Premature LH and progesterone rise in intrauterine insemination cycles: analysis of related factors

Premature LH and progesterone surges are associated with different factors and hormonal modulators. The aim of the present study was (i) to investigate the clinical and laboratory factors and (ii) to highlight the importance of different stimulation protocols in associated premature LH and progesterone surges in intrauterine insemination (IUI) cycles. The study involved a retrospective investigation of 75 patients undergoing IUI for infertility treatment (135 IUI cycles) between 1996 and 2000, with initial serum LH concentrations >10 mIU/ml during ovarian stimulation. Ultrasound characteristics, follicular sizes, serum oestradiol, progesterone and LH concentrations and ovarian stimulation protocols were measured. There was a wide range of oestradiol serum concentrations (93-2245 pg/ml) and follicular size (12-25 mm). In 49.6% of cycles, the dominant follicle was <16.5 mm. Patients with >2 follicles measuring <15 mm had higher oestradiol serum concentrations (P = 0.008). Multiple regression analyses revealed no association between these variables and premature LH/progesterone surge. In conclusion, LH/progesterone surges cannot be predicted utilizing clinical parameters normally employed, e.g. ultrasound serum oestradiol assay or ovarian stimulation protocol. Patients with follicles >14 mm or more and with high numbers of small follicles and high oestradiol are at risk of a spontaneous LH surge. These variables can be used to time the administration of GnRH antagonist administration until better predictive factors are demonstrated.     

Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens

OBJECTIVE: To investigate whether luteal E(2) administration reduces size discrepancies of early antral follicles. DESIGN: Prospective, crossover study. SETTING: ART unit, Clamart, France. PATIENT(S): Sixty women and 120 cycles. INTERVENTION(S): On cycle day 3 (baseline day 3), all women underwent measurements of early antral follicles by ultrasound and serum FSH and ovarian hormones. From day 20 until the next cycle day 2, 30 of them received oral 17beta-E(2), whereas the remaining women served as controls. The day after E(2) discontinuation (E(2) day 3) or on subsequent cycle day 3 (control day 3), participants were reevaluated as on baseline day 3. MAIN OUTCOME MEASURE(S): Magnitude of follicular size discrepancies. RESULT(S): Follicular size discrepancies and follicular diameters were significantly attenuated on E(2) day 3 (3.7 +/- 0.5 mm) as compared with baseline day 3 (4.9 +/- 1.0 mm), but not in controls (5.0 +/- 0.8 vs. 4.9 +/- 0.8 mm). FSH (4.3 +/- 1.9 vs. 7.3 +/- 3.3 mIU/mL) and inhibin B (34 +/- 28 vs. 71 +/- 32 pg/mL) levels were consistently lower on E(2) day 3 than on baseline day 3 but remained unchanged in controls. CONCLUSION(S): Luteal E(2) administration reduces the size and improves the homogeneity of early antral follicles on day 3. This approach may be instrumental in synchronizing follicular development during controlled ovarian hyperstimulation.     

Critical analysis of the neural systems organizing innate fear responses

Unconditioned emotional responses elicited by exposure to a predator have served as the prototypical exemplar for analyses of the behavioral biology of fear-related emotionality. However, the primary research model for the study of fear has involved shock-based cue and context conditioning. While these shock-based models have provided a good understanding of neural systems regulating specific conditioned fear-related behaviors (typically freezing), it is not known if the neural systems underlying an array of defensive responses to innate, unconditioned, painless threat stimuli, and conditioning to these stimuli, are the same as those involved in foot shock and its conditioning sequellae. Recent work involving lesions and c-Fos activation in conjunction with predator or predator odor exposure suggest specific neural systems for response to these, potentially different from the systems outlined in Pavlovian fear conditioning studies. As outlined in the present review, these systems include the medial hypothalamic defensive circuit; specific amygdalar and septo-hippocampal territories, involved in processing, respectively, cues related to the predator presence and environmental contextual analysis; and the periaqueductal gray, known to be critically involved in the expression of predator-induced responses. This information may be potentially important in analysis of defense-related psychopathologies and in the design of therapeutic interventions for them.     

Predatory hunting and exposure to a live predator induce opposite patterns of Fos immunoreactivity in the PAG

Considering the periaqueductal gray's (PAG) general roles in mediating motivational responses, in the present study, we compared the Fos expression pattern in the PAG induced by innate behaviors underlain by opposite motivational drivers, in rats, namely, insect predation and defensive behavior evoked by the confrontation with a live predator (a cat). Exposure to the predator was associated with a striking Fos expression in the PAG, where, at rostral levels, an intense Fos expression was found largely distributed in the dorsomedial and dorsolateral regions, whereas, at caudal levels, Fos-labeled cells tended to be mostly found in the lateral and ventrolateral columns, as well as in the dorsal raphe nucleus. Quite the opposite, insect predation was associated with increased Fos expression predominantly in the rostral two thirds of the lateral PAG, where the majority of the Fos-immunoreactive cells were found at the oculomotor nucleus levels. Remarkably, both exposure to the cat and insect predation upregulated Fos expression in the supraoculomotor region and the laterodorsal tegmental nucleus. Overall, the present results clearly suggest that the PAG activation pattern appears to reflect, at least partly, the animal's motivational status. It is well established that the PAG is critical for the expression of defensive responses, and, considering the present findings, it will be important to investigate how the PAG contributes to the expression of the predatory behavior, as well.     

Prevention of thromboembolism in patients with mitral stenosis and associated atrial fibrillation: effectiveness of low intensity (INR target 2) oral anticoagulant treatment

Mitral stenosis (MS) in association with atrial fibrillation (AF) is a clinical condition at high risk for systemic thromboembolism. Although oral anticoagulants greatly reduce the incidence of thromboembolism in these patients, the optimal intensity of treatment has never been tested in specific clinical trials, and current recommendations are derived from studies of nonrheumatic AF. In this study we tested the effectiveness of two different intensities. The study design was carried out as an open randomized prospective study in an anticoagulation clinic. We randomized 103 patients with MS and AF to a low (target INR = 2) or moderate (target INR = 3) anticoagulation regimen. The primary end points were systemic thromboembolism, major bleeding and vascular death. During a mean follow-up of 4.5 years, 1 systemic embolism occurred in the low intensity group (0.41 per 100 pt/yrs, CI 0.01-2.3), and 1 minor stroke occurred in the moderate intensity group (0.40 per 100 pt/yrs, CI 0.01-2.3; p = ns). Major bleeding occurred in 8 patients, with 3 in the low intensity (1.25 per 100 pt/yrs) and 5 in the moderate intensity group (2.0 per 100 pt/yrs, Incidence Rate Ratio 0.6, CI 0.1-3.1; p = ns). Total events (systemic embolism, major bleeding and vascular death) occurred in 7 low intensity patients and 8 moderate intensity patients. As expected, minor bleeding was more frequent in the moderate intensity group of patients, who actually had more intense treatment and required closer monitoring of oral anticoagulant treatment. These data suggest that low intensity anticoagulation, as performed in an anticoagulation clinic, is effective and safe in high risk patients with MS and AF.     

Guidelines on the treatment of chronic coinfection by Trypanosoma cruzi and HIV outside endemic areas

As a result of population migration, Chagas disease is no longer limited to the North and South American continents. In HIV-infected patients, chronic infection by Trypanosoma cruzi behaves as an opportunistic infection in severely immunosuppressed patients and is responsible for high morbidity and mortality. Unlike other opportunistic infections, information on the natural history, diagnosis, treatment, and prevention of Chagas disease is scarce. Spain has the highest number of cases of Chagas disease outside the North and South American continents, and coinfection with HIV is increasingly prevalent. In this article, the Spanish Society for Tropical Medicine and International Health (Sociedad Espa?ola de Medicina Tropical y Salud Internacional) reviews the current situation of coinfection with HIV and T. cruzi infection and provides guidelines on the diagnosis, treatment, and prevention in areas where Chagas disease is not endemic. It also identifies areas of uncertainty where additional research is necessary.     

LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility

Purpose

To verify if polymorphisms of LH (Trp8Arg/Ile15Thr), LH receptor (insLQ), and FSH receptor (Asn680Ser) are associated with endometriosis and infertility.

Methods

This is a prospective case–control study. Sixty-seven patients with endometriosis and infertility (study group) and 65 healthy fertile patients (control group) were enrolled in the study between July 2010 and July 2013. All patients had their endometriosis diagnosis made or excluded by laparoscopic surgery; study group was submitted to the surgery for infertility investigation and control group for tubal ligation. Day-3 serum hormones were collected from all patients. Analysis of nucleotide mutations for LH polymorphisms (Trp8Arg and Ile15Thr), LHR polymorphism (insLQ), and FSHR polymorphism (Asn680Ser) were performed by PCR.

Results

Day-3 FSH, estradiol and LH serum levels were not different between the groups, while CA-125 was higher in patients with endometriosis and infertility. All polymorphisms studied were in Hardy-Weinberg equilibrium. The prevalence of insLQ was significantly higher in patients with endometriosis and infertility (P = 0.005). Allele occurrence in control group was 0.10 versus 0.25 in infertile endometriosis group (P = 0.001). There was no difference regarding Trp8Arg/Ile15Thr (P > 0.05) and Asn680Ser (P > 0.05) prevalence between groups.

Conclusion

This is the first time that prevalence of insLQ was shown to be higher in patients with endometriosis and infertility than in healthy fertile patients. There was no difference in LH and FSHR polymorphisms’ prevalence between groups.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0477-3) contains supplementary material, which is available to authorized users.     

Prenatal Exposure to Glyphosate and Its Environmental Degradate,Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case–Control Study in the PROTECT Cohort (Puerto Rico)

Background: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.Objectives: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case–control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.Methods: GLY and AMPA in urine samples collected at 18±2 (Visit 1) and 26±2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).Results: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56)μg/L for GLY and 0.25 (3.06) and 0.20 (2.87)μg/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity–corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1–3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.Discussion: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case–control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted. https://doi.org/10.1289/EHP7295     

Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating

Binge eating disorder is an addiction-like disorder characterized by episodes of rapid and excessive food consumption within discrete periods of time which occur compulsively despite negative consequences. This study was aimed at determining whether antagonism of Sigma-1 receptors (Sig-1Rs) blocked compulsive-like binge eating. We trained male wistar rats to obtain a sugary, highly palatable diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day under fixed ratio 1 operant conditioning. Following intake stabilization, we evaluated the effects of the selective Sig-1R antagonist BD-1063 on food responding. Using a light/dark conflict test, we also tested whether BD-1063 could block the time spent and the food eaten in an aversive, open compartment, where the palatable diet was offered. Furthermore, we measured Sig-1R mRNA and protein expression in several brain areas of the two groups, 24 h after the last binge session. Palatable rats rapidly developed binge-like eating, escalating the 1 h intake by four times, and doubling the eating rate and the regularity of food responding, compared to Chow rats. BD-1063 dose-dependently reduced binge-like eating and the regularity of food responding, and blocked the increased eating rate in Palatable rats. In the light/dark conflict test, BD-1063 antagonized the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. Finally, Palatable rats showed reduced Sig-1R mRNA expression in prefrontal and anterior cingulate cortices, and a two-fold increase in Sig-1R protein expression in anterior cingulate cortex compared to control Chow rats. These findings suggest that the Sig-1R system may contribute to the neurobiological adaptations driving compulsive-like eating, opening new avenues of investigation towards pharmacologically treating binge eating disorder.     

The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating,Food-Seeking Behavior,and Compulsive Eating: Role of the Nucleus Accumbens Shell

Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic N-methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive NMDA receptor antagonist memantine on palatable food-induced behavioral adaptations using a rat model, which mimics the characteristic symptomatology observed in binge-eating disorder. For this purpose, we allowed male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed-ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding, we tested the effects of memantine on the Chow and Palatable food groups'' intake. Then, we tested the effects of memantine on food-seeking behavior, under a second-order schedule of reinforcement. Furthermore, we investigated the effects of memantine on the intake of food when it was offered in an aversive, bright compartment of a light/dark conflict test. Finally, we evaluated the effects of memantine on FR1 responding for food, when microinfused into the nucleus accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like eating and fully blocked food-seeking behavior and compulsive eating, selectively in the Palatable food group. The drug treatment did not affect performance of the control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion of memantine decreased binge-like eating. Together, these findings substantiate a role of memantine as a potential pharmacological treatment for binge-eating disorder.