Genesis of chromatin and transcription dynamics in the origin of species.

Histone proteins compact and stabilize the genomes of Eukarya and Archaea. By forming nucleosome(-like) structures they restrict access of DNA-binding transcription regulators to cis-regulatory DNA elements. Dynamic competition between histones and transcription factors is facilitated by different classes of proteins including ATP-dependent remodeling enzymes that control assembly, access, and editing of chromatin. Here, we summarize the knowledge on dynamics underlying transcriptional regulation across the domains of life with a focus on ATP-dependent enzymes in chromatin structure or in TATA-binding protein activity. These insights suggest directions for future studies on the evolution of transcription regulation and chromatin dynamics.

SAGA Is a General Cofactor for RNA Polymerase II Transcription.

Prior studies suggested that SAGA and TFIID are alternative factors that promote RNA polymerase II transcription, with about 10% of genes in S. cerevisiae dependent on SAGA. We reassessed the role of SAGA by mapping its genome-wide location and role in global transcription in budding yeast. We find that SAGA maps to the UAS elements of most genes, overlapping with Mediator binding and irrespective of previous designations of SAGA- or TFIID-dominated genes. Disruption of SAGA through mutation or rapid subunit depletion reduces transcription from nearly all genes, measured by newly synthesized RNA. We also find that the acetyltransferase Gcn5 synergizes with Spt3 to promote global transcription and that Spt3 functions to stimulate TBP recruitment at all tested genes. Our data demonstrate that SAGA acts as a general cofactor required for essentially all RNA polymerase II transcription and is not consistent with the previous classification of SAGA- and TFIID-dominated genes.

Predicting pregnancy chances leading to term live birth in oligo/anovulatory women diagnosed with PCOS.

RESEARCH QUESTION: Which patient features predict the time to pregnancy (TTP) leading to term live birth in infertile women diagnosed with polycystic ovary syndrome (PCOS)? DESIGN: Prospective cohort follow-up study was completed, in which initial standardized phenotyping was conducted at two Dutch university medical centres from January 2004 to January 2014. Data were linked to the Netherlands Perinatal Registry to obtain pregnancy outcomes for each participant. All women underwent treatment according to a standardized protocol, starting with ovulation induction as first-line treatment. Predictors of pregnancies (leading to term live births) during the first year after PCOS diagnosis were evaluated. RESULTS: A total of 1779 consecutive women diagnosed with PCOS between January 2004 and January 2014 were included. In the first year following screening, 659 (37%) women with PCOS attained a pregnancy leading to term birth (≥37 weeks of gestational age). A higher chance of pregnancy was associated with race, smoking, body mass index (BMI), insulin, total testosterone and sex hormone-binding globulin (SHBG) concentrations (c-statistic = 0.59). CONCLUSIONS: Predictors of an increased chance of a live birth include White race, no current smoking, lower BMI, insulin and total testosterone concentrations, and higher SHBG concentrations. This study presents a nomogram to predict the chances of achieving a pregnancy (leading to a term live birth) within 1 year of treatment.

De Novo Heterozygous POLR2A Variants Cause a Neurodevelopmental Syndrome with Profound Infantile-Onset Hypotonia.

The RNA polymerase II complex (pol II) is responsible for transcription of all ∼21,000 human protein-encoding genes. Here, we describe sixteen individuals harboring de novo heterozygous variants in POLR2A, encoding RPB1, the largest subunit of pol II. An iterative approach combining structural evaluation and mass spectrometry analyses, the use of S. cerevisiae as a model system, and the assessment of cell viability in HeLa cells allowed us to classify eleven variants as probably disease-causing and four variants as possibly disease-causing. The significance of one variant remains unresolved. By quantification of phenotypic severity, we could distinguish mild and severe phenotypic consequences of the disease-causing variants. Missense variants expected to exert only mild structural effects led to a malfunctioning pol II enzyme, thereby inducing a dominant-negative effect on gene transcription. Intriguingly, individuals carrying these variants presented with a severe phenotype dominated by profound infantile-onset hypotonia and developmental delay. Conversely, individuals carrying variants expected to result in complete loss of function, thus reduced levels of functional pol II from the normal allele, exhibited the mildest phenotypes. We conclude that subtle variants that are central in functionally important domains of POLR2A cause a neurodevelopmental syndrome characterized by profound infantile-onset hypotonia and developmental delay through a dominant-negative effect on pol-II-mediated transcription of DNA.

Longitudinal surface measurements of human blastocysts show that the dynamics of blastocoel expansion are associated with fertilization method and ongoing pregnancy.

BACKGROUND: Despite all research efforts during this era of novel time-lapse morphokinetic parameters, a morphological grading system is still routinely being used for embryo selection at the blastocyst stage. The blastocyst expansion grade, as evaluated during morphological assessment, is associated with clinical pregnancy. However, this assessment is performed without taking the dynamics of blastocoel expansion into account. Here, we studied the dynamics of blastocoel expansion by comparing longitudinal blastocoel surface measurements using time-lapse embryo culture. Our aim was to first assess if this is impacted by fertilization method and second, to study if an association exists between these measurement and ongoing pregnancy. METHODS: This was a retrospective cohort study including 225 couples undergoing 225 cycles of in vitro fertilization (IVF) treatment with time-lapse embryo culture. The fertilization method was either conventional IVF, intracytoplasmic sperm injection (ICSI) with ejaculated sperm or ICSI with sperm derived from testicular sperm extraction (TESE-ICSI). This resulted in 289 IVF embryos, 218 ICSI embryos and 259 TESE-ICSI embryos that reached at least the full blastocyst stage. Blastocoel surface measurements were performed on time-lapse images every hour, starting from full blastocyst formation (tB). Linear mixed model analysis was performed to study the association between blastocoel expansion, the calculated expansion rate (µm2/hour) and both fertilization method and ongoing pregnancy. RESULTS: The blastocoel of both ICSI embryos and TESE-ICSI embryos was significantly smaller than the blastocoel of IVF embryos (beta -1121.6 µm2; 95% CI: -1606.1 to -637.1, beta -646.8 µm2; 95% CI: -1118.7 to 174.8, respectively). Still, the blastocoel of transferred embryos resulting in an ongoing pregnancy was significantly larger (beta 795.4 µm2; 95% CI: 15.4 to 1575.4) and expanded significantly faster (beta 100.9 µm2/hour; 95% CI: 5.7 to 196.2) than the blastocoel of transferred embryos that did not, regardless of the fertilization method. CONCLUSION: Longitudinal blastocyst surface measurements and expansion rates are promising non-invasive quantitative markers that can aid embryo selection for transfer and cryopreservation. TRIAL REGISTRATION: Our study is a retrospective observational study, therefore trial registration is not applicable.

Planning is not equivalent to preparing, how Dutch women perceive their pregnancy planning in relation to preconceptional lifestyle behaviour change - a cross-sectional study.

BACKGROUND: Unhealthy prenatal lifestyle behaviours are associated with adverse pregnancy outcomes, but little is known about what motivates women to comply with preconceptional lifestyle recommendations or consciously plan their pregnancy. Therefore, the objective of this study is to explore the associations between preconceptional lifestyle behaviours, health beliefs and pregnancy planning among Dutch pregnant women. METHODS: In this cross-sectional study based on the data of the APROPOS-II study, 1,077 low-risk pregnant women were eligible for inclusion. Preconception lifestyle behaviours and actively preparing for pregnancy were assessed in relation to planned pregnancies (based on the London Measure of Unplanned Pregnancies) and health beliefs (14 statements). The following preconceptional lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester of pregnancy: fruit intake, vegetable intake, caffeine intake, (second-hand)smoking, alcohol intake, folic acid supplement use and exercise. Data were analysed using multivariate logistic regression analyses. RESULTS: A total of 921 (85.5%) women in our cohort had a planned pregnancy. However, of these women, 640 (69.5%) adequately used folic acid supplements and 465 (50.5%) women consumed alcohol at any point during pregnancy. Of the women considering themselves 'healthy enough and not needing preconception care', 48 (9.1%) women had an adequate vegetable intake, 294 (55.6%) women consumed alcohol at any point during pregnancy and 161 (30.4%) women were either over-or underweight. CONCLUSION: Despite consciously planning their pregnancy, most women did not adhere to preconceptional lifestyle behaviour recommendations. Women's health beliefs and overestimation of their health status seem to interfere with actively planning and preparing for pregnancy. Findings from our study may encourage the development of prospective health-promoting interventions that focus on health beliefs and actively preparing for pregnancy, to improve preconceptional lifestyle behaviours, thereby optimizing the health of future generations.

Exploring male perceptions regarding the need to engage in preconception care - a mixed-method study amongst Dutch (prospective) fathers.

PURPOSE: While most preconception care (PCC) interventions are aimed at women, men are also in need of PCC to reduce risk factors affecting the spermatozoa quality. The objective of this study is to explore male perceptions regarding the need to engage in PCC. MATERIALS AND METHODS: In a mixed-method cross-sectional study, 229 men participated with a questionnaire and 14 individual semi-structured interviews were conducted. Questionnaires data were analysed using multiple regression analyses. The interviews were analysed using thematic analyses. RESULTS: Most men did not retrieve preconceptional information (n = 135; 59.0%) nor visited a preconceptional consult (n = 182; 79.5%). Men who categorised their preconceptional lifestyle as unhealthy (score ≤6 out of 10) less often retrieved information (adjusted OR 0.36 [95% CI 0.14-0.93]) than men with a healthy preconceptional lifestyle. While several men expressed their fear for infertility, this did not lead to an increased uptake of PCC as men felt they were healthy enough already. CONCLUSION: Despite high awareness of the positive influence of a healthy lifestyle, the perceived need for preparing for pregnancy among men remains low. Tailoring preconceptional information towards male needs provides a window of opportunity to improve men's reproductive health and possibly the health of future generations.

Implementation of a first-trimester prognostic model to improve screening for gestational diabetes mellitus.

BACKGROUND: Improvement in the accuracy of identifying women who are at risk to develop gestational diabetes mellitus (GDM) is warranted, since timely diagnosis and treatment improves the outcomes of this common pregnancy disorder. Although prognostic models for GDM are externally validated and outperform current risk factor based selective approaches, there is little known about the impact of such models in day-to-day obstetric care. METHODS: A prognostic model was implemented as a directive clinical prediction rule, classifying women as low- or high-risk for GDM, with subsequent distinctive care pathways including selective midpregnancy testing for GDM in high-risk women in a prospective multicenter birth cohort comprising 1073 pregnant women without pre-existing diabetes and 60 obstetric healthcare professionals included in nine independent midwifery practices and three hospitals in the Netherlands (effectiveness-implementation hybrid type 2 study). Model performance (c-statistic) and implementation outcomes (acceptability, adoption, appropriateness, feasibility, fidelity, penetration, sustainability) were evaluated after 6 months by indicators and implementation instruments (NoMAD; MIDI). RESULTS: The adherence to the prognostic model (c-statistic 0.85 (95%CI 0.81-0.90)) was 95% (n = 1021). Healthcare professionals scored 3.7 (IQR 3.3-4.0) on implementation instruments on a 5-point Likert scale. Important facilitators were knowledge, willingness and confidence to use the model, client cooperation and opportunities for reconfiguration. Identified barriers mostly related to operational and organizational issues. Regardless of risk-status, pregnant women appreciated first-trimester information on GDM risk-status and lifestyle advice to achieve risk reduction, respectively 89% (n = 556) and 90% (n = 564)). CONCLUSIONS: The prognostic model was successfully implemented and well received by healthcare professionals and pregnant women. Prognostic models should be recommended for adoption in guidelines.

Associations between periconceptional lifestyle behaviours and adverse pregnancy outcomes.

BACKGROUND: While the potential adverse outcomes of prenatal exposure to unhealthy lifestyle are widely evidenced, little is known about these exposures in the periconception period. We investigated the associations between lifestyle behaviours and adverse pregnancy outcomes with a unique distinction between preconceptional- and prenatal lifestyle behaviours. METHODS: A secondary analysis took place within a prospective multicentre cohort study in the Netherlands, including 3,684 pregnant women. Baseline characteristics and preconceptional and first trimester lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester. Adverse pregnancy outcomes (hypertensive disorders in pregnancy (HDP), small for gestational age (SGA), gestational diabetes (GDM) and spontaneous preterm birth (sPTB)) were reported by healthcare professionals. Data were collected between 2012 and 2014 and analysed using multivariate logistic regression. RESULTS: Women who are overweight, and especially obese, have the highest odds of developing any adverse pregnancy outcome (adjusted odds ratio (aOR) 1.61 (95 % Confidence Interval (CI) 1.31-1.99) and aOR 2.85 (95 %CI 2.20-3.68), respectively), particularly HDP and GDM. Women who prenatally continued smoking attained higher odds for SGA (aOR 1.91 (95 %CI 1.05-1.15)) compared to the reference group, but these odds decreased when women prenatally quit smoking (aOR 1.14 (95 %CI 0.59-2.21)). Women who did not use folic acid supplements tended to have a higher odds of developing adverse pregnancy outcomes (aOR 1.28 (95 %CI 0.97-1.69)), while women who prenatally started folic acid supplements did not (aOR 1.01 (95 %CI 0.82-1.25)). CONCLUSIONS: Our results indicate that smoking cessation, having a normal body mass index (BMI) and initiating folic acid supplements preconceptionally may decrease the risk of adverse pregnancy outcomes. Therefore, intervening as early as the preconception period could benefit the health of future generations.

Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence.

To increase the efficiency of assisted reproductive techniques (ART), molecular studies have been performed to identify the best predictive biomarkers for selecting the most suitable germ cells for fertilization and the best embryo for intra-uterine transfer. However, across different studies, no universal markers have been found. In this study, we addressed this issue by generating gene expression and CpG methylation profiles of outer cumulus cells obtained during intra-cytoplasmic sperm injection (ICSI). We also studied the association of the generated genomic data with the clinical parameters (spindle presence, zona pellucida birefringence, pronuclear pattern, estrogen level, endometrium size and lead follicle size) and the pregnancy result. Our data highlighted the presence of several parameters that affect analysis, such as inter-individual differences, inter-treatment differences, and, above all, specific treatment protocol differences. When comparing the pregnancy outcome following the long protocol (GnRH agonist) of ovarian stimulation, we identified the single gene markers (NME6 and ASAP1, FDR < 5%) which were also correlated with endometrium size, upstream regulators (e.g., EIF2AK3, FSH, ATF4, MKNK1, and TP53) and several bio-functions related to cell death (apoptosis) and cellular growth and proliferation. In conclusion, our study highlighted the need to stratify samples that are very heterogeneous and to use pathway analysis as a more reliable and universal method for identifying markers that can predict oocyte development potential.

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. METHODS: We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. FINDINGS: We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 µmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 µmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 µmol/L or more (HR 30·50 [8·83-105·30]; p<0·0001). INTERPRETATION: The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 µmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. FUNDING: Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.

Study design of a stepped wedge cluster randomized controlled trial to evaluate the effect of a locally tailored approach for preconception care - the APROPOS-II study.

BACKGROUND: In a previous feasibility study (APROPOS) in a single municipality of the Netherlands, we showed that a locally tailored preconception care (PCC) approach has the potential to positively affect preconceptional lifestyle behaviours. Therefore, we designed a second study (APROPOS-II) to obtain a more robust body of evidence: a larger group of respondents, more municipalities, randomization, and a more comprehensive set of (clinical) outcomes. The aim of this study is to assess the effectiveness and the implementation process of a local PCC-approach on preconceptional lifestyle behaviours, health outcomes and the reach of PCC among prospective parents and healthcare providers. METHODS: This study is an effectiveness-implementation hybrid type 2 trial. This involves a stepped-wedge cluster randomized controlled trial design aiming to include over 2000 future parents from six municipalities in the Netherlands. The intervention has a dual-track approach, focusing on both the uptake of PCC among future parents and the provision of PCC by healthcare providers. The PCC-approach consists of 1) a social marketing strategy directed towards prospective parent(s) and 2) a local care pathway to improve interdisciplinary collaboration. Data will be collected before and after the introduction of the intervention through questionnaires and medical records in each of the participating municipalities. The primary outcome of this study is change in lifestyle behaviours (e.g. folic acid use, smoking and alcohol use). Secondary outcomes are pregnancy outcomes (e.g. miscarriage, preterm birth, gestational diabetes) and the uptake of PCC. Moreover, a process evaluation will be performed, providing information on the efficacy, feasibility, barriers and facilitators regarding the implementation of the intervention. DISCUSSION: The APROPOS-II study introduces a locally tailored PCC-approach in six municipalities in the Netherlands that will contribute to the body of evidence regarding the effectiveness of PCC and its implementation. If this intervention has a positive effect on lifestyle behaviour changes, leading to improved pregnancy outcomes and the future health of prospective parents and their offspring, it could subsequently be upscaled to (inter)national implementation. TRIAL REGISTRATION: Dutch Trial register: NL7784 (Registered June 6th, 2019).

A Mobile App Lifestyle Intervention to Improve Healthy Nutrition in Women Before and During Early Pregnancy: Single-Center Randomized Controlled Trial.

BACKGROUND: Unhealthy nutrition contributes to the worldwide rising prevalence of noncommunicable diseases. As most adverse reproductive outcomes originate during the periconception period, effective interventions targeting this period are needed. Therefore, we developed the lifestyle intervention Smarter Pregnancy to empower women to adapt a healthy diet prior to conception and during early pregnancy and performed a randomized controlled trial. OBJECTIVE: The objectives of this trial were to investigate compliance and effectiveness in women using the Smarter Pregnancy program. METHODS: Women aged between 18 and 45 years who were contemplating pregnancy or <13 weeks pregnant and their male partners living in the urban area of Rotterdam, the Netherlands, were eligible for participation. After baseline screening, the intervention group received personal online coaching based on identified inadequate intakes of vegetables, fruits, and folic acid supplements. The sum of these risk factors was used as a dietary risk score (DRS), ranging from 0 (healthy) to 9 (unhealthy). The control group did not receive coaching. We applied an intention-to-treat principle and used a multivariable linear regression model to evaluate the change in DRS after 24 weeks. Compliance was defined as the percentage of women who completed the screening questionnaire at 24 weeks. RESULTS: Of women recruited, 81.2% (177/218) completed the program (intervention: 91/218, 83.5%; control: 86/218, 78.9%; P=.95). After 24 weeks, the reduction in DRS of women in the intervention group was significantly larger than in the control group (ß=.75, 95% CI 0.18-1.34). This reduction was mainly due to increased vegetable intake (ß=.55, 95% CI 0.25-0.86). CONCLUSIONS: The high compliance and the larger improvements in nutritional behaviors, especially vegetable intake, in women in the intervention group emphasizes the effectiveness of empowering women by using the lifestyle change intervention Smarter Pregnancy. TRIAL REGISTRATION: Netherlands Trial Register: NL3927; https://www.trialregister.nl/trial/3927. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12884-017-1228-5.

The impact of maternal lifestyle factors on periconception outcomes: a systematic review of observational studies.

The main risk factors for important reproductive health issues such as subfertility and perinatal mortality largely originate in the periconception period. To evaluate associations between modifiable maternal lifestyle factors and periconception outcomes, a systematic search was conducted for relevant studies published from 1990 to February 2017 on Embase, Medline, Web of Science, Cochrane database, PubMed and Google Scholar. The initial search identified 6166 articles, of which 49 studies were eligible for inclusion. Fecundity (the capacity to have a live birth) showed significant inverse associations with smoking, alcohol use and poor diet. Studies regarding time to pregnancy showed a decline in fecundity ratios (the monthly conception rate among exposed relative to unexposed couples) with increasing body mass index (BMI). Furthermore, risk of first-trimester miscarriage was found to be increased in smokers, alcohol and caffeine consumers, and with increasing BMI. Vitamin supplement use showed a decrease in this risk. This review demonstrates that maternal modifiable lifestyle factors affect periconception outcomes. If couples planning a pregnancy are more aware and supported to adopt healthy lifestyles during the periconceptional 'window of opportunity', short-term reproductive health as well as health in later life and even of future generations can be further improved.

Overnight ovarian tissue transportation for centralized cryobanking: a feasible option.

RESEARCH QUESTION: Is overnight transportation of ovarian tissue before cryopreservation in a centralized cryobank from the FertiPROTEKT network feasible? DESIGN: Data from 1810 women with cryopreserved ovarian tissue after overnight transportation from December 2000 to December 2017 were analysed with a focus on transportation, tissue activity parameters and pregnancy, and delivery rates after transplantation. RESULTS: A total of 92.4% of tissue samples arrived at ideal temperatures of 2-8°C, 0.4% were transported at temperatures lower than ideal and 6.4% were transported at temperatures that were too high, generally due to mishandling of the inlayed cool packs of the transportation boxes. In 62 women, 78 tissue transplantations were carried out. A subgroup of 30 women who underwent a single orthotopic transplantation with fulfilled criteria of a complete follow-up after transplantation until the end of study, a premature ovarian insufficiency after gonadotoxic therapy as well as the absence of pelvic radiation, was further analysed. In this group, transplantations into a peritoneal pocket accounted for 90%. Transplants were still active at 1 year and above after transplantation in 93.3%. Pregnancy and delivery rates were 46.7% and 43.3%, respectively, with one ongoing pregnancy at the end of the study. CONCLUSIONS: Overnight transportation for central cryobanking is a feasible concept that results in high reproducible success rates through standardized professional tissue freezing and storage.

Significant reduction in umbilical artery metabolic acidosis after implementation of intrapartum ST waveform analysis of the fetal electrocardiogram.

BACKGROUND: Although the evidence regarding the benefit of using ST waveform analysis of the fetal electrocardiogram is conflicting, ST waveform analysis is considered as adjunct to identify fetuses at risk for asphyxia in our center. Most randomized controlled trials and meta-analyses have not shown a significant decrease in umbilical metabolic acidosis, while some observational studies have shown a gradual decrease of this outcome over a longer period of time. Observational studies can give more insight into the effect of implementation of the ST technology in daily clinical practice. OBJECTIVE: To evaluate the change in frequency of perinatal intervention and adverse neonatal outcome after the implementation of ST waveform analysis of the fetal electrocardiogram from 2000 to 2013. STUDY DESIGN: This retrospective longitudinal study was conducted in a tertiary referral center. A total of 19,664 medium- and high-risk singleton pregnancies with fetuses in cephalic presentation, a gestational age of ≥36 weeks, and the intention to deliver vaginally were included. ST waveform analysis of the fetal electrocardiogram was implemented in the year 2000 and by 2010 all deliveries were monitored using this technology. Data were collected on the following perinatal outcomes: fetal blood sampling, mode of delivery, umbilical cord blood gases, Apgar scores, neonatal encephalopathy, and perinatal death. Longitudinal trend analysis was used to detect changes over time in all deliveries monitored by cardiotocography either alone or in adjunct to ST waveform analysis of the fetal electrocardiogram. Logistic regression was used to correct for possible confounders. RESULTS: The umbilical artery metabolic acidosis rate declined from 2.5% (average rate of 2000 + 2001 + 2002) to 0.4% (average of 2011 + 2012 + 2013) (P < .001), which represents an 84% decrease. This decrease largely occurred between 2006 and 2008, during the Dutch randomized trial on fetal electrocardiogram ST waveform analysis. At this time, approximately 20% of deliveries were monitored using this method. Furthermore, there were significant reductions in fetal blood sampling rate (P < .001). Overall cesarean and vaginal instrumental deliveries decreased significantly (P < .001), but not for fetal distress. There were no changes in the Apgar scores. The incidence of neonatal encephalopathy was significantly lower in the second part of the study (odds ratio 0.39, 95% confidence interval 0.17-0.89). CONCLUSION: There was an 84% decrease in the incidence of umbilical artery metabolic acidosis in all deliveries between 2000 and 2013. The neonatal encephalopathy rate, fetal blood sampling rate, and the total number of cesarean and vaginal instrumental deliveries also decreased.

Placental development and function in women with a history of placenta-related complications: a systematic review.

INTRODUCTION: Women with a history of placenta-related pregnancy complications, such as preeclampsia, intrauterine growth restriction or preterm delivery, have an increased risk for recurrence of such complications. This recurrence is likely the result of underlying endothelial dysfunction that leads to abnormal placentation, especially in complications with an early onset. This study provides an overview of biomarkers of placental development and function in pregnancies from women with a history of placenta-related complications. MATERIAL AND METHODS: A systematic literature search was conducted limited to human studies and including keywords related to a history of placenta-related complications and markers of placental development and function. Two independent reviewers assessed eligibility and quality of 1553 retrieved unique articles. RESULTS: Five articles reporting on placental development and function in women with an obstetric history of preeclampsia (n = 3), intrauterine growth restriction (n = 1) and preterm delivery (n = 2) were eligible for quality assessment. We identified associations between a history of preeclampsia and abnormal placental histological findings at term in the current pregnancy, but found contradictory results regarding presence of uterine artery notching. In women with a history of very preterm delivery (<32 weeks), one study showed associations with abnormal placental histology. CONCLUSION: Literature on the association between a history of placenta-related complications and placental development and function in subsequent pregnancies is scarce and studies are heterogeneous. However, literature shows that placenta-related pregnancy complications are associated with subsequent placental histology.

The effect of a local promotional campaign on preconceptional lifestyle changes and the use of preconception care.

PURPOSE: The objective of this study was to investigate the effect of a local promotional campaign on preconceptional lifestyle changes and the use of preconception care (PCC). MATERIAL AND METHODS: This quasi-comparative study was carried out between February 2015 and February 2016 at a community midwifery practice in the Netherlands. The intervention consisted of a dual track approach (i) a promotional campaign for couples who wish to conceive and (ii) a PCC pathway for health care providers. Questionnaires were collected from a sample of women who received antenatal care during the pre-intervention (n = 283) and post-intervention (n = 257) period. Main outcome measures were preconceptional lifestyle changes and PCC use (defined as searching for information and/or consulting a health care provider). RESULTS: Women who were exposed to the intervention were significantly more likely to make at least one lifestyle change during the preconception period [adjusted OR 1.56 (95% CI 1.02-2.39)]. Women were especially more likely to preconceptionally reduce or quit [adjusted OR 1.72 (95% CI 1.05-2.83)] their alcohol consumption after exposure to the intervention. Although non-significant, it appeared that women who were exposed to the intervention more often prepared themselves for pregnancy by means of independently searching for preconception health information [adjusted OR 1.13 (95% CI 0.77-1.65)] or consulting a health care provider regarding their wish to conceive [adjusted OR 1.24 (95% CI 0.81-1.92)]. CONCLUSIONS: Exposure to a local promotional campaign targeted at preconceptional health was associated with improved preconceptional lifestyle behaviours, especially with regard to alcohol consumption, and has the potential to improve the use of PCC.

Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance.

Periconceptional nutrition and lifestyle are essential in pathogenesis and prevention of most reproductive failures, pregnancy outcome and future health. We aimed to investigate whether personalized mobile health (mHealth) coaching empowers couples contemplating pregnancy to increase healthy behaviour and chances of pregnancy. A survey was conducted among 1053 women and 332 male partners who received individual coaching using the mHealth programme 'Smarter Pregnancy' to change poor nutrition and lifestyle for 26 weeks, depending on pregnancy state and gender. Poor behaviours were translated into a total risk score (TRS) and Poisson regression analysis was performed to estimate associations with the chance of pregnancy adjusted for fertility status, age and baseline body mass index expressed as adjusted hazard ratio (aHR) and 95% confidence interval (95% CI). A lower (a)HR suggests a higher chance of achieving pregnancy. A higher TRS was significantly associated with a lower chance of pregnancy in all women (aHR 0.79, 95% CI 0.72-0.85) and (a)HR was lowest in women whose male partner participated (aHR 0.75, 95% CI 0.61-0.91). This survey shows that empowerment of couples in changing poor nutrition and lifestyle using personalized mHealth coaching is associated with an enhanced pregnancy chance in both infertile and fertile couples.