Altered secretion of Sertoli cells hormones in 2-year-old prepubertal cryptorchid boys: a cross-sectional study.

In cryptorchid boys, failures in germ cell development have been clearly established. Some studies reported some abnormalities in Sertoli cells morphology but the results regarding their endocrine secretion remain controversial. To compare testicular hormone levels in young boys with and without cryptorchidism, we performed a cross-sectional hospital-based study. From surgery appointment records, we identified a case group of boys with unilateral or bilateral cryptorchidism and a control group undergoing dental care, minor osteoarticular or dermal surgery. Blood samples were withdrawn during the surgical procedure to perform testosterone, inhibin B and anti-müllerian hormone (AMH) immunoassays. We included 27 cryptorchid boys and 27 controls aged of 26.6 vs. 24.2 months, respectively (p = 0.172) far from the post-natal mini-puberty and the corresponding hormonal surges. Age-adjusted AMH and inhibin B levels were significantly lower in cryptorchid than in control boys (AMH: 87 ng/mL vs. 135 ng/mL; p = 0.009, inhibin B: 97 pg/mL vs. 133 pg/mL; p = 0.019, respectively). Moreover, AMH and inhibin B levels were significantly lower in the bilateral cryptorchid subgroup, being 50% lower than in the controls (p = 0.011 and 0.019, respectively) and while both hormones levels were independent in controls, they became strongly correlated in bilateral cryptorchid boys (R² = 0.75, p = 0.001). In addition, testosterone levels were still detectable in some boys, with significantly lower levels in cryptorchid group than in controls. Overall, 2-year-old cryptorchid patients presented a simultaneous and significant drop in AMH and inhibin B levels, suggesting a functional defect of Sertoli cells. This deficiency appeared more pronounced in bilateral cryptorchidism and thus, regarding the pivotal role of Sertoli cells in germ cell development, it may explain the compromised fertility found later in men born with such a malformation.

Ejaculation and sperm characteristics in men with cauda equina and conus medullaris syndromes.

STUDY DESIGN: Retrospective. OBJECTIVES: The objective of the study was to describe the type of ejaculation in patients with cauda equina (CE) and conus medullaris (CM) lesions, and to analyse sperm quality. SETTING: France. METHODS: One hundred sixty-six patients with CE and CM lesions were included. Diagnosis was based on clinical (no motor responses, sensation or sacral reflexes) and urodynamic assessments (no detrusor activity). Vibromassage (VM) was used to induce ejaculation according to the recommendations for patients with spinal cord injury. If ejaculation did not occur, oral midodrine was administered in progressive doses. Retrograde ejaculation was systematically sought. Sperm parameters were analysed according to World Health Organisation recommendations (2010). RESULTS: Eighty-nine patients were included. Eleven ejaculated on the first VM trial (four anterograde (AE), six retrograde (RE) and one antero-retrograde (ARE)). Five patients continued trials of VM alone, two of whom ejaculated following a mean 1.9 trials (one RE, one ARE). Twenty-six patients underwent trials of VM+ midodrine, 18 of whom ejaculated following a mean 4.4 trials with a mean dose of 22.5 g of midodrine (2 AE, 13 RE and 5 ARE). Fifty-three ejaculates from 26 patients were analysed. Sperm concentration was low in 90.6% of samples; total necrospermia was found in 65% and asthenospermia in 95% of samples. CONCLUSION: Ejaculation is difficult to induce using VM in patients with CE and CM lesions, and requires high doses of midodrine. Sperm counts were generally low, and asthenospermia and necrospermia were found in the majority of specimens. Cryopreservation of sperm should be systematic in case of medically assisted procreation.

Evidence of a new pattern of ejaculation in men with spinal cord injury: ejaculation dyssynergia and implications for fertility.

OBJECTIVES: To describe the presence of sperm in the prostatic urethra as a stand-alone ejaculation entity and to assess its characteristics. METHODS: Thirty-three patients with anejaculation during sexual stimulation were enroled. Penile vibratory stimulations were carried out following bladder catherization and instillation of a pink buffering medium (Ferticult). Two-step catheterisation was then performed: a catheter was inserted through the urethral sphincter into the prostatic urethra to aspirate its content, and then bladder catheterisation was performed to collect the Ferticult. The procedure was repeated in some patients after at least 1 week. The characteristics of the semen collected from each organ were analysed and compared. RESULTS: A total of 42 trials were obtained from 22 patients. Sperms were found in the prostatic urethra in 21 samples (50%) from 12 patients (11 with spinal cord injury, 1 with diabetes). The colour of all 21 prostatic urethra sperm samples differed from the Ferticult. Sperm motility was greater in 8 samples, sperm count was higher in 10 and pH was different in 10, compared with the bladder samples. The higher overall quality of the sperm allowed cryopreservation in 10 prostatic urethra samples compared with only 5 bladder samples. Four of the five patients who underwent repeated trials had a reproducible pattern of prostatic urethra ejaculation. CONCLUSION: The presence of sperm in the prostatic urethra most probably results from 'ejaculation dyssynergia', a lack of coordination between bladder neck and external sphincter. Sperm from the prostatic urethra should be systematically sought to improve the outcome of assisted reproduction.

Sperm freezing to address the risk of azoospermia on the day of ICSI.

STUDY QUESTION: In which cases is freezing of ejaculated sperm indicated before ICSI? SUMMARY ANSWER: Sperm freezing should be performed only when out of two analyses at least one total sperm count in the ejaculate is lower than 10(6). WHAT IS KNOWN ALREADY: Due to variations in individual sperm parameters, in cases of severe oligozoospermia there is a risk of absence of spermatozoa on the day of ICSI, leading to cancellation of the attempt. Sperm freezing can avoid this problem but little is known of the parameters governing the decision to freeze sperm or not. STUDY DESIGN, SIZE, DURATION: This retrospective study included 247 men who underwent sperm cryopreservation to prevent the risk of azoospermia on the day of ICSI, from 2000 to 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Receiver operating characteristic curve analysis was used to define the threshold value. The lowest total sperm count per ejaculate was studied as a predictive factor for the use of frozen sperm in a total of 593 ICSI attempts. Moreover, 2003 patients who had at least 4 semen analyses for andrological diagnosis have been studied to evaluate the reproducibility of sperm count. To evaluate the psychological impact of sperm freezing, a questionnaire was administered to 84 men who attended for sperm cryopreservation between June and December 2014. The cost of sperm freezing was analysed according to the French prices. MAIN RESULTS AND THE ROLE OF CHANCE: When at least one total sperm count was <10(5) the risk of azoospermia in at least one ICSI attempt was 52% (34/66) versus 3% (5/181) when all counts were ≥10(5) (P < 0.0001). However, the study of the reproducibility of pre-ICSI semen analyses has shown wide variations among ejaculates, and therefore sperm freezing is recommended when one analysis from at least two, showed a sperm count <10(6). Such a policy could allow a saving of about €70 000 by avoiding unnecessary sperm freezings. The psychological impact of sperm freezing was good since >70% of men had positive feelings about this technique. LIMITATIONS, REASONS FOR CAUTION: This was a fairly short-term study and preservation of future fertility was not assessed. It appeared impossible to find a threshold that would predict the risk of azoospermia with 100% accuracy. Therefore there is still a risk of absence of spermatozoa on the day of ICSI despite a good negative predictive value when no total sperm count was lower than 10(5). WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that sperm freezing should be proposed when total sperm count is lower than 10(6) to avoid cancellation of the ICSI attempt due to azoospermia.

Are oxybutynin and trospium efficacious in the treatment of detrusor overactivity in spinal cord injury patients?

OBJECTIVES: To evaluate the efficacy of anticholinergic agents in the treatment of neurogenic overactive bladder (NOAB) and neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients on clean intermittent catheterisation (CIC). METHODS: Chronic suprasacral SCI patients on CIC presenting with at least one urinary leakage a day were included. Urodynamics and voiding diaries were performed at baseline and 1 month follow-up. In case of NDO at baseline, an anticholinergic drug was prescribed. RESULTS: The 231 SCI patients presented with one to five urinary leakages per day (mean 2.1). Urodynamics showed NDO in all patients. A new anticholinergic treatment was started in all, either in monotherapy (134 patients) or in association with the existing anticholinergic drug (oxybutynin+trospium bitherapy, 97 patients). The mean maximum bladder capacity significantly increased from 225 to 441 ml, and the mean involuntary detrusor contractions (IDC) significantly decreased from 67 to 41 cm H2O. Only 75 SCI patients (32%) were fully continent. However, 25 out of these 75 patients showed persistent NDO, with amplitudes of IDC above 40 cm H2O in 12 patients. Incontinence was still found in 156 SCI patients (67%), with an average of 1,2 leakages a day. In 100 patients, amplitudes of IDC remained above 40 cm H2O. There was no statistical difference between patients on anticholinergic monotherapy or bitherapy at follow-up. CONCLUSION: Anticholinergic treatment is not always satisfactory in terms of control of NDO and rarely allows full continence. Urodynamic follow-up is mandatory in all patients, even in those showing clinical continence.

[Evaluation of the management of erectile and ejaculatory dysfunction in a series of 90 patients with spinal cord injuries]. / Évaluation du traitement des dysfonctions érectiles et éjaculatoires dans une série de 90 blessés médullaires.

OBJECTIVE: To evaluate the erectile dysfunction and ejaculatory on patients injured in conus medullaris (CMI) and the efficacy of treatment. METHODS: Ninety patients with injured conus medullaris underwent a retrospective and monocentric study. They have all an assessment of erectile dysfunction and ejaculatory by the International Index of Erectile Function (IIEF-15) and a clinic scenario. We evaluated the erection by a clinical scoring scale (Shrameck). Seventy-seven out of 90 (85.55%) had therapeutic tests to restore erection: prostaglandin (PGE1), phosphodiesterase type 5 inhibitors (PDE5) and Papaverine. Seventy-four out of 90 (82.22%) underwent a penile stimulation tests (VM) more or less associated with Midodrine(®) (alpha mimetic) to cause ejaculation with a systematic search of spermatozoa in urine. Data were entered and analyzed using Microsoft Office Excel. RESULTS: Ninety patients with a complete lesion of the sacral metameres (S2S3S4) were included. They were responding to PGE1, PDE5, respectively 81.63% and 30.76%. The association VM/Midodrine(®) improves ejaculation in 52.63% of cases. Orgasm is absent in all our CMI. CONCLUSION: In this series of BCM patients, we observed a good efficacy of PGE1 and PDE 5 on erection. We also observed positive results of vibromassage and alpha-agonists on ejaculation.

Thermal asymmetry of the human scrotum.

BACKGROUND: Scrotal temperatures in men have been reported to be either similar on both sides or higher on the left than the right scrotum. We aimed to clarify this discrepancy from new data. METHODS: Retrospective analyses of scrotal temperatures in men aged 20-52 years measured every 2 min with probes connected to a data collector in three experiments. In Experiment I, eight men have been submitted to four successive body positions for 15 min each, first naked then clothed. Experiment II involved 11 postal employees working in a standing position for 90 min continuously. Experiment III involved 11 bus drivers and a 90 min period of continuous driving. Outcome parameters were left and right scrotal temperatures. RESULTS: In Experiment I, mean values and kinetics of scrotal temperature differed significantly in the naked and clothed state. In all three experiments, left scrotal temperature in the clothed state was higher than right scrotal temperature in terms of mean values and temperature kinetics. CONCLUSIONS: Lack of thermal symmetry was seen in the right and left scrotum, whether naked or clothed, and this applied regardless of position or activity when clothed. This thermal difference between right and left scrotum could contribute to the asymmetry in the male external genital organs.

Geographic variations in probability of pregnancy in four cities of France.

BACKGROUND: Several studies have described geographic variations in human fecundability, but this phenomenon has almost exclusively been studied at an international level rather than within a given country. Our aim was to describe geographic variations in fecundability, the monthly probability of pregnancy, between four cities of France. METHODS: We conducted a cross-sectional study in four French maternity units from Toulouse, Rennes, Lyons and Paris, among partners of pregnant women. Women were asked about the time to pregnancy (TTP) of their current pregnancy. TTP was analysed with a discrete Cox model allowing to estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for 894 couples. There was no strong evidence of heterogeneity in fecundability between the four compared cities (p=0.05 without adjustment and p=0.25 after adjustment for behavioural and medical factors). The highest fecundability was observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95% CI: 1.01-1.63). Differences in fecundability were smaller between the other cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in Rennes compared to Toulouse. Possible explanations for this finding are discussed. We note that the finding is consistent with previous observations indicating a higher sperm concentration among semen donors in Rennes than in Toulouse.

Selection bias in semen studies due to self-selection of volunteers.

BACKGROUND: Reports of a secular decrease in semen quality remain controversial, particularly due to the possibility of selection bias. We aimed to describe the potential bias due to self-selection of volunteers in semen studies involving fecund men. METHODS: Using data from the French multicentre study REPRHOM, we compared the characteristics of the partners of pregnant women for three levels of participation: completion of a refusal questionnaire (n = 698), agreement to complete the study questionnaires only (n = 676) and agreement to complete the study questionnaires and give a semen sample (n = 331, 13% of the subjects approached). RESULTS: Poorly educated men refused more often to participate than highly educated men. Semen providers were more likely to have experienced unfavourable pregnancy outcomes (odds ratio 1.68, 95% confidence interval 1.14-2.49) compared with participants completing the questionnaires only. Time to pregnancy was similar for all participants. CONCLUSIONS: This study demonstrates the existence of selection bias in semen studies associated with fertility and socio-demographic characteristics of men. The results of semen analysis for this population sample cannot be extrapolated to the whole population from which the volunteers originate. More information is required on who participates, and participation rates should be reported in semen studies to make it possible to interpret the results correctly.

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin.

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.

Cytological detection of spermatozoa: comparison of three staining methods.

Sperm detection can be an important factor in confirming sexual assault in cases of rape. This paper compares three of the most commonly used staining methods cited in the scientific literature: Christmas tree. hematoxylin-eosin, and alkaline fuchsin. The population studied was composed of 174 consenting women seen at the Male Infertility Center in Toulouse. France. The date of their last sexual intercourse was accurately known. Alkaline fuchsin did not seem effective in detecting spermatozoa in vaginal samples. Compared with hematoxylin-eosin, Christmas tree stain appeared to be the most useful test in the first 72 h. Two external factors were associated with decreased detection of spermatozoa: time since in tercourse and sperm volume.

Congenital bilateral absence of the vas deferens: clinical characteristics, biological parameters, cystic fibrosis transmembrane conductance regulator gene mutations, and implications for genetic counseling.

OBJECTIVE: To evaluate relationships between the phenotypic and genotypic characteristics of patients with congenital bilateral absence of the vas deferens (CBAVD). DESIGN: Retrospective study. SETTING: A university hospital urology-andrology department. PATIENT(S): Forty-one men with CBAVD. INTERVENTION(S): CBAVD was diagnosed during surgical and/or ultrasound exploration of the vasa deferentia (VD) (n = 39), or on the basis of impalpable scrotal VD (n = 2). MAIN OUTCOME MEASURE(S): History, clinical and seminal characteristics, and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations including IVS-8 polyT analysis. RESULT(S): A palpable scrotal vas deferens was present as a fibrous cord or nonpermeable duct in 13% of patients undergoing surgical exploration. Seminal vesicles were bilaterally absent in 28% of patients. No CFTR gene mutation or 5T allele was detected in 24.5% of the patients. Two CBAVD patients with renal agenesis carried a CFTR gene mutation (DeltaF508/5T-9T and R117G/7T-9T). CBAVD patients who have both a semen volume of < or =1.0 mL and a semen pH of < 7.0 have a significantly higher risk of severe CFTR gene mutation (OR = 9.12 [95% CI = 1.81-49.50]). CONCLUSION(S): A palpable scrotal vas deferens was found in 13% of CBAVD patients. Semen volume of < or =1.0 mL and semen pH of < 7.0 in CBAVD patients were associated with a higher risk of severe CFTR gene mutations. Patients with CBAVD and renal agenesis should be screened for CFTR gene mutations before assisted reproductive techniques are used.

Increase in scrotal temperature in car drivers.

Several recent studies have reported a gradual decline in sperm production in men. Endocrine disrupters as well as lifestyle have been suggested as risk factors. One lifestyle factor that may affect human fertility is driving a vehicle for a prolonged period. Several authors have suggested that driving position may increase the scrotal temperature. In order to validate this hypothesis we conducted continuous monitoring of scrotal temperature in real conditions, i.e. in men driving a car for a prolonged period. Nine volunteer men were asked to walk outside for 40 min and then to drive a car for 160 min. Scrotal temperatures were measured from thermocouples and values recorded every 2 min on a portable data recorder. Scrotal temperature increased significantly (P < 0.0001) in driving posture after 2 h of driving, reaching a value 1.7-2.2 degrees C higher than that recorded while walking. This link between driving position and increased scrotal temperature indicates a potential exposure of male reproductive function to lifestyle factors.

Occupational heat exposure and male fertility: a review.

In humans, as in most mammals, spermatogenesis is temperature dependent. This temperature dependence has been clearly demonstrated by several experimental studies showing that artificial increases in scrotum or testicle temperature in fertile men reduce both sperm output and quality. Our knowledge of the effects of occupational heat exposure on male fertility comes mostly from a small number of epidemiological studies. We conducted an extensive review of these published reports, focusing on methodology and design (retrospective or prospective; reference group; number of subjects) and principal results (using several indicators such as the time taken to obtain a pregnancy or sperm characteristics). We concluded that occupational heat exposure is a significant risk factor for male infertility, affecting sperm morphology and resulting in delayed conception. The limits and biases involved in this type of research are also discussed.

Clinical characteristics and light and transmission electron microscopic sperm defects of infertile men with persistent unexplained asthenozoospermia.

OBJECTIVE: To determine, with the use of transmission electron microscopy (TEM), the proportion of patients with permanent unexplained asthenozoospermia (<30% motility) who have an abnormality of sperm axonemal and periaxonemal structures. DESIGN: Retrospective study. SETTING: A university-affiliated public hospital. PATIENT(S): Sixty-one infertile men whose semen was submitted to TEM analysis because of persistent unexplained asthenozoospermia. MAIN OUTCOME MEASURE(S): The results of quantitative TEM analysis of the tails of the spermatozoa. INTERVENTION(S): None. RESULT(S): Based on a comparison with the axonemal anomalies observed in nine fertile control patients, the infertile population was divided into three groups: group I, with no detectable axonemal defects (26.2%); group II, with axonemal anomalies in either the midpiece or the principal piece (29.5%); and group III, with axonemal anomalies in both the midpiece and the principal piece (44.3%). However, defects in the mitochondrial sheath, fibrous sheath, and sperm head (acrosomic and postacrosomic cap) were observed in at least 50%, 30%, and 50%, respectively, of the patients in each group. The proportion of dense fiber anomalies of the midpiece increased significantly from group I to group III. No differences were observed between the three groups in sperm characteristics, anamnesis information, or clinical data. CONCLUSION(S): In patients with persistent unexplained asthenozoospermia, the frequent association of periaxonemal anomalies with axonemal deficiencies strongly suggests that axonemal deficiencies are not the unique cause of decreased motility.

Quantification by magnetic resonance spectroscopy of metabolites in seminal plasma able to differentiate different forms of azoospermia.

The aim was to determine whether proton magnetic resonance spectroscopy (1H-MRS) of metabolites such as glycerophosphorylcholine (GPC), choline, citrate and lactate in human seminal plasma can be used to differentiate (i) different azoospermic patients and (ii) different forms of spermatogenic failure including those who had undergone radiation therapy or chemotherapy. Semen samples were provided by men with obstructive azoospermia and spermatogenic failure who had serum follicle stimulating hormone (FSH) values within the normal range and either more or less than normal. Four prominent constituents of seminal plasma were identified by 1H-MRS: GPC, choline, citrate and lactate. The peak area ratios of choline/citrate as well as choline/lactate were significantly different (P < 0.01) between groups with spermatogenic failure and obstructive azoospermia. When the serum FSH values were normal in men with spermatogenic failure and obstructive azoospermia, a significant difference was found in the GPC/choline ratio (P < 0.001). When the FSH values were normal, the GPC/choline ratio appeared to be a very important parameter able to differentiate not only between cases of spermatogenic failure and obstructive azoospermia but also between different forms of spermatogenic failure. These results demonstrate the potential use of 1H-MRS on human seminal plasma in a new approach in the management of male infertility.