Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 22;23(1):525.
doi: 10.1186/s13063-022-06478-4.

Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial

Sam Kafai Yahyavi #  1 , Rune Holt #  2 , Li Juel Mortensen  3 , Jørgen Holm Petersen  4   5 , Niels Jørgensen  6 , Anders Juul  6   7 , Martin Blomberg Jensen  8   9
Affiliations

Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial

Sam Kafai Yahyavi et al. Trials. .

Abstract

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.

Trial registration: Clinical Trials.gov NCT05212337 . Registered on 14 January 2022. EudraCT 2021-003,451-42. Registered on 23 June 2021. Ethical committee H-21040145. Registered on 23 December 2021.

Keywords: Denosumab; Impaired semen quality; Male infertility; Randomized controlled study.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests except that Martin Blomberg Jensen also is the CEO of “XY Therapeutics.”

Figures

Fig. 1
Fig. 1
The expected flow diagram of the progress through the study (CONSORT). Figure legend: An expected CONSORT diagram showing the expected flow of FITMI
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Huynh T. Selected genetic factors associated with male infertility. Hum Reprod Update. 2002;8(2):183–198. doi: 10.1093/humupd/8.2.183. - DOI - PubMed
    1. Krausz C. Male infertility: pathogenesis and clinical diagnosis. Best Pract Res Clin Endocrinol Metab. 2011;25(2):271–285. doi: 10.1016/j.beem.2010.08.006. - DOI - PubMed
    1. Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson A-M, Eisenberg ML, et al. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol Rev. 2016;96(1):55–97. doi: 10.1152/physrev.00017.2015. - DOI - PMC - PubMed
    1. Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jørgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: a randomized clinical trial. J Clin Endocrinol Metab. 2017;103(3):870–881. doi: 10.1210/jc.2017-01656. - DOI - PubMed
    1. Bøllehuus Hansen L, Kaludjerovic J, Nielsen JE, Rehfeld A, Poulsen NN, Ide N, et al. Influence of FGF23 and Klotho on male reproduction: Systemic vs direct effects. FASEB J. 2020;34(9):12436–12449. doi: 10.1096/fj.202000061RR. - DOI - PubMed

Publication types

Associated data