Lyonshastings7761

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline.Background Several studies have found that women who are overweight or obese have an increased risk of miscarriage. There is also some evidence of associations of other aspects of cardiometabolic health, including blood pressure and lipids, with miscarriage risk, although these have not been examined to the same extent as body-mass index (BMI). Methods Our objective was to investigate the risk of miscarriage according to pre-pregnancy cardiometabolic health. We examined pre-pregnancy levels of BMI, blood pressure, fasting insulin and metabolites profile at age 18 and risk of miscarriage by age 24. The study included adult female offspring in the Avon Longitudinal Study of Parents and Children with a pregnancy between 18 and 24 years of age (n=434 for BMI and blood pressure; n=265 for metabolites). We used log-binomial regression to calculate adjusted associations between cardiometabolic health measures and miscarriage. Results The overall risk of miscarriage was 22%. The adjusted relative risks for miscarriage were 0.96 (95% CI 0.92-1.00) for BMI (per unit increase), 0.98 (0.96-1.00) for systolic blood pressure, and 1.00 (0.97-1.04) for diastolic blood pressure (per 1 mmHg increase). Total cholesterol, total lipids and phospholipids in HDL-cholesterol were associated with increased likelihood of miscarriage, but none of the p-values for the metabolites were below the corrected threshold for multiple testing (p-value ≤0.003). Conclusions Our findings indicate no strong evidence to support a relationship between pre-pregnancy cardiometabolic health and risk of miscarriage in young, healthy women who became pregnant before age 24. Future studies are necessary that are able to evaluate this question in samples with a wider age range.

The aim of the study was to investigate pregnancy, obstetric, and neonatal outcomes in women with small (<4 cm) unilateral endometriomas.

This retrospective study included 177 patients 91 patients with small endometriomas and 86 controls with unexplained or tubal factor infertility who were treated at the Süleymaniye Gynecology and Maternity Training and Research Hospital Infertility Unit between January 2010 and July 2015. The groups were matched with regards to demographic characteristics such as age, body mass index, and infertility duration. All of the women in this study conceived via intracytoplasmic sperm injection. We compared pregnancy, obstetric, and neonatal outcomes between these groups.

Women with endometriomas had a higher biochemical pregnancy rate, but lower clinical pregnancy and live birth rates than women with unexplained and tubal factor infertility (p<0.05 for all). However no significant differences were found in terms of obstetric and neonatal complications between the two groups (p>0.05 for all).

In this study, we found that women with endometriomas less than 4 cm were more prone to early pregnancy complications. We also showed that this group did not have any increased risks of late pregnancy, obstetric, and neonatal complications.

In this study, we found that women with endometriomas less than 4 cm were more prone to early pregnancy complications. We also showed that this group did not have any increased risks of late pregnancy, obstetric, and neonatal complications.

This study was conducted to investigate the relationship of semen parameters in samples used for intracytoplasmic sperm injection (ICSI) with fertilization and pregnancy rates in infertile couples.

In this prospective study of Infertile couples with male factor infertility that had undergone ICSI, fractions of the same semen samples obtained for microinjection (to ensure the best predictability) were evaluated to determine the semen parameters and sperm DNA fragmentation index (DFI) on the day of oocyte recovery.

In total, 120 couples completed the study and were subdivided into fertilized (n=87) and non-fertilized couples (n=33). The fertilized couples were further classified into pregnant (n=48) and non-pregnant (n=39) couples. Compared to non-fertilized and non-pregnant couples, fertilized and pregnant couples showed statistically significantly higher sperm viability and percentage of normal sperm morphology, as well as significantly lower sperm DFI values. A receiver operating characteristic curve analysis of data from the 120 ICSI cycles showed that sperm viability, normal sperm morphology percentages, and sperm DFI were significant prognostic indicators of fertilization at cutoff values of 40%, 7%, and 46%, respectively. SMI-4a manufacturer A sperm DFI of 46% showed sensitivity and specificity of 95% and 90%, respectively, for predicting fertilization, and no clinical pregnancies occurred in couples with a sperm DFI above 46%.

Semen parameters from the ICSI day sample, especially sperm viability, normal morphology, and DFI, had an impact on fertilization and pregnancy outcomes in ICSI cycles.

Semen parameters from the ICSI day sample, especially sperm viability, normal morphology, and DFI, had an impact on fertilization and pregnancy outcomes in ICSI cycles.

This study investigated the mRNA expression of gamma-aminobutyric acid (GABA) receptors in the sperm of oligoasthenoteratozoospermic (OAT) and teratozoospermic (TER) men compared to normozoospermic (NOR) men, as well as the relationships between GABA receptor expression and sperm parameters, fertilization rate, and embryo quality.

The mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm was examined using reverse transcription-polymerase chain reaction in three groups of patients NOR (n=32), OAT (n=22), and TER (n=45). The fertilization rate and embryo quality were assessed in 35 patients undergoing Intracytoplasmic sperm injection (ICSI; 10 NOR, 10 OAT, and 15 TER men).

OAT men had significantly higher mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm than NOR men; however, the difference between TER and NOR men was not significant. High levels of these receptors were significantly correlated with low sperm concentration, motility, and morphology, as well as the rate of good-quality embryos (GQEs) at the cleavage stage after ICSI.