Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BackgroundEarly pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 μg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure.ObjectiveThis study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss.Study designWe performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment.ResultsOverall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49).ConclusionNo baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors

Estimators for longitudinal latent exposure models: examining measurement model assumptions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136711/1/sim7268_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136711/2/sim7268.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136711/3/sim7268-sup-0001-Supplementary.pd

Bayesian estimation of associations between identified longitudinal hormone subgroups and age at final menstrual period

Abstract Background Although follicle stimulating hormone (FSH) is known to be predictive of age at final menstrual period (FMP), previous methods use FSH levels measured at time points that are defined relative to the age at FMP, and hence are not useful for prospective prediction purposes in clinical settings where age at FMP is an unknown outcome. This study is aimed at assessing whether FSH trajectory feature subgroups identified relative to chronological age can be used to improve the prediction of age at FMP. Methods We develop a Bayesian model to identify latent subgroups in longitudinal FSH trajectories, and study the relationship between subgroup membership and age at FMP. Data for our study is taken from the Penn Ovarian Aging study, 1996–2010. The proposed model utilizes mixture modeling and nonparametric smoothing methods to capture hypothesized latent subgroup features of the FSH longitudinal trajectory; and simultaneously studies the prognostic value of these latent subgroup features to predict age at FMP. Results The analysis identified two FSH trajectory subgroups that were significantly associated with FMP age: 1) early FSH class (15 %), which displayed initial increases in FSH shortly after age 40; and 2) late FSH class (85 %), which did not have a rise in FSH until after age 45. The use of FSH subgroup memberships, along with class-specific characteristics, i.e., level and rate of FSH change at class-specific pre-specified ages, improved prediction of FMP age by 20–22 % in comparison to the prediction based on previously identified risk factors (BMI, smoking and pre-menopausal levels of anti-mullerian hormone (AMH)). Conclusions To the best of our knowledge, this work is the first in the area to demonstrate the existence of subgroups in FSH trajectory patterns relative to chronological age and the fact that such a subgroup membership possesses prediction power for age at FMP. Earlier ages at FMP were found in a subgroup of women with rise in FSH levels commencing shortly after age 40, in comparison to women who did not exhibit an increase in FSH until after 45 years of age. Periodic evaluations of FSH in these age ranges are potentially useful for predicting age at FMP.http://deepblue.lib.umich.edu/bitstream/2027.42/116209/1/12874_2015_Article_101.pd

Six-month Expulsion of Postplacental Copper Intrauterine Devices Placed After Vaginal Delivery

Background Immediate placement of an intrauterine device after vaginal delivery is safe and convenient, but longitudinal data describing clinical outcomes have been limited. Objective We sought to determine the proportion of TCu380A (copper) intrauterine devices expelled, partially expelled, malpositioned, and retained, as well as contraceptive use by 6 months postpartum, and determine risk factors for expulsion and partial expulsion. Study Design In this prospective, observational study, women who received a postplacental TCu380A intrauterine device at vaginal delivery were enrolled postpartum. Participants returned for clinical follow-up at 6 weeks, and for a research visit with a pelvic exam and ultrasound at 6 months. We recorded intrauterine device outcomes and 6-month contraceptive use. Partial expulsion was defined as an intrauterine device protruding from the external cervical os, or a transvaginal ultrasound showing the distal end of the intrauterine device below the internal os of the cervix. Multinomial logistic regression models identified risk factors associated with expulsion and partial expulsion by 6 months. The area under the receiver operating characteristics curve was used to assess the ability of a string check to predict the correct placement of a postplacental intrauterine device. The primary outcome was the proportion of intrauterine devices expelled at 6 months. Results We enrolled 200 women. Of 162 participants with follow-up data at 6 months, 13 (8.0%; 95% confidence interval, 4.7–13.4%) experienced complete expulsion and 26 (16.0%; 95% confidence interval, 11.1–22.6%) partial expulsion. Of 25 malpositioned intrauterine devices (15.4%; 95% confidence interval, 10.2–21.9%), 14 were not at the fundus (8.6%; 95% confidence interval, 5.2–14.1%) and 11 were rotated within the uterus (6.8%; 95% confidence interval, 3.8–11.9%). Multinomial logistic regression modeling indicated that higher parity (odds ratio, 2.05; 95% confidence interval, 1.21–3.50; P = .008) was associated with expulsion. Provider specialty (obstetrics vs family medicine; odds ratio, 5.31; 95% confidence interval, 1.20–23.59; P = .03) and gestational weight gain (normal vs excess; odds ratio, 9.12; 95% confidence interval, 1.90–43.82; P = .004) were associated with partial expulsion. Long-acting reversible contraceptive method use at 6 months was 80.9% (95% confidence interval, 74.0–86.6%). At 6 weeks postpartum, 35 of 149 (23.5%; 95% confidence interval, 16.9–31.1%) participants had no intrauterine device strings visible. Sensitivity of a string check to detect an incorrectly positioned intrauterine device was 36.2%, and specificity of the string check to predict a correctly positioned intrauterine device was 84.5%. This corresponds to an area under the receiver operating characteristics curve of 0.5. Conclusion This prospective assessment of postplacental TCu380A intrauterine device placement, with ultrasound to confirm device position, finds a complete intrauterine device expulsion proportion of 8.0% at 6 months. The association of increasing parity with expulsion is consistent with prior research. The clinical significance of covariates associated with partial expulsion (provider specialty and gestational weight gain) is unclear. Due to the observational study design, any associations cannot imply causality. The proportion of partially expelled and malpositioned intrauterine devices was high, and the area under the receiver operating characteristics curve of 0.5 indicates that a string check is a poor test for assessing device position. Women considering a postplacental intrauterine device should be counseled about the risk of position abnormalities, as well as the possibility of nonvisible strings, which may complicate clinical follow-up. The clinical significance of intrauterine device position abnormalities is unknown; future research should evaluate the influence of malposition and partial expulsion on contraceptive effectiveness and side effects

Fertility preservation in patients with haematological disorders: a retrospective cohort study

This study investigated the factors associated with utilization of fertility preservation and the differences in treatments and outcomes by prior chemotherapy exposure in patients with haematological diseases. This study included all 67 women with haematological diseases seen for fertility preservation consultation at two university hospitals between 2006 and 2011. Of the total, 49% had lymphoma, 33% had leukaemia, 7% had myelodysplastic syndrome and 4% had aplastic anaemia; 46% had prior chemotherapy; and 33% were planning for bone marrow transplantation, 33% pursued ovarian stimulation and 7% used ovarian tissue banking; and 48% of patients did not pursue fertility preservation treatment. All five cycle cancellations were in the post-chemotherapy group: three patients with leukaemia and two with lymphoma. Patients with prior chemotherapy had lower baseline antral follicle count (10 versus 22) and received more gonadotrophins to achieve similar peak oestradiol concentrations, with no difference in oocyte yield (10.5 versus 10) after adjustment for age. Embryo yield was similar between those who had prior chemotherapy and those who had not. Half of the patients with haematological diseases who present for fertility preservation have been exposed to chemotherapy. While ovarian reserve is likely impaired in this group, oocyte yield may be acceptable

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV