High prevalence of thyroid dysfunction in pregnant women.

BACKGROUND/AIM: Maternal thyroid dysfunction during pregnancy has been associated with adverse obstetric and neonatal outcomes. This prospective study evaluates the prevalence of these disorders in pregnant women. SUBJECTS AND METHODS: Serum levels of TSH, free T4 (fT4), and thyroperoxidase antibodies (TPO-Ab) were measured in 951 women at different gestational ages of pregnancy. Trimester-specific reference ranges for TSH were used to classify pregnant women into five groups: 1) Overt hypothyroidism (OH); 2) Subclinical hypothyroidism (SCH); 3) Isolated hypothyroxinemia (IH); 4) Low TSH (isolated or associated with high fT4); and 5) Normal. A classification was made also according to the lower and upper ranges provided by the manufacturer for thyroid hormones. Pregnant women who were at a high risk of developing thyroid disease were identified. RESULTS: Altogether, 117 women (12.3%) had hypothyroidism and 25 (2.6%) had low TSH. The prevalence of both OH and SCH was higher in the high-risk group than in the low-risk group, but 17.9% of women with hypothyroidism were classified at low-risk. A family history of thyroid disorders and TPO-Ab positivity increased the risk of SCH. Using non-pregnant reference range for TSH, 10.6% of women were misclassificated. CONCLUSIONS: The high prevalence of hypothyroidism observed in this study suggests that accurate thyroid screening with trimester specific reference ranges should be warranted, particularly in areas with mild to moderate iodine deficiencies.

Semen alterations and flow-citometry evaluation in patients with male accessory gland infections.

Male accessory gland infections (MAGI) represent a major cause of male infertility mainly through the secretory dysfunction of the prostate, seminal vesicles, and epididymis. This study was undertaken to evaluate conventional and nonconventional sperm parameters in these patients, therefore 150 patients with MAGI were selected. Each of them underwent to two sperm analyses and evaluation of DNA fragmentation mitochondrial membrane potential (MMP), phosphatidylserine (PS) externalization, chromatin compactness, by flow cytometry. Results showed that patients with MAGI had a lower sperm progressive motility (11.4 ± 5.0 vs 34.0 ± 7.0%), and percentage of normal forms (9.0 ± 3.7 vs 33.0 ± 13.0%) compared to controls, instead, these patients showed higher number of seminal white blood cells (2.2 ± 1.0 vs 0.4 ± 0.6 106/ml). Patients with MAGI showed a higher number of spermatozoa with DNA fragmentation compared to controls (8.2 ± 3.0 vs 1.0 ± 1.0%). In addition, they have also a higher percentage of spermatozoa with low MMP (28.0 ± 4.0 vs 2.0 ± 2.0%). Patients with MAGI, showed a higher percentage of spermatozoa with PS externalization (8.0 ± 4.0 vs 3.0 ± 3.0%), an early sign of apoptosis, and lower percentage of viable spermatozoa (64.5 ± 12.0 vs 88.0 ± 10.0%). An increased percentage of spermatozoa with abnormal chromatin compactness (18.0 ± 4.0 vs 5.0 ± 3.0%) was found in patients with MAGI. In conclusion, patients with MAGI show alterations of conventional and biofunctional sperm parameters compared to controls. These results suggest to consider the flow cytometry evaluation among the diagnostic tools for male infertility.

Ultrasonographic evaluation of patients with male accessory gland infection.

MAGI is the inflammation of the accessory male glands that notoriously exerts a negative influence on male fertility. The diagnosis is integrated by clinical, laboratory and ultrasound evaluation. In particular, the ultrasound criteria were published in 1999. The aim of this study was to analyse the sensitivity and specificity of additional diagnostic ultrasound criteria as well as of conventional criteria in a selected category of infertile patients with MAGI. To accomplish this, 100 patients with MAGI were evaluated by scrotal and transrectal ultrasound by three different operators. The control group consisted of 100 age-matched healthy men. Statistical analysis was performed to evaluate sensitivity, specificity, positive and negative predictive values, and ROC curve analysis. The results showed that additional ultrasound criteria had a diagnostic accuracy similar to traditional criteria. The threshold value of two criteria for each diagnostic category (traditional and additional criteria) obtained high values of sensitivity and specificity. In conclusion, this study confirms the validity of the ultrasound criteria of MAGI previously published; in addition, it suggests the clinical utility of other indicators in clinical practice with good diagnostic accuracy and finally it establishes a clear threshold ultrasonographic value for the diagnosis of MAGI.

High levels of lipid peroxidation in semen of diabetic patients.

The aim of this study was to evaluate the level of malondialdehyde (MDA) (one of the final products of lipid peroxidation and well-known marker of oxidative stress) in semen of infertile men with type 2 diabetes and to investigate its relationship with their glycaemic control. Forty infertile men with type 2 diabetes were evaluated. The mean ages were 36.5 ± 8.0. Men with diabetes were divided into two groups. Group A (n = 20) with glycated haemoglobin >10% and group B (n = 20) with glycated haemoglobin <7%. A single sample was examined according to the criteria of the World Health Organization (WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 1999, Cambridge University Press). MDA was assessed using the thiobarbituric acid method. MDA concentration in semen of group A patients (0.95 ± 0.35 nmol ml(-1)) was significantly higher than in group B patients (0.43 ± 0.13 nmol ml(-1)) (P value < 0.05) and had negative relationship with sperm density (r = -.717; P value < 0.05), total sperm count (r = -.625; P value < 0.05), progressive motility (r = -.489; P value < 0.05) and normal forms (r = -.545; P value < 0.05). Based on these results, it could be concluded that increase in lipid peroxidation in men with diabetes with poor metabolic control was associated with low sperm quality.

Testicular microlithiasis: analysis of prevalence and associated testicular cancer in central-eastern Sicilian andrological patients.

The aim of this retrospective study was to determine the prevalence of testicular microlithiasis (TM) in central-eastern Sicilian men and to evaluate the association between TM and testicular tumour or infertility. A total of 1056 Sicilian patients underwent scrotal US between 2005 and 2010. TM was found in 106 men with an overall prevalence of 10%; roughly about four times the median prevalence reported in the previous studies (0.6-18.1%). Forty men (3.8%) had a classic TM, whereas 66 (6.2%) had a limited TM. The prevalence of testicular tumour in this cohort was 2.4% (25/1056). At the moment when the testicular tumour was diagnosed, 15 patients (60%) had TM. There was a significant difference (P < 0.01) between the rate of malignancy in men with TM (15/106; 14.2%) and that in men without TM (10/950; 1.1%) with an odds ratio = 16. The prevalence of TM among infertile patients was 18.8%. These data may relate to an increased awareness towards scrotal US examination and/or to the use of more sensitive equipments. The elevated rate of testicular malignancy in men with TM suggests that this US feature may be regarded as a risk factor for testicular tumour.

High frequency of sexual dysfunction in patients with male accessory gland infections.

The aim of this study was to administer to two groups of patients with male accessory gland infection (MAGI), respectively, with positive or negative alterations in ultrasonography, a new diagnostic interview, arbitrarily named structured interview about MAGI (SI-MAGI), to evaluate differences between these groups, especially about the prevalence of sexual dysfunction. After ultrasound examinations, patients with MAGI were divided into two age-matched groups: positive and negative for ultrasound signs (US+ and US-). The SI-MAGI was structured into four domains (urinary tract symptoms, ejaculatory pain or discomfort, sexual dysfunction and quality-of-life impact) for a total of 30 questions with four possible answers. Infertile patients of MAGI US+ group showed scores significantly higher than MAGI US- and healthy control group in all domains (anovaP < 0.005) in relation to scores of patients with MAGI US+ and US-: in domain 1 = 16.0 ± 0.5 vs 9.0 ± 0.5, domain 2 = 21.0 ± 1.0 vs 11.0 ± 1.0, domain 3 = 23.0 ± 0.5 vs 12.0 ± 1.0 and, finally, in domain 4 = 13.0 ± 2.0 vs 6.0 ± 1.0. In particular, a higher frequency of sexual dysfunction (52%) was detected in MAGI US+ group when compared with MAGI US- (28%). This study introduces a specific set of questions, which combined with the sperm analysis, microbiological and ultrasound investigations, that altogether better express the clinical presentation of MAGI. Finally, MAGI US+ group showed a high percentage of sexual dysfunction.

Dysfunction of the endothelial-platelet pathway in patients with erectile dysfunction before and after daily treatment with tadalafil.

Platelet activation results from the exposure of receptors on the surface of the platelet to specific structures on the vessel wall. The aim of this study was to assess the serum concentrations of apoptotic endothelial microparticles (EMPa) and the vitronectin receptor (VR) in patients with erectile dysfunction (ED) before and after treatment with tadalafil. This study included 50 patients with arterial ED. EMPa and VR levels were measured by using flow cytometry. The CD45(neg)-CD144(pos)-annexin V(Pos) events were defined as EMPa, and the CD51(pos)-CD61(pos) events were defined as VR. Patients with ED were evaluated before and after daily treatment with 5 mg tadalafil for 90 days. Patients with arterial ED had serum concentrations of EMPa and VR significantly higher than the control group at baseline. After tadalafil, the serum concentrations of EMPa and VR of the patients with arterial ED were significantly lower than before treatment, but significantly higher than controls. Patients with arterial ED expressed higher levels of both EMPa that are associated with dysfunction of the arterial endothelial pathway and VR-expressing platelet-endothelial elements. Chronic treatment with tadalafil reduced endothelial apoptosis in these patients and also reduced VR expression.

Male accessory gland infection and sperm parameters (review).

Male accessory gland infection (MAGI) has been identified among those diagnostic categories which have a negative impact on the reproductive function and fertility in males (Rowe et al., World Health Organization Manual for the Standardised Investigation and Diagnosis of the Infertile Couple, Cambridge University Press, Cambridge, 1993). MAGI is a hypernym which groups the following different clinical categories: prostatitis, prostate-vesiculitis and prostate-vesiculo-epididymitis. Some of the characteristics they share are: common diseases, mainly have a chronic course, rarely cause obstruction of the seminal pathways, can have an unpredictable intracanicular spread to one or more sexual accessory glands of the reproductive tract, as well as to one or both sides. In this review, we show that all components involving the inflammatory response (from the agents which first trigger it to each component of the inflammatory response dynamic) can deteriorate conventional and/or non-conventional sperm parameters arising from one or more of the following mechanisms: altered secretory function of the epididymis, seminal vesicles, and prostate which reduce the antioxidant properties or scavenging role of the seminal plasma; deterioration of spermatogenesis; and (unilateral or bilateral) organic or functional sub-obstruction of the seminal tract.

Endothelial apoptosis decrease following tadalafil administration in patients with arterial ED does not last after its discontinuation.

Although it is well known that phosphodiesterase V inhibitors, used to treat patients with ED, can improve the endothelial dysfunction in organic vascular forms, few studies have explored the duration of their effect on the endothelium after discontinuation. Therefore, the purpose of this study was to evaluate the serum concentrations of apoptotic endothelial microparticles (EMPa), selected as a marker of endothelial damage, in patients with arterial ED at baseline, during tadalafil administration and 3 and 6 months after its discontinuation. In all, 50 patients with arterial ED were evaluated at baseline and 1 week after administration of tadalafil 5 mg once daily for 90 days. Clinical (International Index of Erectile Function-5 score), instrumental (dynamic penile echo color Doppler) and flow-cytometric (serum EMPa concentrations) analyses were performed before (T0) and 1 week (T1), 3 months (T2) and 6 months (T3) after tadalafil discontinuation. The events CD45(neg)/CD144(pos)/annexinV(pos) were defined as EMPa. At T0, patients with arterial ED had serum EMPa concentration significantly higher than 20 healthy men (controls). At T1, patients with arterial ED showed a serum EMPa concentration significantly lower than T0. The significant difference was maintained, though reduced, at T2 and completely lost at T3. In conclusion, the administration of tadalafil decreased serum EMPa concentration in patients with arterial ED. This positive effect on the endothelial dysfunction disappeared 6 months after tadalafil discontinuation.

Environmental car exhaust pollution damages human sperm chromatin and DNA.

OBJECTIVE: The adverse role of traffic pollutants on male fertility is well known. Aim of this study was to evaluate their effects on sperm chromatin/DNA integrity. METHODS: To accomplish this, 36 men working at motorway tollgates and 32 unexposed healthy men (controls) were enrolled. All of them were interviewed about their lifestyle. Hormone, semen samples, and environmental and biological markers of pollution were evaluated. Sperm chromatin and DNA integrity were evaluated by flow cytometry following propidium iodide staining and TUNEL assay, respectively. RESULTS: LH, FSH, and testosterone serum levels were within the normal range in tollgate workers. Sperm concentration, total sperm count, total and progressive motility, and normal forms were significantly lower in these men compared with controls. Motorway tollgate workers had a significantly higher percentage of spermatozoa with damaged chromatin and DNA fragmentation, a late sign of apoptosis, compared with controls. A significant direct correlation was found between spermatozoa with damaged chromatin or fragmented DNA and the length of occupational exposure, suggesting a time-dependent relationship. CONCLUSION: This study showed that car exhaust exposure has a genotoxic effect on human spermatozoa. This may be of relevant importance not only for the reproductive performance of the men exposed, but also for the offspring health.

Effects of anti-neoplastic treatment on sperm aneuploidy rate in patients with testicular tumor: a longitudinal study.

OBJECTIVE: The adjuvant radio/chemotherapy, usually employed after orchidectomy in patients with testicular tumors, allows a long-term survival with a consequent increased request for fertility. However, little is known about the effects of the anti-neoplastic treatment on sperm cytogenetic asset. Therefore, this prospective, longitudinal study was designed to evaluate the effects of radio- and/or chemotherapy on sperm chromosome. METHODS: Eleven patients with testicular tumor were enrolled and underwent sperm aneuploidy rate evaluation before and after 3, 6, 9, 12, 18, 24, and 36 months from radio- and/or chemo-therapy ending. A double and triple multicolor fluorescence in-situ hybridizations for chromosomes 8, 12, 18, X and Y were used to evaluate the sperm aneuploidy rate. To define normal sperm aneuploidy rate, 18 healthy, normozoospermic men were selected as controls. RESULTS: Before treatment, testicular tumor patients had a higher total sperm aneuploidy rate compared with normal men. Total sperm aneuploidy rate showed a slight, but statistically significant increase 6 months after anti-neoplastic treatment. This increase was mainly related to the high sperm aneuploidy rate found in 2 patients which remained elevated up to 12 months in both of them. CONCLUSION: These results showed that anti-neoplastic treatment caused only slight and transient sperm malsegregation events in patients with testicular tumor. However, since a subset of them had an elevated sperm aneuploidy rate for about 1 yr, we suggest to counsel them to refrain from fatherhood for this length of time.

Arterial erectile dysfunction: reliability of new markers of endothelial dysfunction.

OBJECTIVE: Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. Aim of this study was to evaluate a new immunophenotype of EPC and EMP in patients with arterial erectile dysfunction (AED) compared to psychogenic erectile dysfunction (PED). MATERIALS AND METHODS: One hundred patients (63.2±2.6 yr) with AED were enrolled in this study. Their EPC and EMP concentrations were compared to those of 40 patients with PED (64.2±2.7 yr). EPC (CD45(neg)/CD34(pos)/ CD144(pos)) and EMP (CD45(neg)/CD144(pos)/AnnexinV(pos)) blood concentrations were evaluated by flow cytometry. RESULTS: Patients with AED had significantly higher blood pressure, triglycerides, homeostasis model assessment index of insulin resistance, and cavernous artery acceleration time and intima-media thickness than PED; whereas international index of erectile function 5 score, HDL-cholesterol, and cavernous artery peak systolic velocity was lower than PED. Both EPC and EMP were significantly higher in patients with AED compared to patients with PED. CONCLUSIONS: Patients with AED showed worse metabolic parameters, cavernous artery parameters, and higher EPC and EMP compared to patients with PED. This suggests that AED is an expression of endothelial dysfunction and that EPC and EMP may be considered predictors of endothelial dysfunction in patients with AED.

Hypertrophic-congestive and fibro-sclerotic ultrasound variants of male accessory gland infection have different sperm output.

INTRODUCTION: Male accessory gland infection (MAGI) exerts a negative influence on male fertility which depends upon its extension. Indeed, we have shown that patients with MAGI involving prostate, seminal vesicles and epididymis have worse sperm parameters compared with patients with prostatitis alone or prostate-vesiculitis. Similarly, MAGI extending bilaterally is associated with a worse sperm output. The aims of this study were to evaluate the prevalence of two different additional ultrasound (US) findings (hypertrophic- congestive and a fibro-sclerotic US form) and to evaluate their semen quality. MATERIALS AND METHODS: One hundred infertile patients with MAGI, diagnosed according to the World Health Organization (WHO) 1993 criteria, were evaluated by scrotal and transrectal ultrasound scans. The control group consisted of 100 healthy, age-matched men. RESULTS: The ultrasound examination confirms two separate US variants of MAGI: a hypertrophic-congestive (prevalence of 56%) and a fibro-sclerotic form (prevalence of 29%). Patients with hypertrophic-congestive MAGI showed higher sperm concentration, motility and normal forms, but also higher sperm leukocytes concentration and seminal reactive oxygen species compared to patients with fibro-sclerotic MAGI. However, all these parameters were significantly worse than those observed in the control group. DISCUSSION: Infertile patients with hypertrophic-congestive MAGI have a better sperm quality compared with patients with fibrosclerotic MAGI; however, they showed higher oxidative stress in semen.

Does prolactin induce apoptosis? Evidences in a prostate cancer in vitro model.

BACKGROUND: Prolactin (PRL) regulates prostate growth and differentiation. Some studies have suggested that PRL has a pro-apoptotic effect on a myeloma cell line and in newt spermatogonia. The proliferative effect of PRL on prostate cancer cell lines is, however, a controversial area. AIM: On this account, we evaluated the effects of PRL on the prostate cancer cell lines LNCaP and PC3 apoptosis and proliferation. MATERIALS AND METHODS: LNCaP and PC3 cells were exposed to increasing concentrations of PRL for 24, 48, 72 and 96 hours. Staining with propidium iodide (PI) and TUNEL assay followed by flow cytometry were used to detect apoptosis. LNCaP and PC3 proliferation was assessed by optical microscopy counting. RESULTS: PRL induced a dose-dependent decrease of DNA content and an increase of DNA fragmentation in LNCaP after 96 hours of incubation. These effects were observed with physiological concentrations of PRL and were counteracted by a prolactin receptor antagonist. On the other hand, PRL did not have any effect on DNA content or fragmentation in PC3 cells. No effect of PRL on LNCaP and PC3 proliferation was found. CONCLUSIONS: This study indicates that PRL induces apoptosis in the androgen-responsive cell line LNCaP, whereas no effect was observed in the androgen-insensitive PC3 cell line. These findings suggest that androgen responsiveness may be required for PRL to be effective on prostatic cells.

Testosterone therapy improves the clinical response to conventional treatment for male patients with metabolic syndrome associated to late onset hypogonadism.

AIM: Recently, the clinic characterization of the gonadic male function has been put in tight correlation on the pathogenetic level with the main variables forming the condition of metabolic syndrome (MS); probably the serum testosterone (T) concentration in males is to be considered as an additional parameter completely related to the traditional clinical-metabolic findings. Currently the matter of the substitutive hormonal therapy with androgens is apparently influenced by some important unresolved aspects: 1) who really benefits from the T therapy? 2) are the actual dosage methods of T reliable? 3) which vascular and metabolic targets are to be monitored during the T therapy? METHODS: In an analytical longitudinal study, carried out 12 months long on 60 men (average age 58 years, range 54-63 years) affected by metabolic syndrome (MS) and combined hypogonadism late onset (LOH), authors have evaluated the clinical response (androgenic asset, non-invasive hospital monitoring of the arterial pressure, lipidic asset study, body composition and the biologic resistance to the insulinic action) after conventional medical therapy (insulin-sensibilizing and anti-hypertensive) and after substitutive hormonal therapy with testosterone (T) by transdermic way. A group of five patients with MS and LOH, not treated, was used as group of control. RESULTS: The group of patients treated with T showed a profile of clinical response better than the group of controls. CONCLUSIONS: In conclusion, the seric determination of T is useful to better characterize the dismetabolic patient at the moment of the first level active medical therapy planning on the controls of the main risk factors constituting MS, expressing a potential role of conditioning.

IL-6, TNFalfa, IL-10 in the seminal plasma of patients with bacterial male accessory gland infections after sequential therapy.

AIM: In previous studies the authors have demonstrated a worse spermatic outcome associated to overproduction of ROS in infertile patients with urogenital infections extended to more glands (prostato-vesciculitis, PV) compared to what observed in patients with prostatitis (P) (cat II according to the National Institutes of Health [NIH]). Among the reasons of an inadequate post-therapeutical response, the duration of each therapeutical phase could be the only bias of empirism entrusted only to the monitoring of obvious ''traditional'' end-points, resulting underrated for various reasons (costs, lacking methodological standardization, choice of the cytokines to be monitored). The evaluation of other therapeutical endpoints (cytokine dosage in the seminal plasma; analysis of ROS) is therefore all important. METHODS: In order to evaluate how to optimize the therapeutic response in infertile patients with P o PV chronic-bacterial, the authors wanted to monitor the pattern of the pro-oxidants cytokines TNFalfa, IL-6 in the seminal plasma (met. sandwich ELISA high sensitivity <0.039 pg/mL, R&D System Europe Ltd, UK) and of IL-10 (chosen as antioxidant cytokine) after sequential therapy (antibiotic - non-steroidal anti-inflammatory drugs antioxidant). RESULTS AND CONCLUSIONS: The modifications of the levels of TNFalfa, IL-6 ed IL-10 recorded in the present study during the sequential therapy for P or PV microbic offer some issues for reflection for interesting clinical-diagnostical implications: 1) possible revision of sequences and/or duration of the therapeutical phases in course of PV; and 2) the role to assign to the IL-10 (assumed as anti-inflammatory cytokine).

Incidence of extragenital vascular disease in patients with erectile dysfunction of arterial origin.

This research was carried out to evaluate the prevalence of carotid and/or lower limb artery abnormalities in patients with arterial erectile dysfunction (ED). To this end, patients with ED (Andrology Unit) or suspected peripheral atherosclerosis (Angiology Unit) underwent an independent and parallel echo-Duplex examination. The Andrology Unit examined 167 patients with ED of different etiologies: 52 of them had penile artery insufficiency and consequently their carotids and lower limb arteries had to be evaluated by means of echo-Doppler. In all, 36 out of the 46 patients with nonarterial organic ED and 22 out of the 69 patients with nonorganic ED underwent the same evaluation and served as controls. The Angiology Unit enrolled 457 ED patients who initially underwent echo-Doppler for suspected carotid and/or arterial leg atherosclerosis and subsequently dynamic echo-Doppler. Isolated penile artery insufficiency was found in 23.1 and 25% of the patients evaluated in the Angiology and Andrology Units, respectively. The remaining patients were shown to have ED associated with an atheroma or marked intima-media thickness of the carotid vessels and/or of leg arteries. The frequency of penile arterial insufficiency and of carotid and/or lower limb artery abnormalities was significantly higher (P < 0.01) compared to that found in patients with ED of nonarterial organic or psychogenic origin. Both Units found that the frequency of penile artery insufficiency and carotid or lower limb artery abnormalities was significantly higher than that of penile artery insufficiency alone or plus both carotid and lower limb artery abnormalities. This study showed that penile artery insufficiency is associated with carotid and/or lower limb artery ultrasound abnormalities in about 75% of the cases. Therefore, arterial ED may be regarded as a sign of a more generalized atherosclerosis.

Sperm aneuploidy in infertile men.

A recent line of research has shown that infertile male patients produce cytogenetically abnormal spermatozoa, despite a normal somatic karyotype, as a result of an altered intra-testicular environment that affects negatively the mechanisms controlling chromosome segregation during cell division. The rate of aneuploid spermatozoa production is significantly higher in patients with abnormal sperm parameters compared with those of normozoospermic subjects or infertile patients with normal sperm parameters. All chromosomes are subject to aneuploidy, although at a different rate; the heterochromosomes are more often altered than are the autosomes. A negative correlation has been reported to exist between aneuploidy and the main sperm parameters, suggesting that greater testicular damage is associated with a greater chance of chromosome malsegregation events. Abnormally-shaped spermatozoa are more likely to have chromosome abnormalities, particularly those with an enlarged head. More studies are necessary, however, to evaluate whether other types of sperm head abnormalities are also associated with an abnormal sperm chromosome complement. The possibility of retrieving testicular or epididymal spermatozoa in patients with azoospermia and using them in assisted reproduction techniques has prompted the evaluation of their chromosomal status. Studies have shown that testicular and epididymal spermatozoa have a greater rate of aneuploidy compared with that of ejaculated spermatozoa. Some authors have also shown that patients with non-obstructive azoospermia have a significantly higher sperm aneuploidy rate compared with that of patients with obstructive azoospermia. Sperm aneuploidy seems to have a negative impact on assisted reproduction technique outcome. Although it does not affect the fertilization rate, an elevated sperm aneuploidy rate is associated with a greater rate of pregnancy failure. Nevertheless, some patients with elevated sperm aneuploidy rate can still achieve a pregnancy, but with an increased risk of generating an aneuploid offspring. Thus, sperm aneuploidy evaluation is recommended in infertile patients with abnormal semen parameters, particularly if they undergo IVF programmes.

Corticotrophin-releasing hormone inhibits insulin-like growth factor-I release from primary cultures of rat granulosa cells.

Corticotrophin-releasing hormone (CRH), a neuropeptide which modulates gonadal function during stress, is expressed by several cell types of the rat ovary and is able to suppress oestrogen release from rat granulosa cells. The mechanism of this effect is, however, not known. Since insulin-like growth factor (IGF)-I is produced by rat granulosa cells and exerts a synergistic role with FSH on granulosa cell steroidogenesis, we hypothesised that CRH may suppress oestrogen release from granulosa cells by inhibiting IGF-I release and/or stimulating the release of its binding protein (IGFBP-3). To test this hypothesis, granulosa cells were obtained from immature female Sprague-Dawley rats primed with diethylstilboestrol, and hormone concentrations were measured in the conditioned medium by radioimmunoassay. CRH suppressed oestrogen and IGF-I release stimulated by FSH used at a concentration of 1 IU/l, whereas it did not have any statistically significant effect on oestrogen and IGF-I release in basal conditions or in response to 5 IU/l FSH. The suppressive effects of CRH on oestrogen and IGF-I release were antagonised by a selective CRH receptor antagonist. CRH had no effects on IGFBP-3 release. CRH did not have any effect on oestrogen release stimulated by increasing concentrations of IGF-I and its suppressive effect on FSH-stimulated oestrogen release was overcome by the addition of low doses of exogenous IGF-I. In conclusion, CRH suppressed the release of oestrogen and IGF-I, but not of IGFBP-3. Thus, the inhibitory effects of CRH on oestrogen release could be mediated, partly, by a suppression of the autocrine/paracrine action of IGF-I.

Spontaneous transmission from a father to his son of a Y chromosome microdeletion involving the deleted in azoospermia (DAZ) gene.

Microdeletions of the so-called azoospermia factor (AZF) locus of the Y chromosome long arm (Yq) have been recognized as an etiological factor of severe oligozoospermia or azoospermia. Because of this, patients affected are generally infertile unless assisted reproductive techniques are used. We report the case of an oligozoospermic patient (proband) who inherited an extensive Yq microdeletion from his father through a spontaneous pregnancy. Leukocyte DNA was extracted using a commercially available kit. A total of 22 pairs of sequence-tagged site (STSs) based primers, spanning the entire AZF region, were used for the screening. Both the proband and his father carried a Yq microdeletion of the most distal AZF subregion (AZFc) where the deleted in azoospermia (DAZ) gene is located. The proband's father was a sixty-nine-yr-old man who had 3 other children, 2 females and 1 male. This case adds further evidence that the deletion of the DAZ gene is associated with different phenotypic expressions, including normal fertility.