Secondary infertility due to necrospermia in men with autosomal-dominant polycystic kidney disease: a report of two cases.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the formation of numerous cysts in organs other than the kidneys. Although female patients with ADPKD do not have direct fertility problems, infertility in male patients may arise following the formation of cystic lesions in the lower seminal tract, which impair the function of spermatozoa. Generally, the treatment strategy for necrospermia depends on the severity of sperm viability, and intracytoplasmic sperm injection may be offered to patients with necrospermia. We report two cases of secondary infertility in men with ADPKD. These men experienced an inability to reproduce naturally after the previous birth of a child, suggesting a progressive deterioration of semen quality. Semen analysis showed necrospermia in both patients, and transrectal ultrasound revealed marked dilatation of the seminal vesicles bilaterally. The main cause of secondary infertility in male patients with ADPKD is sperm death resulting from progressive dilatation of seminal vesicles. Further research is needed on the appropriate follow-up schedule for men with ADPKD who desire to reproduce naturally.

[Risk of Male Infertility Due to Testosterone Replacement Therapy for Late-Onset Hypogonadism (LOH)].

Testosterone replacement therapy is widely used for the treatment of late-onset hypogonadism (LOH). However, because exogenous testosterone can suppress the hypothalamic-pituitary-gonadal axis through negative feedback, testosterone replacement therapy may lead to secondary spermatogenic failure and subsequent infertility. We report our experience with male infertility in patients who had received testosterone for LOH. Six of the 4,375 patients who visited our clinic for infertility evaluation had received testosterone replacement therapy for LOH. In these patients, testosterone was administered for 3 to 12 months. In 5 of these 6 patients, blood levels of gonadotropins were markedly suppressed, suggesting hypogonadotropic hypogonadism. In the remaining 1 patient, blood luteinizing hormone and follicle stimulating hormone levels were within the standard reference ranges, but the testosterone level was elevated. Semen findings in these patients ranged from azoospermia to severe oligospermia. Testosterone administration was immediately stopped in all patients. Of the 3 patients who needed prompt recovery of spermatogenesis, 2 received human chorionic gonadotropin (hCG) injection and 1 received clomiphene orally. Semen findings were significantly improved in all patients, except one who was treated with hCG for only one month. Although recovery of spermatogenesis is generally favorable after cessation of testosterone replacement therapy, the recovery period is highly variable among patients. Clinicians treating LOH must recognize that testosterone administration is contraindicated in men who desire to maintain future fertility. LOH patients who wish to preserve fertility should be considered for treatment with clomiphene or hCG.

Ultrasonographically determined size of seminiferous tubules predicts sperm retrieval by microdissection testicular sperm extraction in men with nonobstructive azoospermia.

OBJECTIVE: To investigate the value of the ultrasonographically determined size of seminiferous tubules and other conventional parameters for predicting sperm retrieval by microdissection testicular sperm extraction (micro-TESE). DESIGN: Clinical retrospective study. SETTING: Two urological clinics. PATIENT(S): Eight hundred six men with nonobstructive azoospermia. INTERVENTION(S): Micro-TESE. MAIN OUTCOME MEASURE(S): Sperm retrieval. RESULT(S): Sperm retrieval was successful in 240 (29.8%) of the 806 men. In a receiver operating characteristic analysis of sperm retrieval, the area under the curve (AUC) for seminiferous tubules, assessed as 0, 100, 200, 250, or 300 µm, was no less than 0.82 (95% confidence interval [CI] 0.79-0.85). Sensitivity and specificity at a cutoff point of 250 µm were 76.7% and 80.7%, respectively. An AUC of 0.85 (95% CI, 0.81-0.88) was attained in a parsimonious multiple logistic regression model that included age (<30, 30-39, and 40-59 years), low follicle-stimulating hormone (<14 IU/L), history of cryptorchidism, and sex chromosome abnormality in addition to the diameter of seminiferous tubules. CONCLUSION(S): The gray-scale image in testicular ultrasound was shown to be highly predictive of sperm retrieval in micro-TESE in a large series of men with nonobstructive azoospermia.

Y chromosome microdeletion screening using a new molecular diagnostic method in 1030 Japanese males with infertility.

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

Splicing variant of Cdc42 interacting protein-4 disrupts beta-catenin-mediated cell-cell adhesion: expression and function in renal cell carcinoma.

We have identified an alternative splicing variant in the Cdc42-interacting protein 4 (CIP4) gene in patients with renal cell carcinoma (RCC); almost 50% of the RCCs examined showed an aberrant splicing event in reverse transcription-PCR and the insertion of 19 nucleotides derived from intron9 based on a sequence analysis. This variant (CIP4-V) encodes a premature stop codon, resulting in the loss of a tyrosine phosphorylation site, the Cdc42 binding domain, and the SH3 domain. In this report, we show that overexpression of CIP4-V causes the formation of ubiquitinated aggresomes and a loss of cell-cell adhesion. We determined that CIP4-V increased the beta-catenin tyrosine phosphorylation levels that mediate Fer/Fyn tyrosine kinases and induced beta-catenin mistrafficking from cell membrane to cytoplasmic aggresome. These results indicate that CIP4 is critical for beta-catenin-mediated cell-cell adhesion and may be an important aspect of its functional contribution to RCC, especially with regard to metastasis and invasiveness.

Quantitative estimation of renal blood flow by power Doppler ultrasonography in renovascular hypertensive dogs.

BACKGROUND: We estimated the value of power Doppler (PD) imaging analysis for the quantitative assessment of renal cortical blood flow (RCBF) in chronic two-kidney, one-clip (2K-1C) hypertensive dogs. METHODS: To evaluate the correlation between RCBF and PD signals, RCBF and the mean pixel intensity (MPI) of PD signals were simultaneously obtained at same region in renal cortex under progressive constriction of left main renal artery in five mongrel dogs. RCBF was measured by electrolytic hydrogen gas clearance method, and PD images were transferred to computer and analyzed by the image-analysis software Openlab. To assess the value of quantitative PD imaging analysis on RCBF in renovascular hypertension, in six mongrel dogs with chronic 2K-1C hypertension, PD images in both of clipped kidneys (CK) and non-clipped kidneys (NK) were obtained and analyzed before and 60 minutes after the intravenous infusion of captopril or sodium nitroprusside at 10-minute intervals. RESULTS: There was a linear correlation between RCBF and MPI (r= 0.878, P < 0.0001). MPI in both CK and NK significantly increased after the infusion of captopril, while no significant change was observed in both CK and NK after the infusion of sodium nitroprusside, despite similar reduction of mean arterial blood pressure. CONCLUSION: Our data suggest that the acute inhibition of angiotensin-converting enzyme increased RCBF in both CK and NK of chronic 2K-1C dogs. The quantitative analysis of PD flow signals in kidney is noninvasive and a useful method to evaluate regional changes of renal tissue blood flow in various renal diseases.

Contribution of the renin-angiotensin system to the intrarenal resistive index in chronic unilateral partial ureteral obstruction in dogs.

PURPOSE: We investigated the role of the renin-angiotensin system on intrarenal hemodynamics in chronic unilateral partial ureteral obstruction (UPUO) using Doppler ultrasound (US). METHODS: In 11 dogs with chronic UPUO, we determined the renal resistive index (RI) before and 1 h after the intravenous infusion of an angiotensin-converting enzyme (ACE) inhibitor (captopril), an angiotensin II receptor type 1 (ART1) antagonist (L-158,809), and the combination of these two drugs. Change in resistive index (ΔRI) was calculated as RI after the administration of each tested material minus baseline RI. RESULTS: At the baseline measurement, significant differences in RI were seen between obstructed and nonobstructed kidneys. ACE inhibitor, ART1 antagonist, or the combination of these drugs did not result in any significant changes in RI in either obstructed or nonobstructed kidneys. However, in obstructed kidneys, ΔRI in the combination of ACE inhibitor and ART1 antagonist were significantly greater than those in ACE inhibitor or ART1 antagonist alone, whereas there were no significant differences in those values in nonobstructed kidneys. CONCLUSION: These observations suggest that the renin-angiotensin system in dogs with chronic UPUO may not contribute significantly to the differences in intrarenal RI between obstructed and nonobstructed kidneys. However, the angiotensin-producing pathways and angiotensin II receptor subtypes other than ACE and ART1 may have some different effects between obstructed and nonobstructed kidneys.

[Color Doppler ultrasound for detection of renal arteriovenous fistulas].

OBJECTIVES: Renal arteriovenous (AV) fistula is uncommon, but sometimes causes severe hematuria. To assess the value of color Doppler ultrasound (CD-US) for the detection of renal AV fistula, we retrospectively reviewed our experience with this disease. MATERIALS AND METHODS: Between 1994 and 2001, five patients with renal AV fistula were diagnosed in our institution. Post-biopsy AV fistula of the transplanted kidney was found in 1 patient. Renal AV fistula was detected in 2 patients who presented with gross hematuria. In the remaining 2 patients, renal AV fistula was discovered incidentally during abdominal ultrasonography. We evaluated gray-scale and CD-US imaging in those five patients. RESULTS: In all 5 patients, CD-US showed a whirling flow pattern within an echo-free structure suggesting AV fistula. However, it was difficult to distinguish AV fistula from aneurysm using only CD-US. While pulsed spectral Doppler evaluation of the lesion might be helpful, prompt venous filling on dynamic CT scan and/or renal arteriography was the most definitive sign for diagnosing the renal AV fistula. CONCLUSIONS: CD-US is excellent for demonstrating turbulent blood flow signals within the kidney. However, another radiographic study is required to give a definite diagnosis of renal AV fistula. Due to its low cost, low risk and wide availability, we recommend that CD-US be the first-line imaging procedure for the evaluation of hematuria and renal cystic lesion as well as for followup for renal AV fistula.