Metatranscriptomic profiles of Eastern subterranean termites, Reticulitermes flavipes (Kollar) fed on second generation feedstocks

Background: Second generation lignocellulosic feedstocks are being considered as an alternative to first generation biofuels that are derived from grain starches and sugars. However, the current pre-treatment methods for second generation biofuel production are inefficient and expensive due to the recalcitrant nature of lignocellulose. In this study, we used the lower termite Reticulitermes flavipes (Kollar), as a model to identify potential pretreatment genes/enzymes specifically adapted for use against agricultural feedstocks. Results: Metatranscriptomic profiling was performed on worker termite guts after feeding on corn stover (CS), soybean residue (SR), or 98% pure cellulose (paper) to identify (i) microbial community, (ii) pathway level and (iii) gene-level responses. Microbial community profiles after CS and SR feeding were different from the paper feeding profile, and protist symbiont abundance decreased significantly in termites feeding on SR and CS relative to paper. Functional profiles after CS feeding were similar to paper and SR; whereas paper and SR showed different profiles. Amino acid and carbohydrate metabolism pathways were downregulated in termites feeding on SR relative to paper and CS. Gene expression analyses showed more significant down regulation of genes after SR feeding relative to paper and CS. Stereotypical lignocellulase genes/enzymes were not differentially expressed, but rather were among the most abundant/constitutively-expressed genes. Conclusions: These results suggest that the effect of CS and SR feeding on termite gut lignocellulase composition is minimal and thus, the most abundantly expressed enzymes appear to encode the best candidate catalysts for use in saccharification of these and related second-generation feedstocks. Further, based on these findings we hypothesize that the most abundantly expressed lignocellulases, rather than those that are differentially expressed have the best potential as pretreatment enzymes for CS and SR feedstocks. © 2015 Rajarapu et al

Optimizing intrauterine insemination: A systematic review and meta‐analysis of the effectiveness and safety of clinical treatment add‐ons

Introduction: Intrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add‐on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta‐analysis is to assess the effectiveness and safety of add‐on interventions to the standard IUI protocol and to provide evidence‐based recommendations on techniques used to optimize the clinical outcomes of IUI treatment. Material and Methods: Systematic review and meta‐analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta‐analysis based on random effects was performed for each outcome and add‐on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857. Results: Sixty‐six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09–1.72, I2 = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03–2.01, I2 = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00–1.94, I2 = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions. Conclusions: The findings of this systematic review and meta‐analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add‐ons could benefit specific patient groups

Is Cerebroplacental Ratio A Marker of Impaired Fetal Growth Velocity and Adverse Pregnancy Outcome?

BACKGROUND: The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. OBJECTIVE: The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between low cerebroplacental ratio at term, reduced fetal growth velocity and adverse pregnancy outcome. DESIGN: retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation, and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within two weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio, low abdominal circumference growth velocity (in the lowest decile), and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small for gestational age neonates. RESULTS: The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted OR 2.10; 95%CI 1.71-2.57, p<0.001) and small for gestational age (adjusted OR 3.60; 95%CI 3.04-4.25, p<0.001). After the exclusion of pregnancies resulting in small for gestational age neonates, low cerebroplacental ratio multiples of median remained significantly associated with both low abdominal circumference growth velocity (adjusted OR 1.76; 95%CI 1.34-2.30, p<0.001) and birthweight centile (adjusted OR 0.99; 95%CI 0.998-0.995, p<0.001). The need for operative delivery for fetal compromise was significantly associated with low cerebroplacental ratio (adjusted OR 1.40; 95%CI 1.10-1.78, p=0.006), even after adjusting for both the umbilical artery pulsatility index multiples of median and middle cerebral artery pulsatility index multiples of median. The results were similar even after the exclusion of pregnancies resulting in small for gestational age neonates (adjusted OR 1.39; 95%CI 1.06-1.84, p=0.018). Low cerebroplacental ratio multiples of median remained significantly associated with the risk of operative delivery for presumed fetal compromise (p<0.001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted even after exclusion of small for gestational age births. In appropriate for gestational age sized fetuses, abdominal circumference growth velocity was significantly lower in those with low cerebroplacental ratio multiples of median than in those with normal cerebroplacental ratio multiples of median (p<0.001). CONCLUSION: Cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry

Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial.

BackgroundTime-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging.MethodsWe conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed.Findings1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care).InterpretationIn women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging.FundingBarts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

The role of ovarian reserve markers in fertility and fertility treatment

Scientific abstract Ovarian reserve is a key component influencing reproductive function and fertility. Serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) are established quantitative markers of ovarian reserve. The overall aim of this thesis comprising four work packages was to study the role of AMH and AFC on different aspects of fertility and fertility treatment. Their specific objectives were: 1) To compare per-follicle AMH production in various phenotypes of women with polycystic ovary syndrome (PCOS) and with isolated polycystic ovarian morphology (PCOM). 2) To assess the effect of cigarette smoking on quantitative ovarian reserve markers in sub-fertile women, validating self-reported smoking behavior using biomarkers (breath carbon monoxide levels and urine cotinine levels). 3) To assess the effect of treatment with myo-inositol (MI)/di-chiro inositol (DCI) compared to no treatment, placebo or other treatment on markers of ovarian reserve in women with PCOS combining data from published literature. 4) To assess the association between ovarian reserve markers and embryo quality in women undergoing IVF/ICSI treatment using time lapse imaging technology. The work for the thesis included primary research consisting of three single-centre, observational, cross-sectional studies and one evidence synthesis based on a systematic review of published literature. The study population was subfertile women seeking fertility treatment, and the primary outcome measure was ovarian reserve assessed by serum AMH and AFC. A significantly greater per-follicle AMH production observed in anovulatory phenotypes of PCOS may represent a heightened physiological role of AMH leading to ovulatory dysfunction. In our study, exposure to cigarette smoking in women 35 years seeking fertility treatment did not significantly change the antral follicle pool. The biomarkers of ovarian reserve were not significantly associated with the biomarkers of smoking or lifetime smoking exposure. Based on currently available data, our systematic review reported that evidence is lacking for an effect of inositols on altering ovarian reserve markers or subsequent outcomes following IVF/ICSI treatment. We found no significant association between ovarian reserve markers and embryo quality in women undergoing IVF/ICSI treatment. Their positive association with improved pregnancy outcomes following IVF/ICSI is most likely indirect, through the increased numbers of oocytes retrieved

Analysing adherence to guidelines for time-lapse imaging information on UK fertility clinic websites

This study aims to systematically analyze the provision of information on Time-lapse Imaging (TLI) by UK fertility clinic websites. We conducted an analysis of 106 clinic websites that offer fertility treatment to self-funded patients. The analysis aimed to examine whether these clinics offer TLI, the associated cost for patients, and the clarity and quality of the provided information. Out of the 106 websites analysed, 71 (67%) claimed to offer TLI. Among these websites, 25 (35.2%) mentioned charging patients between £300 and £850, 25 (35.8%) claimed not to charge patients, and 21 (29.6%) did not provide any cost information for TLI. Furthermore, 64 (90.1%) websites made claims or implied that TLI leads to improved clinical outcomes by enhancing embryo selection. Notably, 34 (47.9%) websites did not mention or provide any links to the HFEA rating system. It is crucial to provide patients with clear and accurate information to enable them to make fully informed decisions about TLI, particularly when they are responsible for the associated costs. The findings of this study raise concerns about the reliability and accuracy of the information available on fertility clinic websites, which are typically the primary source of information for patients

Sperm mitochondrial DNA copy numbers in normal and abnormal semen analysis: A systematic review and meta-analysis

Background: Normal mature sperm have a considerably reduced number of mitochondria, which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. Objectives: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the sperm motility. Search strategy: Standard methodology recommended by Cochrane. Selection criteria: All published primary research reporting on the association between mitochondrial DNA copy numbers and semen quality. Data collection and analysis: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. Main results: We included ten studies. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis compared with normal semen analysis (standardised mean difference 1.08, 95% CI 0.74–1.43). Seven studies included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. Conclusions: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis

The definition of unexplained infertility: A systematic review

Background: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice. Objectives: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis. Search strategy: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language. Data collection and analysis: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range. Main results: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies. Conclusions: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care