Fertility and sterility · 2025
Effect of denosumab on semen quality in infertile men selected by serum level of antimüllerian hormone: a randomized controlled trial.
Клиническое исследование II фазыСтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Yahyavi Sam Kafai, Holt Rune, Jorsal Mads Joon, Wall-Gremstrup Gustav, Toft Frederikke Bay, Juel Mortensen Li, Nøhr Bugge, Melsen Linda Magnusson, Prætorius Lisbeth, Nielsen Henriette Svarre, Pinborg Anja, Beck Jensen Jens-Erik, Schwarz Peter, Bennedbæk Finn Noe, Aksglaede Lise, Jørgensen Anne, Jørgensen Niels, Petersen Jørgen Holm, Juul Anders, Blomberg Jensen Martin
Аннотация
OBJECTIVE: To determine whether denosumab could improve sperm concentration in infertile men selected by serum antimüllerian hormone (AMH) ≥ 38 pmol/L. Mouse models, human testicular tissue models, and clinical intervention studies have suggested that the RANKL-inhibitor denosumab, normally used to treat osteoporosis, can improve semen quality in a sub-population of infertile men.
DESIGN: A double-blinded, placebo-controlled, single-center, randomized clinical trial.
SUBJECTS: The study was designed to include 282 infertile men with a planned interim analysis after inclusion of 170 men.
INTERVENTION: The groups were randomized 1:1 to receive either a single subcutaneous injection of denosumab 60 mg or a placebo treatment for 80 days.
MAIN OUTCOME MEASURE: Sperm concentration.
RESULTS: The trial was terminated after the interim analysis (n = 179), with 90 men assigned to denosumab treatment and 89 men to placebo treatment. No difference in sperm concentration was found at day 80 between denosumab and placebo-treated men (difference of -1.0 million/mL [95% CI -2.7, 1.1]). Moreover, no differences in percentages of motile, progressively motile, or morphologically normal spermatozoa were found. An interaction analysis identified a subgroup of men with testis size ≤16 mL and no history of cryptorchidism who had an increase in sperm concentration of 29% (8.5 million/mL at baseline to 11.0 million/mL at day 80) after treatment with denosumab.
CONCLUSIONS: Denosumab did not improve semen quality in infertile men selected on the basis of their serum AMH concentrations. The positive effect of denosumab in a subgroup can only be considered exploratory and needs verification in additional prospective studies.
TRIAL ID: ClinicalTrials.gov: NCT05212337. EudraCT 2021-003451-42.
DESIGN: A double-blinded, placebo-controlled, single-center, randomized clinical trial.
SUBJECTS: The study was designed to include 282 infertile men with a planned interim analysis after inclusion of 170 men.
INTERVENTION: The groups were randomized 1:1 to receive either a single subcutaneous injection of denosumab 60 mg or a placebo treatment for 80 days.
MAIN OUTCOME MEASURE: Sperm concentration.
RESULTS: The trial was terminated after the interim analysis (n = 179), with 90 men assigned to denosumab treatment and 89 men to placebo treatment. No difference in sperm concentration was found at day 80 between denosumab and placebo-treated men (difference of -1.0 million/mL [95% CI -2.7, 1.1]). Moreover, no differences in percentages of motile, progressively motile, or morphologically normal spermatozoa were found. An interaction analysis identified a subgroup of men with testis size ≤16 mL and no history of cryptorchidism who had an increase in sperm concentration of 29% (8.5 million/mL at baseline to 11.0 million/mL at day 80) after treatment with denosumab.
CONCLUSIONS: Denosumab did not improve semen quality in infertile men selected on the basis of their serum AMH concentrations. The positive effect of denosumab in a subgroup can only be considered exploratory and needs verification in additional prospective studies.
TRIAL ID: ClinicalTrials.gov: NCT05212337. EudraCT 2021-003451-42.