Sperm deoxyribonucleic acid fragmentation index at the time of intracytoplasmic sperm injection and standard in vitro fertilization is correlated with lower fertilization but not with blastocyst genetic diagnosis.

Objective: To determine the effects of sperm deoxyribonucleic acid (DNA) fragmentation at the time of fertilization on in vitro fertilization (IVF) outcomes and genetic diagnosis using next generation sequencing. Design: Prospective double-blinded study. Setting: Private Clinic. Patients: Couples (n = 150). Intervention: In vitro fertilization with preimplantation genetic testing for aneuploidy and sperm DNA fragmentation assay, as in sperm chromatin structure assay the day of retrieval. Main Outcome Measures: Laboratory outcomes are listed in the results section. Statistical analysis was performed using JMP, XYLSTAT, and STATA version 15. Results: The sperm DNA fragmentation index (DFI) in the neat ejaculate did not predict fertilization rate, quality, blastulation, or genetic diagnosis. No statistically significant results were obtained comparing <15% with >15%, <20% with >20%, <30% with >30% except for DFI. No statistically significant differences in oocyte source age or male age were observed. No statistically significant differences comparing <15% with >15%, <20% with >20%, <30% with >30% DFI at the time of standard IVF or intracytoplasmic sperm injection (ICSI) were observed for % euploid, aneuploid, mosaic, blastulation, biopsied, or D5/total biopsied. The DFI of >15% had more good quality D3 embryos than the <15% group, as did the >20% group compared with the <20% group. The ICSI fertilization was significantly higher in all 3 lower percentage groups compared with the higher counterpart. Standard IVF had significantly more blastocysts/fertilized suitable for biopsy and more D5/total number biopsied than ICSI embryos despite no difference in DFI. Conclusions: The DFI at fertilization is correlated with decreased fertilization for ICSI and IVF.

A multicentre evaluation of the Elecsys® anti-Müllerian hormone immunoassay for prediction of antral follicle count.

RESEARCH QUESTION: What concentration of anti-Müllerian hormone (AMH) corresponds to an antral follicle count (AFC) >15 for determination of ovarian reserve? DESIGN: A prospective study conducted at 13 US fertility clinics in women aged 21-44 years who presented for AFC evaluation by transvaginal ultrasound. Serum samples were collected at the time of AFC evaluation (menstrual cycle day 2-4). AMH concentrations were measured by the Elecsys® AMH immunoassay; oestradiol and follicle-stimulating hormone (FSH) concentrations were also measured. The serum AMH cut-off able to detect AFC >15 with high sensitivity was determined (derivation cohort). Clinical performance of the AMH assay at the derived cut-off was evaluated (validation cohort). Receiver operating characteristic (ROC) analyses were also performed. RESULTS: In the derivation cohort (n = 306), an optimal serum AMH cut-off value of 1.77 ng/ml was determined to correspond to AFC >15 with 89.63% sensitivity and 69.01% specificity, using the Elecsys AMH assay. In the validation cohort (n = 856), this 1.77 ng/ml cut-off could identify women with an AFC >15 with a sensitivity of 88.34% and a specificity of 68.29%; corresponding positive predictive and negative predictive values were 75.19% and 84.34%, respectively. ROC analyses demonstrated that AMH performed better than oestradiol or FSH in predicting AFC, with area under the curves of 85.7%, 57.1% and 69.7%, respectively, in the validation cohort. CONCLUSION: The Elecsys AMH immunoassay provides a robust and fully automated method to measure serum AMH levels. Women with AMH values below the cut-off of 1.77 ng/ml are unlikely to have AFC >15.

Pilot study to assess visualization and therapy of inflammatory mechanisms after vessel reopening in a mouse stroke model.

After reperfusion therapy in stroke patients secondary inflammatory processes may increase cerebral damage. In this pilot study, effects of anti-inflammatory therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion-weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted images with and without Bis-5HT-DTPA administration were obtained 24 hours after MCAO. Neutrophils, Myeloperoxidase-positive-(MPO+)-cells and microglia, including M1 and M2 phenotypes, were assessed immunohistochemically. Treatment with tacrolimus led to significantly smaller apparent diffusion coefficient (ADC) lesion volume within 24 hours (median -55.6mm3, range -81.3 to -3.6, vs. median 8.0 mm3, range 1.2 to 41.0; P = 0.008) and significantly lower enhancement of Bis-5-HT-DTPA (median signal intensity (SI) ratiocortex, median 92.0%, range 82.8% to 97.1%, vs. median 103.1%, range 98.7% to 104.6%; P = 0.008) compared to the NaCl group. Immunohistochemical analysis showed no significant differences between both groups. Intra-arterially administered anti-inflammatory agents after mechanical thrombectomy may improve treatment efficiency in stroke by reducing infarct volume size and MPO activity.

Dismantling Mindfulness-Based Cognitive Therapy: Creation and validation of 8-week focused attention and open monitoring interventions within a 3-armed randomized controlled trial.

BACKGROUND: While mindfulness-based interventions (MBIs) employ two distinct practices, focused attention (FA) and open monitoring (OM), the integrated delivery of these practices in MBIs precludes understanding of their practice-specific effects or mechanisms of action. The purpose of this study is to isolate hypothesized active ingredients and practice-specific mechanistic target engagement by creating structurally equivalent interventions that differ only by the active ingredient (meditation practice) offered and to test whether the hypothesized components differentially engage the mechanistic targets that they are purported to engage. METHODS: Participants were intended to be representative of American meditators and had mild to severe affective disturbances. Measures of structural equivalence included participant-level (sample characteristics), treatment-level (program structure and duration, program materials, class size, attendance, homework compliance, etc.), and instructor-level variables (training, ratings and adherence/fidelity). Measures of differential validity included analysis of program materials and verification of differential mechanistic target engagement (cognitive and affective skills and beliefs about meditation acquired by participants after the 8-week training). RESULTS: The results indicate successful creation of structurally equivalent FA and OM programs that were matched on participant-level, treatment-level, and instructor-level variables. The interventions also differed as expected with respect to program materials as well as mechanistic targets engaged (skills and beliefs acquired). CONCLUSIONS: These validated 8-week FA and OM training programs can be applied in future research to assess practice-specific effects of meditation.