Cryopreservation of sperm in adults has been performed for decades, and it is well known that spermatozoa survive long-term cryobanking (Sanger et al, 1992). However, for various reasons, the possibility of cryopreservation of sperm from adolescent cancer patients has until now received little attention (Kliesch et al, 1996; Schover et al, 1998; Müller et al, 2000; Bahadur et al, 2002). Nevertheless, cryopreservation of sperm may be even more important in adolescents than in adults, since adolescents have not yet started their families. In our study, only 2 adolescent patients were married, and only 1 had fathered children; by contrast, of the 740 adults, 26% were married, and 14% had become fathers before oncological therapy. However, in a quality-of-life analysis of former oncological patients, about 80% viewed themselves as potential parents, and the vast majority of younger cancer survivors saw their cancer experience as preparing them to be better parents (Schover et al, 1999).
Cryopreservation of sperm is often not discussed with the adolescent patient because examiners harbor uncertainties about semen quality and the sexual maturity of the patient. In addition, there may be difficulties in discussing this sensitive topic with the adolescent and his parents (Bahadur, 2000; Müller et al, 2000). Few data are available on the physiology of semen parameters in pubertal males. In addition, oncological patients may have impaired semen quality even before therapy (Handelsman, 2000). Indeed, in our study, only 17% of the adults and 23% of the adolescents showed normozoospermia as defined by World Health Organization guidelines. Sperm survival may be further decreased because of the freezing and thawing procedure; moreover, in the patients of our study, the total sperm motility was uniformly and severely decreased in the samples after thawing (Table 3). However, despite the poor postthawing sperm survival rates obtained in most oncological patients, ICSI offers the possibility of a pregnancy even if only a single motile sperm is present after thawing (Chen et al, 1996). On the basis of these criteria, successful cryopreservation of sperm was achieved in 93% of the adolescent patients of our study, which is slightly better than the 89% successful cryopreservation obtained in the adult patients of our study. Furthermore, cryopreservation may be considered successful even if only immotile but viable sperm are present. As in other diseases, pregnancies in patients with malignancies have been achieved with immotile but viable sperm, as evidenced by the hypo-osmotic swelling test (Ved et al, 1997).
One possible explanation for these relatively good results, especially in the adolescents, is that only 25% of the patients suffered from a testicular tumor as opposed to 62% of the adults, and the testicular tumor per se may be associated with impaired semen parameters (Petersen et al, 1998).
The adolescent patients of our study had normally developed testicular volumes for persons that age (Zachmann et al, 1974) and, except for 1 patient, all of the them showed normal or above-normal testicular volumes, irrespective of the underlying diagnosis (Figure 1). Spermarche occurs between 11 and 17 years when testicular volumes are between 5 and 20 mL (Hirsch et al, 1979; Nielsen et al, 1986; Kulin et al, 1989; Schaefer et al, 1990). All of the adolescents of our study had testicular volumes greater than 5 mL, and only 1 patient with a mediastinal teratoma (age, 19 years) showed azoospermia. In the adolescents, testicular volumes were correlated with age (Figure 1), serum testosterone (Figure 2a), and sperm count (Figure 2b). However, development of testicular volume was a weak predictor of endocrine maturation, since 41 adolescents had serum testosterone values below the normal adult limit of 12 nmol/L, despite normal or above-normal age-adjusted testicular volumes.
The adolescent patients of our study generally abstained from sexual activity for longer periods than the adults of our study with the same disease. Although this is significant only in patients with lymphomas, abstinence time has not been correlated with sperm concentration, but it has been related positively to ejaculate volume (Cooper et al, 1993; Rolf et al, 1996). The ejaculate volume of the adolescents, which is often low, therefore provides biological evidence for not fully developed androgenicity, a finding that was also observed by Bahadur et al (2002).
To compensate for the low ejaculate volume, several semen samples from the adolescents should be requested, or, if sperm concentrations are high, the ejaculate should be diluted before it is mixed with the cryoprotectant, as very few sperm will be needed from 1 straw for ICSI. However, the reduced ejaculate volume that is often observed is not a major problem in cryopreservation of sperm from adolescents. Because no adverse prognostic factors for successful cryopreservation in adolescents have been identified, cryopreservation of sperm should be offered to all oncological patients, even to those younger than 15 years, who will be subjected to potentially irreversible oncological treatments and who are able to produce semen samples.
This work was supported in part by the German Federal Ministry of Health. The clinical collaboration of physicians from the University of Münster as well as technicians at the Institute of Reproductive Medicine are gratefully acknowledged. We are grateful to Anita Broschk for data documentation and to Susan Nieschlag, MA, for language editing.