OBJECTIVE: Late follicular premature progesterone rise is a complex phenomenon encountered during assisted reproductive technology (ART) treatments; different etiologies can occur in the same patient. Low ovarian responders may be the best example, since higher FSH doses and ovarian aging-related changes may interact and generate a premature progesterone rise. This study aims to explore the correlation between progesterone levels on hCG day and the progesterone-to-follicle index and compare the progesterone-to-follicle index according to ovarian response.
METHODS: We performed a retrospective, observational, analytic, cross-sectional, and cohort study at the Reproductive Endocrinology Department at Centro Médico Nacional 20 de November between January 2015 to January 2020. After verifying for normalcy, a Spearman Rho, Principal Component Analysis, and a simple linear regression model were performed. Treatment cycles were classified according to their ovarian response. Low-ovarian responders were classified according to the Bologna Criteria. Then an ANOVA test was performed to compare each group.
RESULTS: Our results show that the progesterone-to-follicle index correlates best with progesterone levels on hCG day. Comparing all the ovarian responses, low ovarian responders have the highest progesterone-to-follicle index of the four groups.
CONCLUSIONS: Low ovarian responders produce more progesterone per follicle than regular and high responders.

This study aimed to examine the association between interindividual variability in strength changes and in training volume. A total of 26 untrained men completed 4-weeks of isometric knee extension (KE group, n = 12) and hip flexion (HF group, n = 14) training. Each training session comprised four sets of ten isometric contractions, 3-s contractions every 20 s. Training volume, which was defined as impulse during contractions, and maximal voluntary contraction (MVC) torque during KE and HF were evaluated. Based on the magnitude of MVC torque changes, the participants were divided into the high and low responders (n = 13; KE = 6 and HF = 7 per responders). The MVC torque changes (KE, 20.8%; HF, 22.4%) and total training volume did not significantly differ between the two groups. A higher training volume was demonstrated in the low responders than the high responders. The total training volume was positively associated with the MVC torque changes in low responders (r = 0.869%, 95% confidence interval [0.610, 0.960], p < 0.001), but not in high responders [r = 0.229, 95% confidence interval (-0.368, 0.693), p = 0.451], KE or HF group. Results showed that training volume was an important factor in determining the magnitude of strength gains in low responders, and MVC torque could improve by approximately 20% with the use of the study protocol regardless of joint actions involved during training.

The number and quality of embryos generated from the limited number of oocytes retrieved from low responders are important aspects of infertility treatment for these patients. This article focuses on 5 aspects relating to final maturation and laboratory techniques: follicular size at trigger, dual trigger, artificial oocyte activation (AOA), blastocyst transfer, and the role of preimplantation genetic testing for aneuploidy (PGT-A). There is lack of data regarding the role of follicular size, specifically in low-responder patients, but consideration should be given to using broader follicular size criteria when retrieving oocytes in this patient group. Use of dual trigger seems to be a good strategy in low-responder patients on the basis of initial evidence. Use of AOA with calcium ionophore may improve fertilization, embryonic development, and outcomes in cases with previous developmental problems. There is lack of data for low responders, but this promising technique deserves further study. In unselected patients, clinical trial data on blastocyst transfer are conflicting, and no high-quality studies have evaluated whether the live birth rate is higher after blastocyst transfer than after cleavage-stage embryo transfer in low responders. Specific evidence for PGT-A in low-responder patients is also lacking. Preimplantation genetic testing for aneuploidy should be considered in POSEIDON group 2 patients, especially those aged >38 years. Overall, applying the limited data available in combination with patient preference and individual patient characteristics will ensure a patient-centered and evidence-based approach that should optimize fertility outcomes for low responders.

Both thyroid dysfunction and low responsiveness to clopidogrel have been reported to be associated with increased cardiovascular risk. Our study aims at determining the relationship between free triiodothyronine (FT3) and low responsiveness to clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI).
Consecutive patients undergoing elective PCI were enrolled. All patients received a loading dose of 300 mg clopidogrel, and platelet function was assessed by thromboelastography at least 12 h later. Low responsiveness to clopidogrel was defined by an adenosine diphosphate-induced platelet-fibrin clot strength > 47 mm and adenosine diphosphate-induced platelet inhibition rate < 50%. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization.
Of 812 patients included in the study, 289 showed low responsiveness to clopidogrel. The FT3 level was significantly lower in low responders (4.61 ± 0.60 pmol/l versus 4.94 ± 4.66 pmol/l, p = 0.002). Moreover, the percentage of low responders was greater among patients with low FT3 level than among those without (56.1% versus 34.5%, p = 0.007). Logistic regression analysis showed that a FT3 level was independently associated with the risk of low responsiveness to clopidogrel (odds ratio 0.720, 95% confidence interval [CI] 0.533-0.973, p = 0.033). In patients with low responsiveness to clopidogrel, low FT3 was independently associated with increased risk of MACEs (adjusted hazard ratio 3.040, 95% CI 1.077-8.580, p = 0.036) at a median of 19-month follow-up.
Low FT3 was independently associated with increased risks of both low responsiveness to clopidogrel and cardiovascular events in patients undergoing elective PCI.

Chronic intermittent ethanol vapor exposure (CIE) in rodents produces reliable and high blood ethanol concentration and behavioral symptoms associated with moderate to severe alcohol use disorder (AUD)-for example, escalation of operant ethanol self-administration, a feature suggestive of transition from recreational to addictive use, is a widely replicated behavior in rats that experience CIE. Herein, we present evidence from a subset of rats that do not demonstrate escalation of ethanol self-administration following seven weeks of CIE. These low responders (LR) maintain low ethanol self-administration during CIE, demonstrate lower relapse to drinking during abstinence and reduced reinstatement of ethanol seeking triggered by ethanol cues when compared with high responders (HR). We examined the blood ethanol levels in LR and HR rats during CIE and show higher levels in LR compared with HR. We also examined peak corticosterone levels during CIE and show that LR rats have higher levels compared with HR rats. Lastly, we evaluated the levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the nucleus accumbens shell and reveal that the activity of CaMKII, which is autophosphorylated at site Tyr-286, is significantly reduced in HR rats compared with LR rats. These findings demonstrate that dysregulation of the hypothalamic-pituitary-adrenal axis activity and plasticity-related proteins regulating molecular memory in the nucleus accumbens shell are associated with higher ethanol-drinking and -seeking in HR rats. Future mechanistic studies should evaluate CaMKII autophosphorylation-dependent remodeling of glutamatergic synapses in the ventral striatum as a plausible mechanism for the CIE-induced enhanced ethanol drinking and seeking behaviors.

Clinical studies have shown a positive correlation between novelty-seeking behavior and the susceptibility to consume drugs of abuse. Although several animal studies have demonstrated this correlation with psychostimulants or morphine, studies with alcohol have shown conflicting results. The aim of this work was to investigate alcohol-induced motor effects in Wistar rats with different responses to novelty. Animals were classified as Low- (LR) or High-Responders (HR) to novelty, depending on their horizontal activity in an automated open field. Motor activity was recorded in naïve, saline, and alcohol-administered rats at different doses (0.1, 0.25, 0.5, 1.0, or 2.5 g/kg). Horizontal movements, rearings, and stereotyped behaviors were evaluated. After the behavioral test, animals were sacrificed and blood alcohol concentrations (BACs) were measured. Low (0.1 and 0.25 g/kg) and high (2.5 g/kg) alcohol doses decreased horizontal movements in LR animals, whereas 1.0 g/kg increased this parameter in HR rats. Rearings were increased by alcohol 1.0 g/kg in LR animals. In HR rats, alcohol doses of 0.5 and 1.0 g/kg also increased this parameter. Stereotyped behaviors were decreased by an alcohol dose of 2.5 g/kg in LR animals, but were increased by an intermediate dose (1.0 g/kg) in HR rats. Differences in horizontal movements and rearings were found between LR and HR animals at certain ethanol doses. Horizontal movements (0.25 g/kg) and rearings (0.5 g/kg) were lower in LR than HR rats; however, rearings were lower in HR than LR rats at 1.0 g/kg. BACs were similar between LR and HR rats at all ethanol doses. These findings suggest that HR rats are more responsive to the stimulant effects of intermediate alcohol doses, whereas LR animals are sensitive to low/high doses of the drug. Sensitivity to alcohol motor effects may substantially depend on the initial animal\'s response to a novel environment. The stimulant effects of alcohol may constitute important behavioral traits significantly associated with the rewarding properties of the drug.

The recent development of vitrification technologies and the good outcomes obtained in assisted reproduction technologies have supported new indications for freezing and segmentation of treatment. Beyond OHSS prevention and avoidance of embryo transfers in the setting of an adverse endocrinological profile or endometrial cavity, we have witnessed a trend to shift fresh embryo transfers to frozen embryo transfers in many programs. We critically review the available evidence and suggest that freeze-all is not \"for all,\" but should be individualized.

BACKGROUND: Conventional hepatitis B virus (HBV) vaccination fails to achieve efficient protection in about 5-10% of the world population. Hence, different strategies have been adopted to ameliorate HBV antibody titers. This study aimed to evaluate the concurrent application of tetanus-diphtheria (Td) and HBV vaccination on hepatitis B surface (HBs) antibody titer in low-responder healthy individuals.
METHODS: This was a randomized clinical trial, which was implemented among 140 of medical staff working as health-care workers assumed as low-responders. The subjects were randomly allocated to either control or interventional groups. The control and interventional groups received HBV recombinant vaccine while the latter group was also vaccinated through Td. Enzyme-linked immunosorbent assay was applied to measure HBs antibody (HBsAb) titers just before and 6 months after the last vaccination. All data were entered into SPSS software. Independent t-test, paired t-test, and Chi-square or Fisher\'s exact test were applied for data comparison.
RESULTS: Antibody titers of the subjects in the intervention and control groups soared from 49.08 ± 20.08 IU/L to 917.78 ± 204.80 IU/L and from 46.95 ± 18.55 to 586.81 ± 351.77 IU/L, respectively (both P < 0.001); nevertheless, by comparison with control group, variation of antibody titer in the interventional group was significantly higher (P < 0.001).
CONCLUSIONS: Concurrent application of Td and HBV vaccine could effectively enhance protective levels of HBsAb titers in low-responder individuals.

In this retrospective study, the efficiency of carrying out rescue intrauterine insemination (IUI) in low-responder patients undergoing IVF when no oocytes were retrieved after follicular aspiration and when HCG timing was adequate was analysed. A historical control group was used. Over 13 years, women undergoing IVF with failure to obtain oocytes at follicular aspiration underwent rescue IUI if the following criteria were met: adequate HCG timing; one normal tube; motile sperm count after preparation over 3 million/ml; and ultrasound visualization of one to six follicles over 13 mm. The rescue IUI was carried out 1 h after follicular aspiration. Results were compared with those of a standard IUI population (5394 cycles) in the same period. Confidence intervals were calculated using Poisson 97.5% confidence upper tail limits when no event was observed in the study sample. No pregnancies were achieved among the 54 cases who underwent rescue IUI (confidence interval: 0 to 6.8%). This pregnancy rate was lower than that observed in the general IUI population (17.5%) (relative risk, 19.2). After adjusting for age and endometriosis, the relative risk was 11.7. The rescue IUI is an inefficient procedure. Its efficacy is unlikely to exceed 7% pregnancy rate per IUI.