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STUDY QUESTION Can we identify genetic variants associated with ectopic pregnancy by undertaking the first genome-wide association study (GWAS) leveraging two large-scale biobank initiatives? SUMMARY ANSWER We identified two novel genome-wide significant associations with ectopic pregnancy, highlighting MUC1 (mucin 1) as the most plausible affected gene. WHAT IS KNOWN ALREADY Ectopic pregnancy is an important cause of maternal morbidity and mortality worldwide. Despite being a common early pregnancy complication, the genetic predisposition to this condition remains understudied and no large scale genetic studies have been performed so far. STUDY DESIGN, SIZE, DURATION A GWAS meta-analysis including 7070 women with ectopic pregnancy and 248 810 controls from Estonian Biobank and the FinnGen study. PARTICIPANTS/MATERIALS, SETTING, METHODS We identified ectopic pregnancy cases from national registers by ICD (International Classification of Disease) codes (ICD-10 O00), and all remaining women were considered controls. We carried out standard GWAS meta-analysis and additionally annotated GWAS signals, analysed co-localization with quantitative trait loci, estimated genetic correlations and identified associated phenotypes to characterize the genetic signals, as well as to analyse the genetic and phenotypic relationships with the condition. MAIN RESULTS AND THE ROLE OF CHANCE We identified two genome-wide significant loci on chromosomes 1 (rs4971091, P  = 5.32 × 10−9) and 10 (rs11598956, P  = 2.41 × 10−8) potentially associated with ectopic pregnancy. Follow-up analyses propose MUC1 , which codes for an epithelial glycoprotein with an important role in barrier function, as the most likely candidate gene for the association on chromosome 1. We also characterize the phenotypic and genetic correlations with other phenotypes, identifying a genetic correlation with smoking and diseases of the (genito)urinary and gastrointestinal system, and phenotypic correlations with various reproductive health diagnoses, reflecting the previously known epidemiological associations. LARGE SCALE DATA The GWAS meta-analysis summary statistics are available from the GWAS Catalogue (GCST90272883). LIMITATIONS, REASONS FOR CAUTION The main limitation is that the findings are based on European-based ancestry populations, with limited data on other populations, and we only captured maternal genomes. Additionally, further larger meta-analysis or independent studies are needed to validate these findings. WIDER IMPLICATIONS OF THE FINDINGS This study encourages the use of large-scale genetic datasets to unravel genetic factors linked to ectopic pregnancy, which is difficult to study in experimental settings. Increased sample size might bring additional genetic factors associating with ectopic pregnancy and inform its heritability. Altogether, our results provide more insight into the biology of ectopic pregnancy and, accordingly, the biological processes governing embryo implantation. STUDY FUNDING/COMPETING INTEREST(S) N.P.G. was supported by MATER Marie Sklodowska-Curie which received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 813707. This study was funded by European Union through the European Regional Development Fund Project No. 2014-2020.4.01.15-0012 GENTRANSMED. Computations were performed in the High-Performance Computing Center of University of Tartu. The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Study Question: Do differences in blood pressure within the normal range have any impacts on the live birth rate (primary outcome) or biochemical pregnancy rate (beta-hCG positivity), clinical pregnancy rate (heart beating in ultrasound), abortion rate and ectopic pregnancy rate (secondary outcomes) of fresh embryo transfer in women undergoing their IVF/ICSI treatment?Summary Answer: Even rather small differences in baseline blood pressure in women with normal blood pressure according to current guidelines undergoing fresh embryo transfer after IVF/ICSI affects substantially the live birth rate.What Is Known Already: Pre-pregnancy hypertension is a well-known risk factor for adverse pregnancy events such as preeclampsia, fetal growth restriction, placental abruption and adverse neonatal events. It is likewise well known that hypertension during pregnancy in women undergoing ART is associated with adverse pregnancy outcomes. However, whether blood pressure at the high end of the normal range has an impact on ART is unknown.Study Design, Size, Duration: It is a prospective observational cohort study based on a single IVF center between January 2017 and December 2018.Participants/materials, Setting, Methods: Two thousand four hundred and eighteen women with normal blood pressure undergoing fresh embryo transfer after IVF/ICSI at the Reproductive and Genetic Hospital of CITIC-Xiangya were enrolled in this study.Main Results and the Role Of Chance: Blood pressure was measured at the first visit when women consulted the IVF center due to infertility. In women with a successful pregnancy outcome (1487 live births out of 2418 women undergoing fresh embryo transfer after IVF/ICSI), systolic blood pressure (SBP) (114.1 ± 9.48 mmHg versus 115.4 ± 9.8 mmHg, P = 0.001) and diastolic blood pressure (DBP) (74.5 ± 7.5 mmHg versus 75.3 ± 7.34 mmHg, P = 0.006) were lower than in those who did not achieve live births. Multivariate logistic regression analysis revealed that SBP (OR: 0.987, 95% CI: 0.979-0.996, P = 0.004) and DBP (OR: 0.986, 95% CI: 0.975-0.998, P = 0.016) were negatively associated with live birth. Similarly, SBP was significantly negatively related to clinical pregnancy rate (OR: 0.990, 95% CI: 0.981-0.999, P = 0.033), while for DBP the association was not statistically significant (OR: 0.994, 95% CI: 0.982-1.006, P = 0.343). However, both SBP and DBP were positively associated with miscarriage OR: 1.021 (95% CI: 1.004-1.037, P = 0.013) and OR: 1.027 (95% CI: 1.005-1.049, P = 0.014), respectively. Both SBP and DBP were unrelated to biochemical pregnancy (hCG positivity), implantation and ectopic pregnancy rate.Limitations, Reasons For Caution: Whether lowering blood pressure before initiating ART treatment in women with SBP or DBP higher than the thresholds defined in our study will confer a benefit is unknown. Also, we cannot exclude bias due to different ethnicities. Moreover, participants in our study only received fresh embryo transfer, whether the results could apply to frozen embryo transfer is unclear.Wider Implications Of the Findings: Our study challenges the current blood pressure goals in women undergoing fresh embryo transfer after IVF/ICSI. Further studies are needed to figure out the mechanism and effective approach to increase IVF/ICSI pregnancy outcomes.Study Funding/competing Interest(s): Hunan Provincial Grant for Innovative Province Construction (2019SK4012). The authors declare that there were no conflicts of interest in this study.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Is there an increased risk of unplanned peripartum hysterectomy in pregnancies with assissted reproductive technology compared to those without ART?Summary Answer: Although the absolute risks are low, there is an almost five-fold increased risk of unplanned peripartum hysterectomy and 1.7 more unplanned peripartum hysterectomies occur per 1000 deliveries in pregnancies with ART compared to those without ART.What Is Known Already: It has been reported that pregnancies with ART was associated with increased risk of peripartum hysterectomy in one case-control study and in one cohort study.Study Design, Size, Duration: A retrospective cohort study was conducted using a birth cohort from 2014 and 2015 in the United States, which includes more than 7 million births. Propensity score (PS) matching was used to control for confounding.Participants/materials, Setting, Methods: Subjects were divided into two groups: pregnancies with and without ART. We calculated PSs with demographic, clinical and socioeconomic variables, and subjects were matched using the PS with a 1:1 ratio. Subjects comprised 43868 ART pregnancies and 43868 non-ART pregnancies after PS matching. The primary outcome of interest was the risk of unplanned peripartum hysterectomy which was compared by evaluating the relative risk and the risk difference between the two groups after PS matching.Main Results and the Role Of Chance: Baseline characteristics were similar between groups after PS matching. The risk of peripartum hysterectomy in women with ART was 4.947 times that of those without ART (0.0021 [94/43868] vs 0.0004 [19/43868]; 95% confidence interval [CI] 3.022-8.098). The risk difference between two groups was 0.0017 (95% CI 0.0012-0.0022).Limitations, Reasons For Caution: There is a possibility of bias due to unmeasured confounding such as fibroids, previous history of uterine surgery and intrauterine procedures. Misclassification of the exposure and/or the outcome could also influence the results.Wider Implications Of the Findings: Although we found a five-fold increased risk of unplanned peripartum hysterectomy in pregnancies with ART compared to those without ART, the results should be interpreted with caution in a clinical context as the overall number and the absolute risk of unplanned peripartum hysterectomy are very low in either group (1/2325 in the non-ART group, and 1/468 in the ART group). However, it would be appropriate as future research agenda to explore mechanisms and/or etiology underlying this finding.Study Funding/competing Interest(s): No external funding was used and there are no competing interests.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Study Question: Does the risk of adverse outcomes at the time of ectopic pregnancy vary by race/ethnicity among women receiving Medicaid, the public health insurance program for low-income people in the USA?Summary Answer: Among Medicaid beneficiaries with ectopic pregnancy, 11% experienced at least one complication, and women from all racial/ethnic minority groups were significantly more likely than whites to experience complications.What Is Known Already: In this population of Medicaid recipients, African American women are significantly more likely than whites to experience ectopic pregnancy, but the risk of adverse outcomes has not previously been assessed.Study Design, Size, and Duration: We conducted a cross-sectional observational study of all women (n = 19 135 106) ages 15-44 enrolled in Medicaid for any amount of time during 2004-2008 who lived in one of the following 14 US states: Arizona; California; Colorado; Florida; Illinois; Indiana; Iowa; Louisiana; Massachusetts; Michigan; Minnesota; Mississippi; New York; and Texas.Participants/materials, Settings, Methods: We analyzed Medicaid claims records for inpatient and outpatient encounters and identified ectopic pregnancies with a principal diagnosis code for ectopic pregnancy from 2004-2008. We calculated the ectopic pregnancy complication rate as the number of ectopic pregnancies with at least one complication (blood transfusion, hysterectomy, any sterilization, or length-of-stay (LOS) > 2 days) divided by the total number of ectopic pregnancies. We used Poisson regression to assess the risk of ectopic pregnancy complication by race/ethnicity. Secondary outcomes were each individual complication, and ectopic pregnancy-related death. We calculated the ectopic pregnancy mortality ratio as the number of deaths divided by live births.Main Results and the Role Of Chance: Ectopic pregnancy-associated complications occurred in 11% of cases. Controlling for age and state, the risk of any complication was significantly higher among women who were black (incidence risk ratio [IRR] 1.47, 95% CI 1.43-1.53, P < 0.0001), Hispanic (IRR 1.16, 95% CI 1.12-1.21, P < 0.0001), Asian (IRR 1.34, 95% CI 1.24-1.45, P < 0.0001), American Indian/Alaskan Native (IRR 1.34 95% CI 1.16-1.55, P < 0.0001), and Native Hawaiian/Pacific Islander (IRR 1.61, 95% CI 1.39-1.87, P < 0.0001) compared with white women. The ectopic pregnancy mortality ratio was 0.48 per 100 000 live births, similar to that reported in previous US surveillance.Limitations, Reasons For Caution: This is a secondary analysis of insurance claims.Wider Implications Of the Findings: Among women at higher baseline risk of pregnancy complications due to their economic status, women from racial/ethnic minority groups face an additional risk of ectopic pregnancy adverse outcomes compared with whites. Systematic changes to reduce racial disparities are an essential part of improving maternal health in the USA.Study Funding/competing Interests: The Eunice Kennedy Shriver National Institute of Child Health and Human Development (1 K08 HD060663 to D.B.S.). The authors report no conflict of interest.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

BACKGROUND Low plasma sex hormone-binding globulin (SHBG) concentrations during pregnancy have been associated with the risk of developing gestational diabetes mellitus (GDM). Women presenting with polycystic ovary syndrome (PCOS) often exhibit low plasma SHBG concentration and are at increased risk of developing GDM. In this study, we investigate whether SHBG levels before conception are predictive of GDM in women with PCOS. METHODS A total of 50 women with PCOS were enrolled and followed up during pregnancy. Initial endocrine, metabolic and physical features were assessed according to a standardized preconception screening program. At 24–26 weeks of gestational age a 100-g glucose tolerance test was performed to screen for GDM. RESULTS Of the 50 women, 21 (42%) were diagnosed with GDM by a 100-g glucose tolerance test. Waist circumference, BMI, blood pressure, plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and SHBG levels before conception were significantly different between women who did and did not develop GDM. Stepwise logistic regression analysis showed that SHBG was the most significant predictive parameter for GDM (odds ratio 0.92; 95% confidence interval 0.87–0.97), without significant contribution of waist circumference and HOMA-IR. Receiver operator characteristic (ROC) analysis indicated that plasma SHBG (area under the curve 0.86) had the highest predictive value for subsequent development of GDM, however, the limited group size did not allow for calculation of a threshold value of SHBG. CONCLUSIONS In women with PCOS, preconception SHBG levels are strongly associated with subsequent development of GDM. Regression and ROC analysis show that preconception SHBG levels may be a better predictor for GDM in PCOS women compared with waist circumference or HOMA-IR. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of aspirin during in vitro fertilization (IVF) has been investigated for its effect on pregnancy rates after IVF. In most of these studies, aspirin administration was then prolonged throughout the first trimester of pregnancy. By inhibiting vasoconstriction, the use of low-dose aspirin in the first trimester could influence placentation and therefore prevent or delay development of hypertensive pregnancy complications, such as pregnancy-induced hypertension (PIH) and pre-eclampsia (PE). [ABSTRACT FROM PUBLISHER]