By: Sierra Orr, MS Reproductive Science and Medicine, Northwestern University
The opinions expressed in the article are her own.
In the past 20 years, fertility preservation has become a rapidly growing field, as many patients are becoming increasingly more aware of how treatments for varying diseases can place them at risk for infertility. While this is not only limited to the oncologic (cancer) diagnoses, fertility preservation is most often used by oncology patients.
Fertility preservation can also be used by patients that are at risk for infertility due to treatment used for sickle cell anemia, or those that have high risk professions such as individuals enlisted in the military. Within this blog post, we will discuss options for fertility preservation and family building amongst patients with a cancer diagnosis.
This topic is of high importance to me as I am writing my master’s thesis on pediatric oncology patients that pursue fertility preservation, in hopes of offering more options for family building in the future. I hope after reading this blog post, you will learn potential reasons why someone might pursue fertility preservation and understand the importance of understanding risk factors related to fertility that stem from cancer therapies!
Every year, there are 9 million men that are diagnosed with cancer globally, and approximately 200,000 men in the United Kingdom. Common therapies for cancer treatment include chemotherapy and radiation, which are toxic to the reproductive organs of both male and female patients. Fertility preservation (FP) is known as the process of saving eggs, sperm, and/or reproductive tissue so that individuals can use them if they wish to have biological children in the future.
Many patients that are diagnosed with cancer will receive treatment that puts them at an increased risk for infertility. The recent advances in cancer treatment have caused an increase in overall survival rates for cancer patients and increased the need for discussions surrounding fertility preservation. This post aims to provide necessary information for patients with sperm to ensure that they understand their options, as it relates to gonadotoxicity, fertility preservation and future fertility.
In this post we will cover:
Spermatogenesis and the gonadotoxic effects of cancer treatments and how this affects fertility
The basics of fertility preservation, the importance of counselling patients that are at risk for infertility, and the current available options for pre-and post-pubertal male patients
Options for family building for patients that did not have fertility preservation treatment prior to the start of their gonadotoxic therapies
Spermatogenesis and Gonadoxicity Explained
Spermatogenesis is the process of creating sperm from primordial germ cells, or reproductive cells. The process of spermatogenesis occurs in stages, beginning in puberty, and takes place in the testes (the male reproductive organs). Sperm is created from spermatogonial stem cells that work to continuously make sperm.
Males will repeat the process of spermatogenesis from the time they enter puberty, until the end of their life, but the quality and quantity of sperm will gradually decline with age. The purpose of spermatogenesis is to create mature sperm cells that will be able to fertilize an egg, if they come into contact.
Gonadotoxic refers to therapies or treatments, such as chemotherapy and radiation, that can cause direct harm to the gonads, also known as the testes and ovaries. Chemotherapy and radiation, either alone or in combination, are the most common cancer treatment and pose the biggest risk of infertility in both male and female patients. Chemotherapy works by killing rapidly
dividing cells, as it is targeting cancerous cells, but it also damages other noncancerous cell types.
Sperm cells are a cell type that undergoes rapid cell division and can easily be damaged by chemotherapy agents. For individuals that produce sperm, gonadotoxic therapies can cause direct damage to the sperm, lower sperm production, or decrease the ability to make semen.
Depending on the dosage of therapy that a patient receives, it is possible for sperm production to return but it may take several years, and there is no guarantee.
Fertility Preservation and Counselling
Changes to fertility may be temporary or permanent, depending on the therapy received to help treat the affected individual. Chemotherapy is used to effectively target cancerous cells or tissue but can also cause immense damage to the reproductive tissues of the body. Radiation therapy
targeted at the reproductive organs, or near the abdomen/pelvis can cause decreased sperm counts and lower testosterone levels [7]. Radiation can also directly damage the sperm or the primordial germ cells that produce sperm.
As these therapies can be incredibly damaging to the fertility of male patients, it is important that all individuals that face a risk of infertility be counselled by their physicians on the options available to them. Fertility preservation is becoming increasingly important as the survival rate for cancer patients increases each year due to advances in available treatment options. By counseling patients on their options related to FP, everyone will be able to make an educated decision regarding their plans for the future and how they choose to move forward in protecting their reproductive capabilities.
The options for fertility preservation vary for patients that produce sperm, depending on their pubertal status at the time of diagnosis. Prepubertal patients are unable to produce sperm as they have not yet begun the process of spermatogenesis, therefore they are not able to partake in sperm cryopreservation as a method of fertility preservation. Many childhood cancer survivors will develop irreversible azoospermia, or with no sperm in the ejaculate, due to the gonadotoxicity of the treatment on spermatogononial stem cells.
Sperm cryopreservation is considered the gold standard for those that produce sperm, as a means of preserving their fertility [8]. Sperm cryopreservation, more commonly known as sperm banking, has been used for over 40 years to overcome infertility issues for patients undergoing
gonadotoxic therapies [8]. Postpubertal or adult patients that are able to produce a sperm sample are routinely offered sperm banking as a method of FP, if they are at an increased risk of infertility.
The only option available for prepubertal male patients is testicular tissue cryopreservation (TTC), which is still considered experimental as it has not yet resulted in a live human birth. For TTCs, a testicular biopsy is removed and then cryopreserved to preserve the fertility of patients unable to
produce mature sperm.
For many patients, infertility being a long-term effect of cancer therapy can be a very difficult and overwhelming reality to handle. Patients benefit the most from discussing risk factors from their proposed treatment plans and FP options available to them, with their attending physicians.
In the United Kingdom, it is recommended by the National Institute for Health and Care Excellence (NICE) that patients receive fertility preservation counselling as soon as possible, as the threat of infertility can cause psychological distress. It is most commonly recommended to counsel patients regarding their fertility risk prior to the start of any treatment, to allow patients to make as many informed decisions as possible.
Family Building and Planning for the Future
There are different forms of FP available to male patients facing a risk to their fertility due to gonadotoxic therapy. Current options are sperm cryopreservation, testicular sperm extraction (TESE), testicular shielding, and testicular tissue cryopreservation for prepubertal patients.
Testicular sperm extraction is offered for patients unable to produce a sperm sample via masturbation or who have a low sperm count. The sperm is taken directly from the testis and then preserved to be used in the future [9]. Testicular shielding is when a protective covering is placed over the testes to shield them from scatter radiation. For patients able to cryopreserve sperm prior to the initiation of cancer treatment, they can use assisted reproductive technologies (ART) and use their sample to try to conceive a biological
child. Using in vitro fertilization (IVF) methods such as intracytoplasmic sperm injection (ICSI), sperm will be taken from the preserved specimen and directly injected into an oocyte (egg). There is a high success rate associated with using ICSI, with a fertilization rate between 50-80%.
There are options for patients that did not undergo fertility preservation prior to the start of their cancer treatment. Starting with a semen analysis, patients and their physicians will be able to understand the current state of their sperm production and if they can conceive a biological child.
For those that present as azoospermic, there are several options available to them if they wish to become a parent. The use of donor sperm and/or adoption are viable alternative routes that can be used to begin the process of building a family.
Patients choosing to preserve their fertility should work closely with their oncologist and a fertility specialist to ensure that a suitable treatment plan is created with their plans in mind. Fertility preservation services offer patients with an increased risk of infertility the opportunity to work to
save their future potential at conceiving a biological child and building a family.
References:
World Cancer Research Fund. (2023, April 13). UK cancer statistics and Data: World Cancer Research Fund UK. UK Cancer Statistics. https://www.wcrf-uk.org/preventing-cancer/uk-cancer-statistics/
ASCO. (2021, December 14). Fertility concerns and preservation for men. Cancer.Net. https://www.cancer.net/navigating-cancer-care/dating-sex-and-reproduction/fertility-concerns-and-preservation-men
Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Spermatogenesis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10095/
Benedict, C., Thom, B., & Kelvin, J. F. (2016). Fertility Preservation and Cancer. Current Opinion in Supportive & Palliative Care, 10(1), 87–94. https://doi.org/10.1097/spc.0000000000000185
Bastings, L., Baysal, O., Beerendonk, C. C., IntHout, J., Traas, M. A., Verhaak, C. M., Braat, D. D., & Nelen, W. L. (2014). Deciding about Fertility Preservation after specialist counselling. Human Reproduction, 29(8), 1721–1729. https://doi.org/10.1093/humrep/deu136
Borate GM, Meshram A. Cryopreservation of Sperm: A Review. Cureus. 2022 Nov 12;14(11):e31402. doi: 10.7759/cureus.31402. PMID: 36523734; PMCID: PMC9744399.
Valli-Pulaski H, Peters KA, Gassei K, Steimer SR, Sukhwani M, Hermann BP, Dwomor L, David S, Fayomi AP, Munyoki SK, Chu T, Chaudhry R, Cannon GM, Fox PJ, Jaffe TM, Sanfilippo JS, Menke MN, Lunenfeld E, Abofoul-Azab M, Sender LS, Messina J, Klimpel LM, Gosiengfiao Y, Rowell EE, Hsieh MH, Granberg CF, Reddy PP, Sandlow JI, Huleihel M, Orwig KE. Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers. Hum Reprod. 2019 Jun 4;34(6):966-977. doi: 10.1093/humrep/dez043. PMID: 31111889; PMCID: PMC6554046.
National Cancer Institute . (2020, February 24). Male fertility issues and cancer - side effects. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/side-effects/fertility-men
Logan, S., & Anazodo, A. (2019). The psychological importance of fertility preservation counseling and support for cancer patients. Acta Obstetricia et Gynecologica Scandinavica, 98(5), 583–597. https://doi.org/10.1111/aogs.13562
Diaz-Garcia, C. (2022, October 3). ICSI explained: Success rates, risks and what to expect. IVI UK. https://www.ivi.uk/blog/icsi-ivf-success-rates-risks/