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Anaesthetic ejaculation.

Literature on the uncommon symptom of anaesthetic ejaculation and the relevant physiology is reviewed. Seven case vignettes describing the clinical pictures, background histories and common features of this problem are presented, along with some psychometric data. No physical causative factors could be elucidated. The main features shared in common by these men were problems in the recognition and expression of emotions, and a performance orientation. Treatment by sex-therapy procedures was ineffective.

Adult↗

Some clinical and psychometric characteristics of primary and secondary premature ejaculators.

Patients with premature ejaculation (PE) were subdivided into primary (PPE), individuals who had suffered from PE since the beginning of their sexual lives, and secondary (SPE), those who developed the condition after years of satisfactory sexual functioning. PPEs differed from SPEs on a number of clinical and psychometric variables. Clinically SPEs were significantly more likely to manifest a coexisting erectile disorder, reduction in sex drive, and a decrease in arousal during sexual stimulation than SPEs. They were significantly less likely to report high levels of anxiety during coitus. Psychometrically, on the Derogatis Sexual Functioning Inventory, PPEs were significantly more "impaired" than the SPEs as reflected by scores on the Symptoms and Satisfaction scales and the GSSI. They were significantly less impaired on measures of sex drive (e.g., Drive and Fantasy). On the Hamilton Anxiety Rating Scale (HRAS), the PPEs scored as significantly more anxious than the SPEs. The findings suggest that dichotomizing PE into PPE and SPE may be clinically useful, and may have etiologic treatment and prognostic implications.

Adult↗

Mechanism of ejection during ejaculation: identification of a urethrocavernosus reflex.

The ejaculatory mechanism involves 2 reflexes: the "glans-vasal," which seems to bring the semen to the posterior urethra (emission phase of ejaculation), and the "urethromuscular" which ejects it to the exterior (ejection phase). This study investigated the mechanism of bulbocavernosus muscle (BCM) contraction, once the seminal fluid reaches the bulbous urethra. The study included 14 healthy male volunteers (mean age 37 +/- 10.2 SD years). To test the response of the BCM to urethral distension, a 10F balloon-tipped catheter was introduced into the prostatic urethra and filled with saline in increments of 0.25 mL: a needle electrode recorded the response. The balloon was then withdrawn to lie in the membranous. bulbous, and pendulous urethra and the test was repeated at each site. The latency of the muscle response was calculated. The BCM response to each of the anesthetized bulbous urethra and anesthetized BCM was recorded. Distension of the prostatic, membraneous, or pendulous urethra effected no BCM EMG response. Bulbous urethral distension with 0.25 mL of saline also produced no muscle response, whereas distension with 0.5 mL and up to 1.5 mL caused increased EMG activity of the BCM. The muscle response augmented with the increase of the distending volume. The mean latency was 10 +/- 1.3 ms and showed no significant change (p > .05) with the different distending volumes. Neither the anesthetized bulbous urethra nor the anesthetized BCM responded to bulbous urethral distension. The BCM contraction upon distension of the bulbous urethra is probably reflex and mediated through the urethrocavernosus reflex. Small-volume distension did not effect BCM contraction. The latter presumably propels the semen from the posterior to the pendulous urethra. It is suggested that the urethrocavernosus reflex be included in current andrologic investigations for patients with ejaculatory disorders.

Adult↗

Treatment of premature ejaculation after traumatic brain injury.

Premature ejaculation (PE) is the most common male sexual disturbance occurring in the general community. Surveys of sexual dysfunction after traumatic brain injury (TBI) have identified that between 17-36% of males report a number of different post-injury ejaculatory problems, including PE. Whilst there are a number of studies that document effective treatment of PE in the general population, there have been no reports of treatment interventions for this problem amongst males with TBI. This paper reports on the assessment and successful treatment of PE in a young male with severe TBI. The treatment programme trialed combined pharmacotherapy (namely, the application of a topical anaesthetic), behavioural and educational approaches. The case report suggests that existing sex therapy techniques, albeit with modifications to compensate for motor sensory, cognitive and affect related injury sequelae, provide one option for the treatment of PE after TBI.

Behavior Therapy↗

The presence of abnormal spermatozoa in the ejaculate: did apoptosis fail?

With the successful use of Assisted Reproduction, in particular intracytoplasmic sperm injection (ICSI), to treat infertile couples we have become less discriminating with the quality of spermatozoa we use to treat our patients. Numerous studies have shown the presence of nuclear DNA strand breaks in human ejaculated spermatozoa. The reason why human spermatozoa, in particular from men with abnormal semen parameters, possess these abnormalities in their nuclear DNA is still not clear. Two processes that have been linked to the presence of nuclear DNA strand breaks in spermatozoa are anomalies in apoptosis during spermatogenesis or problems in the packaging of the chromatin during spermiogenesis. Understanding the mechanisms responsible for producing abnormal spermatozoa in the human will improve our knowledge about certain causes of male infertility. More importantly, the impact of such sperm, if selected to perform ICSI, needs to be better understood so that any detrimental paternal effects can be avoided.

Apoptosis↗

Timing of oocyte activation, pronucleus formation and cleavage in humans after intracytoplasmic sperm injection (ICSI) with testicular spermatozoa and after ICSI or in-vitro fertilization on sibling oocytes with ejaculated spermatozoa.

In the first study, we evaluated 101 oocytes [2, 4, 6, 8, 16, 18 and 20 h after intracytoplasmic sperm injection (ICSI)] that had been microinjected with testicular spermatozoa. Of the 70 normally fertilized oocytes (69%) 30 (43%) had two pronuclei by 6 h after ICSI. Fifty-one (73%) by 8 h, 69 (99%) by 16 h and four of them by 20 h cleaved to the 2-cell stage. In the second study, 95 cumulus-corona-oocyte complexes (CCOC) were divided into two groups. Forty-seven CCOC were inseminated by conventional in-vitro fertilization (IVF) and 40 metaphase-II oocytes by ICSI. Oocytes were evaluated at 2, 4, 6 (only after ICSI), 8, 10, 12, 18, 20, 22, 24, 26, 28 and 30 h after both ICSI and IVF. After IVF, 35 oocytes were fertilized normally (75%), four of which (11%) had two pronuclei by 8 h, 11 (31%) by 10 h, 27 (77%) by 12 h and 35 (100%) by 14 h. The first cleavages had occurred by 24 h after insemination (four oocytes, 11%). After ICSI, 34 oocytes were fertilized normally (79%), 13 of which (38%) had two pronuclei by 6 h, 27 (79%) by 8 h and 32 (94%) by 10 h. Three oocytes cleaved by 20 h after microinjection (9%) and 19 by 24 h (56%). Pronuclei developed asynchronously in six oocytes after ICSI (18%) as opposed to 16 oocytes after IVF (46%). The results of this study suggest that the timing of pronuclear formation is no different when a testicular spermatozoon is microinjected into the oocytes from when an ejaculated spermatozoon is injected. Secondly, pronuclear development and first cleavage generally take place 4 h sooner after ICSI than after IVF. On the other hand, a higher proportion of oocytes develop two pronuclei asynchronously after IVF than after ICSI.

Adult↗

The outcome of intracytoplasmic injection of fresh and cryopreserved ejaculated spermatozoa--a prospective randomized study.

BACKGROUND: The overall aim of this prospective, randomized study was to compare the reproductive potential of fresh and frozen-thawed ejaculated spermatozoa from oligoasthenoteratozoospermic patients in an intracytoplasmic sperm injection (ICSI) procedure. METHODS: All patients consenting to participate in this study had a sperm sample frozen prior to the start of a cycle. Patients were randomized using a random number table to undergo ICSI with either fresh (group A, n = 118) or frozen-thawed (group B, n = 122) spermatozoa. All prognostic variables were equally distributed among the two groups. RESULTS: The pregnancy rate per started cycle was 29.7% in group A and 38.5% in group B, P > 0.05. A significant difference was observed in the rate of ongoing pregnancies between group A (23.7%) and group B (35.2%), P < 0.05. CONCLUSION: From our data we can conclude that cryopreservation of spermatozoa from men with poor sperm quality does not negatively affect fertilization and pregnancy rates after ICSI. A larger study will be needed to investigate whether the use of cryopreserved spermatozoa can be helpful in selecting the most vital spermatozoa for ICSI.

Adult↗

Assessment of DNA integrity and morphology of ejaculated spermatozoa from fertile and infertile men before and after cryopreservation.

Cryopreservation of human spermatozoa is extensively used in artificial insemination and IVF programmes. Despite various advances in cryopreservation methodology, the recovery rate of functional post-thaw spermatozoa remains mediocre, with sperm motility being significantly decreased after freezing. This aim of this study was to investigate the effects of cryopreservation on both DNA integrity and morphology of spermatozoa from fertile and infertile men. Semen samples were obtained from 17 fertile and 40 infertile men. All samples were prepared by discontinuous Percoll density centrifugation (95.0:47.5). Samples were divided into aliquots to allow direct comparison of fresh and frozen spermatozoa from the same ejaculate. Aliquots for cryopreservation were mixed with a commercial cryoprotectant and frozen by static phase vapour cooling before plunging into liquid nitrogen. Thawing was carried out slowly at room temperature. Sperm DNA integrity was determined using a modified alkaline single cell gel electrophoresis (comet) assay and sperm morphology analysed using the Tygerberg criteria. DNA of semen and prepared spermatozoa from fertile men was found to be unaffected by cryopreservation. In marked contrast, spermatozoa from infertile men were significantly damaged by freeze-thawing. Cryopreservation had a detrimental effect on morphology of semen and prepared samples from fertile and infertile men.

Cryopreservation↗

May-Grünwald-Giemsa stain for detection of spermatogenic cells in the ejaculate: a simple predictive parameter for successful testicular sperm retrieval.

BACKGROUND: Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) have become standard treatments for patients with non-obstructive azoospermia. A diagnostic testicular biopsy for histopathological examination is not always predictive of TESE outcome. Moreover, it is not without potential complications. The aim of this study was to determine the value of various clinical and laboratory parameters, particularly identification of seminal spermatids using May-Grünwald-Giemsa (MGG) stain in predicting TESE results. METHODS: A total of 100 patients with non-obstructive azoospermia was subjected to clinical examination, serum FSH measurement, identification of seminal spermatids and spermatocytes using MGG staining and TESE with multiple testicular sampling. Spermatozoa were retrieved from 49% of patients. Results of TESE were compared with previous parameters in addition to histopathology. RESULTS: Testicular histopathology was, in general, an inaccurate parameter, and identification of testicular spermatids by histology predicted successful TESE in only 74% of cases. Testicular volume and serum FSH concentration also had poor predictive values. Round spermatids were identified in the ejaculate of 83.7% of TESE-positive cases, and in 22% of TESE-negative cases. CONCLUSIONS: The detection of round spermatids in semen by MGG staining provides the greatest predictive value for successful testicular sperm retrieval, and also has the advantages of simplicity, low cost and availability.

Adult↗

Diversity of the inhibitory effects on fertilization by anti-sperm antibodies bound to the surface of ejaculated human sperm.

BACKGROUND: The presence of anti-sperm antibodies (ASA) in males can reduce fecundity. However, it has been shown that there is a diversity of ASA bound to the sperm surface. This study was performed to investigate the inhibitory effects on fertilization by ASA in males. METHODS: ASA were detected using the direct-immunobead test (D-IBT) in 509 semen samples. In some cases, the direct-sperm immobilization test (D-SIT) was carried out. The fertilizing ability of infertile males with ASA was determined as follows; (i) an IVF fertilization rate of >/=50%, (ii) a hemizona index (HZI) of >/=50%, and (iii) pregnancy established without the use of ART. RESULTS: In total, 18 (3.54%) infertile males had ASA on the sperm surface. Except for one male with an absolute indication for ICSI because of severe asthenozoospermia and two males who dropped out of this study, fertilizing ability in 15 males could be determined. Four (26.7%) men did not satisfy the criteria. The existence of sperm immobilizing antibodies on the surface of ejaculated sperm had no impact on fertilization. In four (57.1%) of seven patients who had IB-bound sperm of >/=80%, fertilizing ability was inhibited, while none of the eight patients who had <80% IB-bound sperm had an inhibitory effect on fertilization. There was a significant difference between the two groups (P = 0.01). CONCLUSIONS: Some sperm-bound antibodies are related to the inhibitory effects on fertilization, indicating that a diversity of sperm-bound antibodies exists in males. This result might be one of the reasons for the controversy of the relationship between ASA and male immunological infertility. Based on the present study, a sperm-zona pellucida binding assay should be performed for appropriate decision making in infertile males with ASA.

Adult↗

Ejaculation failure on the day of oocyte retrieval for IVF: case report.

Unexpected ejaculation failure on the day of oocyte retrieval for IVF occurs once or twice a year in our Reproductive Medicine Unit, where approximately 500 oocyte retrievals are performed each year. Two clinical situations which occurred in 2001 are presented. In the first case, sperm were finally obtained by epididymal aspiration and resulted in the fertilization of five oocytes by ICSI. The transfer of two fresh embryos did not result in a pregnancy and the three supernumerary zygotes were cryopreserved. The male patient presented an anxio-depressive episode necessitating psychiatric hospitalization 1 week after the oocyte retrieval. In the second case, no sperm were obtained and the four oocytes were therefore lost. The couple went through a crisis in their relationship and tried another cycle of IVF 10 months later, after the preventive cryopreservation of a sperm sample. On the day of oocyte retrieval the patient was unable to produce a fresh sample but three zygotes were obtained through ICSI using the back-up cryopreserved sperm. Two embryos were transferred but no pregnancy ensued. The clinical decision-making processes for these two cases are described, as well as the measures employed to help prevent these unfortunate situations.

Adult↗

ICSI outcome in patients with transient azoospermia with initially motile or immotile sperm in the ejaculate.

BACKGROUND: In patients with transient azoospermia, few sperm may be found in the ejaculate. We investigated the outcome of ICSI in patients with transient azoospermia. METHODS: Records of patients with transient azoospermia referred during a 42 month period were reviewed. If only immotile sperm were found, the sample was incubated with 30% human serum albumin (HSA) before motility re-assessment. If still immotile, mechanical assessment of sperm viability was utilized. Study groups were: (A) motile sperm; (B) motility achieved by HSA; (C) no motility, but viability assessed by a mechanical technique; and (D) control group with sperm counts from 1 to 5 x 10(6)/ml. There were 57 couples (cycles) in the study group and 43 couples (cycles) in the control group. RESULTS: Age, days of stimulation and endometrial thickness were comparable among groups. In 29.8% of the cycles, only immotile sperm were found. Fertilization and cleavage rates were higher in groups A and D than in groups B and C. Clinical pregnancy rate/cycle and live birth rate/cycle were not different among groups. No congenital malformations were found in newborns. CONCLUSION: Fertilization and cleavage rates were lower in patients with initially immotile sperm compared with those with initially motile sperm and oligoasthenoteratozoospermia patients. Clinical pregnancy and viable pregnancy rates were not statistically different among groups, although when only immotile sperm were present both clinical pregnancy and live birth rate were lower in comparison with cycles with motile sperm.

Ejaculation↗

Oligozoospermia and heat-shock protein expression in ejaculated spermatozoa.

BACKGROUND: Heat-shock protein A2 (HspA2) is correlated with sperm maturity, function and fertility, and a dysfunctional expression of such a gene results in abnormal spermatogenesis. The purpose of this study was to compare HspA2 gene expression in spermatozoa from oligozoospermic men and normozoospermic controls. METHODS: Semen was obtained and analysed according to World Health Organization (World Health Organization, 1999) guidelines, morphology by Kruger's strict criteria. Seventeen patients with oligozoospermia and 21 fertile controls were studied. Total RNA was extracted from ejaculated and Percoll density-gradient-separated spermatozoa followed by semiquantitative RT-PCR analysis. The relative expression level of HspA2 was analysed according to the expression level of the housekeeping beta-actin gene. Serum hormonal profiles (FSH, LH and testosterone) and a peripheral karyotype were also performed. RESULTS: All patients possessed normal karyotype, and no significant hormonal differences were found between the two groups. The study group had significantly lower sperm concentration and normal morphology than the controls. Semiquantitative RT-PCR analysis of HspA2 showed significantly lower expression levels in the oligoteratozoospermic men when compared to controls (P=0.0021). CONCLUSIONS: The HspA2 gene was down-regulated in sperm from infertile men with idiopathic oligoteratozoospermia, suggesting that such anomalies of gene expression might be associated with pathogenesis in some subtypes of male infertility.

Actins↗

Outcome of ICSI with ejaculated spermatozoa in a series of men with distinct ultrastructural flagellar abnormalities.

BACKGROUND: Severe sperm motility impairment results in human infertility, which can be overcome by ICSI. Whether some particular, possibly genetic, flagellar abnormalities can influence embryonic development is a matter of debate. METHODS: Analysis of ultrastructural flagellar abnormalities and ICSI outcomes with ejaculated spermatozoa in a series of 21 infertile patients with asthenozoospermic or dyskinetic spermatozoa due to a primary and specific flagellar abnormality was carried out. RESULTS: Patients were sorted into six categories according to flagellar ultrastructural defects. Oocyte fertilization occurred in the 21 couples with a mean 2PN fertilization rate reaching 61.85%. No difference was observed in the kinetics of in vitro development or in the morphological quality of the embryos between the different types of flagellar abnormalities. Pregnancy occurred in 12 couples (57.1%) and delivery in nine couples (42.86%). Both the implantation rate and the clinical pregnancy rate per cycle were lower in type III abnormalities and in patients with an initial sperm motility less than 5%. CONCLUSIONS: The rate of ICSI success may be influenced by the type of flagellar abnormality. ICSI provides a suitable solution for patients with sperm flagellar defects but raises the question of the consequences of a specific (and primary flagellar) abnormality on oocyte fertilization, on embryo and fetal development as well as on live birth.

Adult↗

Towards a better understanding of RNA carriage by ejaculate spermatozoa.

Research on spermatozoal RNA has made considerable progress since the original reports on its presence appeared in the late 1950s and early 1960s. Through the use of stringent procedures aimed at eliminating contamination artefacts, we now appreciate that a complex cohort of mRNAs persists in the ejaculate cell but that 80S (cytoplasmic) ribosomal complexes are not present in sufficient quantities to support cytoplasmic mRNA translation. Despite this, under certain conditions, at least some cytoplasmic mRNAs can apparently be translated de novo, possibly on mitochondrial polysomes. The detection of mRNA translation by mature spermatozoa essentially supports the earliest research reports on spermatozoal gene expression although the suggested relationship with protein turnover and capacitation is wholly unexpected. We also examine some alternative explanations and roles for RNA carriage, including the RNAs passive retention as a consequence of nuclear shutdown and a more active role in chromatin repackaging, genomic imprinting, gene silencing and post-fertilization requirements of essential paternal RNAs. The recent report of an RNA-mediated epigenetic alteration to phenotype that is likely to be sperm derived is of particular interest in this regard. We finally show that regardless of the biological role(s) of spermatozoal RNA, its utility in infertility studies, particularly when coupled with modern techniques in gene-expression analysis (e.g. microarrays), is obvious. As a wholly non-invasive proxy for the testis, this RNA offers considerable potential as a marker for fertility status and the genetic and environmental influences that could make all the difference between a fertile and an infertile phenotype.

Animals↗

Human epididymal secreted protein CD52 on ejaculated spermatozoa: correlations with semen characteristics and the effect of its antibody.

CD52 is a glycosylphosphatidylinositol-anchored glycoprotein secreted by the epididymis where it is incorporated into sperm membranes. The antigen is common to spermatozoa and lymphocytes, and its role is not known. Quantitative analysis using immunostaining with the monoclonal antibody CAMPATH-1G and flow cytometry indicated positive signals from approximately 80% of viable, washed ejaculated spermatozoa. Staining intensity increased after capacitation overnight, and decreased after short incubation with high density lipoprotein. After incubation of Percoll-washed spermatozoa with CAMPATH-1G, motility was reduced from 83 to 74% after 5 min and from 73 to 52% after 3.5 h. Swimming velocities were reduced by approximately 30% and linearity by 15% in 5 min, but no further decreases were observed over 3.5 h. After 20 min incubation with the antibody, cell viability was decreased by 10 and 20% in freshly washed and capacitated spermatozoa respectively. Comparison of fertile and infertile patients revealed no difference in the percentages of immunostained spermatozoa or in staining intensity and there were no differences in sperm labelling between normozoospermia and teratozoospermia. Compared with normozoospermia, percentages of stained spermatozoa were lower by 20 and 27% in asthenozoospermia and oligozoospermia respectively, whereas staining intensity in asthenozoospermia was less than half that in oligozoospermia. The correlation of percentages of stained spermatozoa with percentages of motile cells suggests the involvement of epididymal CD52 in the maturation of sperm function.

Alemtuzumab↗

Changes of the major sperm maturation-associated epididymal protein HE5 (CD52) on human ejaculated spermatozoa during incubation.

HE5 (CD52) is a glycoprotein which is secreted by the epididymis and which becomes inserted onto maturing spermatozoa. We have previously shown that, in cynomolgus monkey spermatozoa, changes occur upon maturation rendering cryptic the epitope to the monoclonal antibody CAMPATH-1G; the recognition site is then re-exposed during incubation under capacitation conditions. The present study investigated human ejaculated spermatozoa during incubation under similar conditions, using monoclonal antibodies that recognize different epitopes of the HE5 molecule comprising parts of the N-glycan (2E5) or peptide segments, including (CAMPATH-1G) or excluding (097) the glycosylphosphatidylinositol (GPI) anchor, to reveal modifications of sperm surface HE5. Flow cytometric analysis showed equally high percentages (approximately 90%) of viable spermatozoa cross-reacting with the antibodies before and after 6 h incubation. However, during incubation, the staining intensity increased 57% with CAMPATH-1G, 31% with 097, but remained unchanged with 2E5. The lymphocyte CD52 antibody CF1D12 stained only approximately 10% of spermatozoa either before or after incubation. Western blotting of sperm protein extracts using lectins indicated an increase in the exposure of sialic acid residues of HE5 after incubation. These results suggest that during incubation in capacitating conditions, there is an opening up of the HE5 glycoprotein molecule, increasing accessibility of some sialic acid residues and of the core peptide, particularly the GPI anchor.

Antibodies, Monoclonal↗