In vivo biochemical investigation of spermatogenic status: 1H-MR spectroscopy of testes with nonobstructive azoospermia

Objectives To evaluate the biochemical milieu in testes with nonobstructive azoospermia (NOA) by using proton MR spectroscopy (1H-MRS) in detecting differences in testicular metabolites between histological stages of NOA and in assessing the possible presence of spermatozoa before microdissection testicular sperm extraction (mTESE). Methods Forty-nine NOA men and fifty age-matched controls were included in this prospective study. A single-voxel point-resolved spectroscopy sequence with TR/TE (2000/25 ms) was used. NOA testes were classified using the higher Johnsen score (hJS) (group 1, hJS ≥ 8; and group 2, hJS < 8). Nonparametric statistical tests were used to assess differences in normalized metabolite concentrations, defined as ratios of the metabolite concentrations versus creatine concentration between (a) NOA and controls, (b) NOA groups, and (c) NOA with positive and negative sperm retrieval. Results Normalized concentrations of total choline (median 0.396 vs 1.09 mmol/kg, p = 0.002), myo-inositol (median 1.985 vs 3.19 mmol/kg, p = 0.002), and total lipids and macromolecules (TLM) resonating at 0.9 ppm (median 0.962 vs 2.43 mmol/kg, p = 0.024), 1.3 ppm (median 4.88 vs 10.7 mmol/kg, p = 0.043), and 2.0 ppm (median 2.33 vs 5.96 mmol/kg, p = 0.007) were reduced in NOA testes compared with controls. Decreased concentrations of TLM 2.0 (median 3.755 vs 0.436 mmol/kg, p = 0.043) were found in group 2 compared with group 1. Increased normalized concentrations of glutamate were observed in NOA testes with failed sperm retrieval (median 0.321 vs 0.000 mmol/kg, p = 0.028). Conclusions 1H-MRS provides metabolic information about the testis in NOA patients and assesses spermatogenic status before mTESE. Key Points • NOA testes differed from age-matched controls, in terms of reduced normalized concentrations of tChol, mI, and lipids. • TLM 2.0 peaks were found useful in the identification of NOA testes with the presence of foci of advanced spermatogenesis up to the haploid gamete stage. • Glu proved a reliable metabolic signature of spermatogenesis in NOA population by assessing the possible presence of sperm after mTESE.