TOO LATE OR JUST IN TIME? PRESERVING FERTILITY AFTER CANCER TREATMENT HAS BEGUN

Introduction

The ideal time for sperm banking is before cancer therapy begins. But what happens when that opportunity has passed? Each year, countless male cancer patients undergo treatment without having been informed about the risk of infertility or the option of fertility preservation. Some may be told it’s too late. Others may assume all hope is lost. Fortunately, evolving science tells a more optimistic story.

This blog examines the evidence and strategies behind fertility preservation after cancer treatment has begun—or even concluded. Whether the treatment window was missed due to urgency, oversight, or emotional distress, this article provides hope and practical pathways for patients and providers alike.

Understanding the Effects of Cancer Treatment on Fertility

To understand what may still be possible after treatment, it's crucial to first understand how treatments affect the male reproductive system:

Chemotherapy: Alkylating agents such as cyclophosphamide and busulfan are highly toxic to dividing germ cells. The resulting azoospermia can be temporary or permanent, depending on the dose and duration (Meistrich, 2013).
Radiation: Testicular exposure to even low doses of radiation (0.1-1 Gy) can impair spermatogenesis. Doses over 4 Gy can result in irreversible infertility (Rowley et al., 1974).
Surgery: Orchiectomy, retroperitoneal lymph node dissection (RPLND), or pelvic surgery may impair fertility through anatomical disruption or nerve damage affecting ejaculation.
Combined Modalities: Many patients receive a combination of the above, increasing the risk of long-term infertility.

Semen Analysis: A Critical First Step

If treatment has already begun or been completed, the first step is to perform a semen analysis. This non-invasive test measures:

Sperm concentration
Motility
Morphology

Semen quality can vary significantly over time. Some men regain sperm production months or even years after treatment ends, particularly if they received non-alkylating chemotherapy or low-dose radiation.

The general recommendation is to wait 6 to 12 months post-treatment before testing semen parameters, as the testis may gradually recover spermatogenesis.

Post-Treatment Sperm Banking: Still an Option?

If sperm are present in the ejaculate post-treatment, even in low numbers, sperm banking is still possible. In fact, even severely oligospermic samples can be frozen and later used with intracytoplasmic sperm injection (ICSI) to achieve pregnancy.

Studies have shown that men with sperm concentrations as low as 1 million/mL may still have success with ICSI. Thus, banking poor-quality semen is still preferable to waiting and risking complete azoospermia.

When No Sperm Are Present: Exploring Surgical Retrieval Techniques

For men who are azoospermic following treatment, surgical sperm retrieval (SSR) techniques offer a promising alternative:

Testicular Sperm Extraction (TESE): A small tissue sample is taken from the testicle to look for sperm that may be present in isolated tubules.
Microdissection TESE (microTESE): A more advanced method using an operating microscope to find and extract areas of active spermatogenesis. This method maximizes sperm retrieval while minimizing testicular damage (Schlegel, 1999).
Testicular Fine Needle Aspiration (TFNA): Less invasive than TESE but with lower success rates.

The success of SSR varies depending on the treatment received, time since therapy, and baseline testicular function. In post-chemotherapy azoospermic men, microTESE yields sperm in approximately 40-60% of cases (Schlegel, 2009).

Hormonal Evaluation: Clues About Spermatogenic Potential

In azoospermic men, serum hormone levels can help determine whether sperm retrieval is likely to succeed:

FSH (Follicle Stimulating Hormone): Elevated levels suggest testicular damage and impaired spermatogenesis.
LH and Testosterone: Provide context on Leydig cell function and testicular health.
Inhibin B: May provide insight into Sertoli cell function, although its role in predicting SSR success is still under investigation.

An endocrine evaluation is essential for counseling patients on the likelihood of retrieving sperm and considering adjunctive therapies.

Adjunctive Therapies to Enhance Spermatogenesis

Although evidence remains limited, clinicians may employ various off-label hormonal therapies (without FDA approval) in men with azoospermia following primary treatments.

• Gonadotropin therapy (hCG and FSH) demonstrates particular utility in hypogonadotropic hypogonadism by directly stimulating testicular function to promote spermatogenesis.

• Selective Estrogen Receptor Modulators (SERMs) such as clomiphene citrate or tamoxifen work through hypothalamic-pituitary modulation to enhance endogenous gonadotropin production.

• Aromatase inhibitors including anastrozole and letrozole represent an emerging approach, inhibiting testosterone-to-estradiol conversion to improve testosterone/estradiol ratios and amplify gonadotropin secretion.

These interventions require careful patient selection and monitoring, as therapeutic responses vary significantly and all must be administered under close medical supervision.

Experimental and Emerging Options

For patients with no viable sperm, several experimental techniques are in development:

Spermatogonial Stem Cell (SSC) Transplantation: Prepubertal boys who bank testicular tissue may one day benefit from SSC reintroduction to restore fertility.
In Vitro Spermatogenesis: Efforts to mature sperm from stem cells or immature germ cells in the lab may eventually yield clinical applications.
3D Testicular Organoids: Engineered microenvironments that may support in vitro sperm production in the future.

These approaches are not yet clinically available but may transform options for survivors in the coming decade.

Emotional and Psychological Considerations

Many patients feel grief or anxiety upon learning of their infertility. Post-treatment fertility preservation offers not just a medical possibility, but a psychological lifeline:

Restoring Hope: Knowing that options exist can help patients regain a sense of control and optimism.
Supporting Survivorship: Fertility is a key part of long-term quality of life for many survivors.
Informed Decision-Making: Discussing post-treatment options allows patients to make empowered choices.

Fertility counseling and psychological support should be offered alongside medical evaluations.

Conclusion: It's Not Over Until It's Over

The absence of pre-treatment sperm banking should never be considered the end of the fertility story. With options ranging from semen analysis and sperm banking post-treatment to advanced surgical and experimental technologies, many men can still achieve biological fatherhood.

Clinicians must remain vigilant, informed, and proactive in counseling patients who have already started or completed treatment. Post-treatment fertility preservation is not only possible—it is essential to comprehensive survivorship care.

References

Meistrich, M. L. (2013). Male gonadal toxicity. Pediatric Blood & Cancer, 60(4), 531-537.

Rowley, M. J., Leach, D. R., Warner, G. A., & Heller, C. G. (1974). Effect of graded doses of ionizing radiation on the human testis. Radiation Research, 59(3), 665-678.

Schlegel, P. N. (1999). Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Human Reproduction, 14(1), 131-135.

Fujita K, Tsujimura A. Fertility preservation for boys with cancer. Reprod Med Biol. 2010 Aug 7;9(4):179-184.