The Prevalence of Y-chromosome Microdeletions in Oligozoospermic Men: A Systematic Review and Meta-analysis of European and North American Studies.

CONTEXT: European and North American guidelines recommend Y-chromosome microdeletion (YCM) screening in azoospermic and oligozoospermic men with sperm concentrations of <5 million sperm/ml; however, numerous studies have suggested that YCMs are rare when sperm concentrations are >1 million sperm/ml. OBJECTIVE: We systematically reviewed and meta-analyzed European and North American studies to determine the prevalence of a complete YCM in oligozoospermic men with sperm concentrations of >0-1, >1-5, and >5-20 million sperm/ml, and to determine whether 1 or 5 million sperm/ml is the most appropriate sperm concentration threshold for YCM screening. EVIDENCE ACQUISITION: A systematic review of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov was performed for studies assessing the prevalence of a complete YCM in oligozoospermic men in European and North American studies. EVIDENCE SYNTHESIS: Thirty-seven studies were identified during a systematic review (n = 12 492 oligozoospermic men). All complete YCMs in oligozoospermic men were AZFc microdeletions. Eighteen studies contained data conducive to meta-analysis (n = 10 866 men). Comparing the pooled estimated prevalence by sperm concentration, complete YCMs were significantly more common in men with sperm concentrations of >0-1 million sperm/ml (5.0% [95% confidence interval {CI}: 3.6-6.8%]) versus >1-5 million sperm/ml (0.8% [95% CI: 0.5-1.3%], p < 0.001). YCMs were similar in men with sperm concentrations of >1-5 and >5-20 million sperm/ml (0.8% [95% CI: 0.5-1.3%] vs 0.5% [95% CI: 0.2-0.9%], p = 0.14). CONCLUSIONS: In Europe and North America, the majority of YCMs occur in men with sperm concentrations of ≤1 million sperm/ml, with <1% identified in men with >1 million sperm/ml. Male infertility guidelines for North America and Europe should reconsider the sperm concentration screening thresholds to recommend testing for YCMs only for men with sperm concentrations of <1 million sperm/ml. PATIENT SUMMARY: Complete Y-chromosome microdeletions (YCMs) are rare in men with >1 million sperm/ml. Routine screening for YCMs should occur only if sperm concentration is ≤1 million sperm/ml.

Best practice in the diagnosis and treatment of varicocele in children and adolescents.

A varicocele is an abnormal dilation of the pampiniform plexus of veins in the scrotum which begins at puberty in approximately 15% of males. Although common in the general population and often asymptomatic, varicoceles are associated with gonadal dysfunction including testicular atrophy, infertility, and hypogonadism in a subset of men diagnosed later in life. Because of the high prevalence and uncertain pathogenesis, definitive management guidelines for varicoceles diagnosed in the pediatric and adolescent population remain poorly defined. The varicocele is the most common etiology of male factor infertility, and treatment in the pediatric and adolescent population may improve semen quality and improve fecundity in adulthood. Evaluation of the pediatric and adolescent varicocele should include history, physical exam, and measurement of testicular volume with orchidometer or ultrasound. Testicular volume differentials and peak retrograde flow on Doppler ultrasonography are important factors in risk stratification of the pediatric varicocele population. Semen analysis and reproductive endocrine assessment should also be considered as part of the workup for adolescent patients. A variety of treatment approaches exist for varicocele, and while the microsurgical subinguinal approach is the gold standard for the adult population, it has yet to be confirmed as superior for the adolescent population. Referral to an andrologist for the adolescent patient with varicocele should be considered in equivocal cases. While active treatment of varicocele in the pediatric and adolescent population is controversial, it is clear that some untreated patients will suffer symptoms later in life, while overtreatment remains a concern for this large, vulnerable population. Therefore, surveillance strategies and improved accuracy in diagnosis of clinically important pediatric varicoceles prompting treatment are needed in the future.

A review of varicocele repair for pain.

A dilation of the pampiniform venous plexus in the scrotum above the testicle, called a varicocele, affects approximately 15% of the general male population. While the majority is asymptomatic, pain results in up to 10% of cases of varicoceles. The pain associated with varicoceles is typically mild and is described as heavy, achy, or dull-and is usually isolated to the testicle or spermatic cord. Guidelines clearly recommend varicocele repair in males with varicoceles, infertility, and an abnormal semen analysis. While chronic, severe pain is an additional indication for repair, a careful evaluation to rule out other etiologies in addition to a period of conservative management are necessary prior to surgical treatment because of the high incidental prevalence of varicoceles in the general population. Several techniques for varicocele repair have been described, including retroperitoneal, laparoscopic, inguinal, and subinguinal. Additionally, recent adjuncts to improve visualization and identification of critical structures including the operating microscope and microvascular Doppler ultrasound have improved success and complication rates. With careful patient selection, outcomes of varicocele repair with regard to pain are excellent, with over 90% of patients experiencing symptomatic relief. After failure of conservative treatments, a varicocele associated with pain should be considered for repair, and the microsurgical subinguinal approach is the gold standard surgical treatment, offering excellent outcomes while minimizing risk of complications.

Management and counseling of the male with advanced paternal age.

Increasing percentages of children are being born to older fathers. This has resulted in concerns about the potential adverse effects of advanced paternal age. To help clinicians counsel couples, a systemic review was performed to attempt to address questions that these couples may ask: Should routine sperm testing be performed in older males? Should preimplantation genetic diagnosis (PGD) be performed? How do providers counsel patients about risk? Should young males freeze sperm if they plan to delay paternity? Using the terms "advanced paternal age", "semen testing", "preimplantation genetic diagnosis/screening", and "cryopreservation", a comprehensive search was performed in PubMed and the Cochrane Library, and numerous international societal guidelines were reviewed. In total, 42 articles or guidelines were reviewed. There were no limits placed on the timing of the articles. Thirty articles were found to be relevant and beneficial to answering the above questions. Each question was answered separately by the supporting literature. While primary research exists to support the role of semen testing, PGD/preimplantation genetic screening, and sperm banking in males who may be affected by advancing age, comprehensive studies on the possible clinical benefit of these interventions have yet to be performed. As a result, societal guidelines have yet to incorporate distinct best-practice guidelines on advanced paternal age.

The significance of clinical practice guidelines on adult varicocele detection and management.

Varicoceles are the most common correctable etiology of male factor infertility. However, the detection and management of varicoceles have not been standardized. This has led to decades of debate regarding the effect of varicocele on male infertility and subsequently whether repair leads to an improved fertility status. The current body of evidence investigating the role of varicocele and varicocelectomy is weak and conflicting. The stance taken by the AUA and ASRM suggests that there is insufficient outcomes data to support evidenced-based guidelines, citing evidence used to provide current recommendations are generally of a low quality level. On the other hand, the EAU Guidelines give a level 1a of evidence for management of varicoceles that are clinically palpable, associated with subnormal semen analyses and having otherwise unexplained fertility. Besides aiding with clinical varicocele detection and management, clinical practice opinion statements and guidelines aim to direct and strengthen the infrastructure of future studies. We review the current status of opinion statements and guidelines in varicocele and management detection with focus on their application in practice.

Testosterone supplementation in men: a practical guide for the gynecologist and obstetrician.

PURPOSE OF REVIEW: Prescribing habits for the treatment of symptomatic hypogonadism have recently stirred controversy surrounding testosterone replacement therapy. As a result, the gynecologist will need to recognize this iatrogenic form of decreased sperm production in couples seeking fertility advice. We have compiled a review of the current literature on testosterone supplementation pertaining to the gynecologic practice. RECENT FINDINGS: Over the last decade, testosterone use has seen a recent increase including in men desiring to become fathers. Many physicians and hypogonadal men do not recognize that testosterone replacement therapy can have a detrimental effect on spermatogenesis. Fortunately, the cessation of treatment will yield predictable recovery of sperm production for most men. A growing body of evidence supports the use of selective estrogen receptor modulators, such as clomiphene citrate, or human chorionic gonadotropin for the treatment of hypogonadism in men who wish to maintain fertility potential. Recently, the Food and Drug Administration has recommended a labeling update on testosterone products to warn of possible increased risk of venous thromboembolism, cardiovascular events and stroke. SUMMARY: Clinicians should be familiar with current practices involving testosterone replacement therapy and the implications on male factor fertility.

Combination of tadalafil and finasteride for improving the symptoms of benign prostatic hyperplasia: critical appraisal and patient focus.

The evidence suggests that combination therapy for benign prostatic hyperplasia (BPH)-lower urinary tract symptoms (LUTS) using an α-blocker and a 5α-reductase inhibitor has become well accepted. The combination of daily tadalafil and an α-blocker has also demonstrated benefit. This paper addresses combination therapy with daily tadalafil and finasteride for the treatment of BPH-LUTS. Our results demonstrate that use of tadalafil and finasteride represents a logical extension of combination therapies. We analyze a landmark study by Casabé et al that demonstrates improved voiding symptoms as assessed by International Prostate Symptom Scores with a combination of tadalafil and finasteride compared with finasteride and placebo. Study patients had moderate to severe LUTS and prostate volumes >30 g. The additional benefit of improved erectile function as assessed by International Index of Erectile Function-erectile function domain scores with the addition of tadalafil was a secondary benefit. We propose that the ideal patient for combination therapy with tadalafil and finasteride has a prostate volume >30 g and desires additional benefit over monotherapy. For these men, improved erectile function without sexual side effects was a secondary benefit.

Endovascular treatment of vasculogenic erectile dysfunction.

The treatment of erectile dysfunction (ED) has been a fascination involving multiple medical specialities over the past century with urologic, cardiac and surgical experts all contributing knowledge toward this multifactorial disease. With the well-described association between ED and cardiovascular disease, angiography has been utilized to identify vasculogenic impotence. Given the success of endovascular drug-eluting stent (DES) placement for the treatment of coronary artery disease, there has been interest in using this same technology for the treatment of vasculogenic ED. For men with inflow stenosis, DES placement to bypass arterial lesions has recently been reported with a high technical success rate. Comparatively, endovascular embolization as an approach to correct veno-occlusive dysfunction has produced astonishing procedural success rates as well. However, after a thorough literature review, arterial intervention is only recommended for younger patients with isolated vascular injuries, typically from previous traumatic experiences. Short-term functional outcomes are less than optimal with long-term results yet to be determined. In conclusion, the hope for a minimally invasive approach to ED persists but additional investigation is required prior to universal endorsement.

Penoscrotal mass: a rare presentation of herpes simplex virus infection.

A 55-year-old man presents with a 10-cm condylomatous penoscrotal mass. Final pathology after surgical removal reveals a rare vegetative lesion with underlying herpes simplex virus infection. Along with neoplasia, infectious causes must remain in the differential diagnosis in the immunocompromised patient who presents with an atypical lesion.