Abstract
STUDY QUESTION
Is the presence or absence of certain vaginal bacteria associated with failure or success to become pregnant after an in vitro fertilization (IVF) or IVF with intracytoplasmic ...sperm injection (IVF-ICSI) treatment?
SUMMARY ANSWER
Microbiome profiling with the use of interspace profiling (IS-pro) technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment.
WHAT IS KNOWN ALREADY
Live-birth rates for an IVF or IVF-ICSI treatment vary between 25 and 35% per cycle and it is difficult to predict who will or will not get pregnant after embryo transfer (ET). Recently, it was suggested that the composition of the vaginal microbiota prior to treatment might predict pregnancy outcome. Analysis of the vaginal microbiome prior to treatment might, therefore, offer an opportunity to improve the success rate of IVF or IVF-ICSI.
STUDY DESIGN, SIZE, DURATION
In a prospective cohort study, 303 women (age, 20–42 years) undergoing IVF or IVF-ICSI treatment in the Netherlands were included between June 2015 and March 2016.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Study subjects provided a vaginal sample before the start of the IVF or IVF-ICSI procedure. The vaginal microbiota composition was determined using the IS-pro technique. IS-pro is a eubacterial technique based on the detection and categorization of the length of the 16S–23S rRNA gene interspace region. Microbiome profiles were assigned to community state types based on the dominant bacterial species. The predictive accuracy of the microbiome profiles for IVF and IVF-ICSI outcome of fresh ET was evaluated by a combined prediction model based on a small number of bacterial species. From this cohort, a model was built to predict outcome of fertility treatment. This model was externally validated in a cohort of 50 women who were undergoing IVF or IVF-ICSI treatment between March 2018 and May 2018 in the Dutch division of the MVZ VivaNeo Kinderwunschzentrum Düsseldorf, Germany.
MAIN RESULTS AND THE ROLE OF CHANCE
In total, the vaginal microbiota of 192 women who underwent a fresh ET could be analysed. Women with a low percentage of Lactobacillus in their vaginal sample were less likely to have a successful embryo implantation. The prediction model identified a subgroup of women (17.7%, n = 34) who had a low chance to become pregnant following fresh ET. This failure was correctly predicted in 32 out of 34 women based on the vaginal microbiota composition, resulting in a predictive accuracy of 94% (sensitivity, 26%; specificity, 97%). Additionally, the degree of dominance of Lactobacillus crispatus was an important factor in predicting pregnancy. Women who had a favourable profile as well as <60% L. crispatus had a high chance of pregnancy: more than half of these women (50 out of 95) became pregnant. In the external validation cohort, none of the women who had a negative prediction (low chance of pregnancy) became pregnant.
LIMITATIONS, REASONS FOR CAUTION
Because our study uses a well-defined study population, the results will be limited to the IVF or IVF-ICSI population. Whether these results can be extrapolated to the general population trying to achieve pregnancy without ART cannot be determined from these data.
WIDER IMPLICATIONS OF THE FINDINGS
Our results indicate that vaginal microbiome profiling using the IS-pro technique enables stratification of the chance of becoming pregnant prior to the start of an IVF or IVF-ICSI treatment. Knowledge of their vaginal microbiota may enable couples to make a more balanced decision regarding timing and continuation of their IVF or IVF-ICSI treatment cycles.
STUDY FUNDING/COMPETING INTEREST(S)
This study was financed by NGI Pre-Seed 2014–2016, RedMedTech Discovery Fund 2014–2017, STW Valorisation grant 1 2014–2015, STW Take-off early phase trajectory 2015–2016 and Eurostars VALBIOME grant (reference number: 8884). The employer of W.J.S.S.C. has in collaboration with ARTPred acquired a MIND subsidy to cover part of the costs of this collaboration project. The following grants are received but not used to finance this study: grants from Innovatie Prestatie Contract, MIT Haalbaarheid, other from Dutch R&D tax credit WBSO, RedMedTech Discovery Fund, (J.D.d.J.). Grants from Ferring (J.S.E.L., K.F., C.B.L. and J.M.J.S.S.), Merck Serono (K.F. and C.B.L.), Dutch Heart Foundation (J.S.E.L.), Metagenics Inc. (J.S.E.L.), GoodLife (K.F.), Guerbet (C.B.L.). R.K. is employed by ARTPred B.V. during her PhD at Erasmus Medical Centre (MC). S.A.M. has a 100% University appointment. I.S.P.H.M.S., S.A.M. and A.E.B. are co-owners of IS-Diagnostics Ltd. J.D.d.J. is co-owner of ARTPred B.V., from which he reports personal fees. P.H.M.S. reports non-financial support from ARTPred B.V. P.H.M.S., J.D.d.J. and A.E.B. have obtained patents `Microbial population analysis’ (9506109) and `Microbial population analysis’ (20170159108), both licenced to ARTPred B.V. J.D.d.J. and A.E.B. report patent applications `Method and kit for predicting the outcome of an assisted reproductive technology procedure’ (392EPP0) and patent `Method and kit for altering the outcome of an assisted reproductive technology procedure’ by ARTPred. W.J.S.S.C. received personal consultancy and educational fees from Goodlife Fertility B.V. J.S.E.L. reports personal consultancy fees from ARTPred B.V., Titus Health B.V., Danone, Euroscreen and Roche during the conduct of the study. J.S.E.L. and N.G.M.B. are co-applicants on an Erasmus MC patent (New method and kit for prediction success of in vitro fertilization) licenced to ARTPred B.V. F.J.M.B. reports personal fees from Advisory Board Ferring, Advisory Board Merck Serono, Advisory Board Gedeon Richter and personal fees from Educational activities for Ferring, outside the submitted work. K.F. reports personal fees from Ferring (commercial sponsor) and personal fees from GoodLife (commercial sponsor). C.B.L. received speakers’ fee from Ferring. J.M.J.S.S. reports personal fees and other from Merck Serono and personal fees from Ferring, unrelated to the submitted paper. The other authors declare that they have no competing interests.
TRIAL REGISTRATION NUMBER
ISRCTN83157250. Registered 17 August 2018. Retrospectively registered.
Wild bees supply sufficient pollination in Cucurbita agroecosystems in certain settings; however, some growers continue to stock fields with managed pollinators due to uncertainties of temporal and ...spatial variation on pollination services supplied by wild bees. Here, we evaluate wild bee pollination activity in wholesale, commercial pumpkin fields over 3 yr. We identified 37 species of bees foraging in commercial pumpkin fields. Honey bees (Apis mellifera L. Hymenoptera: Apidae), squash bees (Eucera (Peponapis) Say, Dorchin Hymenoptera: Apidae), and bumble bees (Bombus spp., primarily B. impatiens Cresson Hymenoptera: Apidae) were the most active pollinator taxa, responsible for over 95% of all pollination visits. Preference for female flowers decreased as distance from field edge increased for several bee taxa. Visitation rates from one key pollinator was negatively affected by field size. Visitation rates for multiple taxa exhibited a curvilinear response as the growing season progressed and responded positively to increasing floral density. We synthesized existing literature to estimate minimum ‘pollination thresholds’ per taxa and determined that each of the most active pollinator taxa exceeded these thresholds independently. Under current conditions, renting honey bee hives may be superfluous in this system. These results can aid growers when executing pollination management strategies and further highlights the importance of monitoring and conserving wild pollinator populations.
Fall armyworm, Spodoptera frugiperda (J.E. Smith), is a highly mobile insect pest of a wide range of host crops. However, this pest of tropical origin cannot survive extended periods of freezing ...temperature but must migrate northward each spring if it is to re-infest cropping areas in temperate regions. The northward limit of the winter-breeding region for North America extends to southern regions of Texas and Florida, but infestations are regularly reported as far north as Québec and Ontario provinces in Canada by the end of summer. Recent genetic analyses have characterized migratory pathways from these winter-breeding regions, but knowledge is lacking on the atmosphere’s role in influencing the timing, distance, and direction of migratory flights. The Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model was used to simulate migratory flight of fall armyworm moths from distinct winter-breeding source areas. Model simulations identified regions of dominant immigration from the Florida and Texas source areas and overlapping immigrant populations in the Alabama–Georgia and Pennsylvania–Mid-Atlantic regions. This simulated migratory pattern corroborates a previous migratory map based on the distribution of fall armyworm haplotype profiles. We found a significant regression between the simulated first week of moth immigration and first week of moth capture (for locations which captured ≥10 moths), which on average indicated that the model simulated first immigration 2 weeks before first captures in pheromone traps. The results contribute to knowledge of fall armyworm population ecology on a continental scale and will aid in the prediction and interpretation of inter-annual variability of insect migration patterns including those in response to climatic change and adoption rates of transgenic cultivars.
Transgenic maize engineered to express insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has become widely adopted in U.S. agriculture. In 2009, Bt maize was planted on more than ...22.2 million hectares, constituting 63% of the U.S. crop. Using statistical analysis of per capita growth rate estimates, we found that areawide suppression of the primary pest Ostrinia nubilalis (European corn borer) is associated with Bt maize use. Cumulative benefits over 14 years are an estimated $3.2 billion for maize growers in Illinois, Minnesota, and Wisconsin, with more than $2.4 billion of this total accruing to non-Bt maize growers. Comparable estimates for Iowa and Nebraska are $3.6 billion in total, with $1.9 billion for non-Bt maize growers. These results affirm theoretical predictions of pest population suppression and highlight economic incentives for growers to maintain non-Bt maize refugia for sustainable insect resistance management.
Most of the world's crops depend on pollinators, so declines in both managed and wild bees raise concerns about food security. However, the degree to which insect pollination is actually limiting ...current crop production is poorly understood, as is the role of wild species (as opposed to managed honeybees) in pollinating crops, particularly in intensive production areas. We established a nationwide study to assess the extent of pollinator limitation in seven crops at 131 locations situated across major crop-producing areas of the USA. We found that five out of seven crops showed evidence of pollinator limitation. Wild bees and honeybees provided comparable amounts of pollination for most crops, even in agriculturally intensive regions. We estimated the nationwide annual production value of wild pollinators to the seven crops we studied at over $1.5 billion; the value of wild bee pollination of all pollinator-dependent crops would be much greater. Our findings show that pollinator declines could translate directly into decreased yields or production for most of the crops studied, and that wild species contribute substantially to pollination of most study crops in major crop-producing regions.
As part of an insect resistance management plan to preserve Bt transgenic technology, annual monitoring of target pests is mandated to detect susceptibility changes to Bt toxins. Currently ...Helicoverpa zea (Boddie) monitoring involves investigating unexpected injury in Bt crop fields and collecting larvae from non-Bt host plants for laboratory diet bioassays to determine mortality responses to diagnostic concentrations of Bt toxins. To date, this monitoring approach has not detected any significant change from the known range of baseline susceptibility to Bt toxins, yet practical field-evolved resistance in H. zea populations and numerous occurrences of unexpected injury occur in Bt crops. In this study, we implemented a network of 73 sentinel sweet corn trials, spanning 16 U.S. states and 4 Canadian provinces, for monitoring changes in H. zea susceptibility to Cry and Vip3A toxins by measuring differences in ear damage and larval infestations between isogenic pairs of non-Bt and Bt hybrids over three years. This approach can monitor susceptibility changes and regional differences in other ear-feeding lepidopteran pests. Temporal changes in the field efficacy of each toxin were evidenced by comparing our current results with earlier published studies, including baseline data for each Bt trait when first commercialized. Changes in amount of ear damage showed significant increases in H. zea resistance to Cry toxins and possibly lower susceptibility to Vip3a. Our findings demonstrate that the sentinel plot approach as an in-field screen can effectively monitor phenotypic resistance and document field-evolved resistance in target pest populations, improving resistance monitoring for Bt crops.
Abstract
Attosecond chronoscopy is central to the understanding of ultrafast electron dynamics in matter from gas to the condensed phase with attosecond temporal resolution. It has, however, not yet ...been possible to determine the timing of individual partial waves, and steering their contribution has been a substantial challenge. Here, we develop a polarization-skewed attosecond chronoscopy serving as a partial wave meter to reveal the role of each partial wave from the angle-resolved photoionization phase shifts in rare gas atoms. We steer the relative ratio between different partial waves and realize a magnetic-sublevel-resolved atomic phase shift measurement. Our experimental observations are well supported by time-dependent R-matrix numerical simulations and analytical soft-photon approximation analysis. The symmetry-resolved, partial-wave analysis identifies the transition rate and phase shift property in the attosecond photoelectron emission dynamics. Our findings provide critical insights into the ubiquitous attosecond optical timer and the underlying attosecond photoionization dynamics.
Context: Data on the presence, extent, and reversibility of cardiovascular disease in primary hyperparathyroidism (PHPT) are conflicting.
Objective: To evaluate the heart in PHPT, we assessed cardiac ...structure and diastolic function in patients with mild PHPT compared with age- and sex-matched controls.
Design: This was a case-control study.
Settings: The study was conducted in a university hospital Metabolic Bone Diseases Unit.
Participants: Fifty-four men and women with PHPT and 76 controls without PHPT participated in the study.
Outcome Measures: We measured left ventricular mass index (LVMI), the presence of mitral annular calcification, the ratio of early to late diastolic mitral inflow velocities (E/A), and early diastolic velocity of the lateral mitral annulus using Doppler tissue imaging (tissue Doppler e′).
Results: Patients had mild disease with mean (±sd) serum calcium 10.5 ± 0.5 mg/dl and PTH 96 ± 45 pg/ml. LVMI and diastolic function were normal in PHPT. There was no difference in LVMI (98 ± 23 vs. 96 ± 24 g/m2, P = 0.69) or the frequency of mitral annular calcification between PHPT cases and controls. Diastolic function variables (E/A and tissue Doppler e′) were higher (better) in cases compared with controls, although both were within the reference range. PHPT patients with low E/A had higher serum PTH (121 ± 36 vs. 89 ± 46 pg/ml, P = 0.03) and calcium (10.8 ± 0.4 vs. 10.5 ± 0.5 mg/dl, P = 0.05) than those with normal values. Finally, we found LVMI to be inversely associated with serum 25-hydroxyvitamin D in PHPT (r = −0.29, P < 0.05). All findings persisted after adjustment for group differences in cardiovascular risk factors.
Conclusions: Patients with biochemically mild PHPT do not have evidence of increased left ventricular mass, diastolic dysfunction, or increased valvular calcifications. However, the data support an association between low vitamin D levels and the development of left ventricular hypertrophy in this disorder. Finally, the increased serum calcium and PTH levels in those with diastolic dysfunction suggest that disease severity may determine the presence of cardiac manifestations in PHPT.
In mild primary hyperparathyroidism, there is no increased left ventricular mass, diastolic dysfunction, or increased valvular calcifications, but low vitamin D levels may predispose to the development of left ventricular hypertrophy.
Context: Bariatric surgery is common and may be associated with deleterious effects on the skeleton.
Objective: Our objective was to assess bone metabolism and bone mineral density (BMD) after ...Roux-en-Y gastric bypass.
Design and Setting: We conducted a 1-yr prospective longitudinal study at a university hospital bariatric surgery practice and metabolic bone disease unit.
Participants: Participants included 23 obese (mean body mass index 47 kg/m2) men and women, aged 20–64 yr.
Main Outcome Measures: Serum PTH, 25-hydroxyvitamin D, osteocalcin, and urinary N-telopeptide, and BMD were assessed.
Results: Patients lost 45 ± 2 kg 1 yr postoperatively (P < 0.01). PTH increased early (3 months, 43–50 pg/ml; P < 0.001) and urinary calcium dropped (161–92 mg/24 h; P < 0.01), despite doubling of calcium intake (1318–2488 mg/d; P < 0.001). Serum 25-hydroxyvitamin D concentrations were unchanged (23–26 ng/ml), although vitamin D intake increased by 260% (658 IU/d at baseline to 1698 IU/d at 12 months; P < 0.05). Markers of bone remodeling rose (P < 0.01 for both urinary N-telopeptide and osteocalcin), whereas BMD decreased at the femoral neck (9.2%, P < 0.005) and at the total hip (8.0%, P < 0.005). These declines were strongly associated with the extent of weight loss (femoral neck: r = 0.90, P < 0.0001; and total hip: r = 0.65, P = 0.02). Lumbar spine and distal radius sites did not change.
Conclusions: After Roux-en-Y gastric bypass, there was evidence of calcium and vitamin D malabsorption. Bone turnover increased, and hip bone density rapidly declined. The decline in hip BMD was strongly associated with weight loss itself. Vigilance for nutritional deficiencies and bone loss in patients both before and after bariatric surgery is crucial.
Although bee visitation rate to flowers is often used to assess both pollination services and bee abundance, the abundance of social species needs to be assessed by quantifying the number colonies ...instead of the number of foraging individuals. Because accurately quantifying the number of wild bee colonies can be difficult, the relationship of visitation rates provided by foragers and the abundance of colonies contributing those foragers from the surrounding landscape is poorly documented for social species. Here, we use genetic methods and statistical inference to estimate the abundance of wild colonies of Bombus impatiens in the surrounding landscape providing foragers to 30 commercial pumpkin (Cucurbita pepo) fields over 4 yr across a 13,000‐km2 area in Pennsylvania, USA. We show that the abundance of wild colonies in the surrounding landscape providing foragers per field (colony abundance per field) ranges from 291 to 829 colonies per field. Furthermore, colony abundance per field has been stable across years, counties, and field size, resulting in a dilution of foragers from the available colonies across larger fields. Wild colony abundance, when scaled by field size, by expressing colony abundance on a per hectare basis, is predictive of visitation rate. Thus, we document the relationship of wild colony abundance per hectare to visitation rate at a level that provides sufficient pollination to a highly pollinator‐dependent crop. As expected, genetic differentiation among sampled populations is essentially non‐existent across different fields or regions, suggesting a panmictic population. Although many Bombus species are in decline, we document abundant and genetically resilient wild populations of B. impatiens associated with a mass‐flowering crop under current agricultural practices and provide baseline information needed to monitor these wild populations at a time when they face similar stressors implicated in the decline of congenerics.
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