Study design: Literature review. Objectives: Critical review of the literature published on the physiological alterations caused by spinal cord injury (SCI) and their effect on the pharmacokinetic parameters of commonly employed drugs. The review introduces the most recent treatment protocols of a variety of drugs, enabling the modern clinician to apply efficacious and cost-effective solutions to the pharmacological treatment of SCI patients. Methods: Studies published in international indexed journals up to January 2011 were selected from the PubMed database. Results: The review evaluated the sequelae of SCI and their effect on pharmacological processes. The results demonstrated that these alterations affected the pharmacokinetics of drugs commonly administered to SCI patients, such as antibiotics, muscle relaxants, immunosuppressants and analgesics. Conclusion: There are multiple etiologies to SCI and patients present with varying degrees of impairment. Factors such as level of injury and completeness of the injury create a very heterogeneous population within the SCI community. The heterogeneity of this population creates a problem when trying to standardize pharmacokinetic (PK) parameters. It is because of this that specific physiological alterations must be linked to changes in PK and be identified within the clinical setting. This relationship between physiology and PK enables the clinician to be alert for possible pharmacological complications in individual patients based on their clinical manifestations. Future research should aim to develop rigorous therapeutic guidelines tailored to the diverse manifestations of SCI so as to provide effective, affordable and safe pharmacotherapy.Spinal Cord (2011) 49, 955-960;

2.2; p¼0.32) were not significantly different between the dual trigger and hCG alone groups. The oocyte collection (62.5% vs. 64.6%; p¼0.75) and oocyte maturation rates (77.5% vs. 76.2%; p¼0.82) were also comparable. Per embryo transfer, the clinical pregnancy rate (15.2 vs. 12.6; p¼0.96) and ongoing pregnancy rate (13.8 vs. 12.6; p¼0.63) showed no statistical differences.CONCLUSIONS: There was no significant increase in oocyte collection or maturation rates following dual triggering of final oocyte maturation compared with hCG alone in women with POR. POR (Bologna criteria) represents a subgroup of women with a very poor pregnancy prognosis and also a very challenging fertility management. Although the preliminary findings of this trial do not seem to hold promises in favor of an improved outcome with dual triggering of oocyte maturation in this subgroup of women, conclusive evidence are expected only following completion of the recruitment period.SUPPORT: None.

of an association between embryo biopsy and the four groups of ultrasound heartbeats (p¼0.11).. CONCLUSIONS: 1. Embryo biopsy does not increase the chance of monozygotic multiple pregnancies.2. The precise mechanism of monozygotic twinning following ART remains unclear, however this information is important when counseling patients about the risks associated with embryo biopsy.

Study question Can implantation failure (IF) and pregnancy loss be predicted in serum prior to in vitro fertilization (IVF)? Summary answer Tumor necrosis factor (TNFα) and milk fat globule-epidermal growth factor 8 (MFG-E8) levels may serve as serum markers to predict IF and pregnancy loss. What is known already In a normal pregnancy, mediators such as TNFα are released creating a physiological inflammatory response. However, an exaggerated release of TNFα has been associated with IF and recurrent pregnancy loss (RPL). Recent studies demonstrated that TNFα up-regulates the expression of inflammatory factors such as MFG-E8. MFG-E8 is known to modulate implantation by acting at various levels of the trophoblast and endometrial compartments. Hence an overexpression of this protein may result in apoptosis, endometrial damage, and impaired implantation. Study design, size, duration This multicentric prospective controlled pilot clinical study was conducted from January 2016 to January 2020 and included 30 women in their natural cycle in which serum MFG-E8, TNFα, estradiol (E2), and progesterone (P4) levels were quantified in the early proliferative (cycle day 2) and secretory phases (urinary LH + 7 days). Additionally, an endometrial biopsy was obtained on urinary LH + 7 days for MFG-E8 and TNF α protein and gene expression analysis. Participants/materials, setting, methods Women ages 21-35y were recruited from 3 groups: fertile controls (C), unexplained IF (following 3 failed good quality embryo transfers), and RPL (at least 2 unexplained first trimester miscarriages). Patients with history of uterine surgery, abnormal uterine cavity (fibroids, endometrial polyps, adhesions, adenomyosis, and congenital uterine abnormalities), hydrosalpinx, diminished ovarian reserve, harboring chromosomal rearrangements, thrombophilia, or autoimmune diseases were excluded. Main results and the role of chance Ten women were included in each group. No statistical differences were found in age, BMI, AMH, baseline FSH, and baseline antral follicle count among cohorts. Mean serum E2 and P4 levels were similar among all groups in both the proliferative and secretory phases: E2 proliferative (C 69.19±26.64  pg/ml, IF 64.19±32.56  pg/ml, RPL proliferative 57.44±38.51; p = 0.55), E2 secretory (C 164.10±52.57  pg/ml, IF 172.57±121, RPL 173.81±.97.35; p = 0.25), P4 proliferative (C 0.45±0.15 ng/ml, IF 0.45±0.19 ng/ml, RPL 0.53±0.18 ng/ml; p = 0.85), P4 secretory (C 7.42±4.06 ng/ml, IF 7.8±4.56 ng/ml, RPL 8.05±4.38 ng/ml; p = 0.74). Mean serum TNFα levels were significantly higher in both, the proliferative and secretory phases for the RPL group (proliferative RPL 9.98±4.47  pg/ml, IF 4.73±2.56  pg/ml, C 3.42±1.01  pg/ml; p = 0.001 vs secretory RPL 8.67±4.45  pg/ml, C 3.35±0.94  pg/ml, IF 3.85±1.01  pg/ml; p = 0.03). Mean serum MFG-E8 levels were significantly higher in the IF group during the proliferative phase (IF 373±201  pg/ml, RPL 201±115  pg/ml, C 225.58±109.73pg/ml; p = 0.03), but not in the secretory phase (IF 237±101  pg/ml, RPL 189±116  pg/ml, C 199.41±112.43  pg/ml; p = 0.15). Endometrial MFG-E8 mRNA levels were significantly lower in the IF and RPL group compared to C (p = 0.03). TNFα mRNA levels were not statistically significant among groups (p = 0.12). Limitations, reasons for caution This is a pilot study to assess feasibility. Due to the small sample size, the effects of more subtle covariates would not have been detected. Future larger studies are warranted. Wider implications of the findings These novels differentially expressed serum and endometrial markers may provide information on the physiology of implantation and could generate the basis for non-invasive diagnostic tools and therapeutic use of MFG-E8/TNFα antagonists in women with IF and RPL. Trial registration number IIT-2014-100366

RESULTS: 1108 blastocysts derived from 259 IVF/PGT-A cases were included in the study. The groups consisted of 126 cases (n¼ 543 embryos) with elevated DFI and 133 cases (n¼ 565 embryos) with normal DFI. Significant differences were found in mean male age (39.8 AE6, 37.8AE5,p¼0.004), female age (36.2AE4, 34.8AE4, p¼0.007) and cases with normal morphological sperm analysis (37%, 56.3%, p¼0.002) between cohorts. No differences were found in fertilization rate, zygotes achieving cleavage stage, and blastulation rates between study groups. Embryo euploidy rates were comparable (50.2% ( n¼273/543), 46.7%( n¼264/565), p¼0.24).After adjusting for female and male patient's age, BMI, AMH, normal semen analysis and number of biopsied embryos, there were no association with elevated DFI and lower odds of embryo euploidy (OR 1.39, CI95% 0.97-2.0, p¼0.07).CONCLUSIONS: Although multiple studies have reported poor outcomes in patients with elevated DFI, the exact mechanism of action is unclear. Our study analysis showed no correlation between high sperm DNA fragmentation and fertilization, blastulation, or embryo euploidy rates. Our study adds to the expanding body of evidence that shows no significant relationships between elevated DNA fragmentation, embryo development, or chromosomal composition. Future studies assessing the oocyte DNA-repair mechanism following fertilization should be performed to better understand the immediate impact of sperm chromatin damage during ART intervention.References: Zini A, Jamal W, Cowan L, Al-Hathal N (2011) Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet 28: 391AE397.Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles.