Search

Objectives: To evaluate the pharmacokinetic and pharmacodynamic effects of two novel levonorgestrel (LNG)-only contraceptive patches., Study Design: This multi-center Phase I/II trial randomized participants to use a 7-day transdermal patch designed to deliver a 40 mcg or 75 mcg daily LNG dose for 11 consecutive weeks; randomization was stratified by body mass index (BMI) <32 or 32-40 kg/m 2 . Evaluations occurred twice weekly for 5 weeks, then once weekly with supplemental visits for participants reporting a urinary LH surge. We evaluated pharmacokinetics via the weekly trough serum LNG concentrations (≥180 pg/mL considered therapeutic). The primary pharmacodynamic outcomes were cervical mucus and ovulation, evaluated using modified Insler cervical mucus scores and serum markers of ovulation., Results: Randomization yielded similar groups. Of 121 enrolled women, 117 contributed analyzable data. Overall, mean LNG concentrations achieved with use of the 75 mcg patch [value] were roughly double those seen with the 40 mcg dose. Concentrations achieved in higher-BMI women (BMI=32-40 kg/m 2 ) were 50% lower compared to lower-BMI women for both patches. During the study, 94/117 (80%) participants had at least one LNG concentration <180 pg/mL. Insler scores were ≥5 at least once in 102/117 (87%) of participants, and ovulation occurred at least once in 81/117 (69%). Sixty participants (51%) had at least one ovulation following an Insler score ≥5; this occurred most frequently among higher-BMI participants using the lower-dose patch (19/25, 76%)., Conclusions: Women using two investigational LNG patches did not achieve consistent concentrations of LNG >180 pg/mL, an efficacy benchmark established in other studies with LNG implants, and they experienced high rates of ovulation as well as cervical mucus scores not supportive of high contraceptive efficacy., Implications: The novel LNG-only patches in this study may not adequately decrease pregnancy risk, particularly for higher-BMI women. Future studies of LNG-only contraceptive patches will need to employ higher LNG doses and assess the acceptability and safety of such dosing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Amphibian granular glands provide a wide range of compounds on the skin that defend against pathogens and predators. We identified three bufadienolides-the steroid-like compounds arenobufagin, gamabufotalin, and telocinobufagin-from the boreal toad, Anaxyrus boreas, through liquid chromatography mass spectrometry (LC/MS). Compounds were detected both after inducing skin gland secretions and in constitutive mucosal rinses from toads. We described the antimicrobial properties of each bufadienolide against Batrachochytrium dendrobatidis (Bd), an amphibian fungal pathogen linked with boreal toad population declines. All three bufadienolides were found to inhibit Bd growth at similar levels. The maximum Bd inhibition produced by arenobufagin, gamabufotalin, and telocinobufagin were approximately 50%, in contrast to the complete Bd inhibition shown by antimicrobial skin peptides produced by some amphibian species. In addition, skin mucus samples significantly reduced Bd viability, and bufadienolides were detected in 15 of 62 samples. Bufadienolides also appeared to enhance growth of the anti-Bd bacterium Janthinobacterium lividum, and thus may be involved in regulation of the skin microbiome. Here, we localized skin bacteria within the mucus layer and granular glands of toads with fluorescent in situ hybridization. Overall, our results suggest that bufadienolides can function in antifungal defense on amphibian skin and their production is a potentially convergent trait similar to antimicrobial peptide defenses found on the skin of other species. Further studies investigating bufadienolide expression across toad populations, their regulation, and interactions with other components of the skin mucosome will contribute to understanding the complexities of amphibian immune defense.

New medullary bone formation has been observed in rats administered a variety of antineoplastic compounds. Similar effects reported in rats administered granulocyte colony-stimulating factor (G-CSF) were attributed to exaggerated pharmacology of G-CSF as a cytokine and growth factor, resulting in stromal proliferation in addition to the intended hematopoietic effects. Similar phenomena of marrow stromal change are reported among other species in association with various growth factors. Case study summaries of test item-related histopathologic changes in bone marrow, reflecting trabecular and/or endosteal new bone formation, are presented. In each of these cases, it was concluded that the new medullary bone and stromal proliferation did not reflect a primary target-related toxicity; rather, the mesenchymal changes were attributed to nonspecific, secondary effects of cytokines elaborated in response to primary cytotoxic effects on hematopoietic cells with subsequent impact on circulating blood cells. The common features associated with marrow stromal changes in the case studies, as well as with a variety of pharmacologic compounds across several species described in the literature, are hematologic effects and/or changes in growth factor levels and cytokine expression.

Background: While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed., Objective: The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility., Study Design: A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale., Results: Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility., Conclusion: Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice ( N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered >225 μg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114-23. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Since the approval of insulin as the first recombinant therapeutic protein, the prominence of biologic therapies in drug development has grown significantly. Many modalities beyond traditional biologics are now being developed or explored for various indications with significant unmet medical needs. From early traditional replacement proteins to more recent, highly engineered antibodies, oligonucleotides, fusion proteins, and gene constructs, biologic agents have delivered life-changing therapies, despite often having scientifically and technically challenging development programs. This brief review outlines some of the major biotherapeutic classes and identifies the advantages and challenges with the development of these products., (© The Author(s) 2015.)

Study Question: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube?, Summary Answer: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher., What Is Known Already: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy., Study Design, Size, Duration: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively., Participants/materials, Settings, Methods: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle., Main Results and the Role of Chance: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative., Limitations, Reasons for Caution: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital., Wider Implications of the Findings: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child., Study Funding/competing Interests: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee., Trial Registration Number: ISRCTN37002267., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications., Design: Randomized, prospective clinical trial., Setting: Multicenter university-based clinical practices., Patient(s): A total of 900 couples with unexplained infertility., Intervention(s): Collection of baseline demographics, blood samples, and ultrasonographic assessments., Main Outcome Measure(s): Demographic, laboratory, imaging, and survey characteristics., Result(s): Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners., Conclusion(s): The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment., Clinical Trial Registration Number: NCT 01044862., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: Are there improvements in the accuracy of prediction of ectopic pregnancy (EP) in women with early symptomatic pregnancy using human chorionic gonadotrophin (hCG) curves when clinicians consider visits beyond the first 48 h after initial presentation?, Summary Answer: Two hCG values, measured 48 h (2 days) apart, are often not sufficient to accurately predict the outcome of a woman with a pregnancy of unknown location (PUL), but adding a third visit on Day 4 or 7 significantly improved the prediction for 1 in 15 women., What Is Known Already: The use of serial hCG values is commonly used to aid in the prediction of the final diagnosis in women with a PUL. Initial outcome predictions based on two hCG values may often be incorrect., Study Design, Size, Duration: This retrospective multicenter cohort study included 646 women with a PUL, recruited over 2 years. Of these women, 146 were ultimately diagnosed with EP., Participants/materials, Setting, Methods: Women presenting to the emergency room with first trimester pain or bleeding, with a PUL, at least 2 hCG values and a definitive final diagnosis from the University of Pennsylvania, University of Miami and University of Southern California, were recruited from 2007 to 2009., Main Results and the Role of Chance: Using currently recommended prediction rules, adding a third hCG evaluation on Day 4 after initial presentation significantly improved the accuracy of initial prediction from the first two values (48 h apart, or Day 2) by 9.3% (P = 0.015). Adding a third value on Day 7 improved prediction significantly by 6.7% (P = 0.031), compared with prediction based on first two values. The improvement in prediction by assessing four hCG values (Days 0, 2, 4 and 7) compared with three values (Days 0, 2 and 4) was 1.3% and not statistically significant., Limitations, Reasons for Caution: Missing data imputation likely biased results toward the null; predicted outcomes may not match those made by clinicians; and the study does not predict intrauterine pregnancy and spontaneous miscarriage separately., Wider Implications of the Findings: This study provides useful information for the prediction of outcomes for women with a symptomatic first trimester pregnancy of unknown location, but may not be generalizable to all pregnant women., Study Funding/competing Interest(s): Supported by NIH grant numbers R01-HD036455 to Dr Barnhart and Dr Sammel, K24HD060687 to Dr Barnhart, and 5T32MH065218 to Ms. Zee. The authors have no conflicts of interest to declare.

Background: At present, it is unclear which treatment strategy is best for couples with unexplained or mild male subfertility. We hypothesized that the prognostic profile influences the effectiveness of assisted conception. We addressed this issue by analysing individual patient data (IPD) from randomized controlled trials (RCTs)., Methods: We performed an IPD analysis of published RCTs on treatment strategies for subfertile couples. Eligible studies were identified from Cochrane systematic reviews and we also searched Medline and EMBASE. The authors of RCTs that compared expectant management (EM), intracervical insemination (ICI), intrauterine insemination (IUI), all three with or without controlled ovarian stimulation (COS) and IVF in couples with unexplained or male subfertility, and had reported live birth or ongoing pregnancy as an outcome measure, were invited to share their data. For each individual patient the chance of natural conception was calculated with a validated prognostic model. We constructed prognosis-by-treatment curves and tested whether there was a significant interaction between treatment and prognosis., Results: We acquired data from 8 RCTs, including 2550 couples. In three studies (n = 954) the more invasive treatment strategies tended to be less effective in couples with a high chance of natural conception but this difference did not reach statistical significance (P-value for interaction between prognosis and treatment outcome were 0.71, 0.31 and 0.19). In one study (n = 932 couples) the strategies with COS (ICI and IUI) led to higher pregnancy rates than unstimulated strategies (ICI 8% versus 15%, IUI 13% versus 22%), regardless of prognosis (P-value for interaction in all comparisons >0.5), but at the expense of a high twin rate in the COS strategies (ICI 6% versus 23% and IUI 3% versus 30%, respectively). In two studies (n = 373 couples), the more invasive treatment strategies tended to be more effective in couples with a good prognosis but this difference did not reach statistical significance (P-value for interaction: 0.38 and 0.68). In one study (n = 253 couples) the differential effect of prognosis on treatment effect was limited (P-value for interaction 0.52), perhaps because prognosis was incorporated in the inclusion criteria. The only study that compared EM with IVF included 38 couples, too small for a precise estimate., Conclusions: In this IPD analysis of couples with unexplained or male subfertility, we did not find a large differential effect of prognosis on the effectiveness of fertility treatment with IUI, COS or IVF.

Gp340 is a member of the scavenger receptor cysteine-rich family of innate immune molecules and also functions as a tumor suppressor. This study describes a picogram-level assay using electrochemiluminescence technology on the MesoScale Discovery platform. Antibodies were evaluated and the best pair was used to assay whole-mouth stimulated saliva and cervical/vaginal lavage. The assay was tested using specimens obtained from healthy volunteers to determine if gp340 concentration in saliva correlates with levels in vaginal lavage fluid. Interestingly, no correlation was determined between gp340 content in these two fluids., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities., Methods: A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed., Results: The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma., Conclusions: We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non-human primate., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Microbicide gels studied for HIV prevention often are delivered via a single-use vaginal applicator. Using a contraceptive diaphragm such as the SILCS diaphragm for gel delivery could have advantages, including lower cost and additional pregnancy prevention., Study Design: We performed an exploratory, nonblinded, randomized, crossover study among healthy, sexually active, nonpregnant women. Using BufferGel, we evaluated three microbicide delivery methods for gel distribution and retention: SILCS single-sided gel delivery, SILCS double-sided gel delivery and a vaginal applicator (without SILCS). Magnetic resonance images were taken at baseline, after gel insertion, and immediately and 6 h after simulated intercourse. Three women completed all gel delivery methods described in this article., Results: Magnetic resonance imaging analysis indicated similar gel spread in the vagina among all three methods. SILCS single-sided gel application resulted in the most consistent longitudinal coverage; SILCS double-sided gel application was the most consistent in the transverse dimension., Conclusions: Gel coverage was similar with all three methods. These results suggest that the SILCS microbicide delivery system is comparable to vaginal applicators for delivery of gel products intravaginally., (Copyright © 2013 Elsevier Inc. All rights reserved.)

BACKGROUND The term 'pregnancy of unknown location' (PUL) refers to cases where a pregnancy test is positive but the pregnancy cannot be visualized by transvaginal sonography (TVS). Various strategies integrating TVS and serum hCG measures are used to follow-up until the location and/or viability of the pregnancy becomes clear; however, the optimal strategy to predict the outcome of pregnancy in women with PUL is unknown. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic accuracy of the various serum hCG strategies in women with PUL. METHODS We searched Medline and EMBASE for articles which were published (in any language) from 1980 to January 2012 on strategies using serum hCG in women with PUL and reporting on the final outcome of pregnancy. RESULTS From 980 selected titles, 23 articles, all cohort studies, were included. There were 10 studies on a single serum hCG cut-off level, 4 on serum hCG ratio (hCG 48 h/hCG 0 h) and 6 on logistic regression modelling. Three other strategies were reported using serum hCG, serum progesterone and/or uterine curettage findings; each of these strategies comprised a single study. Comparative diagnostic studies have not been performed on the diagnostic value of serum hCG in women with PUL. Included studies showed substantial clinical heterogeneity in the definition of the outcome, and only data for the pregnancy outcome ectopic pregnancy (EP) were suitable for meta-analysis. The receiver operating characteristic curves showed that the serum hCG ratios and logistic regression models had a better performance as compared with an absolute single serum hCG level (as the curve was considerably closer to the diagonal, indicating no diagnostic value). CONCLUSIONS Overall the study was limited by the high clinical heterogeneity of the data but in women with PUL diagnostic strategies using serum hCG ratios, either alone or in logistic regression models, have the best diagnostic performance in the case of EP. Well defined prospective comparative studies using standardized diagnostics and clinical application plus agreed definitions of outcome are required to identify the best strategy to diagnose pregnancy outcome in women with PUL.

Objective: The current evidence concerning the best treatment option for couples with unexplained and male subfertility is inconclusive. Most studies that have evaluated the effectiveness of treatment options, such as expectant management (EM), intrauterine insemination (IUI), with or without controlled ovarian stimulation (COS), and in vitro fertilisation (IVF), have not taken the couples' prognosis into account. It is very likely that the individual prognosis of the couple influences the effect of treatment. Individual patient data analyses allow us to take these prognostic factors into account, and to evaluate their effect on treatment outcome. This study aims to use anonymised data from relevant published trials to perform an individual patient data meta-analysis, evaluating the effect of couples' prognosis on the effectiveness of EM, IUI, with or without COS, and IVF., Methods: Based on earlier systematic reviews and an updated search, randomised controlled trials will be considered for inclusion. Untreated subfertile couples with unexplained or male subfertility included in trials comparing EM, IUI, with or without COS, and IVF are included. Authors of the included studies will be invited to share their original anonymised data. The data will be assessed on validity, quality and completeness. The prognosis of the individual couple will be calculated with existing prognostic models. The effect of the prognosis on treatment outcome will be analysed with marker-by-treatment predictiveness curves, illustrating the effect of prognosis on treatment outcome. This study is registered in PROSPERO (registration number CRD42011001832)., Conclusion: Ultimately, this study may help to select the appropriate fertility treatment, tailored to the needs of an individual couple., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

Medical management has become increasingly popular in the treatment of ectopic pregnancy. Given its convenience, for many it is used as a first-line treatment, however, this is not always the optimal choice for the patient. It is important to understand the options for medical treatment and when it is appropriate to treat a particular patient with medical management, or when one should opt for surgical management. This review outlines the different regimens for methotrexate administration and the associated risks and benefits to medical management.

Objective: To measure and compare placental mRNA expression in the maternal circulation among women with intrauterine and ectopic pregnancies., Methods: Plasma was collected from patients in early pregnancy at risk of ectopic pregnancy. Clinical information was prospectively collected and entered into a dedicated database. mRNA was isolated from maternal plasma and quantitative RT-PCR was performed to measure mRNA for human gonadotropin (hCG) and human placental lactogen (hPL). GAPDH mRNA expression was used as an internal control., Results: Twelve women with ectopic pregnancy and 13 women with intrauterine pregnancy were enrolled. Patients with ectopic pregnancy were 6 times more likely to have undetectable levels of hPL mRNA (relative risk [RR] 6.36; 95% confidence interval [CI], 1.70-23.20; P<0.01). They were also 8 times more likely to have undetectable levels of hCG mRNA (RR 8.64, 95% CI, 1.30-57.10; P<0.01). mRNA copy numbers for hPL and hCG (normalized by GAPDH) were significantly lower in the ectopic group than in the intrauterine group., Conclusion: Placental mRNA is present in the maternal circulation in significantly lower copies in cases of ectopic pregnancy compared with cases of intrauterine pregnancy. Measurement of placental mRNA in the maternal circulation may help to distinguish between intrauterine and ectopic pregnancies., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Introduction: Ectopic pregnancy (EP) remains the leading cause of maternal mortality in the first trimester of pregnancy. In an attempt to expedite the accurate diagnosis of women with EP, research has focused on serum biomarkers that can distinguish EP from other types of pregnancies in women with a pregnancy of unknown location (PUL)., Areas Covered: This review was based on recently published research, as cited on the PubMed database, regarding the major serum biomarkers, which have been evaluated to distinguish EP from failed PULs or normal intrauterine pregnancies (IUPs)., Expert Opinion: At present, there is no single biochemical marker or combination of biomarkers that consistently predicts EP with both high sensitivity and specificity. Current diagnostic strategies in women with a PUL result in costly multiple visits. This approach both burdens the health-care system fiscally and impacts on the psychological morbidity of the individual. What is needed is a cost-effective diagnostic serum biomarker/s test to accurately predict EP in the PUL population. This strategy could significantly reduce follow-up visits, without compromising maternal mortality.

Objective: To determine the cost-effectiveness of medical and surgical management of early pregnancy loss., Design: Analyses of cost, effectiveness, and incremental cost-effectiveness ratios and utilities of a multicenter trial with 652 women with first-trimester pregnancy failure randomized to medical or surgical management., Setting: Analysis of data from a multicenter trial., Patient(s): Secondary analysis of a multicenter trial., Intervention(s): Cost-effectiveness analysis., Main Outcome Measure(s): Cost and effectiveness of competing treatment strategies., Result(s): Cost analysis of treatment demonstrates an increased cost of US$336 for 13% increased efficacy of surgical management. This analysis was sensitive to the probability of an extra office visit, the cost of the visit, and the probability of success. When the surgical arm is divided into outpatient manual vacuum aspiration (MVA) versus inpatient electric vacuum aspiration (EVA), there is an increased cost of $745 for EVA but a decreased cost of $202 for MVA compared with medical management. In general, MVA was found to be more cost-effective than medical management. For treatment of incomplete or inevitable abortion, medical management was found to be less costly and more efficacious. Utilities studies demonstrated that a patient would need to prefer surgery 14% less than medication for its treatment efficacy to be outweighed by the desire to avoid surgery., Conclusion(s): Surgical or medical management of early pregnancy failure can be cost effective, depending on the circumstances. Surgery is cost effective and more efficacious when performed in an outpatient setting. For incomplete or inevitable abortion, medical management is cost effective and more efficacious., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In this study, we have developed mineral coatings on polycaprolactone scaffolds to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO(3)) concentration in mSBF of 4.2 mm, 25 mm, and 100 mm. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue in coatings formed in all HCO(3) concentrations. Mineral coatings with increased HCO(3) substitution showed more rapid dissolution kinetics in an environment deficient in calcium and phosphate but showed re-precipitation in an environment with the aforementioned ions. The mineral coating provided an effective mechanism for growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral mineral-coated PCL scaffolds. We also demonstrated sustained release of all growth factors with release kinetics that were strongly dependent in the solubility of the mineral coating., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Endometriosis is associated with infertility; however, the etiology of this association is unclear, thus complicating management. Several mechanisms of pathogenesis have been proposed; however, no one theory has been implicated. Medical therapy can be helpful in managing symptoms, but does not improve pregnancy rates. The role of surgical treatment remains controversial. There is little data regarding ovulation induction treatments for endometriosis only, whereas superovulation with intrauterine insemination has shown modest improvement in pregnancy rates in women who may have endometriosis. The most effective treatment for endometriosis-associated infertility is in vitro fertilization. Recent focus on proteomics and genetics of the disease may aid in optimizing treatment options.

Objective: To review reasons for suboptimal recruitment for a randomized controlled trial (RCT) of varicocelectomy versus intrauterine insemination (IUI) for treatment of male infertility and to suggest means for improving future study recruitment., Design: Survey of Reproductive Medicine Network (RMN) participating sites., Setting: Reproductive Medicine Network., Patient(s): None., Intervention(s): None., Main Outcome Measure(s): Ascertain reasons for inadequate recruitment and suggest improvements for future varicocelectomy trails., Result(s): This study screened seven and enrolled three couples, with the first couple randomized on June 30, 2010. The study was subsequently stopped on March 30, 2011. The following themes were cited most frequently by sites and therefore determined to be most likely to have played a role in suboptimal recruitment: [1] men must be screened at the beginning of a couple's infertility evaluation, [2] inclusion of infertile women who had failed previous fertility interventions appeared to be associated with the couple's intolerance of a placebo arm, and [3] an apparent bias against the use of unstimulated IUI cycles indicated a prejudicial preference for surgical intervention in the male partner., Conclusion(s): Improved recruitment may be realized through screening infertile men as early as possible while minimizing study-related time commitments. Focused patient education may promote improved equipoise and acceptance of a placebo arm in male infertility studies. Creative approaches to implementing varicocelectomy trials must be considered in addition to having a network of motivated researchers who carry a high volume of possible study participants because very large numbers may need to be screened to complete the clinical trial enrollment., (Published by Elsevier Inc.)

Background: In the female genital tract, vaginal colposcopy, endometrial mucosal integrity and inflammatory mediators are potential in vivo biomarkers of microbicide and contraceptive safety., Study Design: A randomized, blinded crossover trial of 18 subjects comparing effects of nonoxynol-9 vaginal gel (Gynol II; putative inflammatory gel), hydroxyethyl cellulose gel (HEC; putative inert gel) and no gel exposure on endometrial and vaginal epithelial integrity and endometrial and vaginal inflammatory markers [interleukin (IL) 1β, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, tumor necrosis factor α, IL-1RA, IL-10, SLPI)., Results: Gynol II was associated with more vaginal lesions. No endometrial disruptions were observed across conditions. In the vagina, RANTES (p=.055) and IL-6 (p=.04) were higher after HEC exposure than at baseline. In the endometrium, IL-1β (p=.003) and IL-8 (p=.025) were lower after Gynol II cycles than after no gel., Conclusions: Gynol II and HEC may modulate inflammatory markers in the vagina and endometrium. How these changes relate to infection susceptibility warrants further study., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical utility of dilation and curettage (D&C) in diagnosing ectopic pregnancy (EP)., Design: Retrospective cohort study., Setting: University hospital., Patient(s): Clinically stable women (n = 321) who underwent a diagnostic D&C with no visible intrauterine pregnancy (IUP) on transvaginal ultrasound or those with an abnormal hCG trend., Intervention(s): None., Main Outcome Measure(s): EP or IUP made by final pathologic review., Result(s): Overall, 73.2% of the patients were ultimately diagnosed with EP and 26.8% were found to have a nonviable IUP. Those with EPs had significantly lower initial hCGs than those with nonviable IUPs and were more likely to have had a history of an EP. On ultrasound, the overall impression, the presence of free fluid, and the endometrial echo complex correlated well with the final diagnoses but did not have 100% predictive value., Conclusion(s): D&C remains valuable to differentiate EP from nonviable IUP and to avoid misdiagnosis and unnecessary exposure to methotrexate. Low initial hCG values and ultrasound findings such as a thin endometrial echo complex and the presence of free fluid are associated with but are not diagnostic of an ectopic pregnancy., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Some papers appearing in the two leading clinical journals of our specialty have fundamental defects in design, statistical analysis, and reporting. Actual publications are used to illustrate what investigators should and should not do, from initial planning through to their finished manuscript. A more detailed discussion of the most common statistical methods used in reproductive research is given as an online supplement. Some of these deficiencies illustrate the importance of registry of all study parameters for randomized clinical trials, a process covered in greater detail in an accompanying review and required for those manuscripts to be considered. Authors and reviewers need to be more aware of these requirements and common errors and pitfalls so that only quality manuscripts are published., (Copyright © 2011. Published by Elsevier Inc.)

Objective: To improve the interpretation of future studies in women who are initially diagnosed with a pregnancy of unknown location (PUL), we propose a consensus statement with definitions of population, target disease, and final outcome., Design: A review of literature and a series of collaborative international meetings were used to develop a consensus for definitions and final outcomes of women initially diagnosed with a PUL., Result(s): Global differences were noted in populations studied and in the definitions of outcomes. We propose to define initial ultrasound classification of findings into five categories: definite ectopic pregnancy (EP), probable EP, PUL, probable intrauterine pregnancy (IUP), and definite IUP. Patients with a PUL should be followed and final outcomes should be categorized as visualized EP, visualized IUP, spontaneously resolved PUL, and persisting PUL. Those with the transient condition of a persisting PUL should ultimately be classified as nonvisualized EP, treated persistent PUL, resolved persistent PUL, or histologic IUP. These specific categories can be used to characterize the natural history or location (intrauterine vs. extrauterine) of any early gestation where the initial location is unknown., Conclusion(s): Careful definition of populations and classification of outcomes should optimize objective interpretation of research, allow objective assessment of future reproductive prognosis, and hopefully lead to improved clinical care of women initially identified to have a PUL., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the extent to which duration and quality of reproductive endocrinology rotations are associated with residents' knowledge of reproductive endocrinology and infertility., Methods: An anonymous, multiple-choice survey was provided to 4,744 examinees during the 2008 Council on Resident Education in Obstetrics and Gynecology In-Training Examination. The survey queried residents' experiences on their reproductive endocrinology and infertility rotation, satisfaction with the quality and duration of the rotation, and knowledge of reproductive endocrinology and infertility. Binomial regression was used to estimate the relationship between components of the reproductive endocrinology and infertility rotation and self-reported knowledge of reproductive endocrinology and infertility., Results: Forty percent of residents described their knowledge of reproductive endocrinology and infertility as poor. Fewer weeks dedicated to reproductive endocrinology and infertility increased the risk of poor knowledge (P<.001). Required vacation during the rotation and non-reproductive endocrinology and infertility coverage more than two times a week was associated with a 40% increase in risk of perceived poor knowledge (relative risk [RR] 1.38, 95% confidence interval [CI]): 1.20-1.60; and RR 1.40, 95% CI: 1.16-1.70, respectively), while 3 hours of didactics per week were associated with a 61% reduction in risk (RR 0.39, 95% CI: 0.31-0.50)., Conclusion: A number of residents perceive their knowledge of reproductive endocrinology and infertility to be poor. Conflicting commitments during the reproductive endocrinology rotation results in both lower satisfaction and less knowledge. There is the potential to improve resident knowledge of reproductive endocrinology and infertility, and perhaps other aspects of obstetrics and gynecology training, with focused rotations, including didactics., Level of Evidence: II.

On the basis of the documented racial disparities in ectopic pregnancy incidence and mortality we hypothesized that African-American women with ectopic pregnancy would be more likely than white women to have treatment failure with methotrexate. In this retrospective cohort study, a racial disparity in methotrexate effectiveness was not found, but a significant relationship between low socioeconomic status and methotrexate failure was demonstrated., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Current bone tissue engineering strategies aim to grow a tissue similar to native bone by combining cells and biologically active molecules with a scaffold material. In this study, a macroporous scaffold made from the seaweed-derived polymer alginate was synthesized and mineralized for cell-based bone tissue engineering applications. Nucleation of a bone-like hydroxyapatite mineral was achieved by incubating the scaffold in modified simulated body fluids (mSBF) for 4 weeks. Analysis using scanning electron microscopy and energy dispersive x-ray analysis indicated growth of a continuous layer of mineral primarily composed of calcium and phosphorous. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue. In addition to the mineral characterization, the ability to control nucleation on the surface, into the bulk of the material, or on the inner pore surfaces of scaffolds was demonstrated. Finally, human MSCs attached and proliferated on the mineralized scaffolds and cell attachment improved when seeding cells on mineral coated alginate scaffolds. This novel alginate- HAP composite material could be used in bone tissue engineering as a scaffold material to deliver cells, and perhaps also biologically active molecules., (Copyright 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.)

Background: A logistic regression model (M4) was developed in the UK to predict the outcome for women with a pregnancy of unknown location (PUL) based on the initial two human chorionic gonadotrophin (hCG) values, 48 h apart. The purpose of this paper was to assess the utility of this model to predict the outcome for a woman (PUL) in a US population., Methods: Diagnostic variables included log-transformed serum hCG average of two measurements, and linear and quadratic hCG ratios. Outcomes modeled were failing PUL, intrauterine pregnancy (IUP) and ectopic pregnancy (EP). This model was applied to a US cohort of 604 women presenting with symptomatic first-trimester pregnancies, who were followed until a definitive diagnosis was made. The model was applied before and after correcting for differences in terminology and diagnostic criteria., Results: When retrospectively applied to the adjusted US population, the M4 model demonstrated lower areas under the curve compared with the UK population, 0.898 versus 0.988 for failing PUL/spontaneous miscarriage, 0.915 versus 0.981 for IUP and 0.831 versus 0.904 for EP. Whereas the model had 80% sensitivity for EP using UK data, this decreased to 49% for the US data, with similar specificities. Performance only improved slightly (55% sensitivity) when the US population was adjusted to better match the UK diagnostic criteria., Conclusions: A logistic regression model based on two hCG values performed with modest decreases in predictive ability in a US cohort for women at risk for EP compared with the original UK population. However, the sensitivity for EP was too low for the model to be used in clinical practice in its present form. Our data illustrate the difficulties of applying algorithms from one center to another, where the definitions of pathology may differ.

The emerging technology of wireless sensor networks (WSNs) is an integrated, distributed, wireless network of sensing devices. It has the potential to monitor dynamic hydrological and environmental processes more effectively than traditional monitoring and data acquisition techniques by providing environmental information at greater spatial and temporal resolutions. Furthermore, due to continuing high-performance computing development, these data may be introduced into increasingly robust and complex numerical models; for instance, the parameters of subsurface transport simulators may be automatically updated. Early field deployments and laboratory experiments conducted using in situ sensor technology and WSNs indicated significant fundamental issues concerning sensor and network hardware reliability-suggesting that investigations should first be conducted in controlled environments before field deployment. A first step in this validation process involves evaluating the predictive capability of a computational advection-dispersion transport model when incorporating concentration data from a WSN simulation. Data quality is a major concern, especially when sensor readings are automatically fed into data assimilation procedures. The appropriate employment of an independent WSN fault detection service can ensure that erroneous data (e.g., missing or anomalous values) do not mislead the model. Parameter estimation regularization techniques may then deal with remaining data noise. The primary purpose of this study is to determine the suitability of WSNs (and other in situ data delivery technologies) for use in contaminant transport modeling applications by conducting research in a realistic simulative environment.

Objective: To assess the association between recent cigarette smoking (CS) in female and male partners and assisted reproduction technology (ART) outcomes., Design: Cohort prospective study., Setting: University ART program in Chile., Patient(s): One hundred sixty-six couples seeking pregnancy through ART., Intervention(s): Follicular fluid (FF) and serum cotinine concentrations were measured in female partners. Self-reported CS data were collected through personal interviews., Main Outcome Measure(s): The association between female recent smoking, assessed by FF and serum cotinine concentrations, and ART outcomes, such as number of ova retrieved and implantation rates, and the association between self-reported male recent smoking and live birth rates., Result(s): A significant age-adjusted association between increased FF cotinine level and decreased number of ova retrieved was found. The male partner's smoking habit significantly decreased the live birth rate from 21.1% to 7.8%. Serum cotinine concentrations paralleled those of FF., Conclusion(s): The hypothesis of a detrimental effect of recent female smoking over implantation rates is rejected. However, recent male smoking is associated with significantly decreased live birth rates even after adjusting for confounders. Female recent smoking was significantly associated with decreased number of retrieved ova., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Occult ovarian insufficiency is associated with infertility, impaired response to ovarian stimulation, and reduced live birth rates in women treated with assisted reproductive technologies. Although a decline in ovarian follicle number is expected with age, the proximate causes of occult ovarian insufficiency in young women remain poorly understood. Abnormalities in telomere length and telomerase activity in human granulosa cells may serve as molecular markers for this condition., Methods: A cross-sectional study was performed. Subjects (37 yr old or less) undergoing in vitro fertilization were classified as cases of occult ovarian insufficiency or controls with mechanical infertility (male or tubal factor). Granulosa cells were acquired at the time of oocyte retrieval to quantify telomere length and telomerase activity., Results: Fifty-four women were enrolled. Human granulosa cell telomerase activity was demonstrated, and lack of granulosa cell telomerase activity was associated with occult ovarian insufficiency (odds ratio, 11.0; 95% confidence interval, 1.3-495.6; P = 0.02). Telomeres were shorter in women with occult ovarian insufficiency than in controls (relative telomere/single copy gene ratio, 1.88 vs. 3.15; P = 0.039)., Conclusions: Aberrant telomere homeostasis is associated with occult ovarian insufficiency in young women. This finding is consistent with the presence of telomeric attenuation that has been shown in multiple age-related conditions.

Background: To compare luteal phase bleeding and pregnancy outcomes in normogonadotropic patients receiving progesterone vaginal gel (PVG) or intramuscular progesterone (IMP) injections., Methods: In this retrospective cohort study, data from 270 patients (292 cycles) undergoing day-3 fresh embryo transfer were analyzed. PVG, 90 mg daily (170 cycles) or IMP, 50 mg daily (122 cycles) began at egg retrieval., Results: Luteal phase bleeding was significantly more common in the PVG than the IMP group. No significant differences were observed in biochemical pregnancy or spontaneous abortion rates between the two groups. Patients who bled before the pregnancy test had significantly lower total and clinical pregnancy rates than non-bleeders. Total and ongoing pregnancy/delivery rates were higher in the PVG than IMP group, but did not achieve statistical significance., Conclusion: Luteal phase bleeding was more common in the PVG group than the IMP group, but pregnancy was successful in more patients in the PVG group. Luteal phase bleeding is prevented or delayed during IMP treatment, but patients who bled before the pregnancy test, whether using the gel or injected progesterone, had significantly reduced pregnancy rates compared with non-bleeders.

This prospective cohort study tested whether the most common hereditary thrombophilia, factor V Leiden (FVL) mutation, is associated with nonpregnancy after IVF. Factor V Leiden mutation prevalence was very low (1.6%) and had a preliminarily positive association with pregnancy, suggesting that routine testing in a general IVF population for FVL mutation as a cause of IVF failure and infertility is not indicated.

Background: Congenital, nonepidermolytic cornification disorders phenotypically resembling human autosomal recessive ichthyosis have been described in purebred dog breeds, including Jack Russell terrier (JRT) dogs. One cause of gene mutation important to humans and dogs is transposon insertions., Objectives: To describe an autosomal recessive, severe nonepidermolytic ichthyosis resembling lamellar ichthyosis (LI) in JRT dogs due to insertion of a long interspersed nucleotide element (LINE-1) in the transglutaminase 1 (TGM1) gene., Methods: Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Phenotypic information and genotyping with a canine microsatellite marker suggested TGM1 to be a candidate gene. Genomic DNA samples and cDNA generated from epidermal RNA were examined. Consequences of the mutation were evaluated by Western blotting, quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme activity from cultured keratinocytes., Results: Affected dogs had generalized severe hyperkeratosis. Histological examination defined laminated to compact hyperkeratosis without epidermolysis; ultrastructurally, cornified envelopes were thin. Affected dogs were homozygous for a 1980-bp insertion within intron 9 of TGM1. The sequence of the insertion was that of a canine LINE-1 element. Quantitative RT-PCR indicated a significant decrease in TGM1 mRNA in affected dogs compared with wild-type. TGM1 protein was markedly decreased on immunoblotting, and membrane-associated enzyme activity was diminished in affected dogs., Conclusions: Based on morphological and molecular features, this disease is homologous with TGM1-deficient LI in humans, clinically models LI better than the genetically modified mouse and represents its first spontaneous animal model. This is the first reported form of LI due to transposon insertion.

Objective: To evaluate the return to fertility among women planning to become pregnant after the use of a continuous regimen of levonorgestrel 90 microg and ethinyl E(2) 20 microg., Design: Descriptive analysis of pregnancy outcomes after participation in a contraceptive trial., Setting: Multicenter trial., Subject(s): Participants in a phase 3 contraceptive trial who discontinued to become pregnant., Intervention(s): Eligible subjects were contacted at 3 and 12 months after treatment discontinuation to determine if and when they had conceived., Main Outcome Measure(s): Kaplan-Meier analysis displaying the time until conception after oral contraceptive discontinuation., Result(s): In the phase 3 trial, 34 of 2,134 subjects cited a desire for pregnancy as a reason for discontinuation. Of these, 4 were already pregnant before stopping treatment, 4 initiated other contraception, and 5 were lost to follow-up. Of the remaining 21 subjects at risk of pregnancy, the pregnancy rate was 57% at 3 months, 81% at 12 months, and 86% (18 of 21) (95% confidence interval 64% to 97%) at 13 months after discontinuation of treatment., Conclusion(s): These findings suggest that a continuous oral contraceptive with levonorgestrel 90 microg and ethinyl E(2) 20 microg does not delay the return to fertility.

Background: There is an urgent need for the development of a topical microbicide to protect against sexually transmitted infections. We compared distribution and acceptability of four different gel formulations to be used as a vehicle for a microbicide., Study Design: This is a randomized, double-blind comparative study. Six women tested each of the four gels at two different time points. Magnetic resonance imaging (MRI) scans were taken both within 10-15 min following intravaginal gel insertion and 4 h following gel insertion, before and after simulated intercourse at both time points., Results: Vaginal surface contact immediately after insertion ranged from 68% to 92%. Simulated intercourse increased surface contact for all gels (range, 90-106%). After 4 h, surface contact ranged from 86% to 102%. Simulated intercourse at that time resulted in decreased coverage for two gels and increased coverage for two gels. One gel was noted to have consistent broad coverage of the vagina both immediately and 4 h after insertion, increased coverage with simulated intercourse at both time points and the lowest standard deviation of disruption at all time points., Conclusion: MRI used in combination with qualitative assessments of acceptability can be used to select optimal gels for use as vehicles for potential spermicides or microbicides. We conclude that a gel consisting of 3% hydroxypropyl methylcellulose and 1.5% of methyl cellulose is the most promising candidate gel.

Objective: Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense., Method of Study: Eighty-one non-pregnant women were randomized into three groups and instructed to use Milex (CooperSurgical, Inc., Trumbull, CT, USA)diaphragms overnight for 14 days in combination with one of the two acid-buffering microbicide gels [ACIDFORM (Instead Inc., La Jolla, CA, USA) or BufferGel(trade mark) (BG; ReProtect Inc., Baltimore, Maryland)] or placebo gel (K-Y Jelly); Personal Products Inc., Raritan, NJ, USA). Cervicovaginal lavages (CVLs) were performed prior to study entry and on days 8 and 16. Nine soluble mediators of vaginal inflammation or immune defense were measured in CVLs by Bio-Plex or ELISA., Results: Use of diaphragms with placebo or microbicide gel was not associated with increased levels of inflammation markers. Concentrations of secretory leukocyte protease inhibitor (SLPI) were markedly reduced in the BG group., Conclusion: Daily use of a diaphragm with placebo or acidifying microbicide gel did not cause cervicovaginal inflammation. However, diaphragm/BG use was associated with markedly reduced levels of SLPI, an important mediator of innate immune defense. Further studies are warranted to establish the safety of diaphragm/microbicide gel combinations.

Objective: Misoprostol use in early pregnancy may incur a risk of uterine rupture in women with previous uterine surgery., Study Design: We analyzed 488 women who received misoprostol 800 microg vaginally in a study that evaluated medical and surgical management of early pregnancy failure. Subjects received a repeat misoprostol dose if expulsion was not confirmed 2 days after treatment. We compared efficacy, acceptability, and safety in subjects with a history (n = 78 women) or absence (n = 410 women) of uterine surgery, defined as cesarean delivery or myomectomy., Results: Expulsion rates after a single misoprostol dose (69% vs 72%; P = .64) and overall success at 30 days (82% vs 85%; P = .50) were comparable. Pain, bleeding, complications, and acceptability did not differ. No uterine ruptures occurred (95% CI, 0, 3.8%)., Conclusion: Misoprostol treatment for early pregnancy failure had similar success, acceptability, and complications in women with and without previous uterine surgery.

Objective: To compare the safety, efficacy, postprocedure quality of life, and acceptability of manual vacuum aspiration (MVA) performed as an outpatient with electric vacuum aspiration (EVA) performed in a hospital in women experiencing a first-trimester miscarriage., Methods: From a randomized multicenter trial comparing misoprostol with vacuum aspiration for first-trimester loss, data were extracted comparing the safety, efficacy, and acceptability of MVA in an office setting with local anesthesia with EVA in an operating room environment with spinal or general anesthesia or monitored anesthesia care (MAC)., Results: One hundred fifty-seven women underwent EVA or MVA. Efficacy and safety were similar in both groups. Physical and emotional role functioning scores were better in patients undergoing MVA (p=0.01), and fewer patients undergoing MVA missed work or required help at home (p<0.01). However, pain severity scores were better in the EVA arm of the study (p=0.03). There was a trend toward fewer MVA patients recommending or using this procedure again., Conclusions: In patients with early pregnancy loss, treatment with MVA as an outpatient with local anesthesia is an effective and safe alternative to EVA performed in a hospital with conscious sedation or spinal or general anesthesia. Treatment in the outpatient setting allows for a better physical and emotional quality of life postprocedure.

Objective: To identify clinical indicators for success of misoprostol treatment after early pregnancy failure., Methods: A total of 473 women with early pregnancy failure received 800 microg of vaginal misoprostol on treatment day 1. At the follow-up visit on day 3, a second dose was given if expulsion was incomplete. On day 8, vacuum aspiration was offered if expulsion had not occurred. Ultrasonography was used as gold standard for success. A Classification and Regression Tree analysis was undertaken to derive two decision trees for the success of misoprostol treatment on study days 3 and 8., Results: Heavy bleeding after the first dose and an open cervical os were identified as clinical indicators of treatment success on day 3. Treatment success occurred in 84% of women with either or both indicators. Reporting passage of tissue after a second misoprostol dose and old blood in the vagina were potential indicators of treatment success or failure on day 8. A woman with either of these indicators has a 65% chance of treatment success after the second dose. Conversely, a woman with neither indicator on day 8 has a 94% chance of treatment failure., Conclusion: Standard clinical findings may be useful as indicators for success or failure of medical management of early pregnancy failure in settings with limited or no access to ultrasonography. More research to identify even better indicators is warranted.