Recurrent pregnancy loss : diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis

BACKGROUND Recurrent pregnancy loss (RPL) occurs in 1–3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79–1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86–1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55–1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06–4.56). WIDER IMPLICATIONS A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present

Expression of the ggpPS gene for glucosylglycerol biosynthesis from Azotobacter vinelandii improves the salt tolerance of Arabidopsis thaliana

Many organisms accumulate compatible solutes in response to salt or desiccation stress. Moderate halotolerant cyanobacteria and some heterotrophic bacteria synthesize the compatible solute glucosylglycerol (GG) as their main protective compound. In order to analyse the potential of GG to improve salt tolerance of higher plants, the model plant Arabidopsis thaliana was transformed with the ggpPS gene from the γ-proteobacterium Azotobacter vinelandii coding for a combined GG-phosphate synthase/phosphatase. The heterologous expression of the ggpPS gene led to the accumulation of high amounts of GG. Three independent Arabidopsis lines showing different GG contents were characterized in growth experiments. Plants containing a low (1–2 μmol g−1 FM) GG content in leaves showed no altered growth performance under control conditions but an increased salt tolerance, whereas plants accumulating a moderate (2–8 μmol g−1 FM) or a high GG content (around 17 μmol g−1 FM) showed growth retardation and no improvement of salt resistance. These results indicate that the synthesis of the compatible solute GG has a beneficial effect on plant stress tolerance as long as it is accumulated to an extent that does not negatively interfere with plant metabolism

Practice variation in the management of first trimester miscarriage in the Netherlands: a nationwide survey

Objectives. To survey practice variation in the management of first trimester miscarriage in The Netherlands. Methods. We sent an online questionnaire to gynecologists in eight academic, 37 nonacademic teaching, and 47 nonteaching hospitals. Main outcome measures were availability of a local protocol; estimated number of patients treated with curettage, misoprostol, or expectant management; misoprostol regimen; and estimated number of curettages performed after initial misoprostol treatment. Outcomes were compared to the results of a previous nationwide survey. Results. The response rate was 100%. A miscarriage protocol was present in all academic hospitals, 68% of nonacademic teaching hospitals, and 38% of nonteaching hospitals (P = 0.008). Misoprostol was first-choice treatment for 41% of patients in academic hospitals versus 34% and 27% in teaching-and nonteaching hospitals (P = 0.045). There were 23 different misoprostol regimens. Curettage was first-choice treatment in 29% of patients in academic hospitals versus 46% and 50% in nonacademic teaching or nonteaching hospitals (P = 0.007). In 30% of patients, initial misoprostol treatment was followed by curettage. Conclusions. Although the percentage of gynaecologists who are aware of the availability of misoprostol for miscarriage treatment has doubled to almost 100% since 2005, practice variation is still large. This practice variation underlines the need for a national guideline.Marianne A. C. Verschoor, Marike Lemmers, Malu Z. Wekker, Judith A. F. Huirne, Mariëtte Goddijn, Ben Willem J. Mol, and Willem M. Anku

Finding Plastic Patches in Coastal Waters using Optical Satellite Data

Satellites collecting optical data offer a unique perspective from which to observe the problem of plastic litter in the marine environment, but few studies have successfully demonstrated their use for this purpose. For the first time, we show that patches of floating macroplastics are detectable in optical data acquired by the European Space Agency (ESA) Sentinel-2 satellites and, furthermore, are distinguishable from naturally occurring materials such as seaweed. We present case studies from four countries where suspected macroplastics were detected in Sentinel-2 Earth Observation data. Patches of materials on the ocean surface were highlighted using a novel Floating Debris Index (FDI) developed for the Sentinel-2 Multi-Spectral Instrument (MSI). In all cases, floating aggregations were detectable on sub-pixel scales, and appeared to be composed of a mix of seaweed, sea foam, and macroplastics. Building first steps toward a future monitoring system, we leveraged spectral shape to identify macroplastics, and a Naïve Bayes algorithm to classify mixed materials. Suspected plastics were successfully classified as plastics with an accuracy of 86

The use of an ‘acclimatisation’ heatwave measure to compare temperature-related demand for emergency services in Australia, Botswana, Netherlands, Pakistan, and USA

Background: Heatwaves have been linked to increased risk of mortality and morbidity and are projected to increase in frequency and intensity due to climate change. The current study uses emergency department (ED) data from Australia, Botswana, Netherlands, Pakistan, and the United States of America to evaluate the impact of heatwaves on ED attendances, admissions and mortality.Methods: Routinely collected time series data were obtained from 18 hospitals. Two separate thresholds (≥4 and ≥7) of the acclimatisation excess heat index (EHIaccl) were used to define hot days . Analyses included descriptive statistics, independent samples T-tests to determine differences in case mix between hot days and other days, and threshold regression to determine which temperature thresholds correspond to large increases in ED attendances.Findings: In all regions, increases in temperature that did not coincide with time to acclimatise resulted in increases in ED attendances, and the EHIaccl performed in a similar manner. During hot days in California and The Netherlands, significantly more children ended up in the ED, while in Pakistan more elderly people attended. Hot days were associated with more patient admissions in the ages 5-11 in California, 65-74 in Karachi, and 75-84 in The Hague. During hot days in The Hague, patients with psychiatric symptoms were more likely to die. The current study did not identify a threshold temperature associated with particularly large increases in ED demand.Interpretation: The association between heat and ED demand differs between regions. A limitation of the current study is that it does not consider delayed effects or influences of other environmental factors. Given the association between heat and ED use, hospitals and governmental authorities should recognise the demands that heat can place on local health care systems. These demands differ substantially between regions, with Pakistan being the most heavily affected within our study sample

The experiences of women with breast cancer who undergo fertility preservation

STUDY QUESTION: How do women, who have just been diagnosed with breast cancer, experience oocyte or embryo banking? SUMMARY ANSWER: Fertility preservation was a challenging yet welcome way to take action when confronted with breast cancer. WHAT IS KNOWN ALREADY: Fertility preservation for women with breast cancer is a way to safeguard future chances of having children. Women who have just been diagnosed with breast cancer report stress, as do women who have to undergo IVF treatment. How women experience the collision of these two stressfull events, has not yet been studied. STUDY DESIGN, SIZE, DURATION: We performed a multicenter qualitative study with a phenomenological approach including 21 women between March and July 2014. Women were recruited from two university-based fertility clinics. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with breast cancer who banked oocytes or embryos 1-15 months before study participation were eligible. We conducted in-depth, face-to-face interviews with 21 women, which was sufficient to reach data saturation. MAIN RESULTS AND THE ROLE OF CHANCE: The 21 women interviewed had a mean age of 32 years. Analysis of the 21 interviews revealed three main experiences: The burden of fertility preservation, the new identity of a fertility patient and coping with breast cancer through fertility preservation. LIMITATIONS, REASONS FOR CAUTION: Interviewing women after, rather than during, fertility preservation might have induced recall bias. Translation of quotes was not carried out by a certified translator. WIDER IMPLICATIONS OF THE FINDINGS: The insights gained from this study of the experiences of women undergoing fertility preservation while being newly diagnosed with breast cancer could be used as a starting point for adapting the routine psychosocial care provided by fertility clinic staff. Future studies are necessary to investigate whether adapting routine psychosocial care improves women's wellbeing

Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011

STUDY QUESTION: Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population? SUMMARY ANSWER: After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI. WHAT IS KNOWN ALREADY: There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF. STUDY DESIGN, SIZE, DURATION: A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989-2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81-1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84-1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08-2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88-1.81) compared to cancer risk in children not conceived by ART. LIMITATIONS, REASONS FOR CAUTION: The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases. WIDER IMPLICATIONS OF THE FINDINGS: After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women's cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I-II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction &amp; Development, and the Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests. TRIAL REGISTRATION NUMBER:N/A.</p

A core outcome set for trials in miscarriage management and prevention: An international consensus development study

Objective: To develop core outcome sets (COS) for miscarriage management and prevention. Design: Modified Delphi survey combined with a consensus development meeting. Setting: International. Population: Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. Methods: Modified Delphi method and modified nominal group technique. Results: The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks’ gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. Conclusions: This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage