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A randomized clinical trial to evaluate the clinical effects of split- versus single-dose human menopausal gonadotropins in an assisted reproductive technology program.

OBJECTIVE: To compare the effect of twice (split) versus once (single) daily administration of hMG on assisted reproductive technology (ART) cycle parameters. DESIGN: A randomized clinical trial. SETTING: Hospital-based academic ART program. PATIENTS: A total of 171 patients undergoing their initial ART cycle were enrolled. All patients received one of two hMG regimens and were excluded from the study if they were receiving medications other than leuprolide acetate (LA) and hMG for ovulation induction. INTERVENTIONS: Subjects were randomized to receive an initial dose of 300 IU/d of hMG in either split-dose (i.e., 150 IU twice daily) or single-dose fashion for four successive days after down-regulation with LA. Thereafter, their daily dose was individualized, maintaining a split-or single-dose schedule. All cycles were managed in accordance with our standard ART protocols. MAIN OUTCOME MEASURES: Cancellation rate, total hMG requirements, number of days treated with hMG, E2 and P responses, oocyte yield and maturity, fertilization rate, total number of embryos, embryo quality, number of embryos transferred, implantation rate, clinical and ongoing-delivered pregnancy rates. RESULTS: Split-dose hMG administration resulted in a significantly higher implantation rate, but significantly lower normal and polyspermic fertilization rates than single-dose hMG administration. No significant differences were noted between the two dosage protocols with respect to the other outcome measures. CONCLUSIONS: Split-dose hMG administration may be associated with significantly higher implantation rates; single-dose hMG with significantly higher fertilization rates. Although our data also demonstrate a trend toward higher clinical and ongoing-delivered pregnancy rates with split-dose therapy, demonstration of a significant difference would require a multicenter trial. Based on our data, clinicians may want to consider split-dose therapy for patients with repeated implantation failures.

Adult↗

Backward bifurcation in epidemic control.

For a class of epidemiological SIRS models that include public health policies, the stability at the uninfected state and the prevalence at the infected state are investigated. Backward bifurcation from the uninfected state and hysteresis effects are shown to occur for some range of parameters. In such cases, the reproduction number does not describe the necessary elimination effort; rather the effort is described by the value of the critical parameter at the turning point. An explicit expression is given for this quantity. The phenomenon of subcritical bifurcation in epidemic modeling is also discussed in terms of group models, pair formation, and macroparasite infection.

Disease Outbreaks↗

Predictive markers in the late gestation period for retained placenta in black-pied dairy cows under field conditions in France.

A prospective ecopathogical survey was conducted in French commercial dairy herds located in Brittany. Previous production and reproduction data and blood parameters were used to identify predictive indicators of risk for retained placenta (RP) in Black-Pied cows. All the cows had delivered a single calf after a dry period of at least 30 d and had produced milk for at least 30 d. The cows with and without retained placenta were allocated to groups according to herd and interval between antepartum blood sampling and calving. Two groups of cows with (RP-positive group, n = 45) and without (RP-negative group, n = 184) retained placenta were compared. Univariate analysis indicated lower plasma glucose concentration, lower monocyte count and higher red blood cell count in the RP-positive group. A multiple logistic regression was run, with herd and blood sampling to calving interval as the fixed effects. It showed that a high red cell count and a low monocyte count were predictive indicators for retained placenta risk, which was found to be lower at third calving. Relationships of circulating indicators with placental retention etiology are discussed in terms of polyunsaturated fatty acid imbalance, its consequences on monocyte and erythrocyte functions, uterine motility and circulatory disturbances.

Analysis of Variance↗

The design of veterinary vaccination programmes.

The optimal design of a veterinary vaccination programme depends on both the characteristics of the vaccine and the epidemiology of the pathogen or parasite. Relevant vaccine characteristics are the proportion of those vaccinated that are initially protected, the duration of protection and the coverage achieved by the vaccination programme. The most important epidemiological parameter is the basic reproduction number, R0. Mathematical theory can integrate this information to address such questions as: whether it is possible to eliminate an infection; what proportion of hosts must be vaccinated to achieve this: what age should hosts first be vaccinated; and at what interval should hosts be revaccinated? Examples of rabies in foxes and foot-and-mouth disease in cattle suggest that theory can be used to guide the design of vaccination programmes.

Animals↗

[Endocrine profile of patients with post-pill amenorrhea].

"Post-pill amenorrhea" is still a much-debated subject in gynecological endocrinology. The authors therefore studied the reproductive history and endocrinological parameters of 145 patients with the presumptive diagnosis of post-pill amenorrhea, seen in their department during the last two years; 166 cases of secondary amenorrhea served as a control group. The incidence of late menarche (20%), previous oligomenorrhea, and elevated androgen serum levels was high in both groups. There were no significant differences between the two collectives. These findings suggest that although oral contraceptives may have an unfavorable influence on the menstrual cycle, there is no causal relationship between such agents and the development of secondary amenorrhea. It seems that in many cases of presumptive post-pill amenorrhea the common condition of juvenile hyperandrogenemic ovarian insufficiency might be the underlying problem.

Adolescent↗

Growing concern over the safety of using mobile phones and male fertility.

There are growing concerns about the possible hazards of electromagnetic waves emitted by mobile phones on human health. One of the biggest concerns is their possible association with increased risk of cancer and their possible effects on cellular DNA. Electromagnetic waves can inflict their results through both thermal and non-thermal effects. There are many animal studies that show that electromagnetic waves have a wide range of damaging effects on the male reproductive system and sperm parameters. However, similar studies are quite limited in humans, and the results of animal studies should be interpreted with caution when considering their application to humans. Large controlled studies are required before confirming such possible effects on male fertility.

Animals↗

Effects of parenteral di-(2-ethylhexyl)phthalate (DEHP) on gonadal biochemistry, pathology, and reproductive performance of mice.

Male and female mice were treated subcutaneously (sc) with 1-100 ml/kg of di-(2-ethylhexyl) phthalate (DEHP) on d 1, 5, and 10 of the experiment and evaluated at d 21 for reproductive performance, selected biochemical parameters of the gonads, and histological alterations of the gonads. In both male and female treated mice there was a reduction in incidence of pregnancy. There were biochemical suggestions of reduced anabolic activity in the gonads (as reflected by decreased ATPase activity and of RNA, DNA, and protein content), and of increased catabolic activity in the gonads (as reflected by an increase in lysosomal enzyme activity and histological damage). Testicular, but not ovarian, weight was reduced in treated animals. Of the other parameters examined, the ovaries exhibited histological injury at lower doses of DEHP than the testes, but unlike testes, there was not a significant dose-related increase in histopathology. Biochemical changes were dose-related, for the most part, in both ovaries and testes, with the changes being more pronounced in testes. In general, reduced fertility appeared to be the most sensitive indicator for gonadotoxicity from DEHP, followed by biochemical changes and histological evidence of injury to the gonads.

Animals↗

13-week inhalation toxicity study and fertility assessment in rats exposed to atmospheres containing adiponitrile.

Adiponitrile is an aliphatic dinitrile that is used as an intermediate in the synthesis of hexamethylenediamine. In order to asses potential health effects associated with industrial exposure, rats were exposed 6 h/d, 5 d/wk for 4 or 13 wk to atmospheres containing a range of adiponitrile concentrations and observed for signs of toxicity. A fertility assessment was also included as a component of the 13-wk study. Mortality and reduced weight gain were observed within 1 wk only in rats exposed to 493 mg/m3. Evidence of slight anemia was present in rats exposed to 99 mg/m3 and above. There was no histopathological evidence of organ toxicity in about 30 tissues from both sexes exposed up to 99 mg/m3, the highest concentration tested, for 13 wk. In addition, fertility, as monitored by reproductive performance and litter parameters, was normal in both males and females similarly exposed.

Administration, Inhalation↗

Reproductive ecology of the endangered Alpine species Eryngium alpinum L. (Apiaceae): phenology, gene dispersal and reproductive success.

BACKGROUND AND AIMS: Eryngium alpinum (Apiaceae) is an endangered perennial, characteristic of the Alpine flora. Because the breeding system influences both demographic (reproductive success) and genetic (inbreeding depression, evolutionary potential) parameters that are crucial for population maintenance, the reproductive ecology of E. alpinum was investigated. Specifically, the aims of the study were (1) to determine the factors (resources and/or pollen) limiting plant fitness; and (2) to assess the potential for gene flow within a plant, within a patch of plants, and across a whole valley where the species is abundant. METHODS: Field experiments were performed at two sites in the Fournel valley, France, over three consecutive years. Studies included a phenological survey, observations of pollinators (visitation rates and flight distances), dispersal of a fluorescent powder used as a pollen analogue, the use of seed traps, determination of the pollen/ovule ratio, and an experiment to test whether seed production is limited by pollen and/or by resources. KEY RESULTS: E. alpinum is pollinated by generalist pollinators, visitation rates are very high and seed set is resource- rather than pollen-limited. The short flights of honeybees indicate a high potential for geitonogamy, and low pollen and seed dispersals suggest strong genetic structure over short distances. These results are interpreted in the light of previous molecular markers studies, which, in contrast, showed complete outcrossing and high genetic homogeneity. CONCLUSION: S. The study highlights the usefulness of adopting several complementary approaches to understanding the dynamic processes at work in natural populations, and the conservation implications for E. alpinum are emphasized. Although the studied populations do not seem threatened in the near future, long-term monitoring appears necessary to assess the impact of habitat fragmentation. Moreover, this study provides useful baseline data for future investigations in smaller and more isolated populations.

Ecology↗

Effects of snowdrop lectin on Mexican rice borer (Lepidoptera: Pyralidae) life history parameters.

The effects of the snowdrop lectin, Galanthus nivalis agglutinin (GNA), delivered through an artificial diet, on growth, development, and life history parameters of the Mexican rice borer, Eoreuma loftini (Dyar), were evaluated in the laboratory. Incorporation of GNA at three treatment levels, 0.5, 1.0, and 2.0% of total dietary protein, in the larval diet significantly decreased larval survivorship and percentage of adults emerging relative to a control diet lacking GNA, whereas differences were not observed among the three treatment levels. Both larvae and pupae in the control were 8-25% larger than those in the GNA treatments, but differences were not observed between larvae in the GNA treatments. Furthermore, presence of GNA did not affect larval and pupal developmental periods, longevities, and fecundities compared with the control. Mexican rice borer life history parameters, such as net reproductive rate and intrinsic rate of increase, were substantially reduced by the presence of GNA in the diet, but differences were not evident among the three GNA treatment levels.

Animals↗

Transposable elements as population drive mechanisms: specification of critical parameter values.

With a view to the possible use of transposable elements (TEs) as a mechanism to drive genes into insect vector populations, we used a three-parameter density dependent growth equation to examine the critical parameter values that determine whether or not a mobile element will spread and become fixed in a finite diploid vector population. Populations were simulated with parameter values affecting size, reproductive rate, density-dependence, and transposition efficiency of the mobile element. Simulations indicated that an equilibrium was reached quickly, typically in < 50 generations. Even when initially present at < or = 1% of a large population, the mobile element spread quickly and became fixed if transposition efficiency was equal to unity and infertility caused by the element decreased reproductive capacity by as much as 45%. These results were insensitive to the values of basic wild type reproductive rates and density dependence, but population size, transposition efficiency of the element, reproductive rate individuals bearing TEs and initial ratio of TE-bearing to wild individuals modified the outcome. As population size and transposition efficiency decreased in value, TEs became fixed less easily. However, even in populations as small as n = 100, an element with a transposition efficiency > 0.75 that reduces fertility < 25% will become fixed when introduced at a frequency as low as 1% of the total population. These results are consistent with previously reported population genetics models. They suggest that engineered transposons with a wide range of properties may be used to drive genes, such as those for parasite resistance, into wild vector populations.

Animals↗

In vitro and in vivo evaluations of a strain of Boophilus microplus (Acari: Ixodidae) selected for resistance to permethrin.

A strain of Boophilus microplus (Canestrini) was selected fro resistance to permethrin by pressuring larvae with increasing doses (range, 0.05-0.35% [AI]) through successive generations (generations F2-F7). At the beginning of the selection process (F2), the pyrethroid resistant (PR) strain was 5.4 times more resistant to permethrin than the pyrethroid susceptible (PS) strain, and the level of resistance increased in each successive generation of the PR strain, reaching a resistance factor (resistance factor) of 20.9 in the F7 generation. Thus, in only 5 generations the level of resistance in the PR strain was increased by 4-fold. The efficacy of permethrin was evaluated by dipping cattle infested with the PS strain and cattle infested with the F7 generation of the PR strain in a vat at 0.057% (AI) (Coopers Animal Health, Mundelein, IL; recommended concentration). Evaluation of the PS strain showed that untreated cattle produced significantly (P < 0.05) more females with a higher index of reproduction than treated cattle. Additionally, biological factors (female weight, egg mass weight, and percent egg hatch) associated with the untreated females were all significantly (P < 0.05) greater than treated females. Conversely, results obtained from the PR strain showed that tick numbers, index of reproduction value, and biological parameters of females in the untreated group were not significantly different (P > 0.05) from those of the treated group. The overall control achieved in the PS strain (99.2%) was significantly higher (P < 0.05) than that of the PR strain (35.7%). The results of the study as they relate to the United States Boophilus Eradication Program are discussed.

Animals↗

Immune function in turkey breeder hens during the short day prelighting period and renewal of photosensitivity for egg production.

Photorefractoriness (PR) in the turkey breeder hen is characterized by a lack of responsiveness to photoperiods that previously induced or maintained egg production. The consequence of PR is spontaneous regression of ovarian function and cessation of lay. Photosensitivity (PS) may be regained by giving at least 8 wk of short photoperiod (8L:16D) (light restriction). Following the transition from PR to PS, the birds may be photostimulated with long photoperiods, which allows for the recrudescence of ovarian function and normal egg production. Although the return of reproductive viability is the parameter for determining the successful recycle of ovarian function, there are no known reports of the physiological costs of this transition on immune function in the turkey breeder hen. We conducted an experiment to determine the immune responsiveness at various stages of recycle in the turkey breeder hen. Fifty photorefractory birds were selected and distributed equally among five treatment groups (time points). All birds were given an 8-wk period of light restriction (8L:16D) followed by a 12-wk period of photostimulation (16L:8D). The cellular (cutaneous basophil hypersensitivity CBH) and humoral (antibody titer) immune responses were determined in each treatment group (sequential time points): prelight restriction, 2-wk light restriction, 7-wk light restriction, 2-wk photostimulation, and 12-wk photostimulation. After 2-wk light restriction, there was a reduction in the cellular (64.1%) and humoral (59.5%) immune responses from that of the PR hens at the start. After 7-wk light restriction, the humoral responses increased (33.5%) as compared to the 2-wk light restriction time point Upon photostimulation, both the cellular (23.3%) and humoral (52.4%) immune responses were reduced at 2 wk of photostimulation as compared to the prior 7-wk light restriction time point. Finally, there was a rise in cellular (45.7%) and humoral (72.3%) immune responses after 12 wk of photostimulation as compared to the prior 2-wk photostimulation time point. We concluded that recycling of PR turkey hens was associated with altered cellular and humoral immune responses characterized by initial decline then recovery in both the light restriction and the postphotostimulation periods.

Animals↗

Oxidative stress and bioindicators of reproductive function in pulp and paper mill effluent exposed white sucker.

This study investigates oxidative stress and bioindicators of reproductive function in wild white sucker (Catostomus commersoni) collected from environments receiving pulp and paper mill effluent discharges in northern Ontario. Samples were collected over an eight-year period adjacent to three pulp and paper mills using a variety of processing and bleaching techniques. Fish collected downstream of pulp and paper mills within the Moose River basin exhibited elevated hepatic and gonadal 2-thiobarbituric acid reactive substances (TBARS), the presence of which is indicative of oxidative stress in these tissues. Within the Jackfish Bay system, exposure to pulp and paper mill effluent did not elevate hepatic or gonadal TBARS. Hepatic cytochrome P4501A activity (CYP1A) and fatty acyl-CoA oxidase (FAO) activities were frequently increased in livers of Moose River basin fish exposed to pulp and paper mill effluent, while lower activities of both enzymes were found within fish from the Jackfish Bay system. This suggests that oxidative stress may be related to CYP1A and FAO activities. Within the Moose River system, increases in measures of oxidative stress (TBARS, FAO) were generally coincident with decreased levels of 17 beta-estradiol; however, testosterone was often lower in Jackfish Bay system fish without any commensurate changes in oxidative stress. The suite of reproductive and oxidative stress parameters measured in this study varied between seasons and mills suggesting responses to effluent are dynamic and effects are complicated by different receiving environments. The relationship between gonad size, gonadal oxidative stress, and circulating plasma steroids remains unclear.

Androgen Antagonists↗

Effects of perinatal combined exposure to 1,1-dichloro-2,2 bis (p-chlorophenyl) ethylene and tributyltin on male reproductive system.

Prenatal or early postnatal exposure to some synthetic chemicals may affect the later reproductive system of the offspring. There may also be unique responses observed due to exposure to combinations of chemicals that are not observed when the chemicals are present individually. 1,1-Dichloro-2,2 bis (p-chlorophenyl) ethylene (p,p'-DDE) is a persistent metabolite of DDT and tributyltin (TBT) compounds are used primarily as antifouling agents, as they exert biocidal actions. p,p'-DDE and TBT are ubiquitously distributed in the environment. Oral p,p'-DDE and TBT intake through marine products is demonstrated to be high in Japan. Consequently, the foetus and neonate are supposed to be exposed much more to p,p'-DDE and TBT via the maternal body. Therefore, effects of perinatal exposure to p,p'-DDE and/or TBT on the reproductive system after maturation have been investigated in rat male offspring of dams orally administered 125 ppm p,p'-DDE (approximately 10 mg/kg) and 25 ppm TBT (approximately 2 mg/kg) during the gestational and lactational period. In this study, growth retardation attributed to TBT has sustained in rat male offspring after perinatal exposure. However, perinatal exposure to p,p'-DDE and TBT failed to affect the male reproductive organs and sperm parameters in matured male offspring.

Animals↗

Irregular vocal-fold vibration--high-speed observation and modeling.

Direct observations of nonstationary asymmetric vocal-fold oscillations are reported. Complex time series of the left and the right vocal-fold vibrations are extracted from digital high-speed image sequences separately. The dynamics of the corresponding high-speed glottograms reveals transitions between low-dimensional attractors such as subharmonic and quasiperiodic oscillations. The spectral components of either oscillation are given by positive linear combinations of two fundamental frequencies. Their ratio is determined from the high-speed sequences and is used as a parameter of laryngeal asymmetry in model calculations. The parameters of a simplified asymmetric two-mass model of the larynx are preset by using experimental data. Its bifurcation structure is explored in order to fit simulations to the observed time series. Appropriate parameter settings allow the reproduction of time series and differentiated amplitude contours with quantitative agreement. In particular, several phase-locked episodes ranging from 4:5 to 2:3 rhythms are generated realistically with the model.

Adult↗

Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports.

BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26-34 years old; mean BMI was 30.4 kg/m2. 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women.

Journal Article↗

Steroid delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the rat epididymis during development.

delta 4-5 alpha-Reductase activity is apparently regulated by a testicular factor(s) secreted directly into the epididymis, whereas 3 alpha-hydroxysteroid dehydrogenase activity, in this tissue, appears to reflect circulating androgen levels. To test whether the factor(s) regulating delta 4-5 alpha-reductase activity is directly associated with spermatozoa, a developmental study was undertaken to temporally correlate various parameters of the male reproductive tract with enzymatic activities. delta 4-5 alpha-Reductase activity is first detectable at 21 days of age. Activity increases until day 77, after which time enzymatic activity decreases by more than 60%, reaching steady adult values at 105 days. 3 alpha-Hydroxysteroid dehydrogenase activity is detectable as early as 7 days. Levels of this enzyme increase until day 63, after which time constant adult values are maintained until at least 1 yr. Spermatids and/or spermatozoa are first seen in the testes at 42 days, and plateau levels are reached by day 77. Spermatozoa are first seen in the epididymis at 49 days and reach maximal values by 91 days; no significant change occurs thereafter (until 365 days). Increases in seminal vesicle and ventral prostate weights are of a sigmoidal type, paralleling increases in plasma androgens, with the greatest rate of rise between days 35--63. This sigmoidal type of increase in tissue weights and plasma androgens is similar to that seen for epididymal 3 alpha-hydroxysteroid dehydrogenase but markedly different from that found for delta 4-5 alpha-reductase. The importance of delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase activities in the epididymis before the entry of spermatozoa and the decline in delta 4-5 alpha-reductase activity with age is discussed.

3-Hydroxysteroid Dehydrogenases↗