Semen Analysis
The semen analysis is currently the gold standard for assessing
fertility status in males, although it must be recognized that a normal
semen analysis does not assure fertility. A semen analysis is quick,
cost-effective, and non-invasive, and can be performed at any age after
puberty. In 2010 the WHO published the 5th edition ofLaboratory Manual for the Examination and Processing of Human
Semen , providing normal reference ranges based on semen parameters of
men whose partners became pregnant within 12 months of trying to
conceive. Cutoffs above the 5th percentile are
considered normal by WHO criteria, and men with abnormal parameters
should be counseled as to future fertility options (Table 2).(65)
Since chemotherapy easily penetrates the blood-testis barrier,
spermatogonial stem cells are at risk for damage by certain
chemotherapeutic agents.(66) It is well established that degree of
fertility impairment and azoospermia is directly proportionate to type
of cancer treatment; specifically, the dose of alkylating agent. Semen
analyses from 214 male survivors of childhood cancer who had been
treated with alkylating agents revealed rates of 28% and 25% for
oligospermia and azoospermia respectively; in addition, if the
cumulative cyclophosphamide equivalent dose was < 4
gm/m2, 89% of males were normospermic.(67) Radiation
therapy is also known to cause impaired spermatogenesis in a dose
dependent manner.(68) Transient effects on spermatogenesis have been
seen in low doses of radiation therapy with cumulative doses as low as 2
Gy causing transient or even permanent azoospermia.(68) While some men
may permanently lose sperm production as a result of their cancer
treatment, others may have the return of sperm to the ejaculate over a
period of months to years.(69)
While semen analysis is optimal in males desiring information about
fertility status, FSH and Inhibin B may provide information about germ
cell function if patients are unable to provide a semen specimen.(62)
FSH, a hormone produced in the anterior pituitary, can help predict
normal sperm production when its value is normal. FSH values poorly
correlate with specific sperm concentrations,(70) but a systematic
review and combined analysis of individual patient data showed that FSH
above 10.4 IU/L predicted azoospermia in AYA survivors with specificity
81% (95% CI 76%-86%) and sensitivity 83% (95% CI 76%-89%).(71)
Inhibin B has been shown to be decreased in some adult male survivors of
childhood cancer, and is associated with decreased sperm concentration
in males treated for Hodgkin Lymphoma.(72,73) However, Inhibin B does
not perform as well as semen analysis in predicting fecundity and is not
often tested.(74)