Current options for preserving fertility in men with cancer

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Modern therapies against cancer have improved the survival of children and men of reproductive age however treatments such as chemotherapy, radiotherapy and surgery can compromise male fertility. It is important before undergoing any treatment, to learn about the options of preserving fertility by freezing semen or testicular tissue.

Below you have an index with all the points that we will discuss in this article.

Index

Effects of cancer therapies

Of the men who survive cancer in childhood, 46% have a reduced chance of conceiving a child and only 33% have a normal semen quality.

One of the causes for which man's fertility is altered is because his germinal epithelium is very sensitive to radiotherapy and the alkylating agents that make up chemotherapy. Alkylating agents such as mechlorethamine or procarbazine, among others, cause direct damage to DNA and RNA that induce apoptosis.

According to studies conducted, a percentage of 63% of patients treated for Hodgkin lymphoma were azoospermic about 10 years after treatment with alkylating agents.

Regarding testicular radiation, it has been observed that 10 out of 12 children who have received radiotherapy with 24 Gy for leukemia present 5 years later, a dysfunction of Leydig cells. However with a radiation of 12 Gy the effects on these cells are reduced. It seems that irradiation at high doses in the first years of life is more harmful to Leydig cells than irradiation in men when the testicles are adults.

Regarding the effects on the offspring of men treated against cancer, several studies reveal that there has been no increased risk of genetic abnormalities or diseases compared to the normal population, nor an increased risk of malformations or premature babies. However, studies conducted in Denmark and Sweden do show a 17-fold increased risk of congenital anomalies in children born to parents who have survived some type of cancer.

These risks are independent of the way of conception, natural or through assisted reproduction.

Options to preserve fertility in men

Semen freezing is the most reliable option for preserving fertility in adult patients. This freezing should be done before starting the treatment, and if time permits it is advisable to freeze three samples with an interval of 48 hours.

To prevent the formation of crystals during freezing and not to damage the membranes of the sperm cryoprotectants are used, the most used is glycerol.

One of the problems that arise is that many of the men with testicular tumors may initially have subfertility before undergoing chemotherapy or radiation therapy. A study showed that 49.8% of men studied had a concentration below 10 million per ejaculate, 13.8% were azoospermic and 2.6% were not able to obtain a sample. Sometimes the diagnosis of sterility in men is prior to cancer.

Currently thanks to ICSI, it is possible to get pregnant in men with severe oligozoospermia or azoospermia, extracting the sperm by testicular biopsy.

When a permanent infertility develops after a cancer is treated, it is due to the total loss of the spermatogonia that covers the seminiferous tubules and mediates the process of spermatogenesis. When few of these cells are lost, the extraction by sperm microsurgery of this tissue can be a solution. This method has been used in azoospermic patients after chemotherapy with a recovery in 37% of cases.

The most practical thing is to cryopreserve testicular sperm to be able to use them in the future without having to perform any other surgical intervention. Regarding the quality of the frozen sperm, there are authors who obtain an equal pregnancy rate with fresh sperm that with frozen (Baukloh) and others that on the contrary obtain a lower fertilization rate with frozen spermatozoa (Nicopoullos).

As for the technique, it has been seen that slow freezing with DMSO (Dimethyl sulfoxide) better preserves the integrity of the tubular structure than glycerol in the mouse model and 1,2-propanediol in humans. Currently studies are being done with vitrification and show results with good survival and proliferation rate.

Bibliography

Holoch P, Wald M. Current options for preservation of fertility in the male. Fertil Steril. 2011; 96 (2): 286-90.

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