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Male fertility preservation

Advances in the treatment of cancer in young patients have led to great improvements in life expectancy which approaches 80% 5-year survival rate. As a result, fertility preservation and desire for paternity have become a significant issue in this group. A major concern is the negative impact of chemo and radiotherapy on fertility. Up to two thirds of patients are azoospermic following chemotherapy. Recovery of spermatogenesis is strongly dependent upon the chemotherapy and radiation regimen and the patient’s baseline reproductive function.  Alkylating agents seem to have the most profound reproductive effects. Thus men about to have treatment for malignant conditions may have sperm cryopreserved before commencing chemotherapy or radiotherapy. Although pretreatment semen quality may be too poor for IUI, ICSI now has improved the outlook for successful pregnancies. Semen collected during chemotherapy or radiotherapy must not be used because of the likelihood of induced mutations.

Infertile men with conditions such as orchitis or severe primary spermatogenic disorders that might involve progressively declining semen quality such as Klinefelter syndrome, when sperm can be recovered, should also store any live sperm that can be obtained as insurance for the future. A similar approach could be extended to adolescents with risk factors for infertility such as undescended testes in childhood, testicular torsion, and possibly a family history of infertility or a father with a Yq microdeletion. Semen may also be stored after treatment of gonadotropin deficiency or surgery for genital tract obstruction in case of re-stenosis. Storage of sperm before premature death or after a sudden unexpected death is also possible. Although the use of gametes from a dead person is surrounded by complex ethical and legal issues it is permissible in some countries. Semen cryopreservation can also be offered to adolescents. Sperm may be obtainable from the semen or testis after mid puberty. Although only a small proportion of men who store semen may use the frozen sperm, the service provides insurance for future fertility.

 

Methods of collection

Sperm for fertility preservation may be collected in a variety of ways. Ejaculated sperm cryopreservation is the most common technique used as enough sperm is usually found for freezing in majority of men. Unfortunately, some men with testicular and other malignancies may present initially with oligospermia or even azoospermia. This may be related to a basic infertility condition which puts them under higher risk to develop testicular cancer or the stress effect of the disease on spermatogenesis. Some patients will not be able to produce a sample. Some patients are unable to ejaculate for social, religious or medical reasons or may be unfamiliar with masturbation for example peri-pubertal boys. For them, sperm can be retrieved by penile vibratory stimulation, electroejaculation or surgically from the epididymis or the testis as discussed above.

 

Fertility preservation in Prepubertal boys

Preserving fertility in postpubertal boys facing chemotherapy can be achieve similar success rates to those in adults. However fertility preservation in prepubertal boys presents a great challenge as sperm banking is not possible. Alternative strategies have been developed but all are currently experimental. These strategies are based on immature spermatogenic cell cryopreservation as cell suspensions or whole testicular tissue for future fertility restoration using autografting, xenografting or in-vitro spermatogenesis. More research is needed to establish the best approach to generate spermatozoa from immature stem cells via in-vivo or in-vitro maturation. In the meantime, prepubertal tissue preservation should be discussed with the boys and their parents and samples should be banked only after careful counseling emphasizing the experimental nature of this approach.

Post chemotherapy sperm recovery

Various barriers to sperm banking such as prepubertal age, under-referral or inadequate understanding of the sterilizing effect of chemotherapy and defective spermatogenesis before the treatment may have prevented sperm banking. In these patients an approach similar to that used for men with severe primary spermatogenic disorders can be used as recovery of spermatogenesis after gonadotoxic treatments is highly variable. Men with persistent azoospermia following chemotherapy or radiotherapy can be offered microsurgical testicular sperm extraction (TESE) and ICSI as there is some chance of success. Schlegel et al. reported 84 microdissection TESE procedures performed in 73 patients with 43% having sperm retrieved and these produced an average 57% fertilization rate with ICSI and 42% had live births.