Chronic kidney disease, female infertility, and medically assisted reproduction: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol

Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. Trial registration number: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200

Novel thermophilic hemicellulases for the conversion of lignocellulose for second generation biorefineries

The biotransformation of lignocellulose biomasses into fermentable sugars is a very complex procedure including, as one of the most critical steps, the (hemi) cellulose hydrolysis by specific enzymatic cocktails. We explored here, the potential of stable glycoside hydrolases from thermophilic organisms, so far not used in commercial enzymatic preparations, for the conversion of glucuronoxylan, the major hemicellulose of several energy crops. Searches in the genomes of thermophilic bacteria led to the identification, efficient production, and detailed characterization of novel xylanase and α-glucuronidase from Alicyclobacillus acidocaldarius (GH10-XA and GH67-GA, respectively) and a α-glucuronidase from Caldicellulosiruptor saccharolyticus (GH67-GC). Remarkably, GH10-XA, if compared to other thermophilic xylanases from this family, coupled good specificity on beechwood xylan and the best stability at 65 °C (3.5 days). In addition, GH67-GC was the most stable α-glucuronidases from this family and the first able to hydrolyse both aldouronic acid and aryl-α-glucuronic acid substrates. These enzymes, led to the very efficient hydrolysis of beechwood xylan by using 7- to 9-fold less protein (concentrations <0.3 μM) and in much less reaction time (2 h vs 12 h) if compared to other known biotransformations catalyzed by thermophilic enzymes. In addition, remarkably, together with a thermophilic β-xylosidase, they catalyzed the production of xylose from the smart cooking pre-treated biomass of one of the most promising energy crops for second generation biorefineries. We demonstrated that search by the CAZy Data Bank of currently available genomes and detailed enzymatic characterization of recombinant enzymes allow the identification of glycoside hydrolases with novel and interesting properties and applications

Induction of Labor in Women with Previous Cesarean Section and Unfavorable Cervix: A Retrospective Cohort Study

Background: The efficacy and safety of a cervical ripening balloon (CRB) in women with a previous cesarean section (CS) and unfavorable Bishop score are still controversial. Methods: A retrospective cohort study was performed across six tertiary hospitals from 2015 to 2019. Women with one previous transverse CS, singleton cephalic term pregnancy and BS Results: Of the 265 women included, 57.3% had successful vaginal birth. Augmentation improved vaginal delivery (32.2% vs. 21.2%). Intrapartum analgesia was associated with an increased VBAC rate (58.6% vs. 34.5%). Maternal BMI ≥30 and age ≥40 years increased emergency CS rate (11.8% vs. 28.3% and 7.2 vs. 15.9%). Composite adverse maternal outcome occurred in 4.8% of CRB group women and increased to 17.6% when associated with oxytocin. Uterine rupture occurred in one case (0.4%) in the CRB–oxytocin group. Poorer fetal outcome occurred after emergency CS, if compared to successful VBAC (12.4% vs. 3.3%). Conclusions: In women with a previous CS and unfavorable Bishop score, induction of labor with a CRB can be considered safe and effective

Prediction of spontaneous vaginal delivery in nulliparous women with a prolonged second stage of labor: the value of intrapartum ultrasound

Background: A limited number of studies have addressed the role of intrapartum ultrasound in the prediction of the mode of delivery in women with prolonged second stage of labor. Objective: The objective of the study was to evaluate the role of transabdominal and transperineal sonographic findings in the prediction of spontaneous vaginal delivery among nulliparous women with prolonged second stage of labor. Study Design: This was a 2-center prospective study conducted at 2 tertiary maternity units. Nulliparous women with a prolonged active second stage of labor, as defined by active pushing lasting more than 120 minutes, were eligible for inclusion. Transabdominal ultrasound to evaluate the fetal head position and transperineal ultrasound for the measurement of the midline angle, the head-perineum distance, and the head-symphysis distance were performed in between uterine contractions and maternal pushes. At transperineal ultrasound the angle of progression was measured at rest and at the peak of maternal pushing effort. The delta angle of progression was defined as the difference between the angle of progression measured during active pushing at the peak of maternal effort and the angle of progression at rest. The sonographic findings of women who had spontaneous vaginal delivery vs those who required obstetric intervention, either vacuum extraction or cesarean delivery, were evaluated and compared. Results: Overall, 109 were women included. Spontaneous vaginal delivery and obstetric intervention were recorded in 40 (36.7%) and 69 (63.3%) patients, respectively. Spontaneous vaginal delivery was associated with a higher rate of occiput anterior position (90% vs 53.2%, P &lt; .0001), lower head-perineum distance and head-symphysis distance (33.2 ± 7.8 mm vs 40.1 ± 9.5 mm, P = .001, and 13.1 ± 4.6 mm vs 19.5 ± 8.4 mm, P &lt; .001, respectively), narrower midline angle (29.6° ± 15.3° vs 54.2° ± 23.6°, P &lt; .001) and wider angle of progression at the acme of the pushing effort (153.3° ± 19.8° vs 141.8° ± 25.7°, P = .02) and delta-angle of progression (17.3° ± 12.9° vs 12.5° ± 11.0°, P = .04). At logistic regression analysis, only the midline angle and the head-symphysis distance proved to be independent predictors of spontaneous vaginal delivery. More specifically, the area under the curve for the prediction of spontaneous vaginal delivery was 0.80, 95% confidence interval (0.69–0.92), P &lt; .001, and 0.74, 95% confidence interval (0.65–0.83), P = .002, for the midline angle and for the head-symphysis distance, respectively. Conclusion: Transabdominal and transperineal intrapartum ultrasound parameters can predict the likelihood of spontaneous vaginal delivery in nulliparous women with prolonged second stage of labor