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)