Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study

Background Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET. Methods First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups. Results For patients in Group A (n=55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n=48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology+aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p=0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p=0.009). There were no twin pregnancies. Conclusion Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Método de determinação e avaliação da depleção de oxitetraciclina em camarão marinho Method for the determination and evaluation of oxytetracycline depletion in marine shrimp

O objetivo deste trabalho foi validar um método para determinação de resíduos de oxitetraciclina (OTC) em camarões, por meio de cromatografia líquida de alta eficiência, e avaliar, pelo método validado, a depleção de resíduos de OTC em camarões in vivo. Para a validação, foram utilizados camarões isentos de OTC e camarões adicionados de OTC in vitro. Foram estabelecidos: seletividade, tempo de retenção, linearidade (coeficiente de correlação), faixa de trabalho, recuperação relativa, limites de detecção e quantificação do método (LDM e LQM, respectivamente) e repetibilidade. Para o experimento in vivo, rações com 200, 400 e 500 &#956;g g-1 de OTC foram administradas aos camarões durante 14 dias. Foi avaliada a concentração do resíduo desse antibiótico no músculo e na carapaça até 22 dias após a suspensão da droga. O coeficiente de correlação linear foi de 0,9997 para o extrato fortificado da matriz, na faixa de trabalho de 0,02 a 0,4 &#956;g g-1; a recuperação foi de 106±17,1% e os LDM e LQM foram de 0,006 e 0,019 &#956;g g-1, respectivamente. O tempo de residência da droga na carapaça dos animais (de 10 a 13 dias) foi maior em comparação ao tempo de residência no músculo (5 dias).<br>This work aimed at validating a method for the determination of oxytetracycline (OTC) residues in shrimp by means of high performance liquid chromatography (HPLC), and at evaluating the OTC residue depletion in shrimps in vivo using the validated method. The shrimp used for validation were either not submitted or submitted to in vitro OTC addition. Selectivity, retention time, linearity (correlation coefficient), work range, relative recovery, detection and method quantification limits and repeatability were determined. For the in vivo experiment, shrimp were fed with feed medicated with OTC at 200, 400 and 500 &#956;g g-1 for 14 days. Oxytetracycline residue concentration in the animals' muscle and carapace was assessed for up to 22 days after stopping medication. The results obtained were: 0.9997 linear correlation coefficient for the fortified matrix extract within a work range of 0.02-0.4 &#956;g g-1, 106±17.1% recovery and 0.006 and 0.019 &#956;g g-1 detection and quantification limits, respectively. A greater OTC residence time was observed in the carapace (10 to 13 days) when compared to the muscle (5 days)