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Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: a prospective, controlled, randomized clinical study.

OBJECTIVE: To evaluate the effects of treatment with FSH on seminal parameters and spontaneous pregnancy in male infertility. DESIGN: Prospective, controlled, randomized clinical study. SETTING: Infertility center at a university hospital. PATIENT(S): One hundred twelve men affected by idiopathic oligozoospermia. INTERVENTION(S): Patients were randomized into two groups: 62 subjects were treated with 100 IU of recombinant human FSH on alternate days for 3 months, and 50 patients did not receive any treatment. Semen analysis was performed in all subjects at the end of this period of treatment and after the following 3 months. Subjects who had not reached spontaneous pregnancy underwent assisted reproductive techniques. MAIN OUTCOME MEASURE(S): Seminal parameters, testicular cytologic analysis, FSH, LH, T, and inhibin B concentrations. RESULT(S): The treatment group considered as a whole did not show modifications in sperm parameters. However, a subgroup of these (30, 48.4%) had a significant increase of sperm count (responder group). In the period including 3 months after the withdrawal of FSH therapy, we observed a significantly higher spontaneous pregnancy rate in the responder group (5 of 30 [16.7%]) with respect to nonresponder and nontreated groups (1 of 32 [3.1%] and 2 of 50 [4.0%], respectively). Furthermore, the improvement of seminal parameters in the responder group allowed these patients to undergo less frequent IVF-ET/intracytoplasmic sperm injection. CONCLUSION(S): Results from this controlled, randomized clinical trial show that FSH therapy does not improve sperm concentration or pregnancy rate when infertile male patients are chosen solely by the clinical criteria of idiopathic oligospermia and normal FSH concentration. Subgroup analysis, however, does indicate that patients without maturation arrest in addition to the clinical scenario do benefit from medical therapy.

Adult↗

Low doses of lead: effects on reproduction and development in rats.

The effects of exposure to high doses of lead on reproduction and development have been established, but not so those caused by low lead doses or the influence that life stage at which contact with the metal takes place might have. The aim of this work was to study the effects of 200 and 400 ppm lead acetate in drinking water on reproduction and development as well as on renal and hepatic parameters of rats at different life stages, from gestation to 3 mo postweaning. The results indicate a dose-dependent effect on reproduction, with variations in the number of births and in pups' weight. Development was mostly affected at the weaning stage, with hemoglobin levels and erythrocyte numbers significantly decreased. The lead levels in tissues, blood, urine, and feces along with selected renal and hepatic parameters (blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) were determined. There were histological, blood urea nitrogen, alanine aminotransferase, and alkaline phosphatase changes in the first month postweaning. After 3 mo, these changes are no longer evident, possibly because of metabolic adaptation.

Animals↗

Allee effects can both conserve and create spatial heterogeneity in population densities.

In order to determine conditions which allow the Allee effect (caused by biparental reproduction) to conserve and create spatial heterogeneity in population densities, we studied a deterministic model of a symmetric two-patch metapopulation. We proved that under certain conditions there exist stable equilibria with unequal population densities in the two patches, a situation which can be interpreted as conserved heterogeneity. Furthermore, the Allee effect can lead to instability of the equilibrium with equal population densities if some degree of competition is assumed to occur between the subpopulations (non-local competition). This indicates the potential of the Allee effect to create spatial heterogeneity. Neither of these effects appear under biologically realistic parameter values in a model where uniparental reproduction is assumed. We proved that both the between-patch migration intensity and the degree of non-local competition are decisive in determining boundaries between these types of behaviour of the spatial system with Allee effect. Therefore, we propose that the Allee effect, migration intensity, and non-local competition should be considered jointly in studies focusing on problems like pattern formation in space and invasions of spreading species.

Animals↗

[Genetic effects of acute and chronic ionizing irradiation on Pinus sylvestris L., inhabiting the Chernobyl' meltdown area].

The main results of the 12-year radiation-genetic monitoring of radiobiological, cytogenetic, and genetic parameters in Pinus sylvestris forest plantation from the Chernobyl meltdown area are presented. The acute ionizing irradiation at doses > 1 Gy was shown to induce formation of morphoses and depressed growth; at doses > 2 Gy, the reproductive ability of the trees declined. The radiobiological parameters showed a linear or close to linear dose-dependence relationship. The acute irradiation at a dose of 0.5 Gy induced cytogenetic and genetic effects that were significantly higher than the corresponding control values. The relationship between the cytogenetic effects and the absorbed dose was exponential. The dependence of the mutation frequency at specific loci on the absorbed dose was described by a nonlinear curve. The results of cytogenetic analysis of seedlings obtained from seeds annually collected in zones of slight, moderate, and strong damage of Pinus sylvestris L. are presented.

Chromosome Aberrations↗

[Radiation and genetic consequences of ionizing irradiation on population of Pinus sylvestris L. within the zone of the Chernobyl NPP].

Main results of the nineteen year radiation-genetic monitoring of radiobiological, of cytogenetic, and of genetic parameters of Pinus sylvestris L. of forest plantation from the Chernobyl meltdown area are presented. The acute ionizing irradiation at doses >1 Gy induces the formation of morphoses and of depressed growth; at doses >2 Gy, the reproductive ability of the trees declined. The radiobiological parameters shown linear or close to it dose-dependence relationship. The acute irradiation at dose of 0.5 Gy induces cytogenetic and genetic effects that were significantly higher than the corresponding control values. The relationship between the cytogenetic effects and the absorbed dose was exponential. The dependence of mutation frequency at specific loci on the absorbed dose was described by a nonlinear curve. The results of the cytogenetic analysis of seedlings obtained from seeds annually collected in zones of slight, of moderate, and of strong damage of Pinus sylvestris L. are presented.

Cesium Radioisotopes↗

Inhibition of oocyte fertilization by assisted reproductive techniques and increased sperm DNA fragmentation in the presence of Candida albicans: a case report.

The effects of Candida albicans on sperm parameters and the outcome of infertility treatment are unclear. This report describes a lack of fertilization after assisted reproductive techniques and increased sperm DNA fragmentation in an infertile patient with male accessory gland infection due to Candida albicans. He had normal sperm parameters and, therefore, underwent conventional IVF for a female factor of infertility. No spermatozoa or only one spermatozoon per oocyte were found attached to the zona pellucida of the six mature oocytes retrieved. A new semen sample was then requested from the patient to perform intracytoplasmic sperm injection (ICSI) on the same oocytes, but again no fertilization resulted. Candida albicans was detected in the medium where spermatozoa were co-incubated with oocytes and subsequently in the urethral swabs. It did not have any detrimental effect on sperm parameters soon after ejaculation or following separation of motile spermatozoa by swim-up technique. Fertilization failure after assisted reproduction treatment was associated with an increased percentage of motile spermatozoa having chromatin packaging abnormalities, externalization of phosphatidylserine and DNA fragmentation. In conclusion, Candida albicans did not affect sperm parameters, but increased sperm chromatin packaging damage and apoptosis that might have caused fertilization failure after assisted reproduction treatment in this couple.

Adult↗

Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats.

A two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) was conducted in Sprague-Dawley rats. Twenty-five rats of each sex (F0) were exposed by inhalation to 0, 400, 3000 or 8000 ppm MTBE vapor, 6 h a day for 10 weeks prior to mating. Parental animals were then mated within groups for up to 3 weeks. Parental females were exposed during mating, gestation and lactation (starting on day 5); parental males were exposed during mating through delivery of their last litter sired. The F1 adults were selected from the F1 litters and were exposed beginning on postnatal day 28 for at least 8 weeks before mating to produce F2 litters. During exposures to 3000 and 8000 ppm MTBE, group observations included hypoactivity and lack of startle reflex in parental animals from both generations. Parental animals at 8000 ppm were also ataxic. During the pre-mating period, body weights of the 8000 ppm males from both generations and the F1 females were significantly reduced compared to control animals. Transient body weight reduction was also observed in the 3000 ppm F1 males and females during the pre-mating period. Lactational body weights were increased in the 8000 ppm females from both generations. In the F1 generation, increased liver weights were noted in the 3000 and 8000 ppm animals for both sexes, although histopathological examination revealed no treatment-related effects. There were no treatment-related reproductive effects noted in any of the parameters measured in this study. Offspring survival was equivalent among treated and control groups from both generations, and there were no remarkable post-mortem findings. There was, however, a significant increase in dead F2 pups in the 8000 ppm group on postnatal day 4. The F1 litters at 3000 and 8000 ppm had lowered body weights from postnatal days 14-21 and 14-28, respectively. The F2 generation of pups at 3000 and 8000 ppm also exhibited lowered body weights from postnatal days 14-28 and 7-28, respectively. Body weight gains in both the F1 and F2 litters were also reduced for the corresponding time intervals. Thus, exposure to MTBE vapor produced no reproductive toxicity to two generations of Sprague-Dawley rats even in the presence of parental toxicity at 3000 and 8000 ppm. Postnatal toxicity was observed in the offspring of both generations, but only in the presence of maternal toxicity. The no-observed-effect level (NOEL) for both parental and postnatal toxicity is 400 ppm, and the NOEL for reproductive toxicity is at least 8000 ppm.

Administration, Inhalation↗

Coculture of human spermatozoa with reproductive tract cell monolayers can enhance sperm functions better than coculture with Vero cell monolayers.

PURPOSE: In order to develop a better system for support of human sperm function in vitro, we conducted studies to evaluate whether reproductive tract cells are better than non-reproductive tract cells as an adjunt in that regard. METHODS: Human spermatozoa were cocultured with Vero cells, with human oviduct cells and endometrial cells, and without cells (control) for either 1, 4, or 24 hr. Sperm motility was then analyzed with a computer-aided sperm analyzer (CASA-Hamiliton Thron, HTM IVOS Motility Analyzer). Aliquots of spermatozoa incubated for 24 hr were also stained with Hoechst 33258 and FITC-PNA to evaluate the status of acrosome in live cells. RESULTS: Significant differences (P < 0.05) between the oviduct cell and the control groups after 24 hr were evident in the curvilinear velocity (VCL) (81.4 +/- 13.4 vs 60.0 +/- 14.1 microns/sec) and amplitude of lateral head displacement (ALH) (5.2 +/- 0.6 vs 4.1 +/- 0.5 microns). The incidence of acrosome reaction of live sperm was significantly higher in the endometrial cell group than in the controls (25.4 +/- 9.9 vs 6.6 +/- 2.4%; P < 0.001). CONCLUSIONS: Coculture with human reproductive tract cells seems to improve some functional parameters of human spermatozoa. Coincubation with such cell lines, especially oviduct cells, might be a feasible approach to optimization of human spermatozoa for assisted fertilization using subfertile or frozen-thawed samples. We think coincubating human spermatozoa with a human reproductive tract cell line, especially oviduct cells, might be a feasible approach in preparing human spermatozoa for assisted fertilizatioin in subfertile and frozen-thawed semen samples.

Acrosome↗

Infectious diseases, reproductive effort and the cost of reproduction in birds.

Reproductive effort can have profound effects on subsequent performance. Field experiments on the collared flycatcher (Ficedula albicollis) have demonstrated a number of trade-offs between life-history traits at different ages. The mechanism by which reproductive effort is mediated into future reproductive performance remains obscure. Anti-parasite adaptation such as cell-mediated immunity may probably also be costly. Hence the possibility exists of a trade-off between reproductive effort and the ability to resist parasitic infection. Serological tests on unmanipulated collared flycatchers show that pre-breeding nutritional status correlates positively with reproductive success and negatively with susceptibility to parasitism (viruses, bacteria and protozoan parasites). Both immune response and several indicators of infectious disease correlate negatively with reproductive success. Similar relations are found between secondary sexual characters and infection parameters. For brood-size-manipulated birds there was a significant interaction between experimentally increased reproductive effort and parasitic infection rate with regard to both current and future fecundity. It seems possible that the interaction between parasitic infection, nutrition and reproductive effort can be an important mechanism in the ultimate shaping of life-history variation in avian populations.

Animals↗

The toxicological effects following the ingestion of chinook salmon from the Great Lakes by Sprague-Dawley rats during a two-generation feeding-reproduction study.

A two-generation reproduction-feeding study was undertaken with Sprague-Dawley rats to ascertain the effects of ingesting chinook salmon fillets caught in the Credit River, which empties into Lake Ontario (LO), or in the Owen Sound region of Lake Huron (LH). Rats (30/sex/group) were randomly assigned to groups whose dietary protein consisted of casein and/or lyophilized salmon [Group 1: 20% casein (controls); Group 2: 15% casein + 5% LO salmon (LO-5%); Group 3: 20% LO salmon (LO-20%); Group 4: 15% casein + 5% LH salmon (LH-5%); Group 5: 20% LH salmon (LH-20%)]. After 70 days on test, the males and females were mated on a 1:1 basis within diet groups. Approximately 70 days postweaning, one F1 male and one F1 female from 24 litters were mated within diet groups, avoiding sibling matings. At weaning, the F0 and F1 adults and the F1 and F2 neonates not randomly selected for further testing were necropsied. Evaluated parameters included growth, feed consumption, organ weights, reproduction indices, serum chemistry, hematology, and coagulation times. The only statistically significant effects which were present in both generations were increased relative liver and kidney weights of both sexes in the LO-20% and LH-20% groups; the LH-20% females had lower alanine transaminase activity than the controls; the controls had lower creatinine levels than the fish groups and the LO-20% females; the LH-20% and LO-20% males had a lower blood urea nitrogen than the controls; and the LH-20% females had a heavier terminal body weight than the controls and a lower number of red blood cells, hematocrit, hemoglobin values, and mean platelet volume. There was a tendency for the fish-fed groups to grow faster, eat more feed, and have larger litters with heavier pups. Overall, there was little to suggest that the myriad of contaminants in chinook salmon from the Great Lakes presented an appreciable toxicological risk to Sprague-Dawley growth and reproduction.

Animal Feed↗

Frequently subnormal semen profiles of normal volunteers recruited over 17 years.

In order to establish semen profiles for men in the general population, we analysed the semen parameters of 187 men attending the Institute of Reproductive Medicine between 1977 and 1993 as volunteers for clinical studies. If several ejaculates were obtained from the volunteer, only the first ejaculate was used for analysis. More than half of the ejaculates of these healthy men showed at least one abnormal parameter, so that only 46% of the volunteers could be classified as being 'normozoospermic' according to WHO guidelines. Aside from a decrease in the proportion of motile spermatozoa, no change in semen parameters could be detected with advancing age of the volunteers. No negative influence of the presence of a varicocele, the grade of varicocele on a history of maldescended testis on semen parameters was detected. The serum levels of FSH, LH and testosterone showed no significant age-related change over the period of investigation. Follow-up analysis of the fertility on the volunteers revealed a proportion of unwanted barrenness similar to or even lower than that in the general population. The analysis demonstrates that the limits of normality for semen parameters may require redefinition.

Adult↗

Immunologic infertility.

The existence of immunologic infertility is well grounded in the theories of humoral and cell-mediated immunology. Both of these immune system arms can theoretically and experimentally be shown to play roles in states of male factor infertility. Although much progress has been made in relating immunopathology to infertility, several problems plague the investigation and diagnosis: the use of multiple, different assay systems; the lack of properly controlled experimental work; a need to oversimplify a tremendously complex immunologic network for clinical purposes; and a dearth of communication between basic science and clinical investigators. Unlike the established role of humoral or antibody-mediated infertility, the way cell-mediated immunity induces reproductive failure is just beginning to be understood. Two active areas of investigation include a delineation of active immunosuppression in the normal testicular environment and the pathologic deficits induced by cytokines in cases of leukospermia. Other research seeks to define functional, sperm-specific antigens to which autoantibodies are directed and to elucidate the mechanisms of antibody-mediated infertility at various sites in the reproductive tract. The diagnosis of immunologic infertility still remains one of exclusion. When the diagnosis is made, it is necessary to define precisely which functional reproductive deficits exist, through an analysis of semen parameters, postcoital tests, sperm penetration assays, and tests of acrosomal reactivity. This is essential because the therapeutic options are broad and can involve significant side effects and expense. Proven modalities include sperm manipulation, direct sperm insemination, donor insemination, systemic immunosuppression, and assisted reproductive techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Reproductive biology of Lutzomyia shannoni (Dyar) (Diptera: Psychodidae) under experimental conditions.

Baseline biological growth data of Lutzomyia shannoni (Dyar) were compared under two experimental conditions within insulated styrofoam chests and in standard laboratory incubators. The developmental time from egg to adult was 67 and 52 days, respectively. Based on cohorts of 100 females in each experiment, horizontal life tables were constructed. The following predictive parameters were obtained under each of the two conditions: net rate of reproduction (23.5 and 18.0 females per cohort female), generation time (11.4 and 9.4 weeks), intrinsic rate of population increase (0.27 and 0.30), and finite rate of population increment (1.31 and 1.36). The reproductive value for each class age of the cohort females was calculated. The observed parameters were obtained under each experimental condition: net rate of reproduction (1.9 and 2.5 females per cohort female), generation time (11.7 and 9.6 weeks), intrinsic rate of population increase (0.05 and 0.09), and finite rate of population increment (1.06 and 1.10). Vertical life tables were elaborated and mortality was described for every generation in each cohort. In addition, for two successive generations, additive variance and heritability for fecundity were estimated.

Animals↗

Ultrasonic determination of fetal parameters in baboons (Papio anubis)

The use of nonhuman primates to study reproductive physiology, fetal development, and neonatal management often depends on the availability of pregnant and fetal animals of known gestational history. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in olive baboons (Papio anubis). Normal cycling females were bred to proven males by using the degree of perineal swelling and vaginal cytology to determine onset of ovulation. The subjects were evaluated to determine pregnancy beginning 18 days postmating, using an Aloka-650 diagnostic ultrasound unit, equipped with a 7.5 mHz prostate probe and a 5 mHz transabdominal probe. Ten pregnant animals were then evaluated sonographically every 3 days through day 30 and weekly through day 135 (average gestation 184 days). Measurements included gestational sac, greatest-length, biparietal diameter, femur length, head circumference, and abdominal circumference. Using the means and standard deviations, growth curves were constructed, and the data used to develop predicted value charts for gestational age estimation. Using the predicted value charts established in our study, subsequent evaluation of pregnant baboons in our colony disclosed concordance with actual gestational age.

Animals↗

Comparative analysis of blood plasma epidermal growth factor concentrations, hormonal profiles and semen parameters of fertile and infertile males.

The relationship between male reproductive function and the blood plasma level of epidermal growth factor (EGF) is of interest in the light of the role that circulating EGF appears to play in regulating mouse spermatogenesis. We measured the concentrations of EGF in the blood plasma of 39 fertile men (sperm count > 20 x 10(6)/ml) and compared them with those of 31 infertile men (sperm < 20 x 10(6)/ml). Blood plasma levels of follicle stimulating hormone (FSH), luiteinising hormone (LH), prolactin and testosterone were also determined. The infertile patients had mean blood plasma EGF concentrations of 0.75 +/- 0.10 ug/L. The value was significantly lower than that of the fertile group (1.28 +/- 0.14 ug/L; P < 0.005). There were statistically significant differences between the fertile and infertile groups in sperm count, sperm viability, mean forward progression, testosterone, LH and FSH (P values between 0.0001 and 0.023). There was no significant difference in the prolactin concentrations between the two groups. Although overall average blood plasma EGF concentrations are significantly lower in the infertile males, regression analysis failed to reveal any direct relationships among the various parameters studied.

Adult↗

Electronic Raman spectroscopy of the vanadium(III) hexaaqua cation in guanidinium vanadium sulphate: Quintessential manifestation of the dynamical Jahn-Teller effect.

Single-crystal Raman spectra are presented for the salt [C(NH2)3][V(OH2)6](SO4)2, displaying electronic transitions between the trigonal components of the vanadium(III) 3T1g(Oh) ground term. The 3A-->3E(C3) electronic Raman band is centered at approximately 2720 cm-1, and exhibits extensive structure, revealing the energies of the spinor components of the 3E(C3) term for the two crystallographically distinct [V(OH2)6]3+ cations. The data are interpreted in conjunction with parameters previously reported from an electron paramagnetic resonance study of the salt. A satisfactory reproduction of the electronic Raman profile and ground-state spin-Hamiltonian parameters is achieved by employing a (3A plus sign in circle3E)multiply sign in circle e vibronic coupling model, in which the spin-orbit splitting of the 3E(C3) is quenched significantly by the Ham effect, and the intensity of harmonics of the Jahn-Teller active vibration enhanced by their proximity to the electronic Raman bands. The model gives an excellent account of the intensities of the electronic Raman bands, which are shown to depend profoundly on both temperature and the selected component of the polarizability tensor. The electronic Raman profile changes notably upon deuteriation, a result that exposes deficiencies in the single-mode coupling model.

Journal Article↗

[The morphofunctional characteristics of the interstitial endocrinocytes (Leydig cells) of the testes in vertebrates under conditions of seasonal change in reproductive activity].

By means of light and electron microscopy the structural organization of Leydig cells was studied in Rana ridibunda, Lacerta agilis, Columba livia in the periods of reproductive activity and reproductive break. The dynamics of structural changes of some parameters of the testicles (interstitial tissue square, endocrinocytes number, state of the cytoplasm, structural components and the volume of nuclei) was shown in the process of the reproductive activity seasonal changes. Nuclear volume and the degree of the agranular endoplasmic reticulum development were found to correlate. Clear dependence between the Leydig cells functional activity and reproductive activity in lizards and pigeons was demonstrated. This dependence is slightly expressed in frog.

Animals↗

The influence of body condition on 17-beta estradiol levels in relation to vitellogenesis in female Vipera aspis (Reptilia, Viperidae).

Seventy-six wild Vipera aspis females were caught over 3 years and placed in outdoor enclosures; 39 reproduced and 37 did not. Almost all the reproductive females had a body condition index (BCI) greater than 0.70 when vitellogenesis began. Monthly blood samples were taken by cardiac puncture. The main plasma parameters of vitellogenesis were measured by spectrophotometry: total plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, proteins, and albumin. Plasma 17-beta estradiol levels were determined by RIA. Vitellogenesis started soon after hibernation in reproductive females with very high 17-beta estradiol concentrations (average of 4.00 ng/ml) and there was a marked mobilization of maternal reserves (fat bodies, liver, and vertebral bone) associated with very high values of plasma calcium, phosphorus, phospholipids, cholesterol, triglycerides, and proteins. The kinetics of the main plasma components were described throughout the vitellogenesis period (from March to early June), when all plasma parameters differed markedly between reproductive and nonreproductive females. After ovulation, the differences between the two groups of females disappeared except in the case of albumin, which remained at a very low level in reproductive females for 6 months. All nonreproductive females had low 17-beta estradiol plasma levels during vitellogenesis (average of 0.08 ng/ml) and there was no suggestion of mobilization of maternal reserves. After vitellogenesis plasma concentrations of estradiol were low in reproductive (an average of 0.08 ng/ml) and in nonreproductive animals (0.06 ng/ml). Five nonreproductive females kept in the laboratory were estrogenized by 17-beta estradiol silastic implants. The 17-beta estradiol concentrations were close to those measured in reproductive females during vitellogenesis. Maternal reserves were mobilized, with almost all metabolic parameters exhibiting the vitellogenic pattern. When the silastic implants were removed, 17-beta estradiol concentrations dropped sharply to a basal level, but the other components were maintained near the vitellogenic values for several months. In contrast to previous studies on viviparous snakes, these results suggest that in V. aspis 17-beta estradiol levels are linked strictly to vitellogenesis.

Animals↗