Vitamin D and Human Sperm DNA Fragmentation

Effects of Vitamin D on Human Sperm DNA Fragmentation

The purpose of this study will be to investigate if there is a correlation between Vitamin D levels and Sperm DNA Fragmentation. This is a prospective, cohort study. In this study male participants presenting with their partners because of inability to conceive will be recruited for this study. Participants will have a blood sample drawn which will be tested for Vitamin D level. The investigators will then compare sperm DNA fragmentation between normal Vitamin D levels, Vitamin D insufficiency, and Vitamin D deficiency. All infertile males who present to the investigators' infertility clinic have a Semen analysis and Sperm chromatin Structure Assay (SCSA). The research part of the study will be to obtain the Vitamin D level.

Study Overview

• Status: Unknown
• Conditions: Vitamin D Deficiency; Infertility,Male
• Intervention / Treatment: Diagnostic test: Vitamin D

Detailed Description

Vitamin D plays an important role in bone metabolism and has also been discovered to influence male reproduction. Vitamin D binds to the Vitamin D receptor which then can bind to Vitamin D response elements in the DNA which can alter transcription. By changing transcription it can have long term effects on cellular metabolism. Previous studies have demonstrated abnormalities in sperm motility and morphology in males who are Vitamin D deficient. The mechanism by which Vitamin D affects spermatogenesis (formation of sperm) is unknown. One possibly mechanism by which deficient Vitamin D may affect sperm formation is through DNA fragmentation. The head of the sperm contains all the DNA. When a sperm cell is made the DNA in the nucleus must be super compacted to accomplish sperm formation. To sufficiently compact the DNA, first the DNA is 'turned off' and then very tightly wound (or compacted) into toroids (like small tires) which are stacked one on top of another. During this process of compaction the DNA will occasionally break or fragment. The egg can repair the DNA fragmentation as long as there is not a large amount of breakage. If the DNA fragmentation exceeds a certain amount then fertilization and early development of the embryo may be adversely affected. DNA fragmentation can be tested by using the Sperm Chromatin Structure Assay (SCSA), which the investigators currently measure in males who present with their partners with infertility. Previous studies have suggested that the abnormalities in sperm due to vitamin D deficiency may be related to increased DNA fragmentation. This study will assist in understanding the cause of sperm abnormalities in subjects with Vitamin D deficiency.

This is a prospective, cohort study. In this study male patients who present with inability to conceive will be asked to be involved in this study. After agreement with the study, a blood sample drawn which will be tested for Vitamin D level. The investigators will then compare sperm DNA fragmentation between normal Vitamin D levels, Vitamin D insufficiency, and Vitamin D deficiency. All infertile males presenting to the investigators' infertility clinic have a Semen analysis and Sperm chromatin Structure Assay (SCSA). The research part of the study will be to obtain the Vitamin D level.

• Study Type: Observational
• Enrollment (Anticipated): 230

Contacts and Locations

Study Locations

• United States
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Sanford Health Fertility and Reproductive Medicine
      • Contact: Keith Hansen, MD; Phone Number: 605-328-8829; Email: keith.hansen@sanfordhealth.org
      • Contact: Angela Haldeman, RN; Phone Number: 605-328-8800; Email: angela.haldeman@sanfordhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 56 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Male partners of infertile couples. All males who present to our Infertility clinic will be offered participation.

Description

Inclusion Criteria:

• Male with diagnosis of infertility.

Exclusion Criteria:

• Azoospermia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Vitamin D deficiency; The study group will be males discovered to have Vitamin D deficiency.	Diagnostic test: Vitamin D; Blood will be drawn for Vitamin D level
Control group; The control group will be males with normal Vitamin D status	Diagnostic test: Vitamin D; Blood will be drawn for Vitamin D level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sperm DNA Fragmentation	Human Sperm DNA fragmentation will be determined by the Sperm Chromatin Structure Assay.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High DNA stainability	High DNA stainability is determined by the Sperm Chromatin Structure Assay and is consistent with immature sperm.	1 year
Sperm density	This will be determined by microscopic analysis of participant's semen and expressed as millions per milliliter	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI	weight and height will be combined to report BMI in kg/m^2	1 year
Sperm motility	This will be determined by microscopic analysis of participant's semen and expressed as percent motile.	1 year
Sperm morphology	This will be determined by microscopic analysis of participant's semen and will be expressed as percent normal forms.	1 year
Height	Measured by stadiometer and recorded in centimeters.	1 year
Weight	Measured using digital, medical scale	1 year
Tobacco status	Patient will be asked if uses tobacco products: smoke, smokeless	1 year
Race/ethnicity	Patient will self identify race/ethnicity	1 year

Collaborators and Investigators

• Sponsor: Sanford Health

Publications and helpful links

General Publications

• Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jorgensen N. Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Mar 1;103(3):870-881. doi: 10.1210/jc.2017-01656.
• Blomberg Jensen M, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen UN, Olesen IA, Petersen JH, Juul A, Dissing S, Jorgensen N. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod. 2011 Jun;26(6):1307-17. doi: 10.1093/humrep/der059. Epub 2011 Mar 22.
• Bunde E, Hanssen K, Huntington MK. Vitamin D status in eastern South Dakota. S D Med. 2012 Jun;65(6):227, 229, 231.
• Boisen IM, Bollehuus Hansen L, Mortensen LJ, Lanske B, Juul A, Blomberg Jensen M. Possible influence of vitamin D on male reproduction. J Steroid Biochem Mol Biol. 2017 Oct;173:215-222. doi: 10.1016/j.jsbmb.2016.09.023. Epub 2016 Sep 28.
• Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012 Apr;97(4):1153-8. doi: 10.1210/jc.2011-2601. Epub 2012 Mar 22. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2019
• Primary Completion (Anticipated): February 1, 2022
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (Actual): February 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Infertility; Vitamin D Deficiency; Infertility, Male; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: MOD00002311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Plan to share individual participant data (IPD) with researchers who desire information.
• IPD Sharing Time Frame: The data will be available after collection complete and will remain available for 3 years.
• IPD Sharing Access Criteria: Investigator.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No