Clinical trial NCT03829943: Vitamin D and Human Sperm DNA Fragmentation
Official title: Effects of Vitamin D on Human Sperm DNA Fragmentation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infertility,Male
Vitamin D Deficiency
Lead sponsor: Sanford Health
Sponsor class: OTHER
First posted: 2019-02-04
Enrollment: 230
Sex: MALE
Minimum age (years): 21
Maximum age (years): 56
Standard ages: ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male partners of infertile couples. All males who present to our Infertility clinic will be offered participation.

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Male with diagnosis of infertility.

Exclusion Criteria:

* Azoospermia

Primary outcomes:
measure: Sperm DNA Fragmentation
timeFrame: 1 year
Secondary outcomes:
measure: High DNA stainability
timeFrame: 1 year
measure: Sperm density
timeFrame: 1 year
Other outcomes:
measure: Sperm motility
timeFrame: 1 year
measure: Sperm morphology
timeFrame: 1 year
measure: Height
timeFrame: 1 year
measure: Weight
timeFrame: 1 year
measure: BMI
timeFrame: 1 year
measure: Tobacco status
timeFrame: 1 year
measure: Race/ethnicity
timeFrame: 1 year
Locations:
city: Sioux Falls
country: United States
facility: Sanford Health Fertility and Reproductive Medicine
state: South Dakota
Study officials:
References:
citation: 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.
citation: Bunde E, Hanssen K, Huntington MK. Vitamin D status in eastern South Dakota. S D Med. 2012 Jun;65(6):227, 229, 231.
citation: 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.
citation: 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.
citation: 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.