Clinical trial NCT04291495: Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential
Official title: Evaluation of the Effects of Semen Incubation With ANDROSITOL®DGN on Sperm Motility and Mitochondrial Membrane Potential Before and After Oral Supplementation With Antioxidants and Myo-inositol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthenozoospermia
Mitochondrial Damage
Keywords: Male infertility
Sperm parameters
Mitochondrial membrane potential
Lead sponsor: University of Catania
Sponsor class: OTHER
First posted: 2020-03-02
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Mitochondria is the cellular organelle responsible for the production of the energy necessary to fuel sperm motility. It has been demonstrated that mitochondrial efficiency is correlated to the fertilizing capacity of the spermatozoon and to the production of high quality embryos. Mitochondria efficiency is measured in the laboratory setting by evaluating the mitochondrial membrane potential.

Myo-inositol is the most represented stereoisomer of the family of inositols and is the only one physiologically concentrated within the seminal plasma. It is essential for sperm maturation and motility and its deficiency is also associated to a reduced sperm count. Myo-inositol promotes motility and allows recovering a higher number of sperm cells after swim-up, both in normospermic patients and in patients with altered seminal parameters.

Scientific studies have shown that semen samples treated in vitro with ANDROSITOL®DGN, show an improvement in mitochondrial efficiency that results in an increase in spermatozoa progressive motility. Based on the percentage increase in the progressive motility showed by the spermatozoa after incubation with ANDROSITOL®DGN (ANDROSITOL®TEST), it is possible to subdivide the semen samples into three categories: low, medium, and high responders.

The aim of the study is to evaluate whether the in vitro response of spermatozoa to ANDROSITOL®TEST correlates with the in vivo improvement of seminal parameters after oral treatment with antioxidants and myo-inositol.

Detailed description: Mitochondria is the cellular organelle responsible for the production of the energy necessary to fuel sperm motility. It has been demonstrated that mitochondrial efficiency is correlated to the fertilizing capacity of the spermatozoon and to the production of high quality embryos. Mitochondria efficiency is measured in the laboratory setting by evaluating the mitochondrial membrane potential.

Myo-inositol is the most represented stereoisomer of the family of inositols and is the only one physiologically concentrated within the seminal plasma. It is essential for sperm maturation and motility and its deficiency is also associated to a reduced sperm count. Myo-inositol promotes motility and allows recovering a higher number of sperm cells after swim-up, both in normospermic patients and in patients with altered seminal parameters.

Scientific studies have shown that semen samples, both pathological and normal, treated in vitro with ANDROSITOL®DGN - a concentrate solution (66X) containing 133 mg/ml of myo-inositol - show an improvement in mitochondrial efficiency that results in an increase in spermatozoa progressive motility. Based on the percentage increase in the progressive motility showed by the spermatozoa after incubation with ANDROSITOL®DGN (ANDROSITOL®TEST), it is possible to subdivide the semen samples into three categories: low, medium, and high responders. High responders have worst mitochondrial function and lower fertilizing capacity, and could represent the category of patients most benefiting from supplementary oral therapy with antioxidants and myo-inositol.

The aim of our study is to evaluate whether the in vitro response of spermatozoa to ANDROSITOL®TEST correlates with the in vivo improvement of seminal parameters after oral treatment with antioxidants and myo-inositol. To do this, the investigators will enroll at least 13 patients for each category (low, medium, and high responder at ANDROSITOL®TEST) and they will re-evaluate conventional seminal parameters, mitochondrial function, and response to ANDROSITOL®TEST after three months of oral supplementation with ANDROSITOL® (dietary supplement of myo-inositol, vitamin E, L-carnitine, L-arginine, folic acid and selenium). The investigators hypothesize that, following supplementation, high-responder patients will exhibit the best improvement in seminal parameters, in particular in sperm motility. Furthermore, if the mitochondrial function is fully restored, they should respond less to the ANDROSITOL®TEST and could be reclassified as low responders.

Eligibility criteria: Inclusion Criteria:

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Exclusion Criteria:

- Absolute asthenozoospermia

* Leukocytospermia
* Positive semen culture and/or urethral swab
* Human Papilloma Virus (HPV) DNA in semen
* History of cryptorchidism
* 3rd degree varicocele
* Markedly reduced testicular volume
* Decompensated diabetes mellitus and other systemic diseases leading to oxidative stress (e.g. chronic renal failure, liver failure)
* Altered concentrations of the following hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, prolactin, 17β-estradiol
* Alcohol and drug abuse
* Heavy cigarette smoke (≥10 cigarettes/day)
* Body Mass Index (BMI) \>35 kg/m2

Primary outcomes:
measure: Response to the ANDROSI-TEST
timeFrame: T0 and T1 (three months)
measure: Sperm parameters
timeFrame: T0 and T1 (three months)
Secondary outcomes:
measure: Other Sperm parameters (1)
timeFrame: T0 and T1 (three months)
measure: Other Sperm parameters (2)
timeFrame: T0 and T1 (three months)
measure: Effects after therapy (1)
timeFrame: T1 (three months) and T2 (six months - three months after supplementation withdrawal)
measure: Effects after therapy (2)
timeFrame: T1 (three months) and T2 (six months - three months after supplementation withdrawal)
measure: Effects after therapy (3)
timeFrame: T1 (three months) and T2 (six months - three months after supplementation withdrawal)
measure: Effects after therapy (4)
timeFrame: T1 (three months) and T2 (six months - three months after supplementation withdrawal)
Other outcomes:
Locations:
city: Catania
country: Italy
facility: Department of Clinical and Experimental Medicine, University of Catania
Study officials:
affiliation: University of Catania
name: Aldo E. Calogero, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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