Ron Hauser

Varicocele and the testicular-renal venous route: hemodynamic Doppler sonographic investigation.

The aim of this study was to quantify the anatomic and hemodynamic components of the testicular venous drainage for the purpose of understanding their mechanisms of interacting in producing mutual effects, such as nutcracker phenomenon, reflux, and varicoceles. Seventy‐five male subjects were studied at rest and during Valsalva maneuver. Aortomesenteric distance and angle, flow velocity in different segments of the renal veins, testicular vein diameter, and flow inversion were evaluated using standard ultrasound equipment with spectral and color Doppler capabilities. The velocity of flow in the proximal segment of the left renal vein (17.5 cm/s) was found to be significantly lower than that in both the distal left renal vein (121 cm/s) and the right renal vein (37 cm/s). The flow velocity in the proximal left renal vein decreased with decrease in the aortomesenteric distance and angle. Testicular vein diameters greater than 3 mm were statistically associated with decreased superior mesenteric artery angle. A significant association also was found between the left testicular vein diameter (in Valsalva maneuver) and inversion of flow. The decrease in flow velocity in the left renal vein proximal to the bifurcation of the superior mesenteric artery from the aorta supports the nutcracker theory. An association was found between the decrease of superior mesenteric artery angle and the increase in testicular vein diameter. Another association exists between the presence of reflux during Valsalva maneuver and increased testicular vein diameter. These finding were significant only for testicular vein diameter values greater than 3 mm.

Pheochromocytoma in pregnancy: case report and review of the literature.

Pheochromocytoma is a rare disease that may occur during pregnancy. Only a few hundred cases have been published in the literature. Manifestations include hypertension with various clinical presentations, possibly resembling those of pregnancy-induced hypertension, or pre-eclamptic toxemia. Differentiation of these conditions is not always feasible, thus creating a serious risk, because fetal and maternal morbidity and mortality are far higher with pheochromocytoma. Biochemical measurements of catecholamines and their metabolites are apparently a convenient way to establish diagnosis during pregnancy, inasmuch as interpretation of radiological evaluation is complicated by the gravid uterus, and might even be potentially dangerous due to the use of ionizing radiation. More sophisticated methods for evaluation are not always practical during pregnancy. Medical treatment aims at controlling symptoms, mandating the use of alpha- and beta-receptors blockade medication. Surgical intervention is the only possible curative method available, but the critical issue is probably to identify the exact timing during the course of pregnancy for such intervention, or the ability to control symptoms until delivery. Although malignant transformation of pheochromocytoma have been reported, it is extremely uncommon. The overall prognosis is mainly affected by early diagnosis, and multidisciplinarian management.

Sertoli cell maturation in men with azoospermia of different etiologies

OBJECTIVEnTo evaluate the involvement of Sertoli cell in different spermatogenic disorders.nnnDESIGNnRetrospective case-control study.nnnSETTINGnTeaching hospital.nnnPATIENT(S)nAzoospermic men who underwent testicular biopsy for sperm recovery in preparation for intracytoplasmic sperm injection.nnnINTERVENTION(S)nTesticular biopsy evaluation by quantitative immunohistochemistry for the immature Sertoli cell markers anti-Müllerian hormone and cytokeratin 18 (CK-18).nnnMAIN OUTCOME MEASURE(S)nRelative area of immature Sertoli cells in testes with focal spermatogenesis, spermatocyte maturation arrest, or normal spermatogenesis.nnnRESULT(S)nThe relative area occupied by immature Sertoli cells, as revealed by anti-Müllerian hormone and CK-18 expression, was highest in the 11 men with focal spermatogenesis. In the group representing normal spermatogenesis (obstructive azoospermia, 6 men) and in the group characterized by spermatocyte maturation arrest (6 men), the areas occupied by anti-Müllerian hormone- and CK-18-positive cells were minimal.nnnCONCLUSION(S)nDifferent etiologies underlie the spermatogenic disorders reported in this study. In focal spermatogenesis with high anti-Müllerian hormone and CK-18 expression, the spermatogenic impairment is associated with the presence of immature Sertoli cells. The detection of normal mature Sertoli cells in the spermatocyte maturation arrest group indicates that the spermatogenic defect that is accompanied by an impairment of meiosis is intrinsic to the germ line without affecting Sertoli cell differentiation.

Members of the CDY family have different expression patterns: CDY1 transcripts have the best correlation with complete spermatogenesis

The CDY family of genes is of special interest because some of them are included in chromosome-Y microdeletions detected among infertile men and are apparently involved in the spermiogenetic process. In this study, we employed the reverse transcriptase/polymerase chain reaction technique to test the RNA expression of the various transcripts of these genes in testicular biopsies of 84 azoospermic men who had been classified by comprehensive histology and cytology analyses. We also evaluated the feasibility of detecting CDY expression in biopsies taken by testicular sperm extraction versus acquisition by aspiration. There was a significant association between the type of testicular impairment and the expression of CDY1 and CDY2 transcripts. CDY2 was expressed whenever germ cells were present, but CDY1 major and especially CDY1 minor and short transcripts were identified almost exclusively when mature spermatids/spermatozoa were detected. The expression of CDY1 minor and short transcripts detected in aspirated specimens was less efficient than that in testicular tissue acquired by extraction. It is sugested that CDY2 is apparently required in the early stages of spermatogenesis, whereas CDY1 transcripts are required later on in the process. The findings of this study imply different functional roles for CDY isoforms during spermatogenesis. However, in consideration of the high levels of identity between CDY1 and CDY2 (98% at the protein level), the delayed up-regulation of CDY1 transcripts could be attributable to temporal changes in dosage requirements.

Preservation of sperm of cancer patients: extent of use and pregnancy outcome in a tertiary infertility center

Sperm cryopreservation is the best modality to ensure future fertility for males diagnosed with cancer. The extent to which cryopreserved sperm is actually used for impregnation, the fertility treatment options that are available and the success rates of these treatments have not been investigated in depth. The medical records of 682 patients who cryopreserved sperm cells due to cancer treatment were analyzed. Seventy of these patients withdrew their frozen sperm for fertility treatments over a 20-year period (most within the first 4 years after cryopreservation). Sperm quality of different malignancies and outcomes of assisted reproduction treatment (ART) for pregnancy achievement in relation to the type of treatment and the type of malignancy were evaluated. The results showed that the rate of using cryo-thawed sperm from cancer patients for fertility treatments in our unit was 10.3%. Sperm quality indices differed between different types of malignancies, with the poorest quality measured in testicular cancer. Conception was achieved in 46 of the 184 ART cycles (25%), and resulted in 36 deliveries. The use of intracytoplasmic sperm injection (ICSI) methodology yielded a significantly higher pregnancy rate (37.4%) than intrauterine insemination (IUI; 11.5%) and was similar to other groups of infertile couples using these modalities. In vitro fertilization (IVF) failed to produce pregnancies. In conclusion, the rate of use of cryopresseved sperm in cancer patients is relatively low (10.3%). Achievement of pregnancies by ICSI presents the best option but when there are enough stored sperm samples and adequate quality, IUI can be employed. Cryopreservation is nevertheless the best option to preserve future fertility potential and hope for cancer patients.

A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes

Purpose:Up to 1% of all men experience azoospermia, a condition of complete absence of sperm in the semen. The mechanisms and genes involved in spermatogenesis are mainly studied in model organisms, and their relevance to humans is unclear because human genetic studies are very scarce. Our objective was to uncover novel human mutations and genes causing azoospermia due to testicular meiotic maturation arrest.Methods:Affected and unaffected siblings from three families were subjected to whole-exome or whole-genome sequencing, followed by comprehensive bioinformatics analyses to identify mutations suspected to cause azoospermia. These likely mutations were further screened in azoospermic and normozoospermic men and in men proven to be fertile, as well as in a reference database of local populations.Results:We identified three novel likely causative mutations of azoospermia in three genes: MEIOB, TEX14, and DNAH6. These genes are associated with different meiotic processes: meiotic crossovers, daughter cell abscission, and possibly rapid prophase movements.Conclusion:The genes and pathways we identified are fundamental for delineating common causes of azoospermia originating in mutations affecting diverse meiotic processes and have great potential for accelerating approaches to diagnose, treat, and prevent infertility.Genet Med advance online publication 16 February 2017

Assessing the predictive value of hyaluronan binding ability for the freezability potential of human sperm.

OBJECTIVEnTo evaluate the predictive value of a sperm maturation test using the hyaluronan-binding assay (HBA) for freezability potential; and to determine the effect of freezing-thawing on HBA results.nnnDESIGNnProspective study.nnnSETTINGnAndrology laboratory at a teaching hospital.nnnPATIENT(S)nCandidates for sperm bank donation (n = 113) and active sperm bank donors (n = 16).nnnINTERVENTION(S)nSemen analyses including HBA and sperm freezing-thawing.nnnMAIN OUTCOME MEASURE(S)nPercentage of sperm HBA results and other sperm parameters in relation to freezing-thawing results.nnnRESULT(S)nThe predictive value of HBA for high freezability value (>or=40% postthaw motility) was significant. However, 1- and 4-hour percentage of motility had a higher predictive value for good freezability. A better prognostic value than that of HBA resutlts was also found for sperm concentration and percentage of normal morphology. Freezing-thawing had no significant influence on HBA results.nnnCONCLUSION(S)nTo the best of our knowledge this is the first demonstration that sperm maturation, determined by the HBA test, has a low value for predicting freezing-thawing sperm survival.

Localization of the germ cell-specific protein, hnRNP G-T, in testicular biopsies of azoospermic men

The increasing interest in the application of in vitro fertilization techniques in human reproduction has led to a wide use of testicular biopsies to identify the presence of spermatogenic foci in testes of azoospermic men. Histopathologic evaluation of these testicular biopsies is required to determine the spermatogenic state with respect to fertility potential and to rule out preinvasive testicular lesions. Heterogeneous nuclear ribonucleoprotein G-T (hnRNP G-T) is a germ cell-specific protein expressed most prominently during meiosis. We studied the usefulness of hnRNP G-T antibody in the evaluation of these biopsies and reasoned that its germ cell-restricted expression pattern might provide a marker to improve accuracy of diagnosis. Testicular biopsies with various spermatogenic impairments were evaluated immunohistochemically for hnRNP G-T expression. In biopsies exhibiting normal spermatogenesis (obstructive azoospermia), hnRNP G-T was localized in meiotic pachytene spermatocytes and round spermatids. Immunostaining was barely detected when maturation was arrested at the spermatocyte level and not at all in cases of Sertoli cell-only syndrome. Biopsies with a mixed histologic phenotype and minute concentrations of spermatogenesis demonstrated strong immunostaining only in tubules with full spermatogenesis. This distribution pattern of hnRNP G-T enabled instant identification of spermatogenic foci. Thus, exploitation of the hnRNP G-T marker, which is expressed preferentially as meiosis proceeds, enhances sensitivity and accuracy of diagnosis in the histologic evaluation of testicular biopsies.

Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome

PurposeMature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis.MethodsTwo groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups.ResultsClear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group.ConclusionWe conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens.