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Increased sperm count in 25 cases of idiopathic normogonadotropic oligospermia following treatment with tamoxifen.

Twenty-five subfertile men, all presenting with idiopathic normogonadotropic oligospermia, were treated with tamoxifen (20 mg/day) for 4 to 12 months. Semen analysis was performed twice before treatment and at least twice after 3 to 12 months of treatment. In 14 patients, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and plasma testosterone (T) were assayed before treatment, then again after 2 weeks and 12 weeks of treatment. Semen volume, sperm motility, and sperm morphologic characteristics were not modified by tamoxifen. Conversely, a twofold increase of both the mean sperm concentration and the mean total sperm count per ejaculate was observed during treatment (P less than 0.001). Mean values of T, LH, and FSH increased during treatment, but the difference was only significant for T (P less than 0.001) and FSH (P less than 0.05). Ten pregnancies (40% of cases) were reported during the 161 months of treatment.

Adult↗

Age-dependent differences in the effects of 1,2-dibromo-3-chloropropane (DBCP) on fertility, sperm count, testicular histology and hormonal profile in rats.

This study was set up to determine if there are any age-dependent differences in the adverse effects of DBCP on the reproductive system of male rats. Groups of male rats were injected at the ages of 7,30 or 90 days with a single (50 mg kg-1 body weight) or repeated (20 mg kg-1 body weight once a week for 3 weeks) dose of DBCP, dissolved in DMSO. Ninety days after the last injection the males' fertility was estimated and the animals were killed. Blood was collected for future hormone assays, organs were weighed, testes were then taken for histological studies and sperm counts. The results were compared with those of control peers. The results showed that animals injected at the ages of 7 or 90 days under both regimens of treatment were adversely affected. The damage was noted in their fertility rate, sperm production, testicular histology and hormonal profile. Those injected at the age of 30 days showed only an insignificant variation compared with controls.

Age Factors↗

Identification of a Y chromosome haplogroup associated with reduced sperm counts.

In man, infertility is associated with microdeletions of specific regions of the long arm of the Y chromosome. This indicates that factors encoded by the Y chromosome are necessary for spermatogenesis. However, the majority of men with either idiopathic azoospermia or oligozoospermia have grossly intact Y chromosomes and the underlying causes of their infertility are unknown. We hypothesized that some of these individuals may carry other rearrangements or sequence variants on the non-recombining region of the Y chromosome that may be associated with reduced spermatogenesis. To test this hypothesis, we typed the Y chromosome in a group of Danish men with known sperm counts and compared the haplotype distribution with that of a group of unselected Danish males. We found that one class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; P < 0.001) in the group of men with either idiopathic oligozoospermia (defined as <20 x 10(6 )sperm/ml) or azoospermia compared to the control Danish male population (4.6%). This study defines, for the first time, a class of Y chromosome that is at risk for infertility in a European population. This observation suggests that selection may be indeed active on the Y chromosome, at least in the Danish population, raising the possibility that it could alter the pattern of Y chromosome haplotype distribution in the general population.

Alleles↗

Inhibin-B levels in healthy young adult men and prepubertal boys: is obesity the cause for the contemporary decline in sperm count because of fewer Sertoli cells?

Inhibin-B is a heterodimeric glycoprotein produced by Sertoli cells. Although inhibin-B levels are low when seminiferous tubules are damaged, studies in normal monkeys reveal that inhibin-B levels also correlate positively with Sertoli cell number. In this study, we measured inhibin-B levels in healthy young adult men aged 18-24 years and in prepubertal boys aged 5-9 years in relation to body mass index (BMI). Inhibin-B levels declined with increasing obesity in young adult men; values were 26% lower in men who were obese compared to normal-weight men. Sex hormone-binding globulin and total testosterone, but not free testosterone, were also lower with increasing BMI; serum follicle-stimulating hormone and luteinizing hormone levels were unaffected by obesity. In prepubertal boys, by contrast, inhibin-B was unaffected by obesity. We propose that reduced levels of inhibin-B indicate that obese men have fewer Sertoli cells than men of normal weight. Moreover, normal values in obese prepubertal boys suggest that the effect of obesity on inhibin-B is established during puberty. Finally, because each Sertoli cell is thought to support a finite number of germ cells, fewer Sertoli cells in obesity may predispose to a lower sperm count in adulthood. We speculate that the escalating prevalence of obesity and insulin resistance among adolescents might negatively influence male reproductive function for the next generation.

Adolescent↗

Reduced sperm count and normal fertility in male mice with targeted disruption of the ADP-ribosylation factor-like 4 (Arl4) gene.

The ADP-ribosylation factor-like protein 4 (ARL4) is a 22-kDa GTP-binding protein which is abundant in testes of pubertal and adult rodents but absent in testes from prepubertal animals. During testis development, ARL4 expression starts at day 16 when the spermatogenesis proceeds to the late pachytene. In the adult testis, the ARL4 protein was detected in pre- and postmeiotic cells, spermatocytes, and spermatides, but not in spermatogonia and mature spermatozoa. Mouse Arl4-null mutants generated by targeted disruption of the Arl4 gene were viable and grew normally; male as well as female Arl4(-/-) mice were fertile. However, inactivation of the Arl4 gene resulted in a significant reduction of testis weight and sperm count by 30 and 60%, respectively, without reduction of litter size or frequency. It is suggested that the disruption of Arl4 produces a moderate retardation of germ cell development, possibly at the stage of meiosis.

ADP-Ribosylation Factors↗

Exposure of juvenile guppies to three antiandrogens causes demasculinization and a reduced sperm count in adult males.

It has been thoroughly established that the fungicide vinclozolin and the persistent DDT metabolite p,p'-DDE, can function as antiandrogens in mammals in a manner similar to the therapeutic antiandrogen flutamide. In mammals, these chemicals bind the androgen receptor and prevent the transcription of the associated genes causing abnormal sexual development and demasculinization. There are few similar studies in fish and so far it has not been demonstrated that these chemicals have any antiandrogenic effects in this group. In the present study, juvenile guppies (Poecilia reticulata) were fed sublethal doses of vinclozolin, p,p'-DDE or flutamide from birth to adulthood. At sexual maturity, we measured a suite of male sexual characteristics that are known to be under androgen control. All three chemicals caused a reduction in the orange display coloration, inhibited gonopodium development, reduced the sperm count and suppressed courtship behaviour, in a manner consistent with antiandrogen action. Only the gonodosomatic index was unaffected by the treatments. In addition, the three chemicals skewed the sex ratio at adulthood and caused delayed maturation. The altered characters are all considered to be important for male mating success and their impairment indicates that antiandrogens may seriously compromise male reproductive fitness.

Androgen Antagonists↗

Distribution of sperm counts in suspected infertile men.

Probit plots of sperm concentration for 1711 suspected infertile men (those with azoospermia being excluded) were compared for the untransformed and loge-, square root- and cube root-transformed values. For the distribution of sperm concentrations, which was highly skewed towards low values, the square-root transformation produced the most normal (Gaussian) distribution. Loge and cube-root transformations caused skewing towards high values. Such treatment of the data should always be considered before using parametric statistical tests to make comparisons between sperm concentrations of groups of men.

Humans↗

Performance of the postwash total motile sperm count as a predictor of pregnancy at the time of intrauterine insemination: a meta-analysis.

OBJECTIVE: To assess the performance and clinical value of the postwash total motile sperm count (postwash TMC) as a test to predict intrauterine insemination (IUI) outcome. DESIGN: Meta-analysis of diagnostic tests. SETTING: Tertiary fertility center. PATIENT(S): Patients undergoing IUI. INTERVENTION(S): None. RESULT(S): We detected 16 studies that reported on postwash TMC at insemination and IUI outcome. Summary receiver operating characteristics (ROC) curves indicated a reasonable predictive performance toward IUI outcome, and, at cut-off levels between 0.8 to 5 million motile spermatozoa, the postwash TMC provided a substantial discriminative performance. At these cut-off levels, the specificity of the postwash TMC, defined as the ability to predict failure to become pregnant, was as high as 100%; the sensitivity of the test, defined as the ability to predict pregnancy, was limited. CONCLUSION(S): The postwash TMC at insemination could potentially be used in counseling patients for either IUI or IVF. However, to enable patient counseling before the start of treatment, further studies are needed to establish the accuracy of a postwash TMC during the fertility workup rather than at insemination.

Female↗

Fructose and hormone levels in semen: their correlations with sperm counts and motility.

Levels of fructose, growth hormone (GH), prolactin (HPr), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 5alpha-dihydrotestosterone (DHT) were determined in semen. The samples were obtained from patients attending an infertility clinic and separated into four groups according to the number of spermatozoa. Levels of HPr, LH, and FSH showed significant positive correlations with sperm counts. Significant differences in fructose and hormone levels were found between various groups. Expressed as concentrations of hormones or fructose per milliliter of semen, none of the hormones showed a significant negative correlation with sperm motility whereas fructose showed a significant negative correlation. Expressed as amounts per ejaculate of semen, only prolactin showed a significant positive correlation with sperm motility. The significance of these findings is discussed.

Cell Count↗

Evaluation of proteohormon concentrations in serum and seminal fluid and its relationship with sperm count.

The measurement of FSH, LH, and PRL in serum and seminal fluid of 105 men attending a male infertility clinic and 21 men of proven fertility (controls) did not reveal an interrelationship between the spermatozoal count and the level of the proteo-hormones in both biological fluid except for FSH, which was significantly higher in the serum of men with low as compared to normal sperm count (p less than 0.01). FSH in seminal fluid was significantly lower (p less than 0.01), and LH-like activity significantly higher (p less than 0.01) than in serum, while there was no difference between the respective levels of PRL. These results could be confirmed in 4 patients with azoospermia due to occlusive disease, and in 1 out of 2 vasectomized men. It was demonstrated for the first time that the higher concentration of "LH" in seminal fluid as compared to serum was due to the presence of HCG-beta or a HCG-like material cross-reacting with the antiserum against LH.

Adult↗

[Efficiency of conventional glass wool and SpermFertil columns with respect to ROS-reduction, leukocyte reduction, and CASA-generated sperm counts in semen].

OBJECTIVE: Glass wool filtration has proved to be useful to separate motile from defective spermatozoa and leukocytes in semen from patients with oligozoospermia and azoospermia. With regard to that, we set out to investigate the efficiency of two widely used filter systems. MATERIAL AND METHODS: Semen from 10 patients attending the Dept. of Andrology, FSU Jena, were investigated with home-made coarse glass wool filters and SpermFertil columns regarding elimination of reactive oxygen species (ROS) and enrichment of semen with motile and progressive spermatozoa. RESULTS: Filtration with home-made glass wool columns did not affect the percentage of motile spermatozoa but increased that of progressive spermatozoa. The whole cell count was decreased by a third. Leukocytes were reduced by half and ROS by more than half. SpermFertil columns increased the percentage of both motile and progressive spermatozoa and the whole cell count was decreased severely. Leukocytes were eliminated almost completely, as were ROS. CONCLUSIONS: Our results show the higher potential of SpermFertil columns to enrich semen specimens with motile and progressive spermatozoa and to almost completely eliminate leukocytes and ROS in comparison to home-made glass wool columns. However, SpermFertil columns reduce the whole cell count to about 10% of the original cell count.

Adult↗

The effect of varicocelectomy on sperm count, motility, and conception rate.

One hundred and eighty-seven male partners of involuntarily infertile couples were evaluated and found to have dilatation of the left spermatic vein. One hundred and forty-nine underwent varicocelectomy and achieved a statistically significantly improved conception rate as compared with the nonoperated group. Although 70.5% of men whose wives subsequently conceived had improved semen count and motility postoperatively, no parameter distinguished these men from other patients with similar improvement who remained infertile.

Female↗

Processed total motile sperm count correlates with pregnancy outcome after intrauterine insemination.

OBJECTIVES: To determine the impact of processed total motile sperm (PTMS) count on pregnancy after partner intrauterine insemination (IUI). IUI is generally attempted before proceeding to more expensive and invasive assisted-reproductive techniques such as intracytoplasmic sperm injection. Several semen parameters have been shown to correlate with IUI outcome and may be useful when counseling couples. METHODS: Four hundred thirty-eight couples with diverse causes of infertility underwent 1114 cycles of husband IUI during a 39-month period. The clinical and semen parameters were recorded for each couple and each insemination. The parameters were compared between those couples who achieved a pregnancy and those who did not. RESULTS: The total number of pregnancies was 120, resulting in a pregnancy rate per cycle of 10.8% and a couple pregnancy rate of 27.4%. On multivariable logistic regression analysis, the PTMS count was independently associated with fertility after IUI (P = 0.0014). Moreover, the pregnancy rate was significantly lower for couples with less than 10 million PTMS (P <0.05). CONCLUSIONS: The results of this study have demonstrated that the PTMS count independently predicts success with IUI. Cycles with less than 10 million total motile sperm are significantly less likely to result in a pregnancy. If cause-specific therapy has failed, alternatives to IUI should be considered for couples when the PTMS count is less than 10 million.

Adult↗

Structural abnormalities in spermatids together with reduced sperm counts and motility underlie the reproductive defect in HIP1-/- mice.

Huntingtin interacting protein 1 (HIP1) is an endocytic adaptor protein with clathrin assembly activity that binds to cytoplasmic proteins, such as F-actin, tubulin, and huntingtin (htt). To gain insight into diverse functions of HIP1, we characterized the male reproductive defect of HIP1(-/-) mice from 7 to 30 weeks of age. High levels of HIP1 protein were expressed in the testis of wild-type mice as seen by Western blots and as a reaction over Sertoli cells and elongating spermatids as visualized by immunocytochemistry. Accordingly, major structural abnormalities were evident in HIP1(-/-) mice with vacuolation of seminiferous tubules caused by an apparent loss of postmeiotic spermatids and a significant reduction in mean profile area. Remaining spermatids revealed deformations of their heads, flagella, and/or acrosomes. In some Sertoli cells, ectoplasmic specializations (ES) were absent or altered in appearance accounting for the presence of spherical germ cells in the epididymal lumen. Quantitative analyses of sperm counts from the cauda epididymidis demonstrated a significant decrease in HIP1(-/-) mice compared to wild-type littermates. In addition, computer-assisted sperm analyses indicated that velocities, amplitude of lateral head displacements (ALH), and numbers and percentages of sperm in the motile, rapid, and progressive categories were all significantly reduced in HIP1(-/-) mice, while the numbers and percentages of sperm in the static category were greatly increased. Taken together, these various abnormalities corroborate reduced fertility levels in HIP1(-/-) mice and suggest a role for HIP1 in stabilizing actin and microtubules, which are important cytoskeletal elements enabling normal spermatid and Sertoli cell morphology and function.

Animals↗

Sensitivity of human spermatozoa to various isolation procedures: differences in relation to sperm counts.

The aim of the present work was to examine the sensitivity of human spermatozoa from oligospermic and normospermic semen samples to manipulations in the course of isolation by generally used procedures. To this end we performed protein and DNA estimations in spermatozoa isolated by procedures differing in rigorousness (washings with Ringer's buffer and a medium containing ficoll) as well as microscopic examinations of washed sediments. The results showed that the washed sediments contained, in addition to spermatozoa, materials containing protein and DNA, possibly deriving from the breakage of sperm cells. These materials increased in amount with the decrease of original sperm counts. We suggest that abnormal spermatozoa, whose percentage usually increases with the severity of oligospermia, are more sensitive to damage than the normal ones.

Buffers↗