Adolescent Testicular Sperm Retrieval

Abstract

A 16-year-old male presented to a community hospital with 2 weeks of decreased urinary flow, which ultimately progressed to urinary retention. An indwelling Foley catheter was placed, and initial evaluation revealed no laboratory abnormalities. Magnetic resonance imaging (MRI) of the abdomen and pelvis demonstrated an enhancing mass within the anterior prostate measuring 4.2 × 5.2 × 4.6 cm. A right femoral head lesion was also noted. Percutaneous biopsy of the prostatic lesion confirmed a diagnosis of embryonal rhabdomyosarcoma, and further staging evaluation revealed Stage 4, high-risk disease. The patient was transferred to a tertiary-care pediatric hospital for treatment with the following chemotherapeutic regimen: vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, dactinomycin, and human IgG1 monoclonal antibody. The total cyclophosphamide equivalent dose (CED) for the planned treatment regimen was 16,290 mg/m².

Review Questions and Answers

• Q1. What is the dose-dependent impact of chemotherapy and radiotherapy upon long-term fertility potential?

• A1. Spermatogonia and spermatogonial stem cells are highly chemosensitive, rendering these cells vulnerable to a variety of chemotherapeutic agents [12]. The deleterious effect on spermatogenesis is most pronounced among the alkylating agents, where there is a dose-dependent risk of gonadotoxicity with increasing cumulative doses. The cyclophosphamide equivalent dose (CED) has emerged as the best predictor of long-term fertility in men who receive therapy with alkylating agents [13]. Normospermia is typically seen in patients with CED less than 4000 mg/m², though approximately 10% of patients with this low-dose exposure will have either oligospermia or azoospermia. Radiation therapy also impairs spermatogenesis by inducing DNA damage or apoptosis in spermatogonia [14]. Spermatogenesis may be impaired with doses as low as 0.15 Gy. Reversible azoospermia can result from doses of 0.35 Gy, and permanent azoospermia typically results from cumulative doses of >2.5 Gy. Semen parameters nadir approximately 4–6 months after therapy, and recovery of spermatogenesis, when present, may occur up to 18 months following treatment [15, 16].

• Q2. What are the outcomes of sperm retrieval if non-obstructive azoospermia persists after conclusion of therapy?

• A2. MicroTESE is the preferred approach to non-obstructive azoospermia in this setting, as it typically yields higher success than conventional TESE [17]. In men with azoospermia secondary to alkylating agents, microTESE has a 37% success rate for sperm retrieval [18].

• Q3. What is the risk of birth defects in the offspring of men with a history of cancer?

• A3. For men receiving chemotherapy or radiotherapy, there may be concern regarding transmission of germline mutations to future offspring. A large study of adult cancer survivors found no difference in the incidence of cytogenetic syndromes, single-gene disorders, and simple malformations between the offspring of cancer survivors and those of healthy controls (3.4% versus 3.1%) [19]. Nonetheless, patients are typically encouraged to defer family planning until approximately 1–2 years after completion of therapy in order to reduce the perceived risk of transient DNA damage or aneuploidy during the period immediately following therapy.

• Q4. What are the success rates with use of cryopreserved sperm for assisted reproductive technologies (ART) in patients with malignancy?

• A4. For men who do not have return of sperm in the ejaculate after the completion of cancer therapy, cryopreserved sperm are typically used for efforts at conception with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). The IVF success rates for patients banking sperm prior to cancer therapy are quite good, with one study reporting fertilization rates up to 71.4%, though these rates were lower among men with specific malignancies such as testis cancer or lymphoma [20]. An additional series reported a 66% live birth rate when cryopreserved sperm were used for IVF and intracytoplasmic sperm injection (ICSI) [21].