Fertility outcomes and management of long-term pubertal testosterone replacement sequelae in Oliver-McFarlane syndrome: a case report and literature review.

BACKGROUND

Oliver-McFarlane syndrome (OMCS) is an extremely rare autosomal recessive disorder caused by biallelic mutations in the PNPLA6 gene, characterized by retinal dystrophy, trichomegaly, neurodevelopmental impairment, and combined pituitary hormone deficiencies. Hypogonadotropic hypogonadism (HH) is a frequent endocrine manifestation; however, the long-term reproductive consequences and fertility potential in affected males have not been previously described.

CASE DESCRIPTION: We report the case of a 33-year-old man with genetically confirmed OMCS who presented with primary infertility and non-obstructive azoospermia following prolonged testosterone replacement therapy initiated in childhood for pubertal induction. The patient exhibited congenital HH, evidenced by micropenis in infancy, absent spontaneous puberty, persistently low gonadotropins, and severely reduced testicular volume. After discontinuation of exogenous testosterone, prolonged combined gonadotropin therapy with human chorionic gonadotropin and recombinant follicle-stimulating hormone resulted in partial testicular growth and biochemical response but failed to induce sperm in the ejaculate. Following nearly two years of optimized hormonal stimulation, microdissection testicular sperm extraction (micro-TESE) was performed, revealing focal spermatogenesis with successful retrieval and cryopreservation of motile spermatozoa for intracytoplasmic sperm injection.

CONCLUSIONS

This case represents, to our knowledge, the first report of fertility management and successful surgical sperm retrieval in a male patient with OMCS. It highlights the potential reversibility of infertility in syndromic congenital HH and underscores the critical impact of pubertal management strategies on long-term reproductive outcomes. Early consideration of gonadotropin-based therapy, multidisciplinary follow-up, and fertility-preserving approaches may be essential to optimize future reproductive potential in patients with OMCS and related disorders.