Effects of Physical Activity at High Altitude on Hormonal Profiles in Foreign Trekkers and Indigenous Nepalese Porters.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-ß-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

Sperm recovery and ICSI outcomes in men with non-obstructive azoospermia: a systematic review and meta-analysis.

BACKGROUND: Factor affecting sperm retrieval rate (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in patients with non-obstructive azoospermia (NOA) have not been systematically evaluated. In addition, although micro-TESE (mTESE) has been advocated as the gold standard for sperm retrieval in men with NOA, its superiority over conventional TESE (cTESE) remains conflicting. OBJECTIVE AND RATIONALE: The objective was to perform a meta-analysis of the currently available studies comparing the techniques of sperm retrieval and to identify clinical and biochemical factors predicting SRR in men with NOA. In addition, PRs and live birth rates (LBRs), as derived from subjects with NOA post-ICSI, were also analysed as secondary outcomes. SEARCH METHODS: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR derived from cTESE or mTESE in patients with NOA and their specific determinants were included. Data derived from genetic causes of NOA or testicular sperm aspiration were excluded. OUTCOMES: Out of 1236 studies, 117 studies met the inclusion criteria for this study, enrolling 21 404 patients with a mean age (± SD) of 35.0 ± 2.7 years. cTESE and mTESE were used in 56 and 43 studies, respectively. In addition, 10 studies used a mixed approach and 8 studies compared cTESE with mTESE approach. Overall, a SRR per TESE procedure of 47[45;49]% (mean percentage [95% CI]) was found. No differences were observed when mTESE was compared to cTESE (46[43;49]% for cTESE versus 46[42;49]% for mTESE). Meta-regression analysis demonstrated that SRR per cycle was independent of age and hormonal parameters at enrolment. However, the SRR increased as a function of testis volume. In particular, by applying ROC curve analysis, a mean testis volume higher than 12.5 ml predicted SRR >60% with an accuracy of 86.2% ± 0.01. In addition, SRR decreased as a function of the number of Klinefelter's syndrome cases included (S = -0.02[-0.04;-0.01]; P < 0.01. I = 0.12[-0.05;0.29]; P = 0.16). Information on fertility outcomes after ICSI was available in 42 studies. Overall, a total of 1096 biochemical pregnancies were reported (cumulative PR = 29[25;32]% per ICSI cycle). A similar rate was observed when LBR was analysed (569 live births with a cumulative LBR = 24[20;28]% per ICSI cycle). No influence of male and female age, mean testis volume or hormonal parameters on both PR and LBR per ICSI cycle was observed. Finally, a higher PR per ICSI cycle was observed when the use of fresh sperm was compared to cryopreserved sperm (PR = 35[30;40]%, versus 20[13;29]% respectively): however, this result was not confirmed when cumulative LBR per ICSI cycle was analysed (LBR = 30[20;41]% for fresh versus 20[12;31]% for cryopreserved sperm). WIDER IMPLICATIONS: This analysis shows that cTESE/mTESE in subjects with NOA results in SRRs of up to 50%, with no differences when cTESE was compared to mTESE. Retrieved sperms resulted in a LBR of up to 28% ICSI cycle. Although no difference between techniques was found, to conclusively clarify if one technique is superior to the other, there is a need for a sufficiently powered and well-designed randomized controlled trial to compare mTESE to cTESE in men with NOA.

Early varicocelectomy by percutaneous scleroembolization improves seminiferous tubules spermatozoa release in the adolescent phase of testicular growth.

Varicocele is a rather common andrological condition in adolescents, which can adversely affect testicular growth and seminal parameters, leading to infertility in about 20% of adults. The aim of this study was to investigate if treating varicocele before the age of 18 is a beneficial option to improve testicular hypotrophy and seminal parameters and if minimally invasive techniques could be an appropriate treatment choice for adolescent varicocele associated with spermatic vein reflux. A percutaneous scleroembolization was performed in sixty-four consecutive young patients (13-19 years old) with left varicocele, preceded by a fluoroscopy. In thirty-four of them, semen samples were also collected. We examined semen samples and testicles dimensions before and after percutaneous varicocelectomy, compared to a nonoperated control group, with a six-month follow-up. Total sperm count and sperm morphology were significantly increased in the intervention group. Left testicular volume significantly increased in both groups, while only correction of varicocele improved spermatozoa release per unit of testis volume. We conclude that early varicocelectomy by percutaneous scleroembolization significantly ameliorates seminiferous tubules activity in the critical adolescent phase of testicular growth. It is suggested that adolescents should be; offered varicocele repair as soon as possible in order to improve reproductive potential.

Levothyroxine supplementation on assisted reproduction technology (ART) outcomes in women with subtle hypothyroidism: a retrospective study.

The need for treating subclinical hypothyroidism (SCH) in women undergoing assisted reproduction technology (ART) is under debate. Moreover, it is known that controlled ovarian hyperstimulation (COH) protocols may impair the thyroidal axis. Therefore, we evaluated if levothyroxine (L-T4) supplementation in SCH women before undergoing ART positively affects the main reproductive outcomes. We retrospectively analyzed in vitro fertilization (IVF) data of 4147 women submitted to 6545 cycles in a tertiary care IVF Center (January 2009-December 2014). L-T4 (1.4-2.0 mcg/kg) treatment was offered to all women with a pre-cycle TSH >2.5 mIU/L before starting COH and main ART outcomes were compared in euthyroid and L-T4-treated women undergoing ART. Among 4147 women, 1074 (26%) were affected by SCH and were treated with L-T4 before COH was started. No statistically significant differences among L-T4-treated and euthyroid women group were observed regarding pregnancy rate, respectively, per cycle (27.67% vs 26.37%; p = .314) and per embryo transfer (30.13% vs 29.17%; p = .489), live birth rate, respectively, per cycle (21.58% vs 20.38%; p = .304) and per embryo transfer (23.49 vs 22.54%; p = .449) and the rest of primary and secondary efficacy endpoints. Early L-T4 treatment for infertile women with a subtle thyroid dysfunction may mitigate and protect from the negative effects of SCH in the setting of ART, and may preventively overcome also the negative impact of COH on thyroidal axis.

Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis.

BACKGROUND: Specific factors underlying successful surgical sperm retrieval rates (SRR) or pregnancy rates (PR) after testicular sperm extraction (TESE) in adult patients with Klinefelter syndrome (KS) have not been completely clarified. OBJECTIVE AND RATIONALE: The aim of this review was to meta-analyse the currently available data from subjects with KS regarding SRRs as the primary outcome. In addition, when available, PRs and live birth rates (LBRs) after the ICSI technique were also investigated as secondary outcomes. SEARCH METHODS: An extensive Medline, Embase and Cochrane search was performed. All trials reporting SRR for conventional-TESE (cTESE) or micro-TESE (mTESE) and its specific determinants without any arbitrary restriction were included. OUTCOMES: Out of 139 studies, 37 trials were included in the study, enrolling a total of 1248 patients with a mean age of 30.9 ± 5.6 years. The majority of the studies (n = 18) applied mTESE, 13 applied cTESE and in one case testicular sperm aspiration (TESA) was used. Additionally, four studies used a mixed approach and in one study, the method applied for sperm retrieval was not specified. Overall, a SRR per TESE cycle of 44[39;48]% was detected. Similar results were observed when mTESE was compared to cTESE (SRR 43[35;50]% vs 45[38;52]% for cTESE vs micro-TESE, respectively; Q = 0.20, P = 0.65). Meta-regression analysis showed that none of the parameters tested, including age, testis volume and FSH, LH and testosterone (T) levels at enrollment, affected the final SRR. Similarly, no difference was observed when a bilateral procedure was compared to a unilateral approach. No sufficient data were available to evaluate the effect of previous T treatment on SRR. Information on fertility outcome after ICSI was available for 29 studies. Overall a total of 218 biochemical pregnancies after 410 ICSI cycles were observed (PR = 43[36;50]%). Similar results were observed when LBR was analyzed (LBR = 43[34;53]%). Similar to what was observed for SRR, no influence of KS age, mean testis volume, LH, FSH or total T levels on either PR and LBR was observed. No sufficient data were available to test the effect of the women's age or other female fertility problems on PR and LBR. Finally, no difference in PR or LBR was observed when the use of fresh sperm was compared to the utilization of cryopreserved sperm. WIDER IMPLICATIONS: The present data suggest that performing TESE/micro-TESE in subjects with KS results in SRRs of close to 50%, and then PRs and LBRs of close to 50%, with the results being independent of any clinical or biochemical parameters tested.

Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data.

Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to possess insulin-mimetic properties and to improve insulin resistance, especially in women with polycystic ovary syndrome. However, it has not been determined if this relationship exists also in children. Based on these previous findings, we hypothesized that inositol could be effective in improving insulin sensitivity in children with insulin resistance. To evaluate this hypothesis, we administered both inositol formulations before carrying out an oral glucose tolerance test (OGTT) in a group of obese insulin-resistant male children with high basal insulin levels and compared the values obtained with an OGTT previously conducted without inositol, in the same group, with unchanged BMI. Our results confirm that myoinositol and D-chiro inositol acutely reduce insulin increase after glucose intake mainly in children with high basal insulin level.

Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk.

The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.

Activation of the immune system and sperm DNA fragmentation are associated with idiopathic oligoasthenoteratospermia in men with couple subfertility.

Ejaculates from men without known causes for male subfertility and asymptomatic for genital tract inflammation showed infiltration of macrophages, and their activation state (HLA-DR(+)) was negatively correlated with semen parameters and positively correlated with sperm DNA damage. An activation of the immune system is thus detectable in idiopathic oligoasthenoteratozoospermia of unknown origin.

Physical exercise at high altitude is associated with a testicular dysfunction leading to reduced sperm concentration but healthy sperm quality.

OBJECTIVE: To explore the effect of physical exercise at high altitudes (HA) on male reproductive system. DESIGN: Prospective study. SETTING: Andrology Clinic, University of L'Aquila, Italy. PATIENT(S): Seven male mountaineers involved in an expedition at 5,900 m. INTERVENTION(S): Semen analysis, sperm DNA fragmentation with flow cytometry, and reproductive hormone levels. MAIN OUTCOME MEASURE(S): Hormone levels were evaluated at sea level (SL) at baseline (SL-pre), after 22 days of exercise at HA (intermediate), and after 10 days upon reaching SL (SL-post). Sperm parameters, percentage of sperm with fragmented DNA, and body composition measures were evaluated at SL-pre and at SL-post. RESULT(S): A reduction of sperm concentration, of body mass index (BMI), of waist circumference, and of percentage of body fat was observed at SL-post compared with SL-pre values. Increased levels of FSH and PRL were observed at the intermediate point, and normalized at SL-post, whereas T was higher at SL-post compared with SL-pre levels. CONCLUSION(S): Physical exercise at HA is associated with a testicular dysfunction leading to a reduced sperm concentration probably through an altered spermiation. The improved body composition after physical exercise might explain the higher T levels observed after the expedition.

Altered ultrastructure of mitochondrial membranes is strongly associated with unexplained asthenozoospermia.

OBJECTIVE: To explore the contribution of an altered structure of sperm mitochondria to human asthenozoospermia. DESIGN: A retrospective study. SETTING: Andrology Clinic, University of L'Aquila. PATIENT(S): Fifteen ejaculates with forward motility (FM) ≥ 50%, and 57 asthenozoospermic ejaculates (FM <50%, sperm vitality >50%), including 14 ejaculates with systematic genetic defects of tail principal piece, and 43 ejaculates with unexplained asthenozoospermia. INTERVENTION(S): Fifty sections of tail middle piece (MP) were blindly analyzed by transmission electron microscopy in each ejaculate for normal mitochondrial membrane organization, after exclusion of tails with disrupted cell membranes. MAIN OUTCOME MEASURE(S): Percentage of MPs with normal mitochondrial membranes (% normal MPs). RESULT(S): Percent normal MPs showed a strong correlation with forward motility. Variation of % normal MPs explained a 45% variation of sperm motility at multivariate linear regression analysis, confirming the strong association between the two parameters in a population including ejaculates with normal motility and with unexplained asthenozoospermia. Percent normal MPs was significantly reduced in severe unexplained asthenozoospermia (FM <10%; n = 16) compared with samples with normal motility (FM ≥ 50%; n = 15); 21% (10.5%-38%) and 68% (52%-73%), respectively. CONCLUSION(S): Structural defects in mitochondrial membranes represent a main feature of severe unexplained asthenozoospermia.

Seminal macrophages in ejaculates from men with couple infertility.

Seminal macrophages are occasionally reported though their relevance in the evaluation of human ejaculate is unknown. Activated macrophages, engaging in sperm phagocytosis (spermiophages), might represent a marker of innate immunosystem activation. We investigated whether the presence of spermiophages in non-leukocytospermic ejaculates from men complaining for couple infertility is associated with altered sperm features. Four hundred and thirty-four ejaculates were retrospectively analysed after excluding samples with antisperm antibodies, or a leukocyte number >or=1 x 10(6)/mL. Semen quality was compared in samples with or without spermiophages detected with transmission electron microscope. Presence of spermiophages, observed in 27% of ejaculates, was associated with a decreased number of sperm total count (p < 0.0001), of sperm forward motility (p = 0.048), and to an increased fraction of degenerating sperm (p = 0.0002) compared to ejaculates without spermiophages. A low number of total ejaculated sperm and an increased number of degenerating sperm independently predicted the presence of spermiophages (odds ratio 1.72; 95% confidence intervals 1.10 to 2.28 and odds ratio 1.85; 95% confidence intervals 1.19 to 2.88 respectively). Data demonstrate that activated macrophages, a marker of the innate immunosystem activation, are frequently observed in non-leukocytospermic ejaculates of men suffering for couple infertility and this may be associated with altered sperm parameters. Ultrastructural analysis gives qualitative informations, hence sensitive quantitative tests should better define the association between semen activated macrophages and oligoasthenozoospermia and the possible relevance of this finding in the clinical evaluation of the male partner of couple infertility.

Treatment of erectile dysfunction reduces psychological distress.

Mental stress is a risk factor for cardiovascular events in men with vascular risk factors (VRFs) and is also associated with erectile dysfunction (ED), a frequent complaint of men with VRFs. The aim of this study was to investigate the effect of inhibition of phosphodiesterase-5 or of placebo in men with ED and VRFs on self-evaluated psychological distress, erectile function and quality of sexual life. Thirty-six men with ED and VRFs were randomized to 4 weeks of tadalafil (20 mg/every other day) or placebo treatment. Sexual Health Inventory for Men (SHIM), questions 1-3 of Life Satisfaction (LiSat) questionnaire, Symptom Check-List-90R, a multidimensional inventory exploring psychological dimensions were applied before and after treatment. The SHIM score improved after treatment with tadalafil compared with baseline and with placebo (F = 10.38; p = 0.0030). Sexual life satisfaction (LiSat-2) was significantly improved after tadalafil and after placebo, but a strong positive correlation was observed between LiSat-2 and SHIM score after tadalafil treatment (r = 0.59, p = 0.0003) and not after placebo (r = 0.22, p = 0.189). Psychological features were significantly changed after treatment, although a specific effect of tadalafil vs. placebo was observed only for interpersonal sensitivity (F = 4.48; p = 0.042). Obsessive-compulsive dimension, depression, anxiety, psychoticism were significantly improved in the tadalafil group and in the placebo group, although the improvement was always more relevant after treatment with tadalafil. These preliminary data suggest that a short treatment of ED reduced psychological distress and improved quality of sexual life in men with VRFs.

Inhibition of phosphodiesterase type 5 with tadalafil is associated to an improved activity of circulating angiogenic cells in men with cardiovascular risk factors and erectile dysfunction.

Circulating angiogenic cells (CACs) contribute to repair of the vessel wall and dysfunctional CACs are associated to endothelial dysfunction in men with vascular risk factors (VRFs). We investigated whether inhibition of phosphodiesterase type 5 (PDE5) in men with erectile dysfunction (ED) and VRFs is accompanied to changes of CACs and to changes of endothelial function. Thirty-six men with ED and VRFs were randomised to 4 weeks of tadalafil (20mg/other day) or placebo treatment. The number of ex vivo expanded functional CAC's, identified by uptake of 1,1'-dioctadecyl-3, 3,3', 3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (DiLDL) and concomitant Ulex europaeus agglutinin I (UEA-1) binding, was determined at baseline and after treatment. The number of cells double positive for DiLDL and for UEA-1, per high-power field fluorescence microscopy was significantly reduced in patients compared to 10 controls (26.88+/-6.3 and 74.41+/-17.1, respectively; P<0.0001) and was markedly increased after tadalafil treatment (40.69+/-13.07 versus 25.82+/-6.49; P<0.0001). The percentage variation of CACs number and of flow-mediated dilation in the brachial artery by ultrasound after treatment was significantly associated to the presence of endothelial dysfunction at baseline. In conclusion, the increased number of functional CACs after tadalafil treatment suggests a beneficial effect of prolonged PDE5 inhibition on vascular homeostasis.

Isolated teratozoospermia: a cause of male sterility in the era of ICSI?

Single structural defects involving the totality of ejaculated sperm are among rare cases of untreatable human male infertility. This form of infertility is of genetic origin and is generally transmitted as an autosomal recessive traits. Acrosome agenesis or globozoospermia results from perturbed expression of nuclear proteins or from an altered Golgi-nuclear recognition during spermiogenesis. Failed fertilization after intracytoplasmic sperm injection (ICSI) of acrosomeless sperm is consistent with an inability of sperm to activate oocytes. Acephalic spermatozoa result from a head-neck defect due to a failure of migration of the tail anlagen and related centriole to the caudal pole of spermatids. An abnormal sperm centrosome function may explain the defective embryo cleavage after ICSI with sperm carrying a fragile head-neck junction. Primary cilia dyskinesia (PCD) and dysplasia of the fibrous sheath (DFS) are isolate defects associated with absent or greatly reduced sperm motility due to an abnormal ciliary structure and function (PCD) or to a disorganized fibrous sheath (DFS). Numerous defective genes are potentially involved in human isolated teratozoospermia but such defects have not been defined at the molecular level in most cases. IVF-ICSI is the only available method for obtaining live births with sperm carrying these defects, but the outcome is poor and the genetic risk for the subsequent generation can not be determined.

Penile duplex pharmaco-ultrasonography of cavernous arteries in men with erectile dysfunction and generalized atherosclerosis.

Assessment of cavernosal perfusion in men with erectile dysfunction (ED) relies on Doppler spectrum analysis of pharmachologically stimulated peak systolic velocity (sPSV) in cavernous arteries but its accuracy in identifying men affected by a cavernosal perfusion disorder correlated with atherosclerosis remains undefined. We estimated by B-mode ultrasound, the accuracy of sPSV of cavernous arteries to identify ED with an expected cavernosal perfusion disorder. This was predicted by an elevated intima-media thickness (IMT) of common carotid arteries, a reference methodology to estimate the degree of generalized atherosclerosis, in men exposed to vascular risk factors (VRFs). sPSV and IMT were evaluated in 269 men with ED, 49 had no VRFs, 100 were overweight with/or without hyperlipidaemia, 120 were affected by type 2 diabetes and/or essential hypertension. sPSV was significantly lower (p<0.05) in patients with VRFs associated with atherosclerosis (IMT>or=1 mm) (n=39) than in men with no VRFs and no atherosclerosis (n=49). sPSV correlated negatively with age (p<0.0001), with serum% of glycated haemoglobin (p=0.010) and with carotid artery IMT (p=0.013). An sPSVor=1 mm combined to the exposure to VRFs. The ultrasonographic evaluation of sPSV had a very limited accuracy in discriminating ED with an expected cavernosal perfusion disorder, based on the presence of a generalized atherosclerosis in men with VRFs.

Utrastructural analysis of asthenozoospermic ejaculates in the era of assisted procreation.

OBJECTIVE: To define by transmission electron microscopy (TEM) analysis, the prevalence of sperm tail defects of genetic origin among men suffering for a reduced or absent sperm motility. DESIGN: A retrospective study. SETTING: Andrology Clinic, University of L'Aquila, Italy. PATIENT(S): The 120 ejaculates of infertile men with a forward motility (FM) < or =20% were compared to 200 ejaculates with a FM >20%. All ejaculates had a sperm vitality >50%. INTERVENTION(S): Some 25-50 tails were analyzed by TEM in each ejaculate. MAIN OUTCOME MEASURE(S): Receiver operating characteristics (ROC) analysis was applied by plotting the FM of cases with or without genetic tail defects detected by TEM. RESULT(S): The area under the ROC curve was 0.96 (95% confidence interval 0.92-0.98). The positive predictive accuracy for genetic tail defects in ejaculates with 0% FM was 46%. Three of 17 cases with genetic tail defects were classified as false negative when TEM analysis was restricted to ejaculates with 0% FM. A FM < or =7%, allowed the identification of all cases with genetic tail defects. CONCLUSION(S): The TEM analysis identifies sperm tail defects of genetic origin and should be restricted to ejaculates with severe asthenozoospermia (< or =7% motile sperm) and sperm vitality >50%.

Intima-media thickening of common carotid arteries is a risk factor for severe erectile dysfunction in men with vascular risk factors but no clinical evidence of atherosclerosis.

PURPOSE: The association of erectile dysfunction (ED) with vascular damage in men without clinical atherosclerosis is unknown. By B-mode ultrasound we evaluated intima-media thickness (IMT) of common carotid arteries, a measure of vascular damage, in men reporting ED with or without vascular risk factors (VRFs) but no clinical atherosclerosis. MATERIALS AND METHODS: IMT of common carotid arteries was evaluated in 270 men with ED. A total of 50 men (mean age +/- SD 39.84 +/- 12.5 years) had no VRFs, 100 (mean age 47.92 +/- 10.94 years) were overweight and/or had hyperlipidemia, and 120 (mean age 53.95 +/- 9.73 years) were affected by type 2 diabetes and/or essential arterial hypertension. RESULTS: IMT was significantly lower in men with no VRFs compared to men with VRFs (p <0.05), and correlated with the severity of ED evaluated through the Sexual Health Inventory for Men (p = 0.0008). Of men with VRFs 17.7% (39 of 220) showed an IMT score indicative of vascular damage (1.00 mm or greater), while only 1 man with no VRFs had a high IMT. Men with VRFs and a high carotid IMT score demonstrated more severe ED, were older and had a higher serum level of C-reactive protein compared to men with VRFs and an IMT of less than 1.00 mm (p <0.05). A high IMT score but not an increased measure for each VRF, including aging, significantly increased the risk of severe ED (odds ratio 2.6, confidence interval 1.1 to 5.9) even after controlling for smoking and drugs associated with ED. CONCLUSIONS: ED in men with VRFs was the only clinical correlate of unrecognized atherosclerosis of common carotid arteries.

The contractile wall of the caput epididymidis in men affected by congenital or postinflammatory obstructive azoospermia.

The transport and storage of spermatozoa in the epididymis depend on the contractile activity of its tubular wall. It is not known what differences exist in the contractile wall of the human epididymis in cases of obstructive azoospermia. The contractile wall in the tubules of the caput epididymidis was analyzed by light microscopy and transmission electron microscopy in 10 azoospermic men, 5 with a bilateral congenital absence of vas deferens (CBAVD) and 5 with a bilateral postinflammatory congestive obstruction of the epididymis. Five specimens from the same region of the caput epididymidis, obtained from fertile men who had undergone an orchidectomy because of testicular cancer, served as controls. No differences were observed between congenital and congestive obstructions. The contractile wall in caput tubules proximal to the obstructed level was strongly thickened when compared with controls (62.98 +/- 5.84 micro; 80.82 +/- 7.72 micro vs 19.59 +/- 2.23 micro, respectively, for congestive and congenital obstructions vs controls; P <.0001 vs controls), and the spindle-shaped myoid cells, which formed the contractile wall in normal cases, were replaced by large smooth muscle cells (SMCs) that showed features of coexisting contractile and secretory functions. The former included crowded cytoplasmic bundles of thin myofilaments (5-6 nm in diameter) converging to a large number of dense bodies, numerous micropinocytotic vesicles of the plasma membrane, and a continuous cell basement membrane. The presence of a developed rough endoplasmic reticulum and a Golgi complex, associated with the accumulation of thick layers of pericellular basement membrane-like material and ground substance, was indicative of a secretory phenotype of SMCs. The increased mechanical forces on the epididymal wall upstream from the obstruction might eventually activate the differentiation of myoid cells into SMCs, leading to an altered physiology of the contractile wall that could have possible clinical relevance in the case of microsurgical epididymovasostomy.

Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis.

Degeneration of human male germ cells was analysed by means of light (LM) and transmission electron (TEM) microscopy. The frequency of degenerating cells was correlated with that of Fas-expressing germ cells in human testes with normal spermatogenesis (n = 10), complete early maturation arrest (EMA) (n = 10) or incomplete late maturation arrest (LMA; n = 10) of spermatogenesis. LM analysis of testis sections with normal spermatogenesis indicated that degenerating germ cells were localized in the adluminal compartment of the seminiferous epithelium. TEM showed that apoptotic cells were mostly primary spermatocytes and, to a lesser extent, round or early elongating spermatids. Apoptotic germ cells appeared to be eliminated either in the seminiferous lumen or by Sertoli cell phagocytosis. An increased number of degenerating cells was observed in testes with LMA as compared with normal testes and testes with EMA of spermatogenesis (P < 0.001, Wilcoxon's rank sum test). Comparison of these results with those obtained from immunohistochemistry experiments demonstrated a tight correlation between the number of apoptotic cells and the number of Fas-expressing germ cells (P = 0.001, Spearman's rank = 0.69). These findings suggest that altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells.