Speaker- Robert E. Brannigan 

Fertility preservation is crucial for males throughout their lifespan, with three patient groups: adult, adolescent, and prepubertal. About half of men will develop cancer, and many desire to have pregnancies later in life. However, 85% and 76% 5-year survival rates for men up to 19 and 44 years respectively. Male infertility is common after treatment for many malignancies, and persistent infertility can result after cancer treatment. Cytokines disrupt the hypothalamic-pituitary-gonadal (HPG) axis, immune responses can cause damage to the germinal epithelium, and systemic processes like fever and malnutrition can adversely affect fertility. 

 

The Seacoast Network in France has discovered that cancer diagnosis often leads to impaired fertility in patients with testicular germ cell tumors and lymphoma. These patients have lower sperm concentrations and motilities and higher levels of sperm DNA damage, which can negatively impact reproductive outcomes. Cancer therapies, including radiation, chemotherapy, and surgery, can also adversely affect male fertility. Patients with less than two gray radiations typically have their sperm counts down by three months but recover well. 

Fertility preservation is crucial in chemotherapy regimens for patients with various diseases like ALL, Hodgkin's disease, and soft tissue sarcomas. High-risk alkalinity agents like cyclophosphamide and diphosphamide can cause fertility impairment, while lower-risk drugs like vincristine and methotrexate are used. Patients with Hodgkin's disease need to decrease sperm counts before rebounding, while sarcoma patients require high-dose occluding agents to prevent azoospermia and fertility loss. 

Before surgery, it's crucial to discuss potential fertility effects with patients to prevent angry reactions. Certain surgeries, such as testicular cancer, bladder and prostate cancer, colon cancer, and central nervous system surgery, can affect fertility by removing testicular cells, disrupting the ductal system, or affecting sperm production. 

Fertility preservation in males is crucial for comprehensive care, as outlined by the American Society of Clinical Oncology (ASCO) in 2006. Other professional societies, including ASCO, the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), the American Academy of Pediatrics, and the American Urological Association (AUA), have also published guidelines on fertility preservation. Key takeaways include discussing potential adverse effects of cancer therapies, reserving sperm before gonadotoxic therapies, repeating semen testing 12-24 months after therapy completion, and discussing Tessie as a treatment option.

 

Over 90% of males can provide a semen sample through masturbation for fertility preservation, even in sick men and inpatients. However, for azoospermic, ejaculated, or aspermia patients who cannot be treated with other treatments, Oncotesi is an option. Schrader and colleagues found that 14 out of 31 azoospermic men with testicular cancer and lymphoma successfully retrieved sperm. In patients with lymphoma, eight out of 17 patients successfully extracted and frozen sperm. Therefore, Oncotussi should be considered for these azoosperm patients due to the risks of irreversible fertility issues with cancer therapies. 

A 31-year-old Brazilian male with bilateral synchronous testicular tumors was successful to achieve pregnancy with Onco-TESE sperm after bilateral orchiectomy. The sperm was frozen and used in IVF to achieve a pregnancy at 39 weeks. The study examined predictors for spermatogenesis in patients considering Onco- TESE procedure. Small tumor size was a positive prognostic indicator for spermatogenesis, but larger tumor sizes did not exclude sperm presence in testicles affected by cancer. Onco-TESE should be strongly considered for similar patients.

 

A study on teenage boys revealed that many are not receiving sperm banking after an adult fertility preservation program was established. Over 50% of pediatric oncologists in the US do not use ASCO recommendations when treating adolescent patients with cancer, and over 80% use them only half the time or less. The lack of infrastructure in pediatric hospitals highlights the importance of fertility preservation for teenage patients.

 

A study by Orwig and colleagues at Pittsburgh and Oregon demonstrated that cryopreserved prepubertal testicular tissue can be autonomously grafted into castrated rhesus monkeys to produce functional sperm. After 8-12 months, hormone levels were normal, and complete spermatogenesis was observed. The sperm was then used in in vitro fertilization (IVF) to create embryos, highlighting the potential of cryopreserved testicular tissue in fertility preservation.

Fertility preservation for adult males can be easily achieved by following clear guidelines and avoiding assumptions about future biological fatherhood. Effective, streamlined care should not interfere with oncologic care. Adolescents should be considered vulnerable and have their guidelines applied. Collaboration with basic science investigators is crucial for prepubertal males, focusing on new techniques to help this cohort.

Early adolescence is crucial for identifying and freezing sperm in Klinefelter syndrome patients, but testicular sperm extraction is not recommended due to high retrieval rates later in life. Focusing on freezing ejaculated sperm when available is recommended. Pubertal stage assessment and communication with patients are essential for determining sperm presence. Regulatory concerns regarding tumor-free testicular tissue use and potential contamination risks in cancer patients' sperm extraction are addressed. 

 

European Society of Human Reproduction and Embryology, July 7-10, Amsterdam, The Netherlands







Other Conference Highlights