analysis of semen parameters, largely controlled for these
confounders and observed an increase in sperm counts with
no changes in motility and morphology.
When comparing the study cohort with two previously
studied cohorts of Danish men, more men in the study cohort
for Jørgensen et al. had arbitrarily defined ‘‘suboptimal’’
sperm concentrations and fewer normal forms than in the
comparison cohorts. The investigators concluded that Danish
men are at increased risk for subfertility and utilization of
assisted reproductive technologies (ART). This conclusion is
disconcerting, largely because few conclusive data support a
decline in male, or couple, fertility in Denmark or globally.
Although crude birth and conception rates in Denmark
have declined [3,4], it is difficult to separate cultural reasons,
such as the use of contraception and abortion, from biological
or environmental reasons for this decline. One must also
remember that semen quality cannot be used to define
fertility. Furthermore, risk factors for ART for either male or
female fertility failure are incompletely defined, and no
statistical model incorporating all fertility risk factors exists.
Therefore, the conclusion that a decrement in sperm motility
or normal morphology is resulting in a decline in fertility,
despite an increase in sperm count, may be erroneous.
Conﬂicts of interest:
The authors have nothing to disclose.
 Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for
decreasing quality of semen during past 50 years. BMJ 1992;305:
 Olsen GW, Bodner KM, Ramlow JM, Ross CE, Lipshultz LI. Have
sperm counts been reduced 50 percent in 50 years? A statistical
model revisited. Fertil Steril 1995;63:887–93.
 Jensen TK, Sobotka T, Hansen MA, Pedersen AT, Lutz W, Skakkebaek
NE. Declining trends in conception rates in recent birth cohorts of
native Danish women: a possible role of deteriorating male repro-
ductive health. Int J Androl 2008;31:81–92.
 UN data: crude birth rate. United Nations Web site.
. Updated August 25, 2011.
Alexander W. Pastuszak, Larry I. Lipshultz
Scott Department of Urology, Baylor College of Medicine,
Houston, TX, USA
*Corresponding author. Scott Department of Urology,
Baylor College of Medicine, 6624 Fannin St, Ste. 1700,
Houston, TX 77030, USA.
Re: Effects of the Reduced Form of Coenzyme Q
(Ubiquinol) on Semen Parameters in Men with Idio-
pathic Infertility: A Double-Blind, Placebo Controlled,
Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S
J Urol 2012;188:526–31
This randomized, double-blind, placebo-controlled trial was
undertaken by Safarinejad et al. to investigate the effects of
ubiquinol, the reduced form of coenzyme Q
semen quality in men presenting with primary idiopathic
infertility. The study’s population was composed of 228 men
with at least 2 yr of idiopathic infertility diagnosed by at least
two semen analyses confirming oligoasthenoteratozoosper-
mia.The menwere randomizedintotwogroupsand underwent
26 wk of treatment, during which the subjects in the experi-
mental group received a once-daily oral dose of 200 mg ubi-
quinol following a meal, whereas those in the control group
followed by a 12-wk treatment-free phase. Throughout the
duration of the study, the investigators measured semen
parameters, serum hormone levels, and seminal plasma anti-
oxidant activity to assess treatment efficacy.
Following the 26-wk treatment period, the investigators
found statistically significant increases in sperm density,
motility, and morphology in the experimental group
compared to controls. Hormonal analysis demonstrated a
significant decrease in serum follicle-stimulating hormone
levels with an accompanying increase in inhibin B, as well
as a decrease in luteinizing hormone and a (nonsignificant)
increase in testosterone, in the experimental group. Seminal
plasma catalase–like and superoxide dismutase–like activ-
ity were also significantly increased in the ubiquinol group
versus placebo group following treatment. Discontinuation
of ubiquinol with the treatment-free period saw seminal
parameters regress toward baseline values, although signifi-
cant differences in sperm density and motility were
maintained. Finally, correlation coefficients revealed a
positive association between ubiquinol treatment duration
and sperm density, motility, and morphology.
Based on these findings, the authors concluded that
ubiquinol administration results in significant seminal
parameter improvements in infertile men with idiopathic
Management of idiopathic male infertility remains an enig-
matic challenge. In the absence of any medically or surgically
correctable etiologies, approximately two-thirds of practicing
urologists are using empirical medical therapies in an attempt
to achieve a favorable hormonal profile to treat these patients
. Such medications, including clomiphene citrate and ana-
strozole, are not expressly FDA approved for male infertility
treatment, and they have not been conclusively shown to
achieve treatment efficacy when used empirically. Recently,
more attention has been directed toward the use of antioxi-
dant supplementation to address the contributory role of
oxidative stress and subsequent sperm DNA damage in the
EUROPEAN UROLOGY 62 (2012) 1195–1200