Hypophosphatemia is a frequent finding in infertile men and is associated with low motile sperm count

STUDY QUESTION: Is serum phosphate linked with semen quality and reproductive hormones in infertile men?

SUMMARY ANSWER: Hypophosphatemia is a frequent finding in infertile men and is associated with lower number of motile sperm.

WHAT IS KNOWN ALREADY: Phosphate is available in fluid from all segments of the male reproductive tract in concentrations manyfold higher than in serum. However, the role of phosphate in male fertility is largely unknown.

STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 1242 men referred due to infertility between January 2017 and May 2020 at the Department of Growth and Reproduction, Rigshospitalet, Copenhagen.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Each man underwent a physical examination, had semen parameters assessed, and had blood analyzed prospectively for concentrations of phosphate, ionized calcium, alkaline phosphatase, parathyroid hormone, serum 25-hydroxyvitamin D (25OHD), and reproductive hormones. After 246 men were excluded due to serious comorbidities, 1242 were included in the analyses.

MAIN RESULTS AND THE ROLE OF CHANCE: Infertile men have a high prevalence of mild (25.5%, 0.66-0.80 mmol/l) and moderate hypophosphatemia (10.9%, 0.32-0.65 mmol/l). The percentages of motile spermatozoa and progressively motile spermatozoa were lower in men with moderate hypophosphatemia than in men with mild hypophosphatemia or normophosphatemia (44%, 49%, 51%, P = 0.040, and 32%, 35%, 41%, P = 0.036, respectively). The total numbers of motile and progressively motile spermatozoa were also lower (13, 12, 18 million, P = 0.009, and 10, 9, 14 million, P = 0.006, respectively). Serum concentrations of total and free estradiol were highest in men with moderate hypophosphatemia (97.5, 96.2, 92.1 pmol/l, P = 0.004, and 2.4, 2.3, 2.2 pmol/l, P = 0.034, respectively).

LIMITATIONS, REASONS FOR CAUTION: The study question is compromised by the descriptive study design. It remains to be shown whether there exist a causal link between serum phosphate and semen quality in infertile men.

WIDER IMPLICATIONS OF THE FINDINGS: As fertility stands as a critical concern in the world, there is a need to find regulators of fertility during adulthood to identify possible treatments. Therefore, the precise mechanisms through which hypophosphatemia may impact sperm motility remain needs to be further clarified.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Novo Nordisk Foundation, Beckett Foundation, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Candys Foundation, and The Innovation Foundation. There was no influence from any sponsor on the study design, and the authors have nothing to declare.

TRIAL REGISTRATION NUMBER: N/A.