Impact of Ionizing Treatment on the Nuclear Structure of Human Spermatozoa.

NCT ID: NCT04715828

Last Updated: 2021-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-01-01

Study Completion Date

2022-01-01

Brief Summary

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Differentiated thyroid cancer is the third cause of cancer in young men of childbearing age. Its treatment by irradiation with Radioactive Iodine 131 therapy (RAT) could alter spermatogenesis and result in azoospermia and permanent infertility. A preventive gametes cryopreservation was recommended before RAT, but without mentioning a period of teratogenic risk transmissible to the offspring. To date, RAT impact on human sperm nucleus is poorly known or even unknown, notably on telomere length.

Our objective is to define RAT effects on human sperm nucleus by in vitro irradiation exposure of human spermatozoa to mimicking that of the gonads in the context of irradiation with iodine131 used for thyroid cancer. We will analyze standard sperm parameters, major DNA alterations and telomere length using molecular and cellular assays. Nucleus morphology and chromatin organization will also be analyzed using 3D bio-imaging. This study will permit to optimize the indications for the preservation of fertility.

Detailed Description

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Our main objective is to measure the in vitro impact of irradiation treatment on sperm nuclear quality such as DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and notably sperm telomere length (STL).

The secondary objectives are :

* to measure RAT impact on sperm parameters (vitality, motility and morphology)
* to measure the impact of cryopreservation on chromatin organisation and nucleus morphology
* to evaluate RAT impact on human sperm cells in comparison with cryopreservation
* to evaluate the impact of different doses and types of irradiation on human sperm cells
* to establish relations between potential alterations of standards sperm parameters (vitality, motility and morphology) and nuclear sperm parameters (DNA fragmentation and oxidation, chromatin condensation and organisation, nucleus morphology and STL.

Our final goal is to provide a significant improvement of men fertility diagnosis and optimize our fertility preservation practices.

To this end, we will expose ejaculated human spermatozoa (n = 90) at different (low and moderate) doses of gamma or X photons to mimic gonads irradiation. Absorbed doses by the samples were calculated using the GATE Monte Carlo platform (version 8.2). Experiment geometry settings were modelled as three dimension voxelized volumes inside the software by assigning a shape, size, distance and density for all the volumes created. All measurements will be made on surplus samples from men undergoing routine semen analysis at the Center for Reproductive Medicine, after receiving their written informed consent. Semen samples are collected and subdivided into 3 arms to analyse sperm quality after:

* irradiation exposure (3 conditions);
* a freezing- thawing cycle;
* fresh state: negative control without treatment.

Before (fresh state) and after each treatment we will analyse:

* standard semen parameters (vitality, motility and morphology) in accordance with WHO, 2010;
* STL using Flow FISH, q-PCR and q-FISH;
* chromatin condensation (chromomycin A3);
* DNA oxidization (8-OHdG residues);
* DNA fragmentation (TUNEL);
* 3D nucleus structure using 3D bio-imaging.

Conditions

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Sperm Preservation Irradiated Semen

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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control arm "fresh"

Fresh semen treated without irradiation before cryopreservation

Cryopreserved semen

Intervention Type OTHER

sperm will be frozen in Cryosperm® cryoprotectant medium (Origio). The samples will be packaged in previously identified high security straws (Cryobiosystem). Slow freezing of the straws will be carried out using the Nanodigicool® programmable device (Cryobiosystem).

control arm "cryopreserved"

cryopreserved semen without irradiation (n=60)

Cryopreserved semen

Intervention Type OTHER

sperm will be frozen in Cryosperm® cryoprotectant medium (Origio). The samples will be packaged in previously identified high security straws (Cryobiosystem). Slow freezing of the straws will be carried out using the Nanodigicool® programmable device (Cryobiosystem).

acute irradiation at low dose

Pelvis scanning : acute irradiation (1 or 2 second) using low dose (n=30),

Acute and low irradiation

Intervention Type OTHER

sperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy

long irradiation at low dose

Bone scintigraphy : long irradiation (3h) using low dose (n=30),

Long and low irradiation

Intervention Type OTHER

sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours.

long irradiation at medium dose

Radioactive Iodine 131 therapy (RAT) applied for thyroid cancer : long irradiation (3h) using medium dose (n=60),

Long and medium irradiation

Intervention Type OTHER

sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours

Interventions

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Cryopreserved semen

sperm will be frozen in Cryosperm® cryoprotectant medium (Origio). The samples will be packaged in previously identified high security straws (Cryobiosystem). Slow freezing of the straws will be carried out using the Nanodigicool® programmable device (Cryobiosystem).

Intervention Type OTHER

Acute and low irradiation

sperm sample will be placed on the scanner's processing table to be exposed for 1 to 2 seconds. Several dose levels will then be made in order to limit the value of 17 mGy

Intervention Type OTHER

Long and low irradiation

sperm sample will be exposed to gamma radiation by adding a solution of Tc99m for 3 hours.

Intervention Type OTHER

Long and medium irradiation

sperm sample will be exposed to gamma radiation by adding a solution of I131 for 3 hours

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Man less than 45 years
* Man undergoing routine semen analysis at the Center for Reproductive Medicine, accepting the research protocol and signing the associated consent will be included in the protocol without distinction of physical criteria.

Exclusion Criteria

\-
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Agence de La Biomédecine

OTHER_GOV

Sponsor Role collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hanae PONS-REJRAJI, PhD

Role: STUDY_CHAIR

CHU de Clermont-Ferrand

Locations

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CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Lise Laclautre, PharmD

Role: CONTACT

04 73 75 49 63 ext. 34

Facility Contacts

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Lise Laclautre, PharmD

Role: primary

04 73 75 49 62 ext. 33

Other Identifiers

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2020 PONS-REJRAJI

Identifier Type: -

Identifier Source: org_study_id

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