a transcriptional factor crucial for adrenal and gonadal organogenesis. Pathogenic variants of <i>NR5A1</i> are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance including disorders of sex development and oligospermia-azoospermia in 46,XY adults. Preservation of fertility remains challenging in these patients. The aim was to offer fertility preservation at the end of puberty in an <i>NR5A1</i> mutated patient. The patient was born of non-consanguineous parents, with a disorder of sex development, a small genital bud, perineal hypospadias, and gonads in the left labioscrotal fold and the right inguinal region. Neither uterus nor vagina was detected. The karyotype was 46,XY. Anti-M&#xfc;llerian hormone (AMH) and testosterone levels were low, indicating testicular dysgenesis. The child was raised as a boy. At 9 years old, he presented with precocious puberty treated by triptorelin. At puberty, follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone levels increased, whereas AMH, inhibin B, and testicular volume were low, suggesting an impaired Sertoli cell function and a partially preserved Leydig cell function. A genetic study performed at almost 15 years old identified the new frameshift variant NM_004959.5: c.207del p.(Phe70Ser<i>fs</i>*5) at a heterozygous state. He was thus addressed for fertility preservation. No sperm cells could be retrieved from three semen collections between the ages of 16 years 4 months and 16 years 10 months. A conventional bilateral testicular biopsy and testicular sperm extraction were performed at 17 years 10 months of age, but no sperm cells were found. Histological analysis revealed an aspect of mosaicism with seminiferous tubules that were either atrophic, with Sertoli cells only, or presenting an arrest of spermatogenesis at the spermatocyte stage. We report a case with a new <i>NR5A1</i> variant. The fertility preservation protocol proposed at the end of puberty did not allow any sperm retrieval for future parenthood.