As outlined above, the ultimate recoverability of sperm production
and function after therapy is multifactorial. The potential for
recovery depends on the chemotherapeutic agents used, degree of
injury to the developing germ cells caused by ionizing radiation, and
extent of surgically induced injury to the neurovascular mechanism
responsible for sperm delivery. Recovery from the effects of
chemotherapy, radiation, and surgery are variable and may take up to
10 years after therapy is completed.
Watchful waiting and observation during this time period is
reasonable if the patient is young and does not strongly desire to
father children immediately after therapy. With the use of assisted
reproductive techniques (see discussion below), patients with severe
oligoasthenospermia may initiate pregnancies as early as 6 months
after receiving therapy.
The ages of the patient and spouse correlate strongly with fertility
potential. Other factors that may influence the timing of pregnancy
include: the presence of other offspring, familial support, fear, and
stress associated with cancer and cancer treatment.
Currently available cytoprotective techniques to limit testicular
injury from the damaging effects of cancer and chemotherapy are
ineffectual. Inhibition of pituitary control of spermatogenesis by
administering gonadotropin-releasing hormone agonists has improved
the recovery of spermatogenesis in animal models. The suppression of
active spermatogenesis decreases the sensitivity of dividing stem
cells to chemical and radiation injury.[33,55,56] These attempts at
downregulating germ cell production have not been successful in humans.
Reactive oxygen species are severely injurious to developing germ
cells. Research is underway to develop effective antioxidant therapy
to protect spermatogenesis in a series of animal models.
Administration of the antioxidants N-acetylcysteine and ascorbate
before therapy with procarbazine has been effective in preserving
spermatogenesis in an animal model. Parallel studies in humans have
not been published. The development of new gonadotropin agonists, as
well as reactive oxygen scavengers, may, in the future, decrease
testicular injury from chemotherapeutic and radiation treatment regimens.
Patients with moderate to severe oligoasthenospermia should be
referred to reproductive centers to explore the possibility of
utilizing assisted reproductive techniques. The past decade has shown
tremendous growth in this field. Present reproductive techniques
(intrauterine insemination, in vitro fertilization, and
intracytoplasmic sperm injection) permit the conception and birth of
a child even in cases of severe oligoasthenospermia. A complete
overview of assisted reproductive techniques is beyond the scope of
In vitro fertilization or intracytoplasmic sperm injection are often
successful in patients with male factor infertility secondary to
cancer or cancer therapy, whereas intrauterine insemination can be
used in patients with ejaculatory abnormalities. The principle factor
in choosing a reproductive technique is the number of total motile
sperm available in the ejaculate or harvested specimen. Intrauterine
insemination is successful when total motile sperm count exceeds 10
million. In vitro fertilization can be successful with a total motile
sperm count of greater than 5 million. Intracytoplasmic sperm
injection requires only a few motile sperm (between 10 and 20), which
can be directly inserted into the ooplasm. The success rate of
intracytoplasmic sperm injection (take-home baby) in
cancer patients is approximately 20% per cycle.
Cryopreservation of Sperm
Patients who have a malignancy should consider cryopreservation of
sperm prior to the initiation of therapy, and those who wish to
preserve their sperm should be referred to a reproductive center.
With present assisted reproductive techniques and improved techniques
of cryopreservation, it is possible to bank fertile sperm even from
severely oligoasthenospermic patients.[58-60] The only sperm count
that is not acceptable for cryopreservation is repetitive azoospermia.
Successful pregnancies are possible with sperm obtained from
cryopreserved testis biopsy specimens. Cadaveric germ cell harvest
with subsequent cryopreservation has also been performed.
A principle concern among men of reproductive age who are undergoing
anticancer therapy is the subsequent possibility of fathering
children with significant birth defects. Although chemotherapy and
ionizing radiation cause significant DNA injury, the potential for
transmitting genomic defects to offspring is remote, as evidenced by
the failure to detect an increase in structural or functional
abnormalities among children fathered by men who underwent
chemotherapy 1 or more years before conception. No significant
increase in major or minor genetic defects has been observed in the
offspring of parents who have had cancer or undergone cancer therapy.
Since the majority of chemotherapeutic agents injure spermatids and
spermatozoa, these cells rapidly lose their function and cannot
fertilize an ovum. Cytotoxic abnormalities in sperm DNA prevent the
introduction of damaged DNA into the oocyte. It is reasonable to
recommend, however, that men delay attempting to father children for
6 months after completing chemotherapy or radiation therapy, to allow
regeneration of developing spermatozoa.
No increase in genetic defects has been found in cancer patients who
have undergone assisted reproductive techniques. Patients should
be counseled however, that these techniques have only been effective
for the past decade, and data are insufficient to rule out the
genetic transmission of a birth defect.
New techniques in multimodality cancer therapy have significantly
improved the outlook of young men with cancer. The current emphasis
on decreasing the side effects of therapy offers an optimistic view
regarding reproductive function in these men. Familiarity with the
physiologic mechanisms relating to cancer and male factor infertility
will allow health-care providers to incorporate these discoveries
into the treatment regimen. Utilization of new assisted reproductive
techniques and, possibly in the future, cytoprotective measures
should decrease the incidence of infertility in male cancer patients
to near zero.
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