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Outcomes of multifetal pregnancy reduction in multiple pregnancies achieved by intracytoplasmic sperm injection using ejaculated, testicular, or epididymal sperm.

OBJECTIVE: To report the pregnancy outcome after transabdominal multifetal pregnancy reduction in multiple pregnancies achieved by intracytoplasmic sperm injection. METHODS: One twin and 13 triplet pregnancies obtained by intracytoplasmic sperm injection underwent pregnancy reduction. Pregnancies were achieved with ejaculated sperm in 8, testicular sperm in 3, and epididymal sperm in 2 of these cases. All triplet pregnancies were reduced to twins at 10-12 weeks' gestation by transabdominal potassium chloride injection. A twin pregnancy with spina bifida affecting 1 fetus was reduced to singleton at 18 weeks of pregnancy. RESULTS: There was no failed procedure and no pregnancy loss within the first 4 weeks after the procedure. A complete miscarriage (7.1%) developed in 1 case at 17 weeks' gestation which was due most probably to the incompetent cervix. In utero fetal death occurred in 1 fetus of another reduced pregnancy. Three of the reduced pregnancies delivered at term, after 37 completed weeks, four premature deliveries occurred between 31 and 35 gestational weeks, and four pregnancies were ongoing beyond 25 weeks' gestation. A total of 16 fetuses, from seven twin and two singleton pregnancies, were delivered without perinatal mortality. CONCLUSIONS: Although the sample size was small, our experience indicates that the reduction of triplets obtained by sophisticated infertility treatments such as intracytoplasmic sperm injection using testicular or epididymal sperm seems to be a safe method and can be effectively used.

Abortion, Spontaneous↗

Semen parameters in Macaca mulatta: ejaculates from random and selected monkeys.

Semen samples were collected by rectal probe electroejaculation techniques from groups of adult male rhesus monkeys. Mean values for 249 ejaculates from 100 monkeys were a sperm concentration of 419.43 x 10(6)/cm3 with 53.9% of the sperm showing progressive movement. Sperm concentration showed a positive rank correlation coefficient with sperm motility. Significant motility and concentration differences were found among groups. Seasonal differences were noted but were not significant. The study provides data that will aid investigators who are screening animals for studies involving reproductive potential.

Animals↗

Differential diagnosis of testicular mass by cytological examination of seminal fluid collected by ejaculation or prostatic massage.

The cytological examination of the seminal fluid of 3 patients with painless testicular masses was performed using an ordinary conventional technique. Neoplastic cells appeared in the ejaculate or fluid from prostatic massage of all patients. The final pathologies were seminoma, choriocarcinoma and mixed teratocarcinoma. Malignant cells were no longer found in the seminal fluid after orchiectomy. This sample, noninvasive technique plus further flow cytometric study of cellular DNA contents is a great help in the preoperative differential diagnosis of testicular masses.

Adult↗

Paroxetine treatment of premature ejaculation: a double-blind, randomized, placebo-controlled study.

Seventeen male outpatients with premature ejaculation were randomly assigned to treatment with paroxetine (N = 8) or placebo (N = 9). After a first week dose of 20 mg/day, the paroxetine regimen was increased to 40 mg/day for 5 weeks. Patients and their female partners were interviewed separately. Patients treated with paroxetine had significantly greater clinical improvement than the patients given placebo.

Adult↗

Single- and multiple-dose pharmacokinetics of dapoxetine hydrochloride, a novel agent for the treatment of premature ejaculation.

Dapoxetine is a serotonin transporter inhibitor currently in development for the treatment of premature ejaculation. This randomized, 2-sequence, 2-treatment crossover study assessed the single- and multiple-dose pharmacokinetics of dapoxetine following once-daily administration of dapoxetine 30 mg and 60 mg to healthy male volunteers. Dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations reached approximately 1 hour after dosing; plasma concentrations after single doses of dapoxetine decreased rapidly to approximately 5% of peak concentrations by 24 hours. Elimination was biphasic, with an initial half-life of approximately 1.4 hours and a terminal half-life of approximately 20 hours. Dapoxetine showed time-invariant pharmacokinetics and dose proportionality between doses, and its pharmacokinetics was unaffected by multiple dosing. The pharmacokinetics of dapoxetine metabolites, desmethyldapoxetine and dapoxetine-N-oxide, was similarly unaffected by multiple dosing. There were no serious adverse events; the most commonly reported adverse events were diarrhea, dizziness, and nausea.

Administration, Oral↗

Pharmacokinetics of dapoxetine, a new treatment for premature ejaculation: Impact of age and effects of a high-fat meal.

Dapoxetine is being developed as a treatment for premature ejaculation and has demonstrated rapid absorption and elimination in previous pharmacokinetic studies. Two open-label studies were conducted in healthy men: a parallel-group pharmacokinetic and safety study in young and elderly men and a randomized crossover food-effect study. Maximal plasma dapoxetine concentrations (C(max)) were similar in young and elderly men (338 and 310 ng/mL, respectively), as were the corresponding area under the plasma concentration versus time curve (AUC) values (2040 and 2280 ng x h/mL, respectively). When coadministered with food, C(max) was reduced by 11% (398 vs 443 ng/mL in the fed and fasted states, respectively), and the peak was delayed by approximately 30 minutes, indicating that food slowed the rate of absorption; however, systemic exposure to dapoxetine (ie, AUC) was not affected by food consumption. Thus, age or consumption of a high-fat meal has only a modest impact on dapoxetine pharmacokinetics in healthy men.

Adolescent↗

The effect of streptozotocin-induced diabetes on the rat seminal vesicle: A possible pathophysiological basis for disorders of ejaculation.

In the streptozotocin (STZ)-diabetic rat major increases in noradrenaline concentration and content of the seminal vesicles were evident as early as 7 weeks following induction of hyperglycemia and returned toward normal after 34 weeks of hyperglycemia. There were significant reductions in the concentration and content of dopamine at 19-42 weeks of diabetes, and small occasionally significant reductions in the content of serotonin and adrenaline, particularly around 19-26 weeks after STZ treatment. The uptake of tritiated noradrenaline in the diabetics was increased at 12 weeks compared to the controls, and decreased to control levels with increasing age. Release of tritiated noradrenline was increased in response to electrical field stimulation and high potassium solutions, and raising calcium concentration caused increased release at rest and during electrical stimulation. Immunohistochemical demonstration of tyrosine hydroxylase was increased during the period when the noradrenaline concentration and content were elevated. It is concluded that there are significant changes in the sympathetic innervation of the seminal vesicle during the course of STZ diabetes, and that alterations in the reuptake, release, and synthesis of the neurotransmitter noradrenaline may contribute to changes in the concentration of the amine in the tissue. It is possible that the changes observed are related to the remodeling and regrowth of sympathetic nerve endings damaged in the early stages of hyperglycemia. These changes may also contribute to disorders of ejaculation in diabetes.

Animals↗

Autocrine regulation of insulin secretion in human ejaculated spermatozoa.

A striking feature of insulin expression is its almost complete restriction to beta-cells of the pancreatic islet in normal mammals. Here we show that insulin is expressed in and secreted from human ejaculated spermatozoa. Both insulin transcript and protein were detected. In addition, the large differences in insulin secretion, assessed by RIA, between noncapacitated and capacitated sperm suggest a role for insulin in capacitation. Insulin had an oscillatory secretory pattern involving glucose dose-dependent increases and significant decreases during the blockage of an insulin autocrine effect. It appears that the effect of glucose on the fertilizing ability of sperm is mediated by glucose metabolism through the pentose phosphate pathway. Then we evaluated the autocrine effect of sperm insulin on glucose metabolism by studying the activity of glucose-6-phosphate dehydrogenase, the key rate-limiting enzyme in the pentose phosphate pathway. The simultaneous decrease in both insulin release and glucose-6-phosphate dehydrogenase activity induced by blocking the autocrine insulin effect with three different procedures (blockage of insulin release by nifedipine, immune neutralization of the released insulin by antiinsulin serum, and blockage of an insulin intracellular effector such as phosphotidylinositol 3-kinase by wortmannin) strongly suggests a physiological role of sperm insulin on these two events. Insulin secretion by spermatozoa may provide an autocrine regulation of glucose metabolism based on their energetic needs independent of systemic insulin. In conclusion, these data open a new area of study in male reproduction.

Autocrine Communication↗

Leptin secretion by human ejaculated spermatozoa.

INTRODUCTION: Leptin action is a dynamic area of investigation that continues to broaden beyond the basic lipostatic model originally envisaged. Here, we show that leptin is expressed in and secreted from human ejaculated spermatozoa. METHODS: By RT-PCR, Western blot, and immunofluorescence techniques, we have demonstrated that human sperm express leptin. RIA method evidenced leptin secretion. Phosphatidyl-inositol-kinase-3 (PI3K)/Akt pathway was examined by PI3K activity assay and Western blot. Leptin and insulin regulation of glycogen synthesis was evaluated by glycogen synthase activity (GSA). RESULTS: The large differences of leptin secretion between uncapacitated and capacitated sperm suggest a functional role for leptin in capacitation. Indeed, in uncapacitated sperm, leptin enhances both cholesterol efflux and protein tyrosine phosphorylation. In uncapacitated sperm, both insulin and leptin increased PI3K activity, Akt S473, and glycogen synthase kinase-3 S9 phosphorylation. Interestingly, during capacitation, concomitantly to the massive release of both hormones, we observed a strong reduction in the phosphorylation of glycogen synthase kinase-3 S9, kinase downstream of Akt that regulates the glycogen synthase. Our results from GSA showed that the enzymatic activity was significantly higher in uncapacitated than in capacitated sperm. Particularly, in uncapacitated sperm, GSA appeared to depend on the hormones concentration, because the enzymatic activity was stimulated at low doses, whereas it was inhibited at high doses. Moreover, both leptin and insulin regulate in autocrine fashion sperm glycogen synthesis. CONCLUSION: Leptin secretion by sperm suggests that the male gamete may be able to modulate its metabolism independently by systemic leptin. These data open new considerations about leptin significance in male fertility.

Blotting, Southern↗

Human ejaculated spermatozoa contain active P450 aromatase.

The generation of cytochrome P450 aromatase (P450arom) and estrogen receptor (ER) knockout mice has raised new interest in the physiological role of estrogens in male reproduction. Testicular expression of P450arom, the enzyme that converts androgens into estrogens, has been shown in both somatic and germ cell types in several species, whereas in humans, testicular expression is confined to the somatic cells. The aim of this study was to determine whether P450arom is present in human ejaculated spermatozoa. Using RT-PCR and specific primers, we amplified the highly conserved helical, aromatic, and heme-binding sequences of the conventional human P450arom from RNA isolated from human spermatozoa. Employing a rabbit polyclonal antiserum directed against human placental P450arom, immunoblotting analysis demonstrated aromatase protein expression, which was localized primarily to the tail and midpiece of spermatozoa. Measurement of enzymatic activity using a sensitive (3)H(2)O aromatase assay revealed that activity was enhanced by the 2'-O-dibutyryl cAMP and completely inhibited in the presence of the specific aromatase inhibitor, letrozole. These results represent the first demonstration that human spermatozoa are a potential site of estrogen biosynthesis. The physiological relevance of estrogen synthesis in spermatozoa remains to be elucidated and opens a new area of investigation in male fertility.

Aromatase↗

Behaviour of ejaculated spermatozoa from bull, boar and ram during thin-layer countercurrent partition in aqueous two-phase systems.

Ejaculated spermatozoa from bulls, boars and rams were subjected to thin-layer countercurrent partition in aqueous two-phase systems composed of dextran T500 and polyethylene glycol 6000 (PEG) in sucrose-based Hepes-buffered media. In the basal system, the great majority of spermatozoa tended to partition with the dextran-rich bottom phase; however, by including very low levels of phosphate, they could be made to partition increasingly with the PEG-rich top phase (complete at 10 mM phosphate). A procedure was developed for carrying out four separations simultaneously under identical conditions, whereby it could be shown that distribution varied with the number of spermatozoa in the sample. In the case of bull, the effect of cell number could be reduced considerably by inclusion of small quantities of seminal plasma in the phase system, but no such effect was found for ram or boar. Considerable variation in distribution pattern was seen between samples, which did not appear to be due to technical inconsistency. Livability in the phase systems was also variable, and we believe that PEG may exert a detergent-like effect on the sperm surface that is exacerbated in highly defined media free of protective proteins.

Animals↗

Recommendations for the management of retarded ejaculation: BASHH Special Interest Group for Sexual Dysfunction.

We present the British Association of Sexual Health and HIV (BASHH) special interest group in sexual dysfunction recommendations for the management of retarded ejaculation. The recommendations outline the physiology, prevalence, definitions, aetiological factors and patient assessment for this sexual problem. We suggest treatment strategies, recommendations for management and an auditable outcome.

Adolescent↗

Recommendations for the management of premature ejaculation: BASHH Special Interest Group for Sexual Dysfunction.

We present the British Association for Sexual Health and HIV (BASHH), Special Interest Group for Sexual Dysfunction updated recommendations for the management of premature ejaculation. The recommendations outline the physiology, prevalence, definitions, aetiological factors and patient assessment for this common sexual problem. Behavioural, local and systemic pharmacological treatments are discussed along with general recommendations and auditable outcomes.

Adolescent↗

Retarded ejaculation - a review.

Retarded ejaculation, now termed the male orgasmic disorder is not only difficult to manage, but also the scientific evidence for aetiology, treatment and outcome is poor. This is compounded by incomplete consensus regarding definition from the scientific community. In this review, we intend to collate the available information on this sexual problem including definitions, possible aetiological factors and treatment options.

Ejaculation↗

Effect of ejaculation intervals on semen quality in cats.

The relationship between ejaculation intervals and semen quality in 4 male cats aged 3-5 years was investigated in this study. Semen was collected 10 times at intervals of every day, every other day, and every three days using an artificial vagina. Semen was collected consecutively twice on the day of semen collection, and the semen quality was examined. In semen collected every day, the number of sperm in the first collection decreased, and the frequency of immature sperm rapidly increased after the 4th day. In semen collected every other day and every three days, although the semen volume markedly varied among the animals on both first and second collections, the volume remained stable for each animal, the number of sperm was similar in the first and second collections, but was clearly larger in the first collection (p<0.01). Sperm motility and abnormality were stable among the various intervals and between the first and second collections in each animal.

Animals↗

Retrograde ejaculation and male infertility.

Incompetence of the internal urethral sphincter causes semen to pass into the bladder. Infertility can be successfully treated by restoring normal ejaculation or by sperm retrieval techniques.

Ejaculation↗