The harmful effects of cancer and tumours on male fertility are multifactorial. They may be secondary to the disease process itself, or therapeutic interventions.
With the introduction and development of assisted reproduction, the reproductive prospects for young men who are treated for cancer have totally changed, and it has become possible to achieve a high number of pregnancies. All these factors have led us to advise patients treated for cancer, who harbour reproductive desires, to use methods to preserve their fertility before starting treatment.
Testicular cancer and Hodgkin’s disease are the most common malignant diseases affecting young men of reproductive age. Multimodal therapies have significantly improved survival rates in young patients with cancer.
However, these therapies are often aggressive and unwanted side effects are very common. Chemotherapy and radiotherapy have an adverse effect on spermatogenesis.
The adverse effects of chemotherapy on spermatogenesis are variable, depending on the types of chemotherapeutic agent used, its dosage and the treatment time. Some of the drugs used are particularly toxic to the male reproductive system, including: cyclophosphamide, chlorambucil, busulfan, and vinblastine. Patients who survive some cancers such as bone sarcomas, Hodgkin’s disease, lymphoma, non-Hodgkin’s lymphoma, and leukemia, and who are treated with these drugs are usually at risk of suffering infertility, since it is not possible to predict with certainty whether spermatogenesis parameters will return to normal after therapy.
The damage caused by chemotherapy may have a multiple cell involvement (Leydig , Sertoli , and germ cells) or selective from each cell type. Men who receive high doses of chemotherapy before certain procedures, such as bone marrow transplants, often lose their fertility as a result of the destruction of seminiferous tubules.
The radiation of the prostate or testicles can cause sterility or infertility, which in many cases is permanent. In some men, the return to fertility may take up to 5 years, but will depend on various factors such as the total dose received (over 4-5 Gy doses usually cause permanent azoospermia, and doses below these levels can result in reversible oligo or azoospermia) , the radiation field and the patient’s age.
Notably, Sertoli and germ cells are more sensitive to radiation tan Leydig cells, so hormonal changes are minor in these treatments. Moreover, the administration of therapeutic doses of radiation to the cranial area can damage the hypothalamus, leading to abnormal hormone production and causing infertility. Fortunately, hormone deficiency can be resolved with appropriate replacement therapy.
Inguinal Orchiectomy is the first treatment for testicular cancer; in case of removal of both testicles (bilateral orchiectomy), it is not possible to maintain fertility. If a single testis is removed, fertility may be affected to different degrees.
Other surgical procedures such as retroperitoneal lymphadenectomy (primary retroperitoneal node dissection), can damage nerve connections and have a negative effect on normal ejaculation.
Prostate cancer surgery (prostatectomy) can cause damage to the innervation of the penis and accessory glands, leading to impaired fertility and sexual dysfunction. These consequences are particularly relevant in young men who have not yet had descendants.
Surgery can be performed elsewhere in the body (in rare cases) where there are tumours and is appropriate, and can be carried out before or after chemotherapy or radiation therapy, although such treatment after surgery is much more complicated.
The negative effects on spermatogenesis in men treated for cancer are in many cases dependent on the time between treatment and semen analysis, the type of treatment and dose as well as the type of cancer and other parameters of the disease which make it difficult to predict the fertile capacity in the male afterwards.
In some cases, reproductive capacity will be recovered, while in others, sperm production will not be recovered ; or despite recovering production, sperm will not have full functionality. Recovering normal levels in seminogram is not the same as recuperating fertility.
It is estimated that between 15 and 30% of treated men will remain sterile even years after stopping treatment. Moreover, the recovery of spermatogenesis is related to the number of type A spermatogonia remaining intact in testis after therapy.
However, although a small percentage of males will not recover spermatogenesis, a certain percentage will produce sperm, although levels will remain below normal levels established by the World Health Organization. As a result, they are potential candidates for needing the help of assisted reproductive techniques.
It should be noted that assessment of the potential fertility of a semen sample is more than just sperm count, its motility and morphology. The molecular physiology of sperm plays a fundamental role in fertilization in early embryonic development, implantation and live healthy newborn. It reflects the reproductive success.
Therefore, the study of different aspects of physiology that can be altered as a result of cancer treatment, such as apoptosis, DNA integrity or chromosomal abnormalities (see above) is essential to rule out functional abnormalities in sperm recovered after antineoplastic therapy.
Cryopreservation of sperm is a safe and effective means of preserving fertility and should be offered to all patients with cancer before undergoing chemotherapy, radiation or surgery. Recent advances in assisted reproduction (IVF and ICSI) have made it possible for almost all samples, regardless of semen quality, to be usable for proper oocyte fertilization. Furthermore, testicular sperm extraction is possible in patients with cancer and non-obstructive azoospermia, providing these patients and their partners with reproductive opportunities.
Although the tumour process itself can affect semen quality, reproductive results using sperm frozen before cancer treatment are more favorable than in patients with azoospermia caused by chemotherapy or radiotherapy, where these agents would harm sperm cells temporarily or irreversibly . These data, therefore, justify the need to freeze sperm before cancer treatment for preserving fertility, thereby significantly increasing the reproductive potential and at the same time, the quality of life for cancer patients who wish to become parents.
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