TY - JOUR

T1 - Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study)

T2 - study protocol for a randomized controlled trial

AU - Yahyavi, Sam Kafai

AU - Holt, Rune

AU - Mortensen, Li Juel

AU - Petersen, Jørgen Holm

AU - Jørgensen, Niels

AU - Juul, Anders

AU - Jensen, Martin Blomberg

PY - 2022

Y1 - 2022

N2 - Background: Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study.Methods/design: FITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion.Discussion: We describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need.

AB - Background: Infertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study.Methods/design: FITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion.Discussion: We describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need.

KW - Denosumab

KW - Male infertility

KW - Impaired semen quality

KW - Randomized controlled study

KW - VITAMIN-D

KW - BONE

KW - OSTEOPROTEGERIN

KW - DIFFERENTIATION

KW - FERTILITY

KW - LIGAND

KW - WOMEN

U2 - 10.1186/s13063-022-06478-4

DO - 10.1186/s13063-022-06478-4

M3 - Journal article

C2 - 35733213

VL - 23

JO - Trials

JF - Trials

SN - 1745-6215

IS - 1

M1 - 525

ER -