Late Effects of Cancer Therapies on Gonadal Function, Fertility, Efficiency of Fertility Preservation Procedures and Pregnancy Outcomes

NCT07622537 | Not Yet Recruiting DMC

• 1 other identifier: V1.0-17/03/2026
• Study Type: observational
• Target: 4,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

In the past two decades, evidence-based knowledge on the prevalence and risk factors for fertility impairment, including infertility, following cancer and numerous cancer treatment regimens has significantly increased. However, data remains mostly insufficient for individualized prediction of (future) fertility potential, including success of artificial reproductive technologies (ART). Furthermore, therapies have become increasingly complex. Recent treatment regimens have continuously implemented novel treatment approaches (e.g. immune therapies such as checkpoint inhibitors) for which no comprehensive data regarding its impact on fertility and pregnancy outcomes is available, yet. It is crucial to carefully balance risk-benefit between fertility preservation (FP) procedures and potential of gonadal function/fertility impairment, to examine the efficiency and safety, as well as to assess patients' satisfaction regarding the FP procedures. Answering these questions is highly relevant as it has been shown that fertility capacity and post-treatment gonadal function may represent a significant part of the quality of life in young cancer survivors. The study therefore aim to set up a large-scale network structure of emerging data collection programmes to evaluate the gonadotoxic risks, including the prevalence and course of ovarian/testicular dysfunction and/or fertility impairment and premature ovarian insufficiency/oligo/azoospermia following specific treatments, identification of further risk factors and predictive markers to enhance precision survivorship research in this field. Additionally, data on the use of fertility preservation/fertility treatment and patients' satisfaction related to these procedures in Europe shall be analysed to support patient-centric care. Reproductive health counselling should not be restricted to evaluating the individual risk of gonadotoxicty and offering fertility preservation to those at risk. It also includes the sexual health, the use of post-cancer treatment contraception for those recommended to delay attempting pregnancy after a cancer diagnosis and the identification of potential obstetrical and neonatal risks to provide individualized, risk-adapted follow-up during pregnancy. An increased risk of obstetrical and neonatal complications has been reported for several conditions, including preterm delivery, pre-eclampsia, cardiac dysfunction, and gestational diabetes. Most available studies are based on population registry and lack of detailed information on critical factors such as the impact of the timing of pregnancy, method of conception or the type of cancer treatment received (e.g pelvic irradiation, anthracycline, targeted therapy, immunotherapy…), all of which may influence the outcomes. The main objectives of this retrospective analysis of European ongoing adolescent and young adult (AYA) cancer patient cohorts are:

• To establish harmonized databases with clinical data on pre- and post-cancer therapy and reproductive outcomes in AYA patients followed longitudinally.
• To evaluate the impact of cancer treatment on long-term fertility according to cancer type and individual patients' characteristics (pre- and post-treatment) in male and female AYA populations.
• To evaluate effect of cancer therapies on ovarian function in female AYA patients
• To evaluate long-term effect on the endocrine function of the testis in male AYA patients i.e., the frequency of hypogonadism.
• To evaluate the obstetrical and neonatal outcomes according to the disease and treatment.

Conditions

Cancer; Infertility; Late Effects; Male Fertility; AYA Cancer Survivors; Female Fertility

Keywords

cancer treatment induced late effects; infertility after cancer; AYA cancer survivours

Outcome Measures

Primary Outcomes (9)

• Constitution of the RedCap database

  Constitution of a centralized RedCap database based on the collected variables from 4000 individuals diagnosed with cancer at age 15-39.

  June 2030

• Treatment impact on AMH (1)

  Percentage of included patients in which AMH decreases to below detection limit and percentage of AMH decrease if AMH stays above detection limit.

  June 2030

• Incidence of azoo/oligo/normozoospermia

  Incidence of azoo/oligo/normozoospermia through the analysis of sperm parameters pre/post treatment

  June 2030

• Prevalence of pregnancy, obstetrical and neonatal outcomes according to the type of disease (1)

  Prevalence of pregnancy, obstetrical and neonatal outcomes according to the type of disease

  June 2030

• Treatment impact on AMH (2)

  Change of menses pattern pre/post treatment.

  June 2030

• Treatment impact on AMH (3)

  Prevalence of POI post treatment.

  June 2030

• Treatment impact on AMH (4)

  Role of individual genetic backgrounds in menstrual function abnormalities and ultra-low or undetectable AMH levels.

  June 2030

• Prevalence of pregnancy, obstetrical and neonatal outcomes according to the type of disease (2)

  Influence of disease type and stage on the obstetrical outcomes.

  June 2030

• Prevalence of pregnancy, obstetrical and neonatal outcomes according to the type of disease (3)

  Influence of disease type and stage on the neonatal outcomes.

  June 2030

Secondary Outcomes (19)

• Incidence and type of FP according to the type of cancer and treatments.

  June 2030

• Safety of FP procedures (1).

  June 2030

• ART induced pregnancy (1)

  June 2030

• Incidence of overt and compensated hypogonadism

  June 2030

• Correlation between hormonal values/routine sperm parameters and clinical characteristics

  June 2030

Study Arms (3)

Sub-cohort A: Gonadal function in females

Sub-cohort B: Gonadal function in males

Sub-cohort C: Survival and pregnancy outcomes

Eligibility Criteria

• Age: 15 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

AYA cancer patients aged 15-39 at diagnosis and treated for their disease at any of the participating study centers

You may qualify if:

• Female and male cancer patients aged between 15 and 39 years at diagnosis.
• First diagnosed with any cancer disease between 01/01/2000 and 31/12/2025
• Treated with chemotherapy and/or targeted therapy/immunotherapy and/or radiotherapy/ radioactive iodine therapy and/or testis/scrotal or gynaecological surgery.
• Information on treatment received available.

You may not qualify if:

• Pre-existing known POI at cancer diagnosis
• Cancer treated by surgery alone (except gynaecological/testicular surgery)
• Data from second malignant neoplasm diagnose and treatment
• Adult subject of a measure of legal protection and/or patients with serious mental disorders

Sponsors & Collaborators

• Karolinska Institutet: lead
• University of Edinburgh: collaborator
• Tartu Ülikooli Kliinikum: collaborator
• Linkoeping University: collaborator
• University of Leeds: collaborator
• INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE: collaborator
• UNIVERSITATSKLINIKUM HEIDELBERG: collaborator
• Region Stockholm: collaborator
• University of Leipzig: collaborator
• University of Florence: collaborator
• European Commission: collaborator
• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: collaborator
• Ospedale Policlinico San Martino: collaborator
• The Netherlands Cancer Institute: collaborator
• Université Libre de Bruxelles: collaborator
• MEDIZINISCHE UNIVERSITAT INNSBRUCK: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Patients will be carefully selected for recontact and included in the Sub-studies collecting blood and sperm samples, focusing on specific aspects of both ovarian and testicular toxicity. In cases where existing samples are available, efforts will be made to harmonize sample collection and data generation protocols.

MeSH Terms

Conditions

Neoplasms; Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Central Study Contacts

Kenny A Rodriguez-Wallberg, Professor, MD

CONTACT

+46852481213; kenny.rodriguez-wallberg@ki.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: June 3, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): July 31, 2035
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share