Derailing individualized ovarian stimulation

No abstract available

Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials

Objective To compare antimüllerian hormone (AMH) and antral follicle count (AFC) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics. Design Retrospective analysis of individual study center data in two multicenter trials. Centers that provided >10 patients were included in the analysis. Setting A total of 19 (n = 519 patients) and 18 study centers (n = 686 patients) participating in a long GnRH agonist trial (MERIT) and a GnRH antagonist trial (MEGASET), respectively. Patient(s) Infertile women of good prognosis. Intervention(s) Long GnRH agonist or GnRH antagonist cycles. Main Outcome Measure(s) Correlation between AMH and AFC, and oocyte yield by each study center for each trial. Results(s) Antimüllerian hormone was more strongly correlated with oocyte yield than AFC: r = 0.56 vs. r = 0.28 in the GnRH agonist cohort, and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort. The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers: 17 (89%) and 15 (83%) centers in the long GnRH agonist and GnRH antagonist trial, respectively. Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model: AMH, R2 = 0.29 and 0.23; AFC: R2 = 0.07 and 0.07; AMH + AFC: R2 = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials, respectively. Conclusions(s) Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both randomized trials utilizing GnRH agonist and GnRH antagonist protocols. Antral follicle count provided no added predictive value beyond AMH.</p

Gestational diabetes mellitus- right person, right treatment, right time?

Background: Personalised treatment that is uniquely tailored to an individual’s phenotype has become a key goal of clinical and pharmaceutical development across many, particularly chronic, diseases. For type 2 diabetes, the importance of the underlying clinical heterogeneity of the condition is emphasised and a range of treatments are now available, with personalised approaches being developed. While a close connection between risk factors for type 2 diabetes and gestational diabetes has long been acknowledged, stratification of screening, treatment and obstetric intervention remains in its infancy. Conclusions: Although there have been major advances in our understanding of glucose tolerance in pregnancy and of the benefits of treatment of gestational diabetes, we argue that far more vigorous approaches are needed to enable development of companion diagnostics, and to ensure the efficacious and safe use of novel therapeutic agents and strategies to improve outcomes in this common condition

Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation in IVF/ICSI cycles

Background This secondary analysis aimed to identify predictors of low (&#60;6 oocytes retrieved) and high ovarian response (&#62;18 oocytes retrieved) in IVF patients undergoing controlled ovarian stimulation with corifollitropin alfa in a gonadotropin-releasing hormone (GnRH) antagonist protocol. Methods Statistical model building for high and low ovarian response was based on the 150 μg corifollitropin alfa treatment group of the Pursue trial in infertile women aged 35–42 years (n = 694). Results Multivariable logistic regression models were constructed in a stepwise fashion (P &#60;0.05 for entry). 14.1 % of subjects were high ovarian responders and 23.2 % were low ovarian responders. The regression model for high ovarian response included four independent predictors: higher anti-Müllerian hormone (AMH) and antral follicle count (AFC) increased the risk, and higher follicle-stimulating hormone (FSH) levels and advancing age decreased the risk of high ovarian response. The regression model for low ovarian response also included four independent predictors: advancing age increased the risk, and higher AMH, higher AFC and longer menstrual cycle length decreased the risk of low ovarian response. Conclusions AMH, AFC and age predicted both high and low ovarian responses, FSH predicted high ovarian response, and menstrual cycle length predicted low ovarian response in a corifollitropin alfa/GnRH antagonist protocol

A case of large bowel obstruction secondary to twin pregnancy

No abstract available

What's the most effective way to screen patients with a family history of colon cancer?

The best approach hinges on the number, degree, and age of relatives diagnosed with colorectal cancer (CRC) or adenomatous polyps (AP). Screening should begin at 40 years of age for patients with a family history of CRC or AP in at least 1 first-degree relative or CRC in at least 2 second-degree relatives (strength of recommendation [SOR]: B, extrapolation from systematic reviews)

Genome-wide association study identifies common and low-frequency variants at the AMHgene locus that strongly predict serum AMH levels in males

Anti-Müllerian hormone (AMH) is an essential messenger of sexual differentiation in the foetus and is an emerging biomarker of postnatal reproductive function in females. Due to a paucity of adequately sized studies, the genetic determinants of circulating AMH levels are poorly characterized. In samples from 2815 adolescents aged 15 from the ALSPAC study, we performed the first genome-wide association study of serum AMH levels across a set of ∼9 M ‘1000 Genomes Reference Panel’ imputed genetic variants. Genetic variants at the AMH protein-coding gene showed considerable allelic heterogeneity, with both common variants [rs4807216 (PMale = 2 × 10−49, Beta: ∼0.9 SDs per allele), rs8112524 (PMale = 3 × 10−8, Beta: ∼0.25)] and low-frequency variants [rs2385821 (PMale = 6 × 10−31, Beta: ∼1.2, frequency 3.6%)] independently associated with apparently large effect sizes in males, but not females. For all three SNPs, we highlight mechanistic links to AMH gene function and demonstrate highly significant sex interactions (PHet 0.0003–6.3 × 10−12), culminating in contrasting estimates of trait variance explained (24.5% in males versus 0.8% in females). Using these SNPs as a genetic proxy for AMH levels, we found no evidence in additional datasets to support a biological role for AMH in complex traits and diseases in men

Apgar score and the risk of cause specific infant mortality: a population based cohort study of 1,029,207 livebirths

Background&lt;p&gt;&lt;/p&gt; The Apgar score has been used worldwide as an index of early neonatal condition for more than 60 years. With advances in health-care service provision, neonatal resuscitation, and infant care, its present relevance is unclear. The aim of the study was to establish the strength of the relation between Apgar score at 5 min and the risk of neonatal and infant mortality, subdivided by specific causes.&lt;p&gt;&lt;/p&gt; Methods&lt;p&gt;&lt;/p&gt; We linked routine discharge and mortality data for all births in Scotland, UK between 1992 and 2010. We restricted our analyses to singleton livebirths, in women aged over 10 years, with a gestational age at delivery between 22 and 44 weeks, and excluded deaths due to congenital anomalies or isoimmunisation. We calculated the relative risks (RRs) of neonatal and infant death of neonates with low (0–3) and intermediate (4–6) Apgar scores at 5 min referent to neonates with normal Apgar score (7–10) using binomial log-linear modelling with adjustment for confounders. Analyses were stratified by gestational age at birth because it was a significant effect modifier. Missing covariate data were imputed.&lt;p&gt;&lt;/p&gt; Findings&lt;p&gt;&lt;/p&gt; Complete data were available for 1 029 207 eligible livebirths. Across all gestational strata, low Apgar score at 5 min was associated with an increased risk of neonatal and infant death. However, the strength of the association (adjusted RR, 95% CI referent to Apgar 7–10) was strongest at term (p&#60;0·0001). A low Apgar (0–3) was associated with an adjusted RR of 359·4 (95% CI 277·3–465·9) for early neonatal death, 30·5 (18·0–51·6) for late neonatal death, and 50·2 (42·8–59·0) for infant death. We noted similar associations of a lower magnitude for intermediate Apgar (4–6). The strongest associations were for deaths attributed to anoxia and low Apgar (0–3) for term infants (RR 961·7, 95% CI 681·3–1357·5) and preterm infants (141·7, 90·1–222·8). No association between Apgar score at 5 min and the risk of sudden infant death syndrome was noted at any gestational age (RR 0·6, 95% CI 0·1–4·6 at term; 1·2, 0·3–4·8 at preterm).&lt;p&gt;&lt;/p&gt; Interpretation&lt;p&gt;&lt;/p&gt; Low Apgar score at 5 min was strongly associated with the risk of neonatal and infant death. Our findings support its continued usefulness in contemporary practice

Five-minute Apgar score and educational outcomes: retrospective cohort study of 751 369 children

Background: The Apgar score is used worldwide for assessing the clinical condition and short-term prognosis of newborn infants. Evidence for a relationship with long-term educational outcomes is conflicting. We investigated whether Apgar score at 5 min after birth was associated with additional support needs (ASN) and educational attainment. Methods: Data on pregnancy, delivery and later educational outcomes for children attending Scottish schools between 2006 and 2011 were collated by linking individual-level data from national educational and maternity databases. The relationship between Apgar score and overall ASN, type-specific ASN and educational attainment was assessed using binary, multinomial and generalised ordinal logistic regression models, respectively. Missing covariate data were imputed. Results: Of the 751 369 children eligible, 9741 (1.3%) had a low or intermediate Apgar score and 49 962 (6.6%) had ASN. Low Apgar score was independently associated with overall ASN status (adjusted OR for Apgar ≤3, OR 1.52 95% CI 1.35 to 1.70), as well as ASN due to cognitive (OR 1.26, 95% CI 1.09 to 1.47), sensory (OR 2.49 95% CI 1.66 to 3.73) and motor (OR 3.57, 95% CI 2.86 to 4.47) impairments. There was a dose-response relationship between Apgar score and overall ASN status: of those scoring 0–3, 10.1% had ASN, compared with 9.1% of those scoring 4–7 and 6.6% of those scoring 7–10. A low Apgar score was associated with lower educational attainment, but this was not robust to adjustment for confounders. Conclusions: Apgar scores are associated with long-term as well as short-term prognoses, and with educational as well as clinical outcomes at the population level

With development, list recall includes more chunks, not just larger ones.

The nature of the childhood development of immediate recall has been difficult to determine. There could be a developmental increase in either the number of chunks held in working memory or the use of grouping to make the most of a constant capacity. In 3 experiments with children in the early elementary school years and adults, we show that improvements in the immediate recall of word and picture lists come partly from increases in the number of chunks of items retained in memory. This finding was based on a distinction between access to a studied group of items (i.e., recall of at least 1 item from the group) and completion of the accessed group (i.e., the proportion of the items recalled from the group). Access rates increased with age, even with statistical controls for completion rates, implicating development of capacity in chunks. (PsycINFO Database Record (c) 2010 APA, all rights reserved