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Laparoscopic ovarian drilling in polycystic ovary syndrome.

BACKGROUND AND OBJECTIVE: Patients with polycystic ovary syndrome (PCOS) treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The aim of the present study was to evaluate the efficacy of laparoscopic ovarian drilling (LOD) on the endocrinologic, clinical parameters and reproductive outcome of clomiphene-resistant anovulatory infertile patients with PCOS using monopolar diathermy. MATERIAL AND METHODS: Forty-five clomiphene-resistant anovulatory women with PCOS have participated in the study. Serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH), fasting insulin and glucose levels, body mass indexes, modified Ferriman Gallwey (FG) hirsutism scores of the subjects are recorded before and after the procedure. Endocrinologic and clinical profile and reproductive outcome of the patients were analysed. RESULTS: Ovarian drilling was successfully employed without any surgical complications and mean +/- S.D. duration of follow-up time was 29.73 +/- 10.64 months. In the follow-up period 93.3% of the subjects were recorded to have regular cycles and 64.4% pregnancy rate was achieved, spontaneously. The serum levels of T, free T, LH, LH:FSH ratio, insulin and FG scores were significantly reduced after LOD, although glucose levels and glucose/insulin ratio remained unchanged. CONCLUSION: In choosing ovulation induction method in clomiphene resistant PCOS patients, LOD may avoid or reduce the risk of OHSS and multiple pregnancy than gonadotrophins with the same success rate of conception. The high pregnancy rate, and economic aspect of the procedure offer an attractive management for patients with PCOS.

Adult↗

Determining when contamination is pollution - weight of evidence determinations for sediments and effluents.

Contamination is simply the presence of a substance where it should not be or at concentrations above background. Pollution is contamination that results in or can result in adverse biological effects to resident communities. All pollutants are contaminants, but not all contaminants are pollutants. Differentiating pollution from contamination cannot be done solely on the basis of chemical analyses because such analyses provide no information on bioavailability or on toxicity. Effects-based measures such as laboratory or field toxicity tests and measures of the status of resident, exposed communities provide key information, but cannot be used independently to determine pollution status. Laboratory studies can be predictive, but are rarely realistic. Measures of resident communities include innate natural variability and cannot easily distinguish between adaptation to contamination (a genetic process) and acclimation (a physiological process that may decrease energy reserves, possibly reducing such critical population-level parameters as reproduction). Finally, contaminant effects may not only be direct but also indirect; predicting such effects requires knowledge of the system under study as well as appropriate use of lines of evidence (LOE) such as toxicity tests directed to key species. Consequently, in sediments, effluents or other inputs/environmental compartments, determining when contamination is or may in future become pollution, requires a weight of evidence (WOE) assessment using different LOE appropriate to the situation under investigation. WOE investigations provide two different types of information: definitive conclusions regarding pollution; or, information as to what additional, investigative studies are necessary for definitive conclusions. Effectively, a WOE assessment comprises an initial screening-level ecological risk assessment (ERA), which may be followed by a detailed-level ERA if key uncertainties need to be resolved.

Geologic Sediments↗

Earthworm responses to Cd and Cu under fluctuating environmental conditions: a comparison with results from laboratory exposures.

Laboratory toxicity tests are usually conducted under stable ambient conditions, while exposures in ecosystems occur in a fluctuating climate. To assess how climate influences the toxicity of Cu and Cd for the earthworm Lumbricus rubellus, this study compared effects for life-cycle parameters (survival, reproduction), cellular status (lysosomal membrane stability), gene expression (transcript of the metal binding protein metallothionein-2) and tissue metal concentration measured under outdoor conditions, with the same responses under constant conditions as measured by Spurgeon et al. [Spurgeon, D.J., Svendsen, C., Weeks, J.M., Hankard, P.K., Stubberud, H.E., Kammenga, J.E., 2003. Quantifying copper and cadmium impacts on intrinsic rate of population increase in the terrestrial oligochaete Lumbricus rubellus. Environmental Toxicology and Chemistry 22, 1465-1472]. Both metals were found to significantly influence earthworm reproduction, compromise lysosomal membrane stability and induce MT-2 gene expression in the outdoor system. Comparison with physiological and life-cycle responses in the laboratory indicated similar response patterns and effect concentrations for Cu. For Cd, lysosomal membrane stability and MT-2 expression showed comparable responses in both exposures. Juvenile production rate, however, gave different dose response relationships, with the EC-(50) in the outdoor test approximately half that in the laboratory test. A difference in Cd accumulation was also seen. Overall, however, the comparison indicated only a marginal effect of environmental fluctuations typical for northern temperate Europe on earthworm sensitivity to the two metals.

Animals↗

Terrestrial avoidance behaviour tests as screening tool to assess soil contamination.

To assess soil quality and risk assessment, bioassays can be useful tools to gauge the potential toxicity of contaminants focusing on their bioavailable fraction. A rapid and sublethal avoidance behaviour test was used as a screening tool with the earthworm Eisenia andrei and the isopod Porcellionides pruinosus, where organisms were exposed during 48 h to several chemicals (lindane, dimethoate and copper sulphate, for isopods and carbendazim, benomyl, dimethoate and copper sulphate for earthworms). Both species were also exposed to soils from an abandoned mine. For all bioassays a statistical approach was used to derive EC50 values. Isopods and earthworms were able to perceive the presence of toxic compounds and escaping from contaminated to clean soil. Furthermore the behaviour parameter was equally or more sensitive then other sublethal parameters (e.g. reproduction or growth), expressing the advantages of Avoidance Behaviour Tests as screening tools in ERA.

Animals↗

Effects of methyltestosterone on reproduction in the Japanese quail (Coturnix coturnix japonica).

Although the hormone-mediated effects of the synthetic androgenic hormone methyltestosterone (MT) are well characterized in mammals, little is known about endocrine and other toxic effects on reproduction in birds. In a one-generation study, MT was administered to adult Japanese quail (12 pairs per group) at dietary dose levels of 0, 10, 50, and 110 ppm for a period of 3 weeks. Reproductive performance was severely affected in the groups receiving 50 and 110 ppm MT. In females, the egg-laying rate was reduced not only related to the dose administered but also to the duration of treatment. The administration of 110 ppm, and to a lesser extent, of 50 ppm MT resulted in an immediate and dramatic decrease in the total number of eggs laid, which complicated reliable assessment of other reproduction-related parameters. In males, the findings suggested inhibition of spermatogenesis at dose levels of 50 ppm and above, resulting in a subsequent reduction in male fertility.

Anabolic Agents↗

Biologically relevant tetraazamacrocyclic complexes of manganese: synthetic, spectral, antimicrobial, antifertility and antiinflammatory approach.

The testicular sperm density, sperm morphology, sperm motility, density of cauda epididymis spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed for [Mn(N(4)MacL(n))(NO(3))(2)] (where N(4)MacL(n) represents the tetraazamacrocyclic ligand molecule with n=1-4) type of complexes. An attempt also has been made to correlate the structural aspects of the compounds with their anti-inflammatory activity. The 14-18 membered tetraamide macrocyclic ligands N(4)L(1)-N(4)L(4) used during these investigations have been prepared by the condensation of 1,2-diaminoethane or 1,3-diaminopropane with malonic or succinic acid in the presence of condensing reagents, dicyclohexylcarbodiimide and 4-dimethylaminopyridine. On reduction, these macrocyclic ligands give a new series of tetraazamacrocyles [N(4)MacL(n)] and their complexes with manganese(II) nitrate. The ligands and their complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, mass and X-ray structural analyses. An octahedral geometry for these complexes has been confirmed by spectral studies. On the basis of the chemical composition, the representation of the complexes as [Mn(N(4)MacL(n))(NO(3))(2)] has been established. The ligands and their complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential.

Animals↗

Health and production measures for smallholder pig production in Kikuyu Division, central Kenya.

A longitudinal study was carried out in Kikuyu Division (a peri-urban area in central Kenyan highlands) between January 1999 and December 1999 to estimate the baseline parameters on reproductive performance of the sow, as well as health and productivity of grower and preweaning pigs of smallholder herds. Data were collected on 155 breeding pigs, 795 grower pigs and 801 preweaning piglets in 74, 50 and 40 smallholder herds, respectively, using record cards that were updated during monthly visits. The sow-level medians were: weaning-to-service interval 3 months; interfarrowing interval 6.4 months; number of live-born piglets 9.0; and number of piglets weaned per litter 7.5. The piglet crude morbidity incidence risk was 29%. The cause-specific incidence risks for the important health problems encountered in preweaned piglets were diarrhea (4.3%), pruritus (17.1%), and skin necrosis (4.2%). The estimated crude mortality incidence risk to 8 weeks of age was 18.7%. The cause-specific mortality incidence risks to 8 weeks of age for the important causes of mortality were overlying (9.9%), savaging (2.4%), unviable piglets (2.0%) and unknown (1.9%). Overall, 78.8% of the total live-born piglet mortality occurred during the first week postpartum with 69% of these deaths being caused by overlying. The grower-pig crude morbidity incidence risk was 20% and the cause-specific incidence risks of the important health problems encountered were gut edema (1.3%), pruritus (21.1%), and unknown (2.3%). The crude mortality incidence risk was 3.8% and the important causes were gut edema and unknown causes (cause-specific mortality incidence risks of 1.3 and 1.6%, respectively). The median weight:age ratio and average daily weight gain for the grower pigs were 5.1 kg/month of age and 0.13 kg/day, respectively. For preweaning pigs, the median average daily weight gain was 0.13 g/day.

Animal Husbandry↗

Prenatal developmental toxicity study with 7-hydroxymatairesinol potassium acetate (HMRlignan) in rats.

Plant lignan 7-hydromatairesinol, a novel precursor of the mammalian lignan enterolactone was evaluated in a prenatal developmental toxicity study conducted in the Wistar rat. Mated female rats were fed diets containing 0, 0.25, 1, and 4% (w/w) of 7-hydroxymatairesinol in the form of potassium acetate complex (HMRlignan; potassium acetate level approximately 20% w/w within the preparation) for days 0-21 of gestation. Test substance intake was calculated to be 0.14-0.18, 0.46-0.74, and 1.19-2.93 g/kg body weight/day for the low, mid, and high-dose groups, respectively. The rats were sacrificed on day 21 of the gestation period and examined for standard parameters of reproductive performance (fecundity index, gestation index, number of corpora lutea, number of implantations, pre- and post-implantation loss, number of early- and late resorptions, number of live- and dead fetuses, sex-ration and the weight of the reproductive organs). The fetuses were examined for external, visceral, and skeletal alterations. The results from this study showed no effects on reproductive performance or any treatment related findings following external, visceral, and skeletal examination of the fetuses. However, approximately half of the mated dams of the high-dose failed to thrive due to an unexpected large decrease in their food intake, and were sacrificed early. Body weights of the remaining animals of the high-dose group were decreased. Food consumption was decreased in all treatment groups during the first three days of the gestation period as a result of decreased palatability of the feed. In conclusion, the no-observed-effect level (NOEL) for maternal effects was 1%, whereas the NOEL for fetal development following daily oral HMRlignan administration throughout the gestation was equivalent to 4% in the diet.

Administration, Oral↗

Comparison of sperm parameters, in vitro fertilization results, and subsequent pregnancy rates using sequential ejaculates, collected two hours apart, from oligoasthenozoospermic men.

OBJECTIVE: To evaluate the effect of second consecutive ejaculate collected 2 hours after the first one from infertile men on sperm quality and fertilization and pregnancy rates (PRs) in IVF. DESIGN: A prospective case-control study. SETTING: In vitro fertilization unit of a university hospital. PATIENTS: Thirty-nine consecutive infertile patients with oligoasthenozoospermia scheduled for IVF-ET. MAIN OUTCOME MEASURES: Two consecutive ejaculates were obtained 2 hours apart and were assessed for volume, sperm count, motility, morphology, and quality of swim-up fraction. The subsequent fertilization, cleavage, and PRs (as defined by the appearance of intrauterine gestational sac) were compared between the two ejaculates. RESULTS: In 28.2% of the individuals the semen analysis of the first ejaculate precluded proceeding with IVF. A statistically significant improvement was shown in sperm cell motility (31.9% +/- 20.7% versus 15.6% +/- 15.3%) and in motile count after swim-up (4.9 +/- 4.5 versus 2.6 +/- 3.1 x 10(6) sperm). No improvement could be demonstrated in sperm density or morphology. The volume of the second ejaculate was decreased significantly as compared with the first one. The fertilization rate, the cleavage rate, and PR were all increased when oocytes were exposed to sperm from the second ejaculate compared with oocytes exposed to sperm from the first ejaculate. The overall PR in our series was 25.6%. CONCLUSIONS: We suggest that in the group of infertile men with oligoasthenozoospermia, whose partners are scheduled for IVF-ET, if on the day of retrieved oocytes insemination, the ejaculate is of unacceptable quality, a second ejaculate collected 2 hours after collection of the initial ejaculate may produce a sample that exhibits improvements in both semen parameters and reproductive potential.

Adult↗

Characterization of idiopathic premature ovarian failure.

OBJECTIVE: To characterize women with idiopathic premature ovarian failure (POF) by their ovarian ultrasonographic appearances to establish the prevalence of follicular activity and relationship to autoimmunity, estrogen status, and historical background. DESIGN: Retrospective analysis of clinical, endocrine, autoimmune, ultrasonographic, and bone densitometry parameters. SETTING: Reproductive Endrocrinology Clinics of The Middlesex Hospital, London, United Kingdom. PATIENTS: Data from 135 women with idiopathic POF were analyzed. A reference group of 18 women with normal ovarian function, studied in their follicular phase, was used for comparison of endocrine and ultrasound data. A reference group of 57 women with normal ovarian function was used for comparison of bone densitometry measurements. MAIN OUTCOME MEASURES: Serum E2 concentrations, autoantibody screen, ultrasonographic measures of ovarian volume, uterine cross-sectional area and endometrial thickness and dual roentgenogram bone mineral densitometry of the lumbar spine. RESULTS: The detection of ovaries by ultrasound (in 76%) and follicular activity (in 60% of patients) was associated with higher bone mineral density compared with women in whom ovaries could not be identified. Of 13 patients presenting with primary amenorrhea, ultrasonography identified ovaries in 62% and follicles in 38% whereas 38% had positive autoimmunity. Evidence of autoimmunity was found in 31% of patients overall and these were indistinguishable from the nonautoimmune remainder in every respect. CONCLUSIONS: Ovarian follicular activity, previously considered to be rare, as in the "resistant ovary syndrome," is found in the majority of women with POF using pelvic ultrasonography. Patients presenting with primary amenorrhea have a similar degree of ovarian function, determined by ultrasound, and autoimmunity as those presenting with secondary amenorrhea. The role of autoimmunity in the pathogenesis of POF is not distinguished from nonautoimmune ovarian damage by the measurements made in this study.

Adolescent↗

First ovulation and ketone body status in the early postpartum period of dairy cows.

The effect of ketone body status on occurrence of first ovulation during early lactation was assessed in 84 multiparous dairy cows under field conditions. Animals were equally distributed across 8 farms and were controlled by the same herd fertility monitoring program. Cows were visited twice antepartum and 6 times postpartum at weekly intervals between 5:30 and 8:30 AM. On these occasions, body condition scores and milk yields were measured, blood and milk samples were taken, cows were gynecologically examined, and parameters of reproduction were determined. The onset of first ovulation was specified by milk progesterone determination and rectal palpation. Cows starting postpartum ovarian cyclicity within or after 30 d were classified as early and late responders (ER and LR, respectively). Resumption of the estrous cycle within 30 d postpartum is considered optimal under practical conditions, and classification based on this threshold value resulted in groups of equal size and equal distribution of ER + LR cows within farms. Ketone bodies measured were beta-hydroxybutyrate in serum and acetoacetate and acetone in serum and milk. Blood serum and milk ketone body concentrations during the first 6 wk of lactation were higher in LR than in ER, whereas plasma glucose and nonesterified fatty acid and milk fat, protein and urea concentrations did not differ between groups. Maximal concentrations of ketone bodies from parturition to first ovulation were better predictors of the onset of the estrous cycle than mean or minimal concentrations over the same period. Milk acetone and serum beta-hydroxybutyrate concentrations provided the most reliable information with regard to resumption of ovarian activity of all ketone bodies.

3-Hydroxybutyric Acid↗

Effect of level of feed intake on the development of gastrointestinal parasitism in growing lambs.

A study was conducted to examine the role of nutrition in the development of gastrointestinal (GI) parasitism, performance and pathophysiology of parasitism in female lambs. Forty-four months old ewe lambs received for 6 weeks 0, 1500 or 7000 L(3) larvae of Teladorsagia circumcincta in two doses per week. The animals were given access to a pelleted diet to meet energy requirements for gaining weight close to their potential (H) or approximately 50% of it (L). The level of protein in the diet was 20-30% above requirements for both planes of nutrition. Measurements of body weight, serum pepsinogen concentration and faecal egg counts were taken at weekly intervals. All animals were slaughtered 2 weeks after the last larval dosing for estimation of worm count, carcass composition and reproductive tract development. Voluntary intake of infected animals decreased by approximately 10%. Both nutrition and infection influenced lamb performance and carcass composition. However, no direct effects on reproductive tract parameters due to the presence of infection were observed. The level of L(3) infection showed a significant effect not only on faecal egg counts and on worm burden, as it could be expected, but also on the proportion of females to males, which increased significantly with the level of infection. While the plane of nutrition did not show a significant effect on faecal egg counts or on worm burden, surprisingly, both female worm size and their fecundity decreased significantly with the level of nutrition. This response was accompanied by a significant increase in the concentration of circulating eosinophils suggesting that the immune response of lambs consuming high levels of energy was enhanced compared to that of lambs kept on a restricted diet. Results herein show that in young female lambs fed on adequate levels of protein, an improvement in energy supply does not only improve carcass characteristics but clearly enhances the development of resistance to GI nematodes infection. This may have decisive management implications for the control of parasitic infections in sustainable production systems.

Animals↗

Investigation of the teratogenic potential of a zingiber officinale extract in the rat.

The teratogenicity of EV.EXT 33, a patented Zingiber officinale extract, was examined in Wistar SPF rats according to GLP Guidelines. EV.EXT 33 was administered by oral gavage in concentrations of 100, 333, and 1000 mg/kg, to three groups of 22 pregnant female rats from days 6 to 15 of gestation. For comparison, a fourth group received the vehicle, sesame oil. Body weight and food and water intake were recorded during the treatment period. The rats were killed on day 21 of gestation and examined for standard parameters of reproductive performance. The fetuses were examined for signs of teratogenic and toxic effects.EV.EXT 33 was well tolerated. No deaths or treatment-related adverse effects were observed. Weight gain and food consumption were similar in all groups during gestation. Reproductive performance was not affected by treatment with EV.EXT 33. The examination of fetuses for external, visceral, and skeletal changes showed no embryotoxic or teratogenic effects of EV.EXT 33. Based on these results, it was concluded that EV.EXT 33, when administered to pregnant rats during the period of organogenesis, caused neither maternal nor developmental toxicity at daily doses of up to 1000 mg/kg body weight.

Abnormalities, Drug-Induced↗

Assessment of the perinatal effects of maternal ingestion of Solanum malacoxylon in rats.

A perinatal study was performed to verify the toxic effects of Solanum malacoxylon, which contains a glycoside conjugated to Vitamin D(3). In the gestational study, female rats received S. malacoxylon leaves in the diet at 0, 0.1, 0.2, 0.5, and 1% from days 6 to 21 of pregnancy. At 21 days of gestation, blood samples were taken from the dams for evaluation of serum Ca and P. A laparotomy was performed and the rats were examined for standard parameters of reproductive performance. Fetuses were examined for skeletal changes and histopathologic evaluation. In the second trial, dams were fed diets containing 0 or 0.1% S. malacoxylon leaves during the gestation and lactation periods. After weaning, all animals were euthanized and biochemical and histopathologic evaluations were performed. The biochemical evaluation showed increase in Ca and P levels in females from all experimental groups; however, this effect did not occurred in a dose-related manner. Pups from dams exposed during gestation and lactationi also showed increased Ca and P levels. Fetal data suggested a delay of fetal development manifested by decreased body weight and skeletal alterations. There was also a reduction in live fetuses. Histopathologic study revealed alterations of the soft tissue in litters from dams given 1% dietary S. malacoxylon during pregnancy and 0.1% during pregnancy and lactation. These findings support our hypothesis that Vitamin D(3) glycoside crosses the placenta and suggests milk transfer of this substance.

Abnormalities, Drug-Induced↗

Use of primate folliculogenesis models in understanding human reproductive biology and applicability to toxicology.

The nonhuman primate reproductive system provides an excellent model for studying basic physiological processes applicable to humans. This article reviews hormonal observations and experimental manipulations useful in the evaluation of ovarian events in various stages of the reproductive life. As the need arises, primate reproductive toxicological studies may clarify questions relevant to human risk evaluations. Evaluation of reproductive toxicological observations may reveal biological parameters defining premature reproductive failure.

Animals↗

Interpretation of serological surveillance data for measles using mathematical models: implications for vaccine strategy.

Serological surveillance of measles immunity has been carried out in England since 1986/7. Results from sera collected in 1989-91 revealed that the proportion of school age children who were susceptible to measles was increasing, following the introduction of the measles, mumps and rubella vaccination programme in October 1988. Mathematical models are used to interpret these data and determine whether this increasing susceptibility is sufficient to allow a resurgence of disease from the low levels achieved by 1993. The models summarize serological profiles by a single parameter, the reproduction number R, which quantifies the level of herd immunity in the population. Results showed that there was cause for concern over the levels of susceptibility to measles, with an epidemic of over 100,000 cases likely in 1995/6. These predictions are consistent with trends in the incidence and age distribution of measles and have enabled the planning of a major vaccination campaign.

Adolescent↗

Accumulation of deleterious mutations and equalization of parental contributions in the conservation of genetic resources.

Typical management strategies for the conservation of endangered species in captivity, such as equalization of family sizes, deal with the need for maintaining genetic variability and low levels of inbreeding, and for preventing the population from adapting to captivity. But they also produce a reduction in the intensity of natural selection, so that deleterious mutations can accumulate more easily in small populations. We have carried out computer simulations to investigate the effect of equalizing contributions on the accumulation of deleterious mutations. The models include effects on fecundity and viability, and account for different sets of mutational parameters and reproductive rates. The effect of relaxation of selection under captive conditions was also investigated. Our results suggest that equalization of family sizes does not produce a particularly high threat to small conserved populations, at least in the short term (up to about 20 generations), and the more efficient preservation of genetic variability seems to be a clear advantage of the procedure.

Computer Simulation↗

Time empty and ketone body status in the early postpartum period of dairy cows.

This study aimed to assess the effect of ketone body status early postpartum on time empty in 74 multiparous dairy cows under field conditions. Animals were equally distributed across eight farms and were controlled by the same herd-fertility-monitoring programme. Cows were visited twice antepartum and six times postpartum at weekly intervals between 0530 and 0830 a.m. On these occasions, body condition scores and milk yields were measured, blood and milk samples were taken, cows were gynaecologically examined, and parameters of reproduction were recorded. Cows with a time empty of less or more than 80 days were classified as early and late conceiving cows (EC and LC, respectively). A time empty of 80 days results in calving-to-calving intervals of 1 year and classification based on this threshold value resulted in groups of equal size and equal distribution of EC and LC within farms. Ketone bodies measured were beta-hydroxybutyrate in blood and acetoacetate and acetone in blood and milk. Blood and milk ketone body concentrations, as well as the ratios of acetoacetate and acetone to beta-hydroxybutyrate, over the first 6 weeks postpartum were higher in LC than in EC, whereas plasma glucose and non-esterified fatty acids and milk fat, protein and urea concentrations did not exhibit clear differences between groups. Ketone body concentrations were as good predictors of time empty as ketone body ratios and might have practical impact in herd-fertility-monitoring programmes.

Acetoacetates↗