SUN-131 - An Interesting Case of Primary Testicular Spermatogenic Failure

Introduction: Male factor infertility is a common contributor to infertility and may result from impaired spermatogenesis despite intact hypothalamic-pituitary signaling. Azoospermia affects approximately 1% of men and accounts for 10 -15% of male infertility, with non-obstructive azoospermia (NOA) representing the most severe form of spermatogenic failure. Elevated follicle-stimulating hormone (FSH) is a key biochemical marker distinguishing primary testicular failure from obstructive causes. We present a case of NOA with preserved androgen production and normal karyotype.

Case presentation: A 34-year-old male with prediabetes and hypertension presented with 14 months of infertility. History was notable for remote blunt testicular trauma during high school. Initial morning labs showed total testosterone 270 ng/dL (RR: 246–916), free testosterone 76.5 pg/mL (RR: 35–155), elevated FSH 23.5 mIU/mL (RR: 1.4–18.1), and normal LH 7.05 mIU/mL (RR: 1.5–9.3). Repeat testing at 7:40 AM showed total testosterone 300 ng/dL, estradiol 35.9 pg/mL (RR: 0–39), low SHBG 10.75 nmol/L, elevated FSH 24.6 mIU/mL, and mildly elevated LH 10.22 mIU/mL. Other anterior pituitary hormones were normal. MRI of the sella revealed no pituitary abnormalities, and scrotal ultrasound was unremarkable. Karyotype analysis demonstrated 46, XY with normal G-banding. Semen analysis revealed a 2.3 mL sample with zero sperm count and no motile sperm. The patient was referred to a fertility specialist for further evaluation.

Discussion: This patient’s persistently elevated FSH, azoospermia, and borderline total testosterone with preserved free testosterone are consistent with primary testicular spermatogenic failure with intact Leydig cell function. Elevated FSH reflects Sertoli cell dysfunction and is present in a large portion of men with NOA, correlating with seminiferous tubule damage. Normal ejaculatory volume and intact pituitary function argue against obstructive azoospermia or secondary hypogonadism. Although karyotype was normal, genetic causes remain common; chromosomal abnormalities and Y-chromosome microdeletions account for 20-30% of azoospermia, with microdeletions found in 5-10% of NOA cases. Sertoli cell-only syndrome, present in up to 15 -30% of testicular biopsies in NOA, is characterized by germ cell absence and isolated FSH elevation. Definitive diagnosis requires testicular biopsy. Rarely, FSH receptor mutations ( < 1%) may cause elevated FSH with impaired spermatogenesis.

Conclusion: Primary testicular spermatogenic failure should be suspected in infertile men with azoospermia and elevated FSH, even with normal testosterone and karyotype. Accurate diagnosis is essential for genetic evaluation, fertility counseling, and management.

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