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UROLOGY either placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg), after 3 days of sexual abstinence. Despite the absence of any sexual stimulation, 10%, 41%, 26% and 55% of men in the placebo, sildenafil, tadalafil and vardenafil groups, respectively, were able to achieve ≥60% base or tip rigidities (P
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 KEY ADVANCES IN MEDICINE JANUARY 2012 | S83
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CARDIOLOGY ACUTE CORONARY SYNDROMES
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gene that encodes steroid 11β-hydr
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