open access: Nature Reviews: Key Advances in Medicine

ather information on the 95 th percentile of
semen analysis data. As such, they inform
the reader that 95% of men who achieve
pregnancy within 12 months of trying will
have sperm concentrations of >15 million
cells/ml, >40% of observed sperm demonstrating
good movement, and >4% of sperm
with normal morphology.
Unfortunately, these criteria do not
predict the likelihood of achieving a pregnancy
in the following 12 months, which
is typically when urologists first see these
patients in consultation. Furthermore, the
reference range must be viewed as a continuum,
given that many patients at the low
end of the range might still achieve pregnancy,
and men at the high end might not.
The nondefinitive nature of these guidelines
confirms the need for further sophisticated
testing—such as DNA fragmentation analysis,
oxidative stress analysis and sperm
evaluation for genomic, proteomic and
metabolic factors—in certain cases of
male factor or unexplained infertility. For
example, a patient whose semen parameters
fall within the new reference ranges but
has not achieved pregnancy might benefit
from DNA fragmentation testing to identify
subtle sperm abnormalities. Esteves et al. 2
have analyzed the new reference values
and highlight further issues that may face
the urologist, including whether the referral
of male partners will decrease, whether
we were previously overtreating our male
patients and how to better interpret these
reference values by focusing on the 50 th
percentile of data.
Over the past decade, progress in the
field of assisted reproduction has led to a
change in the management of severe male
factor infertility not amenable to medical
or surgical correction. Currently, intracytoplasmic
sperm injection (ICSI) is
the treatment of choice for patients who
suffer from either severe oligospermia
or non obstructive azoospermia (NOA).
Historically, any motile sperm present in the
ejaculate would be preferentially utilized for
ICSI. Alternatively, if no sperm were found
in the ejaculate, sperm surgically extracted
from the testis were used instead. When
very low numbers of sperm were present
in the ejaculate and initial ICSI results with
motile ejaculated sperm were poor, then
testis sperm was considered.
Evidence against this ejaculate-first
approach was recently reported by Hauser
et al., 3 who found that fertilization rates in
patients with relative or virtual azoospermia
were higher when fresh or frozen-thawed
testicular sperm cells were used than when
ejaculated sperm cells were used. This
finding is particularly interesting considering
that although more motile sperm
cells were found in the ejaculated specimens
than in the testicular samples, the
quality of embryos from testicular sperm
(fresh and frozen) was significantly higher
than of those from ejaculated sperm. This
observa tion led the authors to conclude that
it is the source of sperm cells, and not their
motility, that plays a crucial role in fertility
outcome. This pilot study suggests a possible
role for testicular sperm extraction
(TESE) coupled with ICSI in patients with
severe oligo asthenospermia or relative or
virtual azoo spermia.
If testicular sperm leads to better fertility
outcomes, does it matter if fresh or
frozen-thawed testicular spermatozoa are
retrieved? According to Hauser et al., 3 the
answer is yes. While frozen-thawed spermatozoa
may be more conveniently obtained,
the researchers found that for patients with
virtual or relative azoospermia, fresh testis
sperm yielded better implantation rates
than frozen testicular sperm.
Although these results support the use
of fresh testicular sperm for patients with
relative or virtual azoospermia, there is
still no consensus on the best approach for
retrieving testis sperm from men with pure
NOA. This year, the value of diagnostic testis
biopsy in the era of ICSI was addressed by
Kalsi et al., 4 who provide evidence that
microsurgical TESE (m-TESE)— introduced
by Schlegel and Li 5 in 1998—is the optimum
sperm retrieval method in patients with
NOA, preferential to fine-needle aspira tion
and traditional TESE.
Researchers were able to successfully
retrieve spermatozoa from 50 of 100 men
with NOA who underwent m-TESE at their
center, which includes a success rate of 57%
in men with previously failed attempts at
sperm retrieval. The only significant positive
predictor of a successful retrieval was
a previous histological diagnosis of hypospermatogenesis,
and therefore the authors
recommend against the common practice
of performing isolated diagnostic testicular
biopsies on men with NOA, and suggest
instead that biopsy should always be combined
with a TESE procedure. Therefore,
the take home message for any urologist
treating a patient with NOA is to either
proceed with a combined diagnostic testis
biopsy and send tissue to an andrology laboratory
for processing and cryo preservation,
or to refer the patient to a reproductive
Key advances
UROLOGY
■ The updated 5 th edition of the WHO
semen guidelines includes significant
changes from prior versions and is the
first edition to include evidence-based
data 1
■ In certain cases, testicular sperm may
be used for intracytoplasmic sperm
injection, in preference to ejaculated
sperm, for patients with relative or virtual
azoospermia 3
■ Diagnostic testis biopsy alone (without
tissue processing) has limited value
in the management of nonobstructive
azoospermia 4
■ The underlying cause of hematospermia
can be evaluated using transrectal
ultrasonography 6
■ Finasteride is a feasible treatment
option for men with recurrent idiopathic
hematospermia 7
urologist who has this capability. Our
current approach is to begin with a standard
TESE and if no sperm are observed to
proceed with an immediate m-TESE.
Abnormal findings in ejaculate are not
always related to male factor infertility. In
fact, one of the most frequently encountered
problems in general urology is hematospermia,
which can be a cause of great
concern and anxiety for affected men. Until
recently, hematospermia was assumed to
be idiopathic and patients were reassured
that their condition was benign. A recent
study by Zhao et al., 6 however, may alter the
urologist’s approach to hematospermia. In
their study, researchers performed transrectal
ultrasonography on 270 men with
hematospermia, and found abnormalities
in 95% of the cohort. These abnormalities
were universally benign in patients under
40 years of age, including prostatic calcifications,
ejaculatory duct calculi, and benign
prostatic hyperplasia. Patients over the age
of 40 years, however, were significantly
more likely to have a malignant disease; 8
Courtesy of A. Kilchevsky, Yale–New Haven Hospital, USA
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