Effect of Cannabis Consumption on Sperm Nuclear Quality in Infertile Men

Not Applicable

• Conditions: Teratozoospermia

• Registration Number: NCT02932527
• Lead Sponsor: University Hospital, Rouen

Brief Summary

Lifestyle and environmental factors can disrupt development and testicular function. In France, cannabis is the most widely used illicit substance and about 8% of adults between 18 and 64 years smoke cannabis at least once a year, and mostly men under 45 years. Endocannabinoids are lipid mediators that share some effects with the active ingredients of cannabis. Cannabis and endocannabinoids act via two types of endogenous receptors which were detected at different levels of the reproductive system and are involved in the central and local regulation of the gonad. Cannabis use may alter the normal regulation of the endocannabinoid system. In males, the regulation of the endocannabinoid system is critical for Sertoli and Leydig cells functions, germ cell differentiation, maturation of sperm nucleus and sperm quality. The cannabis can have a negative impact on sperm parameters, capacitation and acrosome reaction. Cannabinoids may decrease testosterone synthesis and induce apoptosis of Sertoli cells. Studies on the effect of cannabinoids on male fertility are scarce or nonexistent in infertile men because of ethical considerations and bias due to consumption often underreported. Investigators hypothesized that cannabis use may alter sperm nuclear quality. Investigators want to explore this hypothesis conducting a multicentric prospective study exposed/non-exposed in infertile men who are consulting for Medically Assisted Reproductive Technologies (ART). To reach this study, it is planned to include a total of 200 subjects taking into account any exclusions.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-07
• Study First Submitted QC: 2016-10-11
• Study First Posted: 2016-10-13
• Study Start: 2017-08-29
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-14
• Last Update Posted: 2018-05-17
• Primary Completion: 2020-08
• Study Completion: 2020-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 200

Inclusion Criteria

• Male Patient,
• Patient age ≥ 18 years,
• Infertile patient with isolated teratozoospermia or associated with asthenozoospermia and / or oligozoospermia and / or necrozoospermia, defined according to WHO recommendations (WHO guidelines, 2010) and the David amended classification (Auger et al, 2001) for teratozoospermia
• Patient with normal constitutional karyotype (46, XY).
• Smoking tobacco,
• Drinking ≤ 20 g (2 units) / day,
• Patient exposed : Cannabis user for over 3 months and consuming at least weekly (≥ 1 / week) [questionnaire and positive blood detection of Delta-9-Tetrahydrocannabinol (THC) and / or its derivatives (11-hydroxy-THC and 11-nor-9-carboxy-THC)].
• Unexposed : No cannabis user (questionnaire and negative blood detection of Delta-9-THC and its derivatives) matched for age (+/- 2.5 years) with exposed patients included,

Exclusion Criteria

• Patient age > 60 years
• Patient with azoospermia
• Patient previously exposed to gonadotoxic treatment (chemotherapy, radiotherapy, androgen therapy and other gonadotoxic treatments),
• Patient with professional toxic exposure,
• Patient consuming other recreational drugs,
• Patient with severely impaired sperm parameters and sperm counts <1 million,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Evaluation of spermatic aneuploidy rate	Day 1	Spermatic aneuploidy rate is evaluated for patients exposed and not exposed to cannabis

Secondary Outcome Measures

Name	Time	Method
Evaluation of consumption level	Day 1	Consumption level are evaluated for patients exposed to cannabis, using questionnaire
Evaluation of cannabinoids level in blood	Day 1	cannabinoids levels in blood are evaluated for patients exposed and not exposed to cannabis
Total sperm count	Day 1
Percentage of mobile spermatozoa	Day 1
Percentage of morphologically abnormal spermatozoa	Day 1
Mean vacuole area threshold	Day 1	Mean vacuole area threshold is measured with Receiver Operating Characteristic curves
Correlation coefficient between vacuole areas and sperm DNA fragmentation	Day 1	Correlation coefficient between vacuole areas and sperm DNA fragmentation are evaluated by TUNEL analysis
Correlation coefficient between vacuole areas and abnormal chromatin condensation	Day 1	Correlation coefficient between vacuole areas and abnormal chromatin condensation is evaluated by aniline blue staining
Correlation coefficient between vacuole areas and telomere number, distribution and length	Day 1	Correlation coefficient between vacuole areas and telomere number, distribution and length is evaluated by quantitative FISH

Trial Locations

Locations (3)

Caen University Hospital; 🇫🇷 Caen, France

Lille University Hospital; 🇫🇷 Lille, France

Rouen University Hospital; 🇫🇷 Rouen, France