Two Successful Sperm Aspirations in High-Risk Adolescent and Young Adult Lymphoma Patients Before Initiation of Emergent Therapy

Introduction

As survival rates for adolescent and young adult (AYA) cancer patients improve, fertility preservation (FP) is gaining increased attention.^1,2 AYAs report significant concerns about their fertility potential after therapy.^3,4 Despite this, surveys report that <50% of oncologists provide counseling or referral to fertility specialists before initiation of therapy. ⁵ Time constraints, concerns about treatment delays, and difficulty accessing resources are reported as reasons for not providing counseling. ⁵ Fertility impairment is particularly common in males, affecting more than half of survivors.^6–8 FP among postpubertal males is established and generally noninvasive. In some cases, patients may be deemed too ill or incapable of producing a sample due to the severity of their disease or possible testicular involvement. In these severe cases, patients, as well as their medical team, may feel FP is not an option because treatment needs to be initiated immediately. We present two cases of high-risk AYA patients presenting to a pediatric medical center in critical conditions where testicular sperm aspiration (TESA) was able to be performed in an urgent and safe manner, where there was success in obtaining a sperm sample for cryopreservation before the initiation of chemotherapy.

Case 1

A 16-year-old male presented to the emergency room after several weeks of progressive cough, fatigue, and dyspnea. A chest X-ray demonstrated a large mediastinal mass with pleural effusion and concern for severe respiratory compromise, prompting transfer to our pediatric intensive care unit. Pleural fluid analysis confirmed T cell lymphoma without evidence of peripheral blasts and emergent initiation of chemotherapy was recommended due to ongoing concerns of respiratory failure. Parents and patient expressed interest in FP options, but he was unable to produce a sperm sample for cryopreservation due to the severity of his illness. After consultation with our fertility and reproductive health team (consisting of a fertility navigator, primary oncology team, pediatric urologist, and outside embryology laboratory), a multidisciplinary effort successfully coordinated and procured viable sperm through TESA under conscious sedation, in conjunction with his diagnostic lumbar puncture and bone marrow biopsy procedures before initiation of urgent chemotherapy. TESA and other procedures were organized and performed within 19 hours of arrival to the intensive care unit and chemotherapy was initiated within 28 hours (Table 1).

Case 2

A 19-year-old male presented with a subacute history of low back pain, progressive bilateral lower extremity weakness/sensory changes, and right cranial nerve VII palsy. The only abnormality in initial laboratories was an elevated lactate dehydrogenase. A magnetic resonance imaging (MRI) of the spine showed a retroperitoneal and paraspinal mass that entered the vertebral canal and was compressing the spinal cord at the thoracolumbar junction. An MRI of the brain showed a right temporal soft tissue mass, and focus of enhancement involving the seventh cranial nerve. Positron emission tomography/computed tomography showed not only enhancement of the aforementioned lesions, but also an intense hypermetabolic lesion in the right testicle, with no metabolic lesion in the left testicle. A testicular ultrasound confirmed the area of concern in the right testicle as well as no masses or abnormality of the left. Owing to his spinal cord injury causing paralysis below his waist, this patient was unable to achieve an erection to produce a sperm sample. He and his family expressed interest in sperm cryopreservation, so an official FP consult was placed. After consultation with our fertility and reproductive health team, a multidisciplinary effort involving the key stakeholders identified earlier successfully coordinated and procured viable sperm through TESA of the left testicle under conscious sedation, in addition to performing diagnostic bone marrow biopsies before initiation of urgent chemotherapy. The time sequence of events was similar to those earlier and TESA and other procedures were organized and performed within 24 hours of admission.

Discussion

More than 90,000 AYAs between 15 and 39 years are diagnosed with cancer each year in the United States. ² Although treatment and cure are of primary concern, other factors such as education, overall health, and having children are also paramount to long-term quality of life. ² However, studies continue to show that the medical community falls short of providing patients proper FP counseling and options. ⁵

In males, sperm preservation through masturbation does not require significant time and can even be done from the hospital bed. However, this technique may not always be an acceptable option for every patient. Owing to religious beliefs or sexual inexperience, some patients may not be able or willing to utilize this method. In addition, some patients may have significant presenting symptoms or require initial medical interventions making obtaining a semen specimen through this route impossible. In these instances, other techniques should be considered and addressed in detail with the patient and family. Options may include TESA, testicular sperm extraction (TESE), or electro-ejaculation (EEJ) through prostate stimulation. TESA is a method of sperm retrieval that involves sperm aspiration by inserting a needle in the testis and aspirating fluid and tissue with negative pressure, whereas TESE removes small samples of testicular tissue through a procedure similar to a testicular biopsy and extracting sperm from this tissue. ⁹ EEJ is a technique where a transrectal probe is inserted, under procedural sedation or general anesthesia, and probes are placed in the rectal mucosa near the prostate and seminal vesicles. Pulsatile electrical stimulations are administered until ejaculation occurs. ⁸

Of the techniques mentioned, each has its benefits as well as its limitations. Although TESA and TESE generally result in an adequate sperm sample for future intracytoplasmic sperm injection (ICSI), the number of sperms that are procured are often lower in quantity when compared with ejaculated sperm and may not be adequate for other assisted reproductive techniques, such as intrauterine insemination. ¹⁰ A recent study showed that mean sperm concentrations for patients undergoing TESE were 0.28 × 10⁶/mL, compared with 12.9 × 10⁶/mL in those who underwent successful EEJ. ⁸ In contrast, although EEJ may produce a higher quantity of sperm, this technique may be perceived as more invasive by families, and an EEJ device is not available at many medical centers. In addition, some religions may deem this type of procedure as inappropriate or require approval from religious leaders. ⁸ Although each of the techniques discussed may be successful in obtaining viable sperm samples for cryopreservation, for patients with an oncologic diagnosis, another issue to consider is the effect of their disease on their sperm concentration. Several studies have been published that show patients with hematologic malignancies tend to have a lower sperm count, even before the initiation of chemotherapy.^11,12 This becomes an important consideration during the consultation phase when discussing potential strategies and techniques for future conception.

In both of our patients, TESA was performed in the operating room in conjunction with procedures required for diagnosis and staging to avoid unnecessary treatment delay. The urologist performed the aspiration and cryobiology personnel performed microscopic review to assess viability of sperm. This process was repeated several times to ensure an adequate specimen/sample—multiple mobile sperm were observed. Although pathology presence is standard for reproductive tissue procurement, it is not a routine practice for sperm aspiration procedures. Cryobiology staff performed initial processing and transport of the specimen to their local facility in compliance with Food and Drug Administration regulatory guidelines for reproductive material. At the facility, the specimen was analyzed for number and motility of sperm and then cryopreserved locally. Although overall sperm count was low, both patients were able to provide several vials of viable sperm for cryopreservation for future use through ICSI. The aspiration site was covered with dermabond. Because the patients required other surgical procedures (central line placement, bone marrow aspirate, and biopsy and lumbar puncture) TESA was combined with these interventions without delaying definitive cancer diagnosis or treatment. There was no significant bleeding or hematoma postprocedure. Delayed healing is rare given the small puncture wound, and both patients were able to begin chemotherapy on the day of their procedures.

There are a variety of reasons that patients may not pursue FP opportunities at diagnosis. FP techniques and storage are currently only covered by insurance in seven states (Illinois, New York, Rhode Island, Connecticut, Delaware, Maryland, and New Hampshire) and cost may be a prohibitive factor in an AYA's decision on whether to undertake FP. ¹³ In addition, there may also be misconceptions regarding the time needed for FP, leading either the treating physicians or the patient/family to feel that there is not time to pursue FP before the initiation of treatment, especially if the patient has significant symptoms at presentation. ⁴ In these cases, physicians may forego a discussion, hoping to decrease a perceived burden they may be placing on the patient.^5,14,15 Finally, some have reported that the specific disease itself may influence whether a patient is given fertility information, as it has been shown that male patients with lymphoma, acute lymphoblastic leukemia, or sarcoma are less likely to be told that their future fertility may be affected by the therapy they receive. ⁵ Data regarding safety and efficacy of TESA for obtaining sperm for cryopreservation in patients with solid tumors continues to grow, and there are several case reports in patients with testicular cancer successfully cryopreserving sperm that ultimately led to live births.^16–19 Unfortunately, the literature is not as prolific in patients with hematologic disease, possibly because there may be a theoretical concern for introduction of circulating malignant cells into the testicle with invasive procedures. These concerns must be weighed against the reality that preservation at diagnosis may be the only opportunity for future genetic parenthood for many of these patients and that sperm from TESA can be isolated and used in ICSI; therefore, risk of transfer of malignant material is low and has not been reported to date.^17,18

In summary, these cases demonstrate that TESA with sperm cryopreservation can be successfully performed in “high-risk” pubertal males with significant barriers to traditional collection before initiation of emergent chemotherapy, and should be considered for patients who are unable to masturbate as a means to produce a sperm sample before gonadotoxic therapy. These cases also demonstrate that seamless and timely communication between the primary oncologist and the fertility and reproductive team is essential. With the appropriate infrastructure, including a dedicated navigator, “opt-out” initiatives in the electronic medical record, and support of the key stakeholders, care coordination can be implemented with urgency, allowing for collection to take place within 24 hours of the patient being admitted to the hospital. ²⁰