Sperm Epigenome in Hodgkin Lymphoma (SPELH)

Multiparametric Detection and Preventive Approaches of Cancer Treatment-induced Epigenetic Instability in the Male Germline.

Cancer treatments can have long-term effects on fertility. In men, scientific studies suggest that the process of sperm formation (spermatogenesis) may be disrupted even years after recovery, with potential consequences not only for fertility but also for the health of offspring. The effects of chemotherapy on sperm quality, particularly on DNA packaging (chromatin) and the epigenome, remain poorly understood. Therefore, further in-depth studies are needed to determine whether a history of cancer and chemotherapy treatment may impact the health of children fathered by young male survivors.

We therefore propose to conduct a clinical study aimed at better understanding the mechanisms by which chemotherapies affect spermatogenesis. The results could provide answers by identifying the effects of these drugs on the fertility of young male cancer patients in the long term and the sperm epigenome indicative of the health of the progeny.

Study Overview

• Status: Not yet recruiting
• Conditions: Hodgkin Disease Lymphoma
• Intervention / Treatment: Other: Additional semen samples

Detailed Description

Advances in cancer treatments are raising new health questions for young survivors of the disease. Cancer itself and DNA-targeted treatments can have long-term effects on reproductive health. In men, spermatogenesis may remain impaired even years after recovery, with consequences for fertility and the health of offspring. It is important to note that sperm production can recover after cancer remission. However, men are advised to wait at least one year after the end of treatment before attempting natural conception, as gamete quality may influence reproductive capacity and offspring health. Yet, regardless of the mode of conception (natural or assisted reproduction), the question of whether a history of cancer and its treatment may affect the health of their offspring remains a fundamental issue that has not yet been clearly answered. In-depth studies are needed for this growing population of young cancer survivors who wish to have healthy children.

Where possible, the use of alkylating agents-known for their long-term systemic harmful effects-is being reduced, and less reprotoxic compounds, such as anthracyclines, are favored. Anthracyclines are widely used to treat various cancers prevalent in young men with a favorable survival prognosis and are classified as weakly reprotoxic (i.e., causing a temporary reduction in sperm count). However, they are suspected of having long-term effects on sperm chromatin and epigenome. The establishment of the sperm epigenome is a complex process resulting from multiple nuclear events during spermatogenesis, including chromatin remodeling and compaction that occur during spermiogenesis. These represent windows of opportunity for alteration by xenobiotics. Furthermore, genomic regions undergoing chromatin rearrangements may be more vulnerable to alterations; if these regions are located on key genes for embryonic development or fetal programming, they may predict adverse effects on offspring. In fact, emerging evidence suggests that sperm epigenetic marks could be used clinically to predict fertility and male-mediated developmental toxicity.

Here, we focus on young men with Hodgkin lymphoma (HL), one of the most commonly diagnosed malignant tumors at a young age, with a good prognosis and low risk of relapse, and for which treatment is well characterized using an anthracycline-containing protocol: doxorubicin. This pathology thus represents a large and relevant population of young cancer survivors who will consider parenthood after cancer. Due to interindividual variability, human studies aiming to determine the effects of chemotherapy must be able to compare samples before and after treatment in the same individual. Such published prospective longitudinal studies are rare and often include very few cases, as they require substantial resources, strong links between oncology and reproduction services, and the ability to follow patients over time, even after the end of oncological treatment. A (non-longitudinal) study of the long-term effects of HL treatments demonstrated persistent abnormalities in chromatin structure and DNA integrity. In the study proposed here, we will analyze epigenetic modifications in sperm from HL patients and their evolution after chemotherapy. We hypothesize that HL and its treatment induce persistent alterations up to 2 years after remission.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tony MARCHAND, MD, PhD; Phone Number: +33 02 99 28 42 91; Email: tony.marchand@chu-rennes.fr
• Study Contact Backup: Name: Célia RAVEL, MD, PhD; Phone Number: +33 02 99 26 59 16; Email: celia.ravel@chu-rennes.fr

Study Locations

• France
  • Rennes, France, 35033
    • Centre Hospitalier Universitaire de Rennes
    • Contact: Tony MARCHAND, MD, PhD; Phone Number: +33 02 99 28 42 91; Email: tony.marchand@chu-rennes.fr
    • Contact: Célia RAVEL, MD, PhD; Phone Number: +33 02 99 26 59 16; Email: celia.ravel@chu-rennes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Men aged 18 to 45 years
• Diagnosed with Hodgkin lymphoma
• Treatment-naïve to any cytotoxic therapy
• Whose treatment regimen consists of 4 to 6 cycles of ABVD or BrECADD
• Beneficiaries of the French social security system
• Not opposed to participating in research

Exclusion Criteria:

• Patient receiving abdominal radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epigenetic analysis in semen samples; 30 men with hodgkin lymphoma will be followed during 24 months in order to search epigenetic modifications in male gametes	Other: Additional semen samples; 5 additional semen samples : before chemotherapy, at month 6, 12, 18 and 24 after chemotherapy. Each sperm sample will be stored in liquid nitrogen and sent to Institut National de la Recherche Scientifique (INRS), Quebec, Canada for epigenetic analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in DNA methylation patterns in spermatozoa	Sperm analysis : Methyl-C Capture Sequencing (MCC-seq)	Before chemotherapy, month 6, month 12, month 18, month 24 after chemotherapy
Alterations of histone 3 H3k4me3 retention sites in spermatozoa	Sperm analysis : chromatin immunoprecipitation followed by sequencing (ChIP-seq)	Before chemotherapy, month 6, month 12, month 18, month 24 after chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spermogram exam	Spermogram examination	Before chemotherapy, month 6, month 12, month 18, month 24 after chemotherapy
Identification of known environmental factors impacting spermatogenesis	Patient questionnaire	Month 24 after chemotherapy

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: Institut National de la Recherche Scientifique - Centre Armand Frappier Santé Biotechnologie
• Investigators: Study Chair: Géraldine DELBES, PhD, Institut National de la Recherche Scientifique (INRS), Québec, Canada

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; epigenetic; male gametes
• Other Study ID Numbers: 35RC24_9822_SPELH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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