Testicular Tissue Freezing for Children with Cancer

Overseen By Asma Chattha, MBBS

Age: < 18

Sex: Male

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Psychiatric conditions, Anesthesia risk, Gonadotoxic therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This protocol is being designed to offer testicular tissue cryopreservation to male pediatric patients (0-17 years of age) with fertility threatening medical diagnoses or facing surgery, chemotherapy or radiation therapy that may cause loss of reproductive potential.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial investigators or your healthcare provider.

What data supports the effectiveness of the treatment Testicular tissue cryopreservation for children with cancer?

The research shows that testicular tissue cryopreservation is a feasible and safe option for preserving fertility in young boys with cancer, with a high acceptance rate among families. Although still experimental, the procedure has been successfully implemented in multiple centers, indicating its potential for future use. ^{1 2 3 4 5}

Is testicular tissue freezing safe for children with cancer?

Testicular tissue freezing has been studied in prepubertal and adolescent boys, and while it is considered experimental, it has shown to be generally safe with only minor adverse events reported that did not require medical treatment. ^{1 3 4 6 7}

How is testicular tissue freezing different from other treatments for preserving fertility in children with cancer?

Testicular tissue freezing is unique because it involves preserving immature testicular tissue before cancer treatment, allowing for potential fertility restoration after therapy. Unlike other methods, it is specifically designed for prepubertal boys who cannot produce sperm yet, offering a future option for fertility that other treatments do not provide. ^{1 3 6 7 8}

Research Team

Candace F. Granberg, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for boys aged 0-17 at risk of infertility due to medical treatments or conditions affecting the testicles. It's open to those with a high, intermediate, or low risk of prolonged azoospermia (no sperm), and those needing surgery that may impact fertility. Participants must have two testicles if they're having one removed just for preservation.

Inclusion Criteria

I have two testicles and am considering removal for fertility reasons.

I am at risk of losing my fertility due to treatment or a condition.

Sign informed consent and authorization for release of health information

Exclusion Criteria

I have received chemotherapy or radiation that could affect my fertility.

Diagnosed with conditions preventing informed consent

I am at high risk for complications from anesthesia and surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Testicular tissue cryopreservation procedure is performed for fertility preservation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week post-surgery and then yearly

1 visit (in-person) at 1 week, yearly visits thereafter

Treatment Details

Interventions

• Testicular tissue cryopreservation

Trial Overview The trial is studying the process of freezing testicular tissue in young males who are at risk of losing their reproductive potential due to cancer treatments or other medical interventions. The goal is to preserve future fertility by storing this tissue before it's damaged.

Participant Groups

Group I: Testicular tissue Experimental Treatment 1 Intervention

Children faced with a fertility threatening diagnosis or treatment plan will be offered testicular tissue cryopreservation, particularly if pre-pubescent and without other options to preserve fertility.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

Cryopreservation of immature testicular tissue using 1.5 M DMSO with a controlled slow protocol without seeding (CS-) was found to be the most effective method, preserving tissue architecture and cell viability after thawing.

This method not only maintained testosterone production and tubule growth similar to fresh samples but also provides a reliable way to evaluate cryodamage, which could be useful for future human applications in fertility preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of conditions for cryopreservation of testicular tissue from immature mice. Milazzo, JP., Vaudreuil, L., Cauliez, B., et al.[2022]

A pilot study involving 21 families of prepubertal boys with newly diagnosed malignancies found that 76% consented to testicular biopsy cryopreservation, indicating strong acceptability among parents for this fertility preservation option.

The procedure was performed safely, with 14 out of 16 boys undergoing the biopsy experiencing no negative intraoperative or post-operative effects, suggesting that testicular tissue cryopreservation is a viable option for preserving fertility in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. Ginsberg, JP., Carlson, CA., Lin, K., et al.[2022]

A study involving 34 boys at risk of fertility loss due to cancer treatment showed that most had normal or increased germ cell counts in their testicular tissue, indicating potential for fertility preservation through cryopreservation.

However, abnormal maturation of germ cells was observed in some older patients, suggesting that further research is needed to understand the implications for fertility preservation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer. Pietzak, EJ., Tasian, GE., Tasian, SK., et al.[2018]

Testicular tissue cryopreservation is a feasible and safe option for fertility preservation in prepubertal and adolescent boys undergoing gonadotoxic treatments, with a high acceptance rate of 90% among families in a study involving 35 patients.

The procedure was primarily used for patients with malignancies, particularly those preparing for hematologic stem cell transplantation, and while spermatozoa were found in only one patient, the overall safety profile was good with only two minor adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network. Moussaoui, D., Surbone, A., Adam, C., et al.[2023]

Cryopreservation of immature testicular tissue using a simple vitrification procedure successfully maintained cell viability and tissue function, showing no significant difference in recovery rates compared to fresh tissue.

The study demonstrated that vitrified testicular tissue could differentiate into secondary spermatocytes and exhibited similar levels of cell proliferation and apoptosis as fresh tissue, indicating its potential for fertility preservation in young boys with cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developmental Potential of Vitrified Mouse Testicular Tissue after Ectopic Transplantation. Yamini, N., Pourmand, G., Amidi, F., et al.[2020]

In a study involving testicular tissue from 16 infertile men, DMSO was found to be the most effective cryoprotectant, preserving 70% of the seminiferous tubules' structure after freezing, compared to only 37% with 1,2-propanediol and severe damage with glycerol.

The research indicates that DMSO not only maintains the structural integrity of spermatogonia but also preserves the function of Leydig cells, which continue to release testosterone after cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing cryopreservation of human testicular tissue: comparison of protocols with glycerol, propanediol and dimethylsulphoxide as cryoprotectants. Keros, V., Rosenlund, B., Hultenby, K., et al.[2013]

Cryopreservation of testicular tissue is a promising option for prepubertal boys undergoing cancer treatments, allowing for potential restoration of fertility after therapy.

While techniques for freezing and transplanting testicular tissue have shown success in animal studies, practical applications in humans are still limited, and no live offspring have been born from cryopreserved testicular cells yet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreservation of testicular tissue in young cancer patients. Hovatta, O.[2022]

In a study involving 87 (pre)pubertal boys with cancer, a control slow freezing protocol was found to effectively preserve the architecture and integrity of testicular tissue after thawing, with minimal cryodamage observed.

The number of spermatogonia and the expression of DNA repair markers remained stable post-thawing, indicating that the freezing process does not significantly impact the potential for future fertility preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the architecture and integrity of frozen-thawed testicular tissue from (pre)pubertal boys with cancer. Rives-Feraille, A., Liard, A., Bubenheim, M., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparison of conditions for cryopreservation of testicular tissue from immature mice. [2022]

2. England pubmed.ncbi.nlm.nih.gov

An experimental protocol for fertility preservation in prepubertal boys recently diagnosed with cancer: a report of acceptability and safety. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Histology of Testicular Biopsies Obtained for Experimental Fertility Preservation Protocol in Boys with Cancer. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys: A 6 year experience from a Swiss multi-center network. [2023]

5. Iran pubmed.ncbi.nlm.nih.gov

Developmental Potential of Vitrified Mouse Testicular Tissue after Ectopic Transplantation. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Optimizing cryopreservation of human testicular tissue: comparison of protocols with glycerol, propanediol and dimethylsulphoxide as cryoprotectants. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Cryopreservation of testicular tissue in young cancer patients. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Assessment of the architecture and integrity of frozen-thawed testicular tissue from (pre)pubertal boys with cancer. [2022]