Considerations for Men

Baseline Fertility and Pre-Existing Risks

Before treatment, it is essential to assess male patients’ fertility status and consider factors that might already have reduced fertility.

• Pre-treatment semen analysis — measure sperm concentration, motility, morphology, and sperm DNA fragmentation, if feasible.

• Some men with cancer already present suboptimal semen parameters due to the disease itself (e.g. testicular tumors, hormonal derangements, systemic illness) PMC+2livestrong.org+2

• Age and comorbidities (e.g. varicocele, endocrine disorders) may further reduce baseline reproductive potential.

• Recognizing baseline limitations helps set realistic expectations for post-treatment fertility and guides how aggressively to preserve (e.g. multiple aliquots, repeated sampling).

2. Main Method for Adult Males: Sperm Cryopreservation

2.1 Process Overview

• Collection: Usually by masturbation into sterile container; sometimes multiple samples are collected over days to maximize yield.

• Analysis: Semen is analyzed (volume, count, motility, morphology).

• Processing: The sperm is washed, concentrated, often mixed with cryoprotectants.

• Freezing / Storage: Samples are frozen (vitrification or slow-freeze as appropriate for sperm) and stored in liquid nitrogen under strict temperature control and redundancy.

• Future Use: Thawed sperm can be used in assisted reproduction (e.g., ICSI, IVF).

Sperm cryopreservation is considered the standard-of-care and the most reliable fertility preservation method for postpubertal males ACS Publications+2OUP Academic+2.

2.2 Efficiency & Success Rates

• Meta-analyses show a ≈10% failure-to-cryopreserve rate (i.e., inability to bank sperm) in male cancer patients OUP Academic+1.

• Among successfully cryopreserved samples, utilization rates are relatively low (~9%) in many studies, though longer follow-up often increases use OUP Academic.

• Assisted reproduction outcomes with cryopreserved sperm are encouraging: pregnancy and delivery rates using ICSI are comparable to non-cancer populations in many cases OUP Academic.

3. Special Techniques & Alternative Options

3.1 Surgical Sperm Retrieval (TESE / Micro-TESE / PESA / MESA)

When ejaculated sperm is unavailable (azoospermia, ejaculatory dysfunction), surgical retrieval methods are used:

• TESE (Testicular Sperm Extraction) — open biopsy to extract sperm from testicular tissue.

• Micro-TESE — microsurgical technique to find focal areas of sperm production in the testis.

• PESA / MESA — aspirating sperm from epididymal sources (less invasive).

These methods may be combined with sperm cryopreservation immediately if viable sperm are found. They are particularly useful in:

• Pre-treatment patients who already have very poor semen analysis

• Patients unable to produce ejaculate (neurologic, retrograde ejaculation)

• When urgent fertility preservation is needed and ejaculate is not feasible

3.2 Testicular Tissue Cryopreservation (Experimental)

For prepubertal boys (who do not yet produce mature sperm), or adult men unable to ejaculate or provide semen, testicular tissue cryopreservation is an emerging (experimental) option:

• Tissue containing spermatogonial stem cells (SSC) is harvested and frozen.

• In future, methods such as in vitro spermatogenesis or transplantation may enable sperm production from this tissue Wikipedia.

• This remains investigational and is typically offered only in research-enabled fertility centers.

4. Impact of Cancer Treatments on Male Fertility

4.1 Chemotherapy

• Alkylating agents (e.g. cyclophosphamide, busulfan) are highly gonadotoxic and can damage spermatogonial stem cells.

• High-dose or multiagent regimens increase risk of permanent azoospermia livestrong.org+1.

4.2 Radiation Therapy

• Direct gonadal irradiation (testicles or pelvis) can severely reduce sperm production.

• Scatter radiation or field overlap (e.g. pelvic, abdominal) must be considered.

• Testicular shielding during radiation may help reduce exposure but cannot completely prevent damage Cancer.gov+2PMC+2.

4.3 Targeted Therapy, Hormonal Therapy & Immunotherapy

• Effects of newer agents on male fertility are still under study; some may affect hormone axes or damage germline cells indirectly.

• Hormonal therapies (e.g. androgen deprivation) may suppress sperm production during treatment.

4.4 Combined Treatments & Stem Cell Transplantation

• Combined chemotherapy and radiation exposures have cumulative gonadotoxicity greater than single modalities.

• Pre-transplantation regimens or total body irradiation (TBI) carry high risk of permanent infertility.

5. Timing, Logistics & Coordination

• Early referral is essential: sperm cryopreservation should be offered before starting cancer therapy whenever possible ASCOPubs+2PMC+2.

• In urgent cases, multiple collections over consecutive days may be advisable to maximize stored sperm.

• If time is extremely limited, even a single ejaculate sample is better than none.

• Samples should be handled with minimal delay, maintained at optimal temperature, and transported to the laboratory rapidly.

Coordination is crucial among oncologists, urologists, and fertility specialists to ensure the preservation does not delay cancer treatment and that quality standards are met.

6. Long-term Storage, Usage & Disposition

• Sperm samples can remain viable for many years in cryostorage; some banks report decades of storage without decline in functionality.

• Planning for long-term maintenance costs (storage fees, lab oversight) is part of responsible care.

• Usage of stored sperm may occur through ICSI/IVF or other assisted reproduction methods.

• Disposition policies (e.g., disposal, donation, destruction) must be clarified in consent documents before freezing, especially where multiple requests or changes in circumstances (divorce, death) might arise.

7. Risks, Limitations & Considerations

• Some samples may not contain viable sperm post-thaw due to low initial count or quality.

• Social and psychological factors: Patients may decline preservation due to distress, cost, or timing.

• Utilization rates are relatively low historically (~9%) but may increase with longer follow-up and better patient counseling OUP Academic.

• Ethical and legal issues: Consent, future use by partners or heirs, ownership, and potential conflict in divorce or death situations must be addressed.

• For tissue-based approaches (experimental), future technologies (in vitro spermatogenesis) remain unproven.

8. Clinical Best Practices & Expert Recommendations

1. Offer fertility preservation universally to all postpubertal male patients at diagnosis of any cancer requiring gonadotoxic therapy.

2. Obtain multiple semen samples, if time allows, to maximize stored aliquots.

3. Store multiple aliquots, enabling flexibility and redundancy for future use.

4. Use accredited andrology laboratories with validated cryopreservation protocols and quality assurance.

5. Ensure robust consent and legal documentation regarding sample use, duration, and disposition.

6. Provide counseling and follow-up to survivors about reproductive options, timing of use, and post-treatment fertility evaluation.

7. Track outcomes and contribute to registries to continuously improve male fertility preservation practices