Role of Antioxidants in the Reduction of Oxidative Stress in Infertile Patients (OAT)

Numerous studies verify that the majority of cases of male infertility belong to the group diagnosed with oligoasthenoteratozoospermia (OAT), which means a decrease in the number of sperm in the ejaculate to 15 million / ml, reduced sperm motility of the spermatozoa and morphological disorders of the neck or tail of the sperm.

Genuine scientific studies can not pinpoint the cause of these changes, however, recent advances in science shed light on this issue by confirming the reason, which is as a result of the action of free radicals - oxidative stress.

Study Overview

• Status: Completed
• Conditions: Infertility; Male; Oligoasthenozoospermia
• Intervention / Treatment: Combination product: Antioxidant formula

Detailed Description

The enlightenment project in the field of male infertility in North Macedonia will include a wide team of: students, general practitioners, assistants, professors of pre-clinical subjects, professors and specialists in the field of gynecology, urology and andrologists. The involvement of such a large number of professionals once again verifies the seriousness and determination that this scientific project has.

Investigators hope to contribute generously to:

1. Identifying new cases and taking measures early, in order to overcome fertilization problems;
2. For the first time in North Macedonia there will be a more accurate picture of the prevalence of male infertility;
3. Expanding current scientific knowledge about the role of oxidative stress, its laboratory evaluation, and the impact of antioxidant supplements;
4. Standardization of doses and type of antioxidant supplements that will be used during the realization of this dissertation and evaluation of their clinical effect in men with OAT;
5. After the implementation of antioxidant therapy, investigators expect that the results of live births and spontaneous pregnancies will increase, while the number of miscarriages will decrease;
6. Acquisition of knowledge on laboratory and clinical evaluation techniques of infertile men, which would later lead to the establishment of an andrological laboratory. Investigators anticipate this laboratory to function within the Faculty of Medical Sciences, where all procedures will be performed, from diagnosis to the operation of assisted reproduction techniques (TRA). This, in addition to the material benefit for the benefit of the University of Tetova, also has a benefit in terms of staff, which will be professionalized and trained during the realization of this dissertation.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 4

Contacts and Locations

Study Locations

• North Macedonia
  • Tetovo, North Macedonia, 6338
    • Univeristy of Tetova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• age, 19-45 years;
• infertility, 2 years;
• regular sexual intercourse with a fertile female.
• The female partner was defined as being fertile if she had undergone a negative infertility workup (biphasic basal body temperature, P evaluation in luteal phase, ultrasound ovary and uterus evaluation, and hysterosalpingogram to study tubal patency)

Exclusion Criteria:

• use of antioxidant agents or vitamins within 8 weeks prior to inclusion in the study,
• a history of excessive consumption of alcohol 40 days prior to the start of the trial,
• patients that showed lower than 5% motility and less than 1 × 106/ml sperm concentration, - patients with any acute or chronic disease or
• who are undergoing some kind of treatment with any class of drugs and
• subjects with known hypersensitivity to ingredients in the antioxidant formula.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Infertility male patients; Infertile male patients will receive the antioxidant formula for more than 172 days. Divided in two groups. One will take the active substance, to the other group placebo treatment will be given.	Combination product: Antioxidant formula; Administration of antioxidant formula 3 times a day and once daily.
Placebo Comparator: Control group; Placebo treatment and control and comparative variables will be measured.	Combination product: Antioxidant formula; Administration of antioxidant formula 3 times a day and once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sperm parameters	Concentration (10x6 ml)	6 months
Sperm parameters	Morphology (percentage)	6 months
Sperm parameters	Motility (percentage)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oxidative stress parameters	MDA (mg/ml)	6 months
oxidative stress parameters	Caspase 3 (IU/ml)	6 months
oxidative stress parameters	TAC (IU/ml)	6 months

Collaborators and Investigators

• Sponsor: University of Tetova
• Collaborators: University of Tetova, Faculty of Medical Sciences
• Investigators: Principal Investigator: Vegim Zhaku, MD, PhDc, University of Tetova; Study Chair: Sheqibe Beadini, PhD, University of Tetova; Study Chair: Nexhbedin Beadini, PhD, Univeristy of Tetova

Publications and helpful links

General Publications

• Vegim Zhaku, Ashok Agarwal, Sheqibe Beadini, Ralf Henkel, Renata Finelli, Nexhbedin Beadini and Sava Micic (June 8th 2021). Male Infertility, Oxidative Stress and Antioxidants, Vitamin E in Health and Disease - Interactions, Diseases and Health Aspects, Pınar Erkekoglu and Júlia Scherer Santos, IntechOpen, DOI: 10.5772/intechopen.98204. Available from: https://www.intechopen.com/chapters/77097
• ] Zhaku V, Beadini Sh, Beadini N, Xhaferi V, Golaboska J. The role of semen analysis in the expression of male infertility in southwestern part of North Macedonia (Experiences from 7 municipalities). UNIVERSI-International Journal of Education Science Technology Innovation Health and Enviroment. 2019;5(2):96-104.
• Zhaku V, Beadini Sh, Beadini N, Murtezani B. Combination of Maca, Korean ginseng extract and antioxidant therapy for male with oligoasthenozoospermia: case study. Journal of Hygienic Engineering and Design. 2019; 26(1):28-35.
• Zhaku V, Beadini Sh, Beadini N, Xhaferi V. Role of antioxidants in the diminution of oxidative stress and amelioration of semen parameters in idiopathic male infertility. Acta Medica Balkanica. 2020; 5(9-10):69-80.
• Zhaku V, Beadini Sh, Beadini N, Xhaferi V, Milenkovic T. Oral antioxidants improve sperm motility, sperm concentration and reduce oxidative stress in males with oligo-asthenozoospermia. In: 22nd European Congress of Endocrinology; 5-9 September 2020; Prague, Czech Republic: Endocrine Abstracts (2020) 70 EP581. DOI:10.1530/ endoabs.70.EP581

Helpful Links

• Male infertility, Oxidative Stress and Antioxidants
• ROLE OF ANTIOXIDANTS IN THE DIMINUTION OF OXIDATIVE STRESS AND AMELIORATION OF SEMEN PARAMETERS IN IDIOPATHIC MALE INFERTILITY
• COMBINATION OF MACA, KOREAN GINSENG EXTRACT AND ANTIOXIDANT THERAPY FOR MALE WITH OLIGOASTHENOZOOSPERMIA: CASE STUDY
• Oral antioxidants improve sperm motility, sperm concentration and reduce oxidative stress in males with oligoasthenozoospermia

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 13, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 27, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: oxidative stress; antioxidant; sperm parameters; total antioxidant capacity; Malonedialdehyde
• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants
• Other Study ID Numbers: 22-63/3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Sperm parameters before and after treatment. OS parameters before and after treatment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No