Full text of DOI:10.1007/BF03343795

J. Endocrinol. Invest. 23: 690-696, 2000
Effects of cancer and anti-neoplastic treatment on the
human testicular function
A. De Palma, E. Vicari, I. Palermo, R. D’Agata, and A.E. Calogero
Division of Endocrinology and Master in Andrological Sciences: New Methodologies in Human
Reproductive Medicine, Department of Internal Medicine, University of Catania Medical School,
Catania, Italy
ABSTRACT. Men with testicular neoplasia (TN) and
Hodgkin’s disease (HD) are those who more fre-
quently require treatment for fertility because
these malignancies affect patients during the re-
productive age and because the early diagnosis
and the improved anti-neoplastic treatments cure
most of these patients. Although some of them
can father a child spontaneously, assisted repro-
ductive techniques allow fatherhood to patients
with severe spermatogenesis impairment and this
possibility has raised concern about the long-term
consequence of the testicular damage induced by
chemo- and/or radiotherapy. This paper reviews
the effects of cancer per se and of anti-neoplastic
treatments on gonadal function, sperm aneuploidy
rate and sperm DNA integrity. A debate is still
open as to whether TN or HD per se may impair
spermatogenesis. Many studies have shown that
this is the case, albeit others have challenged this
view. Chemo- and/or radiotherapy affects nega-
tively gonadal function, rendering almost all pa-
tients azoospermics. However, spontaneous preg-
nancies and a high degree of spermatogenesis re-
covery occur with time. A large body of literature
on sperm chromosome complement suggests an
increased rate of structural and numerical chro-
mosome abnormalities in patients with cancer dur-
ing anti-neoplastic treatment. A minority of them
has, however, shown that this effect disappears
with time. An interesting and relatively new as-
pect is the study of sperm DNA integrity in pa-
tients with TN and HD particularly following
chemo- and/or radiotherapy. The scanty informa-
tion available seems to suggest that these patients
have a permanent or at least a long-lasting DNA
fragmentation in their spermatozoa.
(J. Endocrinol. Invest. 23: 690-696, 2000)
©2000, Editrice Kurtis
INTRODUCTION
of patients with testicular germ-cell tumor have a
long-term survival (1) and 66-89% of patients with
Hodgkin’s disease (HD) survive at least 10 years (2).
In addition, the widespread use of micromanipula-
tion reproductive techniques has given a chance al-
so to those patients whose anti-cancer treatment
has impaired spermatogenesis so severely to cause
oligo-azoospermia. All this has raised the question
as to whether cancer patients can procreate safe-
ly, and there is a growing concern about long-term
consequences of the testicular damage induced by
chemo- and/or radiotherapy.
This paper reviews the effects of cancer per se and
of anti-neoplastic treatment on gonadal function,
sperm aneuploidy rate and sperm DNA integrity. A
substantial body of literature has indeed attempted
to evaluate whether the anticancer treatment caus-
es chromosomal segregation errors in germ cells,
resulting in the formation of aneuploid gametes.
We addressed also the question of the integrity of
the DNA carried by the spermatozoon following an-
Cancer has often been encountered in the field of
male infertility because it may affect reproductive
function in many ways. Firstly, several forms of can-
cer may influence directly fertility due to adverse
effects of these malignancies on the testis or on the
endocrine system controlling the testicular function.
Secondly, chemotherapic drugs and/or irradiation,
used for the treatment of these malignancies, are
gonadotoxic. The improved efficacy of anti-neo-
plastic protocols have increased the survival rate of
many of these patients with consequent increased
demand for fatherhood. For example, about 90%
Key-words: Aneuploidy, cancer therapy, Hodgkin, testicular cancer,
sperm DNA.
Correspondence: Dr. Aldo E. Calogero, Istituto di Medicina Interna e
Specialità Internistiche, Cattedra di Endocrinologia, Ospedale Garibaldi,
Piazza S. Maria di Gesù, 95123 Catania, Italy.
E-mail: acaloger@mbox.unict.it
690

Cancer and testicular function
ti-cancer treatment. An intact DNA is, in fact, crucial
for the genetic health and changes can lead to al-
terations in the germ-cell line which result in the in-
heritance of lethal and non-lethal conditions (3).
patients with abnormal sperm parameters. Indeed,
22% of 54 patients with seminomas and 29% of 154
patients with teratomas or mixed tumors had sperm
counts above 10x106 spermatozoa/ml (10).
The effects of chemotherapy alone (cisplatin, eto-
poside and bleomycin) on the sperm output were
evaluated in 30 TN patients, 24 to 78 months fol-
lowing the initiation of treatment (11). Oligozoo-
spermia, defined as total sperm count lower than
40x106 spermatozoa, was found in 7 patients (23%)
and azoospermia in 6 (20%). These patients exhib-
ited also a high incidence of morphologically ab-
normal spermatozoa. However, 8 patients fathered
children, including 3 with documented oligo-
zoospermia. Therefore, TN patients treated with
chemotherapic drugs are at substantial risk for a
persistent semen abnormality, although some of
them are still capable of reproductive capacity de-
spite being oligozoospermic.
SPERM OUTPUT AND TESTICULAR
ENDOCRINE FUNCTION
A number of studies have examined the relation-
ship between anti-tumoral treatment and the go-
nadal function in patients with testicular neoplasia
(TN) and HD. They have taken into account various
end-points of the sperm output as well as the en-
docrine function and have tried to find out whether
there is any relationship with the type of tumor
and/or the type of the treatment given.
Testicular neoplasia
A debate exists as to whether TN has per se a neg-
ative impact on sperm output. Peterson et al. (4)
found a significantly lower sperm concentration and
increased serum FSH levels in 83 consecutive pa-
tients with testicular germ-cell cancer before or-
chiectomy compared to a group of healthy men or
patients with a malignant lymphoma. These findings
suggested that TN affects negatively spermatogen-
esis and that this is not due to a general cancer ef-
fect. In addition, patients with TN had lower levels
of LH, but normal levels of testosterone, 17β-estra-
diol and sex hormone binding globulin. This decre-
ment may relate to the increased human chorionic
gonadotropin (hCG)-stimulated testosterone levels
observed in a sub-group. Reduced sperm quality was
also reported in 18 men with TN which did not
change after orchiectomy, suggesting an impairment
of spermatogenesis also in the contralateral testis (5).
Accordingly, Nijman et al. (6) reported a similar de-
crease of the sperm concentration in patients with
unilateral non-seminomatous tumor of the testis, be-
fore and following orchiectomy, indicative of a dys-
function of the remaining “normal” testis. Peterson
et al. (7) reported a further deterioration of the se-
men quality following the surgical removal of the tu-
mor-affected testis, whereas androgen production
was maintained at the expenses of increased serum
LH levels. Abnormal sperm parameters have also
been found by Carrol et al. (8) in about 70% of a co-
hort of 15 patients with TN. Three of these patients
showed an improvement of their sperm output which
normalized in two of them following unilateral or-
chiectomy as only type of treatment. However, a re-
cent preliminary study challenges the tenet that pa-
tients with TN have impaired spermatogenesis be-
fore surgery, chemo- and/or radiotherapy (9). The
type of TN does not seem to affect the number of
Nijmann et al. (12) evaluated the gonadal function
in 54 patients with disseminated non-seminomatous
TN before and after chemotherapy (cisplatin, vin-
blastine and bleomycin) and surgery. Testosterone
serum levels were at the lower limit of the normal
range in patients treated with chemotherapy, where-
as LH levels remained elevated for 2 years after com-
pletion of treatment. FSH levels were also elevated,
but they showed a tendency to decrease after 2
years. Before treatment, 72% of the patients were
oligo-azoospermics, whereas two years after the dis-
continuation of chemotherapy, 48% had azoosper-
mia or oligozoospermia and 28% had more than
60x106 spermatozoa. However, the proportion of
patients with azoospermia increased from 4 to 28%.
In the course of this study, 8 pregnancies occurred
and one ended in an early spontaneous abortion. In
a previous study (13), 77% of 41 patients with dis-
seminated TN were found oligozoospermics, 17%
had azoospermia and only 6% could meet the mini-
mal requirements for sperm banking. After 2 months
of chemotherapy, 96% became azoospermics. Two-
three months after chemotherapy initiation, howev-
er, only 17% of the 28 patients that could be evalu-
ated were azoospermic and 46% had normal semen
parameters. Thirty-two per cent have impregnated
their wives, resulting in 5 healthy babies, 1 sponta-
neous abortion and 3 ongoing pregnancies. These
results show that significant impairment of sper-
matogenesis exists before therapy, precluding the
possibility of sperm banking in most patients.
Chemotherapy in testicular cancer patients affects
gonadal function, rendering almost all patients
azoospermic. However, a high degree of spermato-
genesis recovery occurs with time. Accordingly, it
has been shown that 30 out of 54 cancer patients
691

A. De Palma, E. Vicari, I. Palermo, et al.
treated with chemo- and/or radiotherapy have sperm
parameters better than or equal to before and only
4 patients (7.5%) became azoospermics (9).
ABVD is associated with a relatively better preser-
vation of the gonadal function.
Gerres et al. (20) evaluated the testicular toxicity of
two different treatment protocols in pediatric HD
patients. Testicular volume, Tanner stage of pubic
hair and genital development were found to be ap-
propriate or slightly delayed for the patients’
chronological age. All 27 patients had normal FSH
and LH levels after two courses of treatment for HD
stages I and IIA with vincristine, etoposide, pred-
nisone and doxorubicin (OEPA). GnRH-stimulated
gonadotropin serum levels were found elevated on-
ly in few patients, thus indicating normal endocrine
function. On the other hand, basal and GnRH-stim-
ulated FSH levels were higher than the two stan-
dard deviation upper limit in 38 and 83% of patients
receiving two cycles of OEPA and two cycles of cy-
clophosphamide, vincristine, procarbazine and
prednisone (COPP), demonstrating a high risk of
oligozoospermia or azoospermia with the latter reg-
imen. Basal LH levels were essentially normal,
whereas stimulated LH levels frequently were ele-
vated. This study suggested a greater testicular
damage in HD patients treated with procarbazine,
etoposide and cyclophosphamide. An interesting
study, conducted in HD patients before (no.=15) or
during (no.=4) puberty, showed that germ-cell
damage was present in all subjects (21). The evalu-
ation was performed at a median of 10 years after
treatment in these long survivors and showed
azoospermia in 12 and oligozoospermia in 6 of
them. The testicular volume was small in all but one
patients and FSH serum levels were elevated and
increased at later follow-ups. In 7 patients LH was
also elevated indicating Leydig cell failure. The tes-
ticular function tended to be better in patients
treated before puberty. However, a definitive con-
clusion cannot be made since all of them were
treated with MOPP, whose testicular toxicity seems
to be greater (19, 20).
Despite some patients with TN improve their sperm
output following chemo- and/or radiotherapy, the
current practice to preserve fertility potential for pa-
tients undergoing gonadotoxic treatment is to cryo-
preserve spermatozoa with a view to using them
later for assisted reproductive treatment. Sperm
cryopreservation has the same detrimental effect
on spermatozoa of patients with TN as in normal
controls. The only difference was related to the
poorer initial semen parameters observed in pa-
tients with TN (14). Thus, this study encourages a
routine sperm banking in patients with TN before
the initiation of any treatment. Interestingly, the tu-
mor type does not seem to affect the post-thaw
sperm quality (15).
Hodgkin’s disease
HD is the most common lymphoma during the re-
productive years and it is almost twice as frequent
in males than in females. As in several other malig-
nancies, decreased fertility exists in males suffering
from HD before treatment or diagnosis (16). Semen
analysis performed in male patients with HD prior to
therapy showed that up to 70% of patients have
azoospermia, asteno- and/or teratozoospermia (17).
Viviani et al. (17) also showed that a similar degree of
dyspermia is observed in patients in the stages I and
II as well as in those in stages III and IV. The effect of
HD on the testis does not appear to be related to a
local infiltration and the patients exhibit a significant
germ-cell hypoplasia and tubular hyalinization at tes-
ticular biopsy (18). However, sperm banking data
showed that only 13 out of 65 HD patients were
oligozoospermics (sperm count below 20x106 /ml).
Forty-four of these patients could be evaluated at
yearly intervals following chemo- and/or radiothera-
py. Although 9 of them were azoospermics, 21 had
improved or equal sperm parameters, showing that
a complete recovery of spermatogenesis is possible
after oncologic treatment (9).
Kurkarni et al. (19) evaluated the gonadal toxicity
of different therapeutic regimens in 38 patients with
HD. Twenty-six were treated with doxorubicin,
bleomycin, vinblastine and decarbazine (ABVD) and
12 with AVBD and COPP or MOPP (cyclophospha-
mide or nitrogen mustard, vincristine, procarbazine
and prednisone). Azoospermia was seen in one pa-
tient from the ABVD group and in 10 patients from
the ABVD/COPP group, and serum FSH levels were
significantly higher in the latter. Three patients
treated with ABVD fathered children post-therapy.
This study therefore shows that treatment with
RADIO-CHEMOTHERAPY AND SPERM
ANEUPLOIDY RATE
The large contribution of chromosome abnormali-
ties to human congenital diseases, mental retarda-
tion, infertility and spontaneous abortions is well
known (22). Therefore a number of studies have at-
tempted to establish the incidence of sperm aneu-
ploidy rate in cancer patients before and after an-
ti-neoplastic treatment.
Testicular neoplasia
Alvarez et al. (23) examined whether testicular ma-
lignancies may cause chromosome instability inde-
692

Cancer and testicular function
pendently of the gonadotoxic effect of the anti-can-
cer treatment. Using the human-hamster fertiliza-
tion system, the authors found no significant dif-
ferences in the frequencies of chromosomal aber-
rations between controls and 4 patients with germ-
cell tumor. However, chemo- and/or radiotherapy
seem to increase the rate of chromosome abnor-
malities. Indeed, Templado et al. (24) found that,
in cancer patients treated with chemo- and/or ra-
diotherapy, the incidence of chromosome abnor-
malities was significantly higher than in controls.
Increased numerical and structural sperm chromo-
some abnormalities have also been reported in pa-
tients who had been treated with chemotherapy
about 2 years before (25). Similarly, Genescà et al.
(26) showed a still elevated incidence of numerical
and structural chromosome abnormalities, in sper-
matozoa from patients treated for testicular cancer
with anti-neoplastic drugs 2-7 years before the
study. In addition, the incidence of chromosomal
aberrations was also significantly greater compared
to a sample of men treated with antitumoral agents
for non-testicular diseases long before the sperm
analysis (26). Thus, the high incidence of structurally
aberrant spermatozoa observed long after anti-
tumoral treatments affects stem spermatogonia and
aberrant cells can survive germinal selection and
produce chromosomally abnormal spermatozoa.
However, other studies have reported no increase in
sperm chromosome aberrations. Jenderny et al. (27)
reported no increase in sperm chromosome aberra-
tions in a cancer patient 9 months after poly-
chemotherapy. A more recent study showed a simi-
lar frequency of disomy before and after chemo-
therapy with bleomycin, etoposide and cisplatin for
chromosomes 1, 12, X and Y, assessed by multicolor
fluorescence in situ hybridization (FISH), except for
chromosome 1 whose disomy however decreased
significantly after chemotherapy. The “sex ratios” and
the frequency of diploid sperm were also not signifi-
cantly different in pre- and post-chemotherapy sam-
ples (28). Similarly, the same group showed no sig-
nificant difference in the frequency of numerical or
structural chromosome abnormalities, evaluated si-
multaneously by sperm karyotyping and multicolor
FISH for chromosomes 1, 12, X and Y, in spermatozoa
from patients with cancer before and 2-13 years after
anti-neoplastic treatment (29).
nisone with or without radiotherapy 3-20 years be-
fore the study. The patients showed an increased, al-
beit not statistically different, rate of spermatozoa with
numerical and structural chromosome aberrations.
Instead they showed a significant increase in the rate
of spermatozoa with hyperploidy. Thus, this study
suggests that chemotherapy, with or without radio-
therapy, can cause chromosome abnormalities in the
sperm of HD patients.
Robbins et al. (31), however, have reported somewhat
discordant results. They studied 8 male patients with
HD treated with novanthrone, oncovin, vinblastine
and prednisone and found a 5-fold increase in sperm
disomies, diploidies and complex genotypes involving
chromosomes 8, X and Y. Increases in sex chromo-
some aneuploidies arose from segregation errors at
meiosis I as well as meiosis II. The aneuploidy effects
were, however, transient declining to pre-treatment
levels within approximately 3 months after the end of
the therapy. Accordingly, sperm karyotyping of a pa-
tient with HD showed multiple structural abnormali-
ties in many spermatozoa immediately after radio-
therapy (day 0), whereas most of the spermatozoa col-
lected 5 weeks later (day 38) exhibited normal
metaphase divisions (32). FISH analysis, performed
shortly after this patient received chemo- and radio-
therapy, showed an increased rate of disomy for chro-
mosomes 1, 6, 11 X and Y both at day 0 and at day
38. The high frequency of 24,XY and 24,XX sperma-
tozoa suggested that both meiosis I and II are affect-
ed and that the X chromosome is frequently involved
in such malsegregation events. The rate of 46,XY
diploidy was also increased (33). This case suggests
that radiotherapy affects the post-meiotic cells (sper-
matids), whereas the patient’s cancer and/or chemo-
therapy are the two major factors that could have af-
fected the dividing spermatogonia and/or spermato-
cytes, resulting in high aneuploidy rates.
SPERM DNA INTEGRITY
Besides a possible effect on sperm chromosome
complement, chemo- and/or radiotherapy may have
more subtle effects on sperm DNA integrity, which
has been shown to be crucial for genetic health and
whose changes can lead to alterations in the germ-
cell line, resulting in the inheritance of lethal and non-
lethal conditions (3). In addition, neoplasia per se may
alter sperm DNA integrity, as shown by a recent study
(34). The authors studied DNA fragmentation (by the
terminal deoxynucleotidyl transferase-mediated dUTP
nick-end labeling and electron microscopy) in 30 pa-
tients with TN and in 28 with HD, before they under-
went chemo- and/or radiotherapy, compared to a
group of 23 healthy normozoospermic men. DNA
Hodgkin’s disease
The incidence of sperm chromosome abnormalities
has been evaluated also in patients with HD. Brandriff
et al. (30) studied the karyotype of spermatozoa from
6 HD patients who had received 2-6 cycles of nitro-
gen mustard, vincristine, procarbazine and pred-
693

A. De Palma, E. Vicari, I. Palermo, et al.
fragmentation was found to be significantly higher in
both groups of patients. Since these patients had sub-
stantially normal sperm parameters, the increased
rate of spermatozoa showing signs of apoptosis may
be regarded as a response to the neoplastic disease
up to the mature male gamete. An interesting finding
is that the patients with TN were studied after surgi-
cal removal of the neoplastic testis. Therefore, the
apoptotic spermatozoa came from the apparent
healthy testis. A similar conclusion can be drawn by an
older study which showed an increased sperm DNA
sensitivity to thermal stress denaturation in 14 pa-
tients with TN following unilateral orchiectomy. These
changes were present up to 15 months following or-
chiectomy, suggesting once again an abnormal sper-
matogenesis in the contralateral testis of the patients
with tumor (35).
lowing chemo- and/or radiotherapy. The scanty in-
formation available seems to suggest that these pa-
tients have a permanent or at least a long-lasting
DNA fragmentation in their spermatozoa. A debate
is still open as to whether TN or HD per se may im-
pair spermatogenesis, as shown by many studies,
albeit others have challenged this view.
REFERENCES
1. Dahl O.
Testicular carcinoma: a curable malignancy.
Acta Radiol. Oncol. 1985, 24: 3-15.
2. Longo D., Young R., Wesley M., Hubbard S., Duffey
P., Jaffe E., De Vita V.J.
Twenty years of MOPP therapy for Hodgkin’s disease.
J. Clin. Oncol. 1986, 4: 1295-1306.
The effects of fludarabine, a commonly used che-
motherapic agent for hematological malignacies,
on sperm DNA were recently evaluated in a patient
with lymphocytic leukemia requesting preservation
of fertility (36). The spermatozoa of this man sho-
wed an elevated degree of DNA damage (evaluat-
ed by the comet assay) even 11 months after the
completion of the treatment. Albeit this case report
does not allow to conclude whether sperm DNA
damage arising during chemotherapy is irreversible,
recent observations in the mouse suggest that it
may indeed be permanent (37). In fact, sperm DNA
damage produced by a single irradiation persists
for up to 3 months (38), a time frame longer than
one spermatogenic cycle.
3. Perreault S.
Gamete toxicology: the impact of new technologies.
In: Korach K. (Ed.), Reproduction and developmental
toxicology.
Marcel Dekker Inc., New York, 1998, pp. 635-641.
4. Petersen P.M., Skakkebaek N.E., Vistisen K., Rorth
M., Giwercman A.
Semen quality and reproductive hormones before
orchiectomy in men with testicular cancer.
J. Clin. Oncol. 1999, 17: 941-947.
5. Demkow T., Faundez R., Madej G.
Sperm, LH FSH, testosterone evaluation in patients
with testicular cancer. Preliminary study.
Ginekol. Pol. 1998, 69: 405-409.
6. Nijman J.M., Schraffordt Koops H., Kremer J.,
Willemse P.H., Sleijfer D.T., Oldhoff J.
Fertility and hormonal function in patients with a non-
seminomatous tumor of the testis.
Arch. Androl. 1985, 14: 239-246.
CONCLUSIONS
Men with TN or HD are those who more frequent-
ly require treatment for fertility because these ma-
lignancies affect patients during the reproductive
age and because early diagnosis and improved an-
ti-neoplastic treatments cure most of these patients.
Although many of them can father a child either
spontaneously or by means of assisted reproduc-
tive techniques, in cases of severe spermatogene-
sis impairment there is a growing concern about
the long-term consequence of the testicular dam-
age induced by chemo- and/or radiotherapy. The
large body of literature on sperm chromosome
complement suggests an increased rate of struc-
tural and numerical chromosome abnormalities in
patients with cancer during anti-neoplastic treat-
ment. However, a minority of them has shown that
this effect is transient and disappears with time. An
interesting and relatively new aspect, which needs
to be further explored, is the study of sperm DNA
integrity in patients with TN and HD particularly fol-
7. Petersen P.M., Skakkebaek N.E., Rorth M.,
Giwercman A.
Semen quality and reproductive hormones before
and after orchiectomy in men with testicular cancer.
J. Urol. 1999, 161: 822-826.
8. Carroll P.R., Whitmore W.F. Jr., Herr H.W., Morse M.J.,
Sogani P.C., Bajorunas D., Fair W.R., Chaganti R.S.
Endocrine and exocrine profiles of men with testicu-
lar tumors before orchiectomy.
J. Urol. 1987, 137: 420-423.
9. Gandini L., Lombardo F., Toselli L., Gilio B., Testani
P., Anselmo A.P., Dondero F., Lenzi A.
Sperm characteristics before and after therapy in pa-
tients with Hodgkin’s disease and testicular neo-
plasma.
J. Endocrinol. Invest. 2000, 23 (Suppl. 8): 28, Abstract
OC9.
10. Hendry W.F., Stedronska J., Jones C.R., Blackmore
C.A., Barrett A., Peckham M.J.
Semen analysis in testicular cancer and Hodgkin’s
694

Cancer and testicular function
disease: pre- and post-treatment findings and impli-
cations for cryopreservation.
23. Alvarez R., Tusell L., Genescà A., Mirò R., Garcia-del-
Muro X., Egozcue J.
Br. J. Urol. 1983, 55: 769-773.
Absence of chromosomal instability in spermatozoa
of men affected by testicular cancer.
Hum. Reprod. 1999, 14: 247-251.
11. Stephenson W.T., Poirier S.M., Rubin L., Einhorn L.H.
Evaluation of reproductive capacity in germ cell tu-
mor patients following treatment with cisplatin,
etoposide, and bleomycin.
J. Clin. Oncol. 1995, 13: 2278-2280.
12. Nijman J.M., Schraffordt Koops H., Kremer J.,
Sleijfer D.T.
24. Templado C., Benet J., Genescà A., Navarro J.,
Caballin MR., Mirò R., Egozcue J.
Human sperm chromosomes.
Hum. Reprod. 1988, 3: 133-138.
25. Jenderny J., Rohborn G.
Gonadal function after surgery and chemotherapy in
men with stage II and III nonseminomatous testicular
tumors.
Chromosome analysis of human sperm. I. First re-
sults with a modified method.
Hum. Genet. 1987, 76: 385-388.
J. Clin. Oncol. 1987, 5: 651-656.
26. Genescà A., Mirò R., Caballin M.R., Benet J., Germa
J.R., Egozcue S.
13. Drasga R.E., Einhorn L.H., Williams S.D., Patel D.N.,
Stevens E.E.
Sperm chromosome studies in individuals treated for
testicular cancer.
Hum. Reprod. 1990, 5: 286-290.
Fertility after chemotherapy for testicular cancer.
J. Clin. Oncol. 1983, 1: 179-183.
14. Agarwal A., Tolentino M.V. Jr., Sidhu R.S., Ayzman
I., Lee J.C., Thomas A.J. Jr., Shekarriz. M.
Effects of cryopreservation on semen quality in pa-
tients with testicular cancer.
27. Jenderny J., Jacobi M., Ruger A., Rohrborn G.
Chromosome aberration in 450 sperm complements
from eight controls and lack of increase after che-
motherapy in two patients.
Urology 1995, 46: 382-389.
Hum. Genet. 1992, 90: 151-154.
15. Padron O.F., Sharma R.K., Thomas A.J. Jr., Agarwal A.
Effects of cancer on spermatozoa quality after cry-
opreservation: a 12-year experience.
28. Martin R.H., Ernst S., Rademaker A., Barclay L., Ko
E., Summers N.
Chromosomal abnormlities in sperm from testicular
cancer patients before and after chemotherapy.
Hum. Genet. 1997, 99: 214-218.
Fertil. Steril. 1997, 67: 326-331.
16. Vigersky R.A., Chapman R.M., Berenberg J., Glass A.R.
Testicular dysfunction in untreated Hodgkin’s dis-
ease.
29. Martin R.
Human sperm chromosome complements in chemo-
therapy patients and infertile men.
Chromosoma 1998, 107: 523-527.
Am. J. Med. 1982, 73: 482-486.
17. Viviani S., Ragni G., Santoro A., Perotti L., Caccamo
E., Negretti E., Valagussa P., Bonadonna G.
Testicular dysfunction in Hodgkin’s disease before
and after treatment.
30. Brandriff B.F., Meistrich M.L., Gordon L.A., Carrano
A.V., Liang J.C.
Chromosomal damage in sperm of patients surviv-
ing Hodgkin’s disease following MOPP (nitrogen
mustard, vincritine, procarbazine, and prednisone)
therapy with and without radiotherapy.
Hum. Genet. 1994, 93: 295-299.
Eur. J. Cancer 1991, 27: 1389-1392.
18. Chapman R.M., Sutcliffe S.B., Malpas J.S.
Male gonadal dysfuction in Hodgkin’s disease: a
prospective study.
J. Am. Med. Assoc. 1981, 245: 1323-1328.
19. Kulkarni S.S., Satry P.S., Siakia T.K., Parish P.M.,
Gopal R., Advani S.H.
31. Robbins W.A.., Marvin M.L., Moore D., Hagermeister
F.B., Weier H.U., Cassel M.J., Wilson G., Eskenazi B.,
Wyrobeck A.J.
Chemotherapy induces transient sex chromosomal
and autosomal aneuploidy in human sperm.
Nat. Genet. 1997, 16: 74-78.
Gonadal function following ABVD therapy for
Hodgkin’s disease.
Am. J. Clin. Oncol. 1997, 20: 354-357.
20. Gerres L., Brawswig J.H., Schelgel W., Jurgens H.,
Schellong G.
32. Rousseaux S., Sèle B., Cozzi J., Chevret E.
Immediate rearrangements of human sperm chro-
mosomes following in vivo irradiation.
The effects of etoposide on testicular function in
boys treated for Hodgkin’s disease.
Cancer 1998, 83: 2217-2222.
Hum. Reprod. 1993, 8: 903-907.
33. Monteil M., Rousseaux S., Chevret E., Pelletier R.,
Cozzi J., Sele B.
21. Heikens J., Berehndt H., Adriaanse R., Berghout A.
Irreversible gonadal damage in male survivors of
pedriatic Hodgkin’s disease.
Cancer 1996, 78: 2020-2024.
22. De Braekeleer M., Dao T.
Increased aneuploid frequency in spermatozoa from
a Hodgkin’s disease patient after chemotherapy and
radiotherapy.
Cytogenet. Cell Genet. 1997, 76: 134-138.
Cytogenetic studies in males infertility: a review.
Hum. Reprod. 1991, 6: 245-250
34. Gandini L., Lombardo F., Paoli D., Caponecchia L.,
Familiari G., Verlenga C., Dondero F., Lenzi A.
695

A. De Palma, E. Vicari, I. Palermo, et al.
Study of apoptotic DNA fragmentation in human
spermatozoa.
37. Morris I.D., Hoyes K.P., Taylor M.F., Woolveridge
I.
Hum. Reprod. 2000, 15: 830-839.
Male reproductive toxicology. A review with special
consideration to hazards to men.
In: Hamamah S., Mieusset R. (Eds.), Male gametes:
production and quality.
35. Evenson D.P., Klein F.A., Whitmore W.F., Melamed M.R.
Flow cytometry evaluation of sperm from patients
with testicular carcinoma.
INSERM, Paris, 1996, pp. 135-150.
J. Urol. 1984, 132: 1220-1225.
38. Haines G., Marples B., Daniel P., Morris I.
DNA damage in human and mouse spermatozoa
after in vitro irradiation assessed by the comet
assay.
36. Chatterjee R., Haines G.A., Perera D.M.D.,
Goldstone A., Morris I.D.
Testicular and sperm DNA damnage after treatment
with fludarabine for chronic lymphocytic leukaemia.
Hum. Reprod. 2000, 15: 762-766.
Adv. Exp. Med. Biol. 1998, 444: 79-93.
696