An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).

Background Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.Objective To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network metaanalysis (registered in PROSPERO: CRD42018112862).Search strategy PubMed, Web of science, Embase and Cochrane database.Selection criteria All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.Data collection and analysis For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.Main results Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.Conclusions These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.Tweetable abstract This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.

aObjective The aim of this study was to investigate whether the risk of developing ischaemic heart disease (IHD) later in life increases with severity and recurrence of gestational hypertensive disease. Design Cross-sectional population-based study.Setting Sweden.Population Women (403,550) giving birth to their first child in Sweden, 1973Sweden, -1982. Of this cohort, 207,054 women who also gave birth to a second child during the same period were analysed separately. Methods All women were followed up for 15 years, starting 4 -14 years after the index pregnancy. Women who suffered from hypertensive disease during pregnancy were compared with women with normal pregnancies with regard to hospitalisation for, or death from, IHD during the follow up period. Main outcome measures Fatal or non-fatal IHD.Results The adjusted incidence rate ratio (IRR) for later development of IHD was 1.6 (95% CI 1.3-2.0) when the first pregnancy was complicated by gestational hypertension without proteinuria, 1.9 (95% CI 1.6 -2.2) for mild pre-eclampsia and 2.8 (95% CI 2.2 -3.7) for severe pre-eclampsia. Women with gestational hypertension in their first pregnancy but not in their second had an adjusted IRR of 1.9 (95% CI 1.5-2.4) for development of IHD. Women with hypertensive disease in both pregnancies had an IRR of 2.8 (95% CI 2.0 -3.9) compared with women with two normal pregnancies. Conclusion Severe hypertensive disease in pregnancy has a stronger association with later development of IHD than has mild hypertensive disease. Recurrent hypertensive disease is more strongly associated with IHD than is non-recurrent disease.

(N Engl J Med. 2016;374:13–22) Preeclampsia is a serious multisystem disorder affecting up to 5% of pregnancies worldwide. A reliable predictor of preeclampsia would be helpful in allowing health care providers to identify women at risk for developing the disorder. Serum levels of circulating maternal soluble fms-like tyrosine kinase 1 (sFlt-1) are known to be elevated in preeclampsia, while levels of placental growth factor (PlGF) are decreased. A high ratio of sFlt-1 to PlGF indicates an increased risk for preeclampsia and could potentially be a more reliable predictor than either of those factors alone. The authors of this study sought to evaluate the ratio as a predictive tool among women with suspected preeclampsia.

Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritoneal fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (nZ25) as well as eutopic endometrium from women without endometriosis (nZ14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.

Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI.

Based on gestational age at diagnosis and/or delivery, pre-eclampsia (PE) is commonly divided into early-onset (<34 weeks) and late-onset (≥34 weeks) forms. Recently, the distinction between ‘placental’ and ‘maternal’ causation has been proposed, with ‘placental’ cases being more frequently associated with early-onset and intrauterine growth restriction. To test whether molecular placental pathology varies according to clinical presentation, we investigated stress-signalling pathways, including unfolded protein response (UPR) pathways, MAPK stress pathways, heat-shock proteins and AMPKα in placentae delivered by caesarean section for clinical indications at different gestational ages. Controls included second-trimester, pre-term and normal-term placentae. BeWo cells were used to investigate how these pathways react to different severities of hypoxia–reoxygenation (H/R) and pro-inflammatory cytokines. Activation of placental UPR and stress-response pathways, including P-IRE1α, ATF6, XBP-1, GRP78 and GRP94, P-p38/p38 and HSP70, was higher in early-onset PE than in both late-onset PE and normotensive controls (NTCs), with a clear inflection around 34 weeks. Placentae from ≥ 34 weeks PE and NTC were indistinguishable. Levels of UPR signalling were similar between second-trimester and term controls, but were significantly higher in pre-term ‘controls’ delivered vaginally for chorioamnionitis and other conditions. Severe H/R (1/20% O2) induced equivalent activation of UPR pathways, including P-eIF2α, ATF6, P-IRE1α, GRP78 and GRP94, in BeWo cells. By contrast, the pro-inflammatory cytokines TNFα and IL-1β induced only mild activation of P-eIF2α and GRP78. AKT, a central regulator of cell proliferation, was reduced in the < 34 weeks PE placentae and severe H/R-treated cells, but not in other conditions. These findings provide the first molecular evidence that placental stress may contribute to the pathophysiology of early-onset pre-eclampsia, whereas that is unlikely to be the case in the late-onset form of the syndrome. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Context:Previous studies have suggested that antimü llerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective:The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design:The study was a prospective cohort study between April 2008 and June 2011. Setting:The study was done at a university-affiliated private infertility center. Patients:The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s):AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures:Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured.Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH Ͻ 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH Ͼ 2.94 ng/mL (75th percentile), P trend Ͻ .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions:AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality. (J Clin Endocrinol Metab 98: 1107-1114, 2013)