Testicular tissue freezing in patients with cancer

Testicular tissue freezing is the extraction and subsequent cryopreservation of this tissue to try to preserve the fertility of a patient who is going to undergo gonadotoxic treatment.

One of the medical cancer treatments’ side effects (chemotherapy and radiotherapy) is the fertility decrease in patients who suffer from it. Fortunately, there are male fertility preservation methods with high chances of reproductive success in the future.

Chemotherapy drugs used against cancer have a cytotoxic effect that affects the tumour and the rest of the body’s tissues, including the reproductive organs. Similarly, radiation can lead to irreversible changes in testicular tissue. Permanent azoospermia associated with these treatments is very common.

The most frequently diagnosed types of cancer are: lymphoma, leukaemia, sarcoma, testicular, colon or rectal cancer, among others. When a child, a young man or an adult man is diagnosed with cancer, it’s important to inform him about the possibility of preserving his fertility. This will reduce your stress and improve your quality of life in the future, although it must be clarified that no method ensures 100% success.

How can male fertility be preserved?

Available male fertility preservation treatments depend on the patient’s sexual maturation degree:

• Most common and least invasive treatment is freezing of ejaculated sperm from masturbation. This is possible as long as sexual maturity has been reached. This is the most effective fertility preservation method in adult males.

• Testicular biopsy and epididymal aspiration are other possibilities, performed when semen cannot be obtained by ejaculation. In these cases, once testicular tissue has been thawed, it will be necessary to perform an ICSI (intracytoplasmic sperm injection) due to the low quality of this type of seminal samples.

• In young boys who have not reached puberty and whose sperm production process (spermatogenesis) has not started yet, the only possible alternative to preserve their fertility for the future is the freezing of immature testicular tissue. This tissue contains spermatogonia, which are stem cells that could give rise to sperm in the future.

What is testicular tissue cryopreservation?

It’s a way to preserve the male’s fertility. Testicular tissue can be obtained by means of a testicular biopsy or by orchiectomy, which consists of the surgical removal of the testicle.

There are different methodologies and protocols for cryopreservation of testicular tissue. For fertile men facing cancer therapy, future freezing and thawing of testicular tissue is straightforward. Once the cancer treatment is finished, with in vitro fertilization treatments the chances of getting a pregnancy are very high.

this procedure effectiveness in children is still in the research and development phase. Methodologies and protocols for preserving the fertility of children undergoing cancer treatments are being studied in multiple hospitals and clinics around the world with good results. It has even been proven that it’s possible to perform this procedure in the initial stages of these therapies.

Will I be able to become a father in the future if I face cancer therapy?

Yes. As long as there’s no prior serious fertility problem, freezing different seminal samples obtained by ejaculation ensures almost 100% the possibility of being a father in the future.

When, in addition to cancer, there’s a previous fertility problem (low seminal quality or azoospermia), a testicular tissue freeze can be attempted. The possibility of pregnancy with this type of seminal sample is also high, provided that motile spermatozoa have been observed in the tissue.

Testes may continue to produce sperm after cancer treatment, but more often than not, with poor quality, or spermatogenesis has completely stopped. If testicular tissue has not been preserved in any way before treatment, an attempt can be made to obtain semen or testicular tissue as previously explained, to check whether the patient is fertile or not.

If patient did not freeze sperm or testicular tissue before treatment and, as a result of this, is diagnosed as azoospermic, he would have to resort to donating sperm from a bank.

Differences between sperm freezing and testicular tissue freezing.

Ejaculate sperm freezing is a procedure performed on everyday basis in all assisted reproductive centres. There’re different protocols, but it’s a very effective treatment.

The freezing of testicular tissue obtained by biopsy or epididymal aspiration is also frequent and routine, but its effectiveness in preserving fertility is somewhat lower, because the samples are usually of lower quality. Additionally, testicular tissue is obtained through invasive surgical procedures.

Bibliography

• Optimizing methods for human testicular tissue cryopreservation and spermatogonial stem cell isolation.Moraveji SF, Esfandiari F, Sharbatoghli M, Taleahmad S, Nikeghbalian S, Shahverdi A, Baharvand H.J Cell Biochem. 2019 Jan;120(1):613-621. doi: 10.1002/jcb.27419. Epub 2018 Sep 22.
• Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers. 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.Hum Reprod. 2019 Jun 4;34(6):966-977.
• Isolation, Cryopreservation, and Transplantation of Spermatogonial Stem Cells. Sinha N, Whelan EC, Brinster RL.Methods Mol Biol. 2019;2005:205-220.
• “Oncofertility” procedures in children and adolescents. Tarasiewicz M, Martynowicz I, Knapp P, Sieczyński P.Pediatr Endocrinol Diabetes Metab. 2019;25(3):144-149.
• Fertility Preservation in Pediatric Oncology Patients: New Perspectives. Gertosio C, Magistrali M, Musso P, Meazza C, Bozzola M.J Adolesc Young Adult Oncol. 2018 Jun;7(3):263-269. doi: 10.1089/jayao.2017.0117. Epub 2018 Jan 18.PMID: 29346023 Review.

Dr Leyre Herrero, a biologist at Instituto Bernabeu