Genetic Markers of Susceptibility to Chemotherapy-induced Ovarian Damage in Cancer Patients Undergoing Ovarian Biopsy for Cryopreservation.

November 26, 2025 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Italian Cancer Registry data show a steady increase in the number of cancer survivors due to advances in treatment. However, these treatments can impair ovarian function, causing premature ovarian insufficiency (POI). Women with POI may experience vasomotor symptoms, infertility, psychological distress, and a significant reduction in quality of life. POI typically occurs before age 40 and is characterized by irregular menstruation and biochemical alterations (elevated gonadotropins and low estradiol). Chronic estrogen deficiency in POI is associated with increased risks of cardiovascular disease, cognitive decline, osteoporosis, psychological issues, and reproductive dysfunction.

Preliminary studies suggest that chemotherapy-induced POI results from genetic changes in ovarian tissue, indicating a crucial role of genetic variations in individual susceptibility. Incidence rates of POI vary widely: about 38% after Hodgkin lymphoma and between 15% and 94% after breast cancer. Currently, there is no personalized pre-treatment risk assessment, complicating informed decision-making regarding ovarian function and fertility.

Fertility preservation options include ovarian tissue and oocyte cryopreservation. This study aims to compare the mutational status of DNA repair genes in ovarian tissue fragments from women who underwent ovarian cryopreservation and completed chemotherapy for lymphoma or breast cancer, categorized into those who developed POI and those who did not. Additionally, the mutational load of these genes will be compared between groups.

The study includes patients aged 18-38 who preserved ovarian tissue before gonadotoxic therapy between 2002 and 2024 at the IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S. Orsola. Two groups will be analyzed:

Group 1: Patients who developed POI after gonadotoxic treatment

Group 2: Patients who did not develop POI

Group assignment will be based on clinical and anamnesis data. Cryopreserved ovarian tissue from all participants will undergo advanced molecular analyses by Next Generation Sequencing (NGS) to assess germline and somatic mutational status and load. The genetic variant analysis, conducted in collaboration with the Computational Genomics Unit of IRCCS AOUBO, will focus on a panel of 26 DNA repair genes. Bioinformatic analysis will be performed using the Ion Reporter platform, with clinically relevant variants validated by orthogonal methods.

The study plans to enroll approximately 50 patients, 25 per group.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Bologna
      • Bologna, Bologna, Italy, 40138
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Reproductive-age patients undergoing chemotherapy treatment for breast cancer or lymphoma, following ovarian biopsy and ovarian tissue cryopreservation at the Cryobank Laboratory for Ovarian Tissue Cryopreservation and Cell Cultures of the Unit of Gynecology and Human Reproductive Pathophysiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di S. Orsola

Description

Inclusion Criteria:

  • Age ≥ 18 and ≤ 38 years at the time of cryopreservation
  • Patient diagnosed with breast cancer or lymphoma, who underwent ovarian biopsy and cryopreservation of ovarian tissue prior to the initiation of gonadotoxic treatment
  • Gonadotoxic therapy completed at least 6 months prior
  • Written informed consent obtained for participation in the study and for the processing of personal, sensitive, and genetic data

Exclusion Criteria:

  • Patients with a history of gonadotoxic treatments prior to ovarian tissue cryopreservation
  • Patients undergoing hormonal therapy that suppresses ovarian function (e.g., GnRH analogs)
  • Presence of other conditions potentially responsible for premature ovarian insufficiency [e.g., BRCA1 and BRCA2 mutations, Li-Fraumeni syndrome, Bloom syndrome, Fanconi anemia, Fragile X syndrome, Cowden syndrome, Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer - HNPCC), Ataxia-Telangiectasia]
  • Family history of premature ovarian insufficiency

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare the mutational status of genes involved in DNA repair mechanisms in ovarian tissue fragments from women who underwent ovarian cryopreservation and completed chemotherapy treatment for lymphoma or breast cancer
Time Frame: At least 6 months after the end of chemotherapy
Onset of POI (Premature Ovarian Insufficiency)
At least 6 months after the end of chemotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare the mutational load of altered genes between women who developed POI and those who did not after undergoing chemotherapy
Time Frame: At least 6 months after the end of chemotherapy
Onset of POI
At least 6 months after the end of chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 23, 2025

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 3, 2026

Study Registration Dates

First Submitted

November 26, 2025

First Submitted That Met QC Criteria

November 26, 2025

First Posted (Actual)

December 8, 2025

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

November 26, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GTM_OCP
  • FERR24RD (Other Grant/Funding Number: Ferring S.p.A.)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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