Are singleton pregnancies after assisted reproduction technology (ART) associated with a higher risk of placental anomalies compared with non-ART singleton pregnancies? A systematic review and meta-analysis.

BACKGROUND: Placental anomalies (placenta praevia, placental abruption, morbidly adherent placenta and cord insertion anomalies) are associated with maternal and fetal morbidity and mortality. It has been suggested these might be more prevalent in pregnancies after assisted reproduction technology (ART). OBJECTIVES: To determine whether ART singleton pregnancies are associated with an increased risk of placental anomalies compared with non-ART singleton pregnancies. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus (January 2018). SELECTION CRITERIA: Cohort studies reporting placental anomalies in ART and non-ART singleton pregnancies. DATA COLLECTION AND ANALYSIS: We report pooled odds ratios (OR) for the comparisons: (1) ART versus SC (spontaneously conceived), (2) ART versus non-ART (unspecified), (3) FET-ART (frozen-embryo transfer) versus SC, (4) ART versus non-ART (subfertile patients). Study quality was assessed using a modified Newcastle -Ottawa scale. MAIN RESULTS: 33 low/moderate quality studies evaluated 124 215 ART and 6 054 729 non-ART singleton pregnancies. Risk of placenta praevia, placental abruption and morbidly adherent placenta was higher in ART than SC pregnancies: odds ratio (OR) (OR 3.76, 95% CI 3.09-4.59); (OR 1.87, 95% CI 1.70-2.06) and (OR 2.27, 95% CI 1.79-2.87) respectively. Risk of placenta praevia and placental abruption was higher in ART than in non-ART (subfertile patients): (OR 2.51, 95% CI 2.12-2.98) and (OR 1.61, 95% CI 1.33-1.95) respectively. Results were similar when comparing ART with unspecified non-ART pregnancies. Risk of placenta praevia was higher, but not significantly so, in FET-ART than in SC pregnancies (OR 2.42, 95% CI 0.63-9.30). CONCLUSIONS: Singleton ART pregnancies are associated with an increased risk of placental anomalies compared with non-ART singleton pregnancies. TWEETABLE ABSTRACT: A review of over 6 million singleton pregnancies finds increased risk of placental anomalies after ART.

Linking effects of anthropogenic debris to ecological impacts.

Accelerated contamination of habitats with debris has caused increased effort to determine ecological impacts. Strikingly, most work on organisms focuses on sublethal responses to plastic debris. This is controversial because (i) researchers have ignored medical insights about the mechanisms that link effects of debris across lower levels of biological organization to disease and mortality, and (ii) debris is considered non-hazardous by policy-makers, possibly because individuals can be injured or removed from populations and assemblages without ecological impacts. We reviewed the mechanisms that link effects of debris across lower levels of biological organization to assemblages and populations. Using plastic, we show microplastics reduce the 'health', feeding, growth and survival of ecosystem engineers. Larger debris alters assemblages because fishing-gear and tyres kill animals and damage habitat-forming plants, and because floating bottles facilitate recruitment and survival of novel taxa. Where ecological linkages are not known, we show how to establish hypothetical links by synthesizing studies to assess the likelihood of impacts. We also consider how population models examine ecological linkages and guide management of ecological impacts. We show that by focusing on linkages to ecological impacts rather than the presence of debris and its sublethal impacts, we could reduce threats posed by debris.

Urban structures provide new insights into interactions among grazers and habitat.

A major challenge in ecology is to understand and predict consequences of environmental changes to biological assemblages. Urbanization and associated alteration and destruction of habitat cause profound changes in local biodiversity and the ecology of and interactions among organisms. This study tested hypotheses about interactions among intertidal species on urbanized shores to examine predictions from their known ecology. On natural shores, grazing limpets, Cellana tramoserica, outcompete the smaller limpets, Patelloida latistrigata. The latter shelter among barnacles. On seawalls in Sydney Harbour (Australia), P. latistrigata were found among and on oysters. C. tramoserica were found directly on walls where there were no oysters. To explain these observations, several models were proposed and tested by manipulative experiments in the field: (1) oysters provide habitat for P. latistrigata; (2) negative interactions with C. tramoserica cause P. latistrigata to move on and among oysters; and (3) in areas with oysters, space available for grazing is insufficient for C. tramoserica to survive well. The results showed that C. tramoserica had a negative impact on the survival of P. latistrigata, although not causing the latter to move onto oysters. The oysters directly and indirectly affected P. latistrigata. First, oysters provided habitat and increased survival of P. latistrigata. Second, oysters influenced the interaction between C. tramoserica and P. latistrigata. This "interaction modification" diminished the negative impact of C. tramoserica. The material used to construct a wall did not directly influence the distribution of the limpets. Maintaining oysters on seawalls is, however, important because of their direct and indirect effects on P. latistrigata. It was possible to predict some processes on urbanized shores from known ecology. Other processes could not be predicted, making it necessary to do experiments to understand how built structures influence biological assemblages. This research contributes to understanding how to conserve biodiversity in urban areas.

The effect on human sex ratio at birth by assisted reproductive technology (ART) procedures--an assessment of babies born following single embryo transfers, Australia and New Zealand, 2002-2006.

OBJECTIVE: To assess the effect on the human sex ratio at birth by assisted reproductive technology (ART) procedures. DESIGN: Retrospective population-based study. SETTING: Fertility clinics in Australia and New Zealand. POPULATION: The study included 13,368 babies by 13,165 women who had a single embryo transfer (SET) between 2002 and 2006. METHODS: Logistic regression was used to model the effect on the sex ratio at birth of ART characteristics [in vitro fertilisation (IVF) or intracytoplasmic sperm insemination (ICSI) SET, cleavage-stage or blastocyst SET, and fresh or thawed SET] and biological characteristics (woman's and partner's age and cause of infertility). MAIN OUTCOME MEASURES: Proportion of male births. RESULTS: The crude sex ratio at birth was 51.3%. Individual ART procedures had a significant effect on the sex ratio at birth. More males were born following IVF SET (53.0%) than ICSI SET (50.0%), and following blastocyst SET (54.1%) than cleavage-stage SET (49.9%). For a specific ART regimen, IVF blastocyst SET produced more males (56.1%) and ICSI cleavage-stage SET produced fewer males (48.7%). CONCLUSIONS: The change in the sex ratio at birth of SET babies is associated with the ART regimen. The mechanism of these effects remains unclear. Fertility clinics and patients should be aware of the bias in the sex ratio at birth when using ART procedures.

Evaluating accuracy and precision of species-area relationships for multiple estimators and different marine assemblages.

This paper evaluates the accuracy and precision of six nonparametric estimators and six regression models for predicting the number of species in an area using random subsamples of that area. Such extrapolations are important for increased understanding of species-area relationships in different assemblages of species to inform ecological theories, and because they have direct implications in many conservation issues. Often, such extrapolations are evaluated by considering how well they fit existing data, rather than the actual number of species in the larger area. Also, many studies have focused on larger species in terrestrial habitats, where numbers of species are quite well known. Assemblages of invertebrates and smaller plants, especially in marine habitats, are less well known, and their distributions are dominated by small-scale variability. We examined species-area relations for two assemblages on boulders from six locations, for rocky shore assemblages in three locations, and for gastropods colonizing artificial habitat. Changing the focus of subsampling relative to the extent of the study and changing the size of the subsamples was also evaluated for subsets of data. Most estimators fitted the number of species poorly, with the second-order Jackknife consistently the best of the nonparametric measures, and the Negative Exponential the best of the regression models. Increasing the number of replicates improved most models, but some only slightly, and others considerably. Changing focus had little effect, probably because marine assemblages such as these vary at small scales as much as at many larger scales. These extensive analyses provide clear evidence about which estimators should not be used for measuring species-area relationships in assemblages such as these, and which will consistently over- or underestimate the number of species. The findings are applicable to many assemblages dominated by small organisms with strong stochastic variation.

Do modified habitats have direct or indirect effects on epifauna?

Replacing natural habitats with artificial structures such as pier-pilings, jetties, and seawalls has important consequences to abundances of biota. It is, however, not often known whether these are direct (the novel habitat alters abundances of some species) or indirect (the novel habitat directly alters some aspect of the behavior or ecology of some species, which, in turn, alter abundances of other species). Marine animals in some modified habitats in Sydney Harbour provide experimental opportunities to test hypotheses to distinguish between direct and indirect processes. Covers of bryozoans and hydroids were greater on kelp growing on pilings than on kelp growing on natural reefs. The epifauna may be affected directly by the pilings or indirectly, i.e., the structure affects characteristics of the kelp which, in turn, influence covers of epifauna. Thus, differences in covers of epifauna on kelp can be due to: (1) factors associated with the primary habitats (pilings vs. reefs), (2) differences between characteristics of the kelp found in each habitat, or (3) an interaction between these factors (habitat and/or type of kelp). Kelp were experimentally transplanted between pilings and reefs, demonstrating that properties of the habitat directly affected covers of epifauna, which were not influenced by the type of kelp that grows on pilings or rocky reefs. Manipulative experiments to unconfound multiple components of habitats influencing disturbances to biota are needed to understand human impacts on natural systems.

Engineering novel habitats on urban infrastructure to increase intertidal biodiversity.

Urbanization replaces natural shorelines with built infrastructure, seriously impacting species living on these "new" shores. Understanding the ecology of developed shorelines and reducing the consequences of urban development to fauna and flora cannot advance by simply documenting changes to diversity. It needs a robust experimental programme to develop ways in which biodiversity can be sustained in urbanized environments. There have, however, been few such experiments despite wholesale changes to shorelines in urbanized areas. Seawalls--the most extensive artificial infrastructure--are generally featureless, vertical habitats that support reduced levels of local biodiversity. Here, a mimic of an important habitat on natural rocky shores (rock-pools) was experimentally added to a seawall and its impact on diversity assessed. The mimics created shaded vertical substratum and pools that retained water during low tide. These novel habitats increased diversity of foliose algae and sessile and mobile animals, especially higher on the shore. Many species that are generally confined to lowshore levels, expanded their distribution over a greater tidal range. In fact, there were more species in the constructed pools than in natural pools of similar size on nearby shores. There was less effect on the abundances of mobile animals, which may be due to the limited time available for recruitment, or because these structures did not provide appropriate habitat. With increasing anthropogenic intrusion into natural areas and concomitant loss of species, it is essential to learn how to build urban infrastructure that can maintain or enhance biodiversity while meeting societal and engineering criteria. Success requires melding engineering skills and ecological understanding. This paper demonstrates one cost-effective way of addressing this important issue for urban infrastructure affecting nearshore habitats.

Evidence necessary for taxa to be reliable indicators of environmental conditions or impacts.

Using taxa as indicators of environmental impacts is widespread. Indicators are chosen because they are considered to be easy to measure, sensitive to stresses and respond to stresses in predictable ways. Here, we review these criteria by addressing the nature of the relationships between some characteristic of taxa and the environmental variables they are supposed to indicate. It is crucial that variables measured as indicators be strongly and consistently correlated (through space and time) with levels of the environmental variables. Appropriate experiments must be done to establish that an observed correlation is causal, or the correlation cannot be considered sufficient to identify a useful indicator. Finally, it is necessary to establish that the taxa directly respond to changes in the environmental variables they are supposed to indicate. Appropriate methodologies to establish these criteria are considered and we evaluate studies in which these criteria have or have not been met.

Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy.

We measured serum alkaline phosphatase isoenzymes and osteocalcin levels in 40 healthy women at 4-week intervals throughout uncomplicated pregnancies and 6 weeks after delivery in 17 women. Serum bone alkaline phosphatase was significantly higher in the third trimester than in early pregnancy (P less than 0.001), and this elevation was still apparent at the end of the puerperium, suggesting increased bone turnover. Serum osteocalcin was not detected (less than 0.2 micrograms/L) after the first trimester in the majority of women, and it reappeared within 48 h after delivery. The disappearance of osteocalcin after the first trimester and its rapid reappearance after delivery suggest placental clearance of this peptide. We conclude that serum osteocalcin measurements cannot be used as a marker of bone metabolism during pregnancy.

Premenopausal bone loss in the lumbar spine and neck of femur: a study of 225 Caucasian women.

Two hundred and twenty-five premenopausal women were studied to evaluate age-related changes in trabecular bone mass. Measurements were made at the lumbar spine and femoral neck by dual photon absorptiometry. It was found that spinal bone density increased significantly from the 20s to reach a peak in the mid-30s. Identical trends were observed in total bone mass and bone mass normalized by length. Bone loss then proceeded at a rate of 1% per year, and by the early 50s, 10% of peak spinal density was lost. There was no peak in femoral neck density; loss commenced in the late 20s and continued at a rate of 0.4% per year. The cumulative premenopausal loss from the femur at 9% was comparable to that in the spine. It is concluded that significant amounts of trabecular bone are lost from both the spine and femoral neck before the menopause. The implications of these findings for the prevention of osteoporosis are discussed.

Suppression of in vitro lymphocyte reactivity to phytohemagglutinin by placental protein 14.

Crude human decidual extracts containing up to 26.6 mg/l of placental protein 14 (PP14) and purified PP14 were assessed for their effects on the in vitro lymphocyte reactivity to phytohemagglutinin (PHA). Both decidual extract and purified PP14 suppressed the mitogenic response to PHA with the suppression being dose-dependent over the range of PP14 concentrations investigated (0-26.6 mg/l). On the specific reduction of the PP14 content by a monoclonal anti-PP14 immunoadsorbant the suppression was reduced. The suppressive activity of PP14 was related to the degree of proliferation of the stimulated lymphocytes. These results suggest that PP14, which is present at peak levels in the first trimester of pregnancy and constitutes up to 10% of the soluble protein content of decidual tissue, may be an immunomodulator important for the survival of the implanting embryo and maintenance of early pregnancy.

The radioimmunoassay of human placental protein 14 (PP14).

The development and validation of a radioimmunoassay for the measurement of human placental protein 14 in maternal serum is described. The mean concentration of this protein in serum from 22 normal pregnant women showed a decline during the third trimester from 120 micrograms/l at 27 weeks gestation to 65 micrograms/l at term. Serum samples from 16 patients with intra-uterine growth retardation tended to contain lower concentrations of placental protein 14, these results reaching significance at weeks 36-38 of gestation. Of seven patients with pre-eclampsia from whom two or more blood samples were taken, four showed increases in concentration of this protein as pregnancy proceeded, compared with the normal pattern of decreasing values.

Scales of spatial patterns of distribution of intertidal invertebrates.

Few comparative studies of spatial patterns at different scales have examined several species in the same habitat or the same species over a range of habitats. Therefore, variability in patterns among species or among habitats has seldom been documented. This study quantifies spatial patterns of a suite of intertidal snails and a species of barnacle using a range of statistical techniques. Variability in densities was quantified from the scale of adjacent quadrats (over a distance of centimeters) to tens of kilometers. Significant differences in abundances occurred primarily at two spatial scales. Small-scale differences were found at the scales of centimeters or 1-2 m and, for many species on many shores, these accounted for most of the variability in abundances from place to place. These are likely to be determined by behavioural responses to small-scale patches of microhabitat. Large-scale differences in abundance were also found in most species at the scale of hundreds of meters alongshore. These are likely to be due to variation in recruitment (and/or mortality) because of limited dispersal by adults of these species. There was little or no additional variation among shores, separated by tens of kilometers, than was shown among patches of shore separated by hundreds of meters. Identification of the scale(s) at which significant differences in abundance are found focus attention on the processes (and the scales at which these processes operate) that influence patterns of distribution and abundance. Some of the advantages and disadvantages of various procedures are discussed.

A method for analysing spatial scales of variation in composition of assemblages.

In several areas of research on ecological assemblages, it is useful to be able to analyse patterns of spatial variation at various scales. Multivariate analyses of dissimilarity or similarity in assemblages of species are limited by problems of non-independence caused by repeated use of the sample-units. Where rank-order procedures are used, no comparative quantitative measurements of dissimilarity at different scales are produced. An alternative method is described that uses the sample's average assemblage (or centroid). These estimates are themselves averaged to give centroids for larger spatial scales. Dissimilarities from the centroids at each scale are then calculated using independent replicates for each scale from those in each sample. The dissimilarity measures can then be examined by analysis of variance to detect spatial scales of differences for each sample at every level of a hierarchy of scales. The method is illustrated using data from mangrove forests and rocky shores, involving up to 97 taxonomic groups (species, other taxa). Differences among assemblages at the scales of sites (tens of meters apart) or locations at shores (hundreds of meters apart) were identified. Consequences of different numbers of replicates are discussed, with some potential problems (and their solutions) in application.

A study of the effect of tibolone on the vagina in postmenopausal women.

Tibolone is a synthetic compound with weak oestrogenic, progestagenic and androgenic properties. It does not appear to stimulate the endometrium, and therefore has appeal to the postmenopausal woman as a 'bleedfree' form of hormone replacement therapy (HRT). In the present study the vaginal cytological findings and symptoms were evaluated in 100 recently postmenopausal women, 50 of whom were started on tibolone 2.5 mg daily and 50 of whom received no medication. After 2 years in the tibolone group, cytological assessment showed a significant increase in the karyopyknotic index (P < 0.001) and maturation value (P < 0.01) whereas there was no change in the control group. Significant symptomatic improvement occurred in vaginal dryness (P < 0.001), dyspareunia (P < 0.001), sexual enjoyment (P < 0.001) and libido (P < 0.05). It is therefore concluded that tibolone has a significant oestrogenic effect on the vagina as demonstrated by vaginal cytology. In addition, improvement in the symptoms of vaginal dryness, dyspareunia, sexual enjoyment and libido occurs.

Early low-lying placentae--ultrasonic assessment, progress and outcome.

A prospective study was carried out using 100 patients with 64 appropriately matched controls, to follow the course of low-lying placentae, diagnosed before 20 wk gestation. 94% of these placentae had moved out of the lower segment by the 32nd wk, while only 2% of the total required a caesarean section for placenta praevia. No evidence of intrauterine growth retardation or increased incidence of preeclampsia was found. In the light of this and other studies, a routine ultrasound re-check of placental position subsequent to 32 wk is deemed unnecessary unless clinically indicated, saving unnecessary maternal anxiety and over-exposure to ultrasound. Since the posterior low-lying placentae are those more likely to remain praevia, it is they that require follow-up scans.

Two fetal antigens (FA-1 and FA-2) and endometrial proteins (PP12 and PP14) isolated from amniotic fluid; preliminary observations in fetal and maternal tissues.

Rabbit antihuman antibodies were derived by the injection of fractions of second trimester amniotic fluid known to contain proteins of endometrial/decidual origin. Using standard separation and absorption procedures, two antibody preparations were generated which demonstrated specificities against two and three proteins, respectively, in line immunoelectrophoresis and crossed immunoelectrophoresis. Analysis against proteins of fetal, maternal, endometrial and placental origin revealed that the bispecific antiserum reacted only with placental protein 14 (PP14; also known as progestagen-dependent endometrial protein, PEP) and one other hitherto undescribed antigen referred to as Fetal Antigen 1 (FA-1) molecular mass 60 kDa; electrophoretic mobility: slow; alpha 1-alpha 2; fast, albumin. The trispecific antiserum demonstrated specifities against placental protein 12 (PP12), alpha-fetoprotein (AFP) and another previously undescribed antigen referred to as Fetal Antigen 2 (FA-2) molecular mass 35 and 140 kDa; electrophoretic mobility: albumin. Following purification, monospecific antisera against each of these proteins (with the exception of AFP) were derived in new rabbits. Maternal and fetal blood, amniotic fluid and aqueous extracts from endometrial/decidual and placental tissues were analysed in rocket immunoelectrophoresis using these antisera to examine the distribution in these tissues. The analyses demonstrated a pattern of distribution typical for proteins of endometrial/decidual origin in these compartments in the case of PP12 and PP14, but suggested that the primary source of origin of FA-1 and FA-2 may be the fetus.

Occult infiltrating placenta previa percreta: an unusual case highlighting the management problems in a young patient.

Placenta previa in association with placenta accreta has been recorded on average in 1 in 500 pregnancies; its association with placenta percreta is a much rarer condition. We report an unusual case of placenta previa which presented as a severe form of occult parasitic infiltration, invading the internal iliac vessels. This was followed by life-threatening complications, despite preventative measures. Use of a prediction index to suspect placenta previa is mentioned.

Quantification of radular marks as a method for estimating grazing of intertidal gastropods on rocky shores.

Wax discs have been used previously on intertidal rocky shores to record the grazing activity of gastropods. This study has evaluated this methodology for recording grazing of four common intertidal microalgal grazers on intertidal shores in New South Wales, Australia. In the laboratory, the four species examined-the patellid limpet, Cellana tramoserica (Sowerby), the trochid, Austrocochlea porcata (A. Adams), the neritid, Nerita atramentosa Reeve and the littorinid, Bembicium nanum (Lamarck)-made distinctive marks in the wax. These allowed identification of each species or combinations of species grazing over the different discs. Field experiments showed that the intensity of grazing, as indicated by the mean number of scratches per disc, was positively related to the number of gastropods in the surrounding area during low tide for C. tramoserica. The number of scratches per disc in any area was correlated with the percentage of discs scratched. The relationship for C. tramoserica was found at two scales-in sites (approximately 3x3 m) and also in plots (50x50 cm) within sites. Therefore, densities that were measured when these limpets were inactive during low tide provided good estimates of grazing activity during high tide. This is largely because these limpets do not move far between where they rest and where they feed. The amount of microalgal food in the vicinity was not correlated with density, nor with grazing intensity. No relationship between density and grazing intensity was found for N. atramentosa, although experiments were only done in the field at one spatial scale (in sites, 3x3 m). Results obtained in the laboratory and in the field show that wax discs are useful to distinguish grazing by different species of gastropods on Australian rocky shores and allow tests of hypotheses about grazing activity at different spatial scales.