CAN MY SON HAVE CHILDREN SOMEDAY? UNDERSTANDING FERTILITY PRESERVATION BEFORE AND AFTER PEDIATRIC CA

The diagnosis of cancer in a child is an overwhelming moment for any parent. Beyond the immediate concerns of the diagnosis and treatment, many parents of prepubescent boys also wonder: What will happen to my son’s ability to have children in the future? While cancer therapies have advanced significantly, they can have long-lasting effects on fertility. This article provides an evidence-based overview of fertility preservation options for prepubescent boys undergoing cancer treatment, including chemotherapy, radiation therapy, and surgery. We will discuss scenarios before treatment begins and after treatment has started, focusing on the role of testicular tissue cryopreservation (TTC) performed through testicular sperm extraction (TESE), and the challenges associated with these approaches.

Understanding the Impact of Cancer Treatment on Fertility in Prepubescent Boys

Cancer treatments are life-saving but often come with side effects that can impact fertility. For prepubescent boys who have not yet begun producing mature sperm, traditional sperm banking is not possible. Instead, fertility preservation relies on preserving the spermatogonial stem cells (SSCs) within the testicular tissue.

Chemotherapy

Chemotherapy, especially treatments involving alkylating agents like cyclophosphamide and ifosfamide, can damage or destroy SSCs. The effect depends on the type, dosage, and duration of chemotherapy. Higher doses and prolonged treatments significantly increase the risk of long-term infertility.

Radiation Therapy

Radiation to the pelvic area, abdomen, or total body irradiation can harm testicular tissue and the developing SSCs. Even low doses can cause subfertility or infertility, and the damage is cumulative.

Surgery

Surgical treatments for cancer that involve the reproductive organs, or that result in trauma to the testicular blood supply, can impair fertility. Additionally, surgeries such as orchiectomy (removal of one or both testicles) have immediate and irreversible effects on reproductive potential.

Fertility Preservation Options: Two Critical Scenarios

Scenario 1: A Child Recently Diagnosed With Cancer Who Has Not Started Treatment

For prepubescent boys who have been newly diagnosed and are about to begin cancer treatment, there is an opportunity to preserve fertility by harvesting and freezing testicular tissue.

Testicular Tissue Cryopreservation (TTC) Through Testicular Sperm Extraction (TESE)

TTC is performed through a surgical procedure known as testicular sperm extraction (TESE). During TESE, a small biopsy of the testicle is removed under general anesthesia. This tissue contains spermatogonial stem cells that are frozen for future use. Although mature sperm are not present in prepubescent boys, the hope is that in the future, advances in medical science will allow for these SSCs to be matured into sperm through in vitro methods or through autologous transplantation.

Challenges of TTC Before Treatment

• Experimental Procedure: While TTC and TESE are increasingly offered at specialized centers, the procedure is still considered experimental.

• Lack of Clinical Success in Humans: To date, no pregnancies have been achieved using SSCs derived from cryopreserved testicular tissue in humans.

• Parental Consent and Psychological Support: Parents must understand the experimental nature of the procedure and weigh the potential benefits against surgical risks and costs.

• Timing: The procedure must be performed before chemotherapy or radiation therapy begins to maximize the number of viable SSCs.

Scenario 2: A Child Who Has Already Undergone Chemotherapy and is Scheduled for a Stem Cell Transplant

The situation becomes more complex for boys who have already received chemotherapy and are preparing for a stem cell transplant. The exposure to chemotherapy agents, especially alkylating agents, reduces the SSC population and may compromise the quality and quantity of tissue that can be harvested.

TTC and TESE After Chemotherapy

• Reduced Viability of SSCs: The number and functionality of SSCs may be significantly diminished following chemotherapy.

• Residual Cancer Cells in Tissue: There is a risk that harvested testicular tissue may harbor malignant cells, making future autologous transplantation risky.

• Lower Success Rates: The likelihood of successful fertility restoration in the future decreases if tissue is collected after chemotherapy.

• Ethical Considerations: Harvesting tissue post-chemotherapy requires in-depth discussions between the medical team and the family regarding realistic expectations and experimental limitations.

Advances in Research and Future Possibilities

In Vitro Maturation

Scientists are working to develop techniques that can mature SSCs in a laboratory setting to produce functional sperm. Animal models have shown promise, but this has not yet translated into clinical success for human patients.

Autologous Transplantation

Another avenue of research is the transplantation of cryopreserved testicular tissue back into the patient after remission. This approach faces two major challenges: ensuring the safety and viability of the SSCs and eliminating the risk of reintroducing malignant cells.

Biomaterial Scaffolds and Tissue Engineering

Researchers are exploring the use of biomaterials to create scaffolds that can support SSC growth and development, potentially aiding in the maturation of these cells into sperm.

Considerations for Parents

1. Early Discussion: Parents should discuss fertility preservation options with their child’s oncologist as soon as a cancer diagnosis is confirmed.

2. Referral to Specialists: Ask for referrals to reproductive endocrinologists or andrology specialists who can explain experimental options like TTC and TESE.

3. Understanding Experimental Nature: Be aware that while hope is strong, success in restoring fertility from cryopreserved testicular tissue is not yet a clinical reality.

4. Future Alternatives: Should fertility preservation efforts not succeed, other options such as donor sperm, adoption, or advances in medical technology may offer paths to parenthood.

Summary Chart: Fertility Preservation in Prepubescent Boys With Cancer

Conclusion

A cancer diagnosis in a young boy brings numerous worries, and the potential impact on fertility adds another layer of complexity. For prepubescent boys, the only fertility preservation option available today is testicular tissue cryopreservation via TESE. Although still experimental, TTC offers hope for future biological fatherhood. Research into maturing SSCs in vitro and safe transplantation techniques continues to advance, and parents should remain informed of these developments. Early discussions with healthcare providers, consultations with fertility preservation specialists, and psychological support for families are essential components of comprehensive cancer care.

References

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