John W. Weedin

Varicocele repair in patients with nonobstructive azoospermia: a meta-analysis.

PURPOSE Multiple small case series have reported sperm in the ejaculate and spontaneous pregnancies in patients with nonobstructive azoospermia after varicocele repair. We hypothesized that men with favorable testicular histopathology on testis biopsy such as maturation arrest or hypospermatogenesis would have a higher probability of success than those with more ablative pathology, eg Sertoli-cell-only. MATERIALS AND METHODS A review of the literature on varicocele repair in patients with nonobstructive azoospermia was performed and 11 publications from the previous 20 years were evaluated. Histopathological data were presented in 8 publications, and were categorized as Sertoli-cell-only, maturation arrest and hypospermatogenesis. Maturation arrest was further differentiated by 4 publications. Early maturation arrest was defined as maturation ending at the secondary spermatocyte and late maturation arrest was defined as maturation ending at the spermatid without spermatozoa present. Success after repair was defined as having sperm in the ejaculate or spontaneous pregnancy. RESULTS A total of 233 patients were analyzed. After varicocele repair 91 (39.1%) patients had motile sperm in the ejaculate and 14 spontaneous pregnancies were reported. Success rates in patients with maturation arrest (42.1%) or hypospermatogenesis (54.5%) were significantly higher than in those with Sertoli-cell-only (11.3%, p <0.001 in both groups). Patients with late maturation arrest had a higher probability of success (45.8%) than those with early maturation arrest (0%, p = 0.007). CONCLUSIONS Infertile men with nonobstructive azoospermia can have improvement in semen analysis and achieve spontaneous pregnancy after repair of clinical varicoceles. This meta-analysis demonstrates that men with late maturation arrest and hypospermatogenesis have a higher probability of success and, therefore, histopathology should be considered before varicocele repair in men with nonobstructive azoospermia.

Aberrations in Pseudoautosomal Regions (PARs) Found in Infertile Men with Y-Chromosome Microdeletions

CONTEXT The pseudoautosomal regions (PARs) of the Y-chromosome undergo meiotic recombination with the X-chromosome. PAR mutations are associated with infertility and mental and stature disorders. OBJECTIVE The aim of the study was to determine whether men with Y-chromosome microdeletions have structural defects in PARs. DESIGN AND PARTICIPANTS Eighty-seven infertile men with Y-chromosome microdeletions and 35 controls were evaluated for chromosomal rearrangements using commercial or custom (X- and Y-chromosome) array comparative genomic hybridization or by quantitative PCR of selected PAR genes. Multisoftware-defined chromosomal gains or losses were validated by quantitative PCR and FISH. RESULTS Array comparative genomic hybridization confirmed the AZF deletions identified by multiplex PCR. All men with Y-chromosome microdeletions and an abnormal karyotype displayed PAR abnormalities, as did 10% of men with Y-chromosome microdeletions and a normal karyotype. None of the control subjects or infertile men without Y-chromosome microdeletions had PAR duplications or deletions. SHOX aberrations occurred in 14 men (nine gains and five losses); four were short in stature (<10th percentile), and one was tall (>95th percentile). In contrast, the height of 23 men with Y-chromosome microdeletions and normal PARs was average at 176.8 cm (50th percentile). CONCLUSIONS Y-chromosome microdeletions can include PAR defects causing genomic disorders such as SHOX, which may be transmitted to offspring. Previously unrecognized PAR gains and losses in men with Y-chromosome microdeletions may have consequences for offspring.

Comprehensive 5-Year Study of Cytogenetic Aberrations in 668 Infertile Men

PURPOSE The causes of male infertility are heterogeneous but more than 50% of cases have a genetic basis. Specific genetic defects have been identified in less than 20% of infertile males and, thus, most causes remain to be elucidated. The most common cytogenetic defects associated with nonobstructive azoospermia are numerical and structural chromosome abnormalities, including Klinefelter syndrome (47,XXY) and Y chromosome microdeletions. To refine the incidence and nature of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 668 infertile men with oligozoospermia and azoospermia. MATERIALS AND METHODS High resolution Giemsa banding chromosome analysis and/or fluorescence in situ hybridization were done in 668 infertile males referred for routine cytogenetic analysis between January 2004 and March 2009. RESULTS The overall incidence of chromosomal abnormalities was about 8.2%. Of the 55 patients with abnormal cytogenetic findings sex chromosome aneuploidies were observed in 29 (53%), including Klinefelter syndrome in 27 (49%). Structural chromosome abnormalities involving autosomes (29%) and sex chromosomes (18%) were detected in 26 infertile men. Abnormal cytogenetic findings were observed in 35 of 264 patients (13.3%) with azoospermia and 19 of 365 (5.2%) with oligozoospermia. CONCLUSIONS Structural chromosomal defects and low level sex chromosome mosaicism are common in oligozoospermia cases. Extensive cytogenetic assessment and fluorescence in situ hybridization may improve the detection rate in males with oligozoospermia. These findings highlight the need for efficient genetic testing in infertile men so that couples may make informed decisions on assisted reproductive technologies to achieve parenthood.

Early Versus Late Maturation Arrest: Reproductive Outcomes of Testicular Failure

PURPOSE There is a paucity of data characterizing infertile men with maturation arrest. We hypothesized that men with early stage maturation arrest could be clinically distinguished from men with late maturation arrest and would have worse reproductive outcomes. MATERIALS AND METHODS We retrospectively reviewed the records of all patients with nonobstructive azoospermia and cryptozoospermia who underwent testis mapping and sperm extraction from 2002 to 2009 and for whom histopathological findings were available. Patients had uniform maturation arrest if multiple biopsies revealed maturation arrest at the spermatogonia/spermatocyte (early maturation arrest) or the spermatid (late maturation arrest) stage. Clinical parameters and pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection were examined. Statistical analysis consisted of univariate and multivariate analysis. RESULTS Uniform maturation arrest was identified in 49 of 219 men (22.3%) undergoing testicular sperm extraction. On multivariate analysis men with maturation arrest had significantly larger testes (p=0.01), decreased follicle-stimulating hormone (p=0.05) and more detectable genetic abnormalities (p=0.01) than men with other histopathological conditions. Men with late maturation arrest had decreased follicle-stimulating hormone (p=0.02), increased testosterone (p=0.03) and a higher sperm retrieval rate at testicular sperm extraction (p=0.01) than men with early maturation arrest. Predictors of successful sperm retrieval were larger testes, cryptozoospermia, late maturation arrest and hypospermatogenesis (each p≤0.05). Pregnancy outcomes for men with maturation arrest were not significantly different from those for men with other histopathological conditions. CONCLUSIONS Maturation arrest is a common, diverse histopathological subtype of severe male infertility. Compared to men with late maturation arrest those with early maturation arrest have increased follicle-stimulating hormone, decreased testosterone and a decreased probability of mature spermatozoa. In vitro fertilization/intracytoplasmic sperm injection outcomes were similar when spermatozoa were discovered during testicular sperm extraction.

The Impact of Proximal Stone Burden on the Management of Encrusted and Retained Ureteral Stents

PURPOSE Managing the encrusted and retained ureteral stent is a potentially complex challenge. To improve surgical planning, we hypothesized that proximal stone burden is the most important factor associated with complicated removal, and that computerized tomography more accurately estimates stone burden than plain film x-ray of the kidneys, ureters and bladder. MATERIALS AND METHODS Records were reviewed of patients undergoing surgical removal of an encrusted and retained ureteral stent or nephrostomy at Ben Taub General Hospital from 2007 to 2009. Preoperative imaging consisted of a plain x-ray of the kidneys, ureters and bladder and/or computerized tomography of the abdomen/pelvis. Each encrusted tube was assessed using the FECal (forgotten, encrusted, calcified) grading system and associated stone burden was calculated. Univariate and multivariate analyses were performed to determine factors associated with the need for multiple surgeries. RESULTS A total of 55 encrusted and retained ureteral stents and 1 nephrostomy were removed from 52 patients. Mean tube duration was 24.9 months. Most tubes were removed endoscopically (94.2%). Of the patients 21.2% required multiple surgical procedures to remove each tube. Computerized tomography graded stone burden more accurately than plain x-ray of the kidneys, ureters and bladder (94.9% vs 64.4%, p = 0.01). Plain x-ray of the kidneys, ureters and bladder underestimated proximal stone burden in 44.4% of patients who underwent multiple surgeries. When dividing stone burden into 3 categories (0 to 100, 101 to 400 and greater than 401 mm(2)) only proximal stone burden correlated with multiple surgeries and surgical complications (p = 0.01 for both). On multivariate analysis only proximal stone burden was associated with multiple surgeries to remove each tube (OR 12.1, 95% CI 1.5-95.9, p = 0.02 for 101 to 400 mm(2) and OR 18.1, 95% CI 1.7-192.8, p = 0.02 for greater than 401 mm(2)). CONCLUSIONS In patients with encrusted and retained ureteral stents accurate determination of the proximal stone burden, preferably by computerized tomography, is important for surgical counseling and planning.

The use of fluorescent in situ hybridization in male infertility

Male factors are implicated in up to 50% of couples being evaluated and treated for infertility with advanced assisted reproductive technologies. Genetic abnormalities, including sperm chromosome aneuploidy as well as structural aberrations, are one of the major causes of infertility. The use of chromosome-specific DNA probes labeled with fluorochromes, particularly the combination with multiple probes, has been used to indirectly study the sperm chromosome by fluorescent in situ hybridization (FISH). Clinically, this technique is also used to assess the sperm of men recovering from gonadotoxic treatment. Recent advances in this technology facilitate the evaluation of sperm aneuploidy. Sperm FISH is a widely used screening tool to aid in counseling couples with severe male factor infertility, especially in cases of prior repeated in vitro fertilization/intracytoplasmic sperm injection failure or recurrent pregnancy loss. Automation of FISH imaging and analysis, as well as the development of emerging techniques such as comparative genomic hybridization, will all contribute to the promise of future diagnostic approaches aimed at improving the quality, ease, and efficiency of aneuploidy analysis.

True duplication of the vas deferens: a case report and review of literature

BackgroundDuplication of the vas deferens is the identification of a second vas deferens within the spermatic cord; it is a rarely reported congenital anomaly. Duplicate vas deferens should not be confused with double vas deferens that describes ipsilateral renal agenesis with a blind ureter ending in the ejaculatory system.Data sourcesWe present a case of duplicated vas deferens, and a PubMed Medline (National Library of Medicine) search was performed using the terms “[duplicated OR double]” and “vas deferens”. Nineteen papers for a total of twenty-two cases (including ours) were identified.ConclusionsDuplication of vas deferens is a rare finding; it is likely under-reported and underrecognized. Failure to recognize this variation can result in injury to the vas deferens or an ineffective vasectomy. Following identification of a suspected duplicated vas deferens, the structure should be tracked from the internal ring down to the epididymis and intra-operative Doppler should be performed. Post-operatively, renal and bladder imaging can be considered though there have been no reported cases of non-testicular genito-urinary anomalies associated with duplicated vas deferens.