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Objective: To evaluate the performance of a new human chorionic gonadotropin (hCG) threshold model to classify pregnancies as viable or nonviable using a longitudinal cohort of individuals with pregnancy of unknown viability. The secondary objective was to compare the new model with three established models., Methods: This is a single-center, retrospective cohort study of individuals seen at the University of Missouri from January 1, 2015, until March 1, 2020, who had at least two consecutive quantitative hCG serum levels with an initial level greater than 2 milli-international units/mL and 5,000 milli-international units/mL or less, with the first interval between laboratory draws no greater than 7 days. Prevalence of correct classification of viable intrauterine pregnancies, ectopic pregnancies, and early pregnancy losses was evaluated with a new proposed hCG threshold model and compared with three established models describing minimum expected rates of hCG rise for a viable intrauterine pregnancy., Results: Of an initial cohort of 1,295 individuals, 688 patients met inclusion criteria. One hundred sixty-seven individuals (24.3%) had a viable intrauterine pregnancy; 463 (67.3%) had an early pregnancy loss; and 58 (8.4%) had an ectopic pregnancy. A new model based on the total additive percent rise of hCG at 4 and 6 days after initial hCG (70% or greater and 200% or greater rise, respectively) was created. The new model was able to correctly identify 100% of viable intrauterine pregnancies while minimizing incorrect classification of early pregnancy losses and ectopic pregnancies as normal pregnancies. At 4 days after initial hCG, 14 ectopic pregnancies (24.1%) and 44 early pregnancy losses (9.5%) were incorrectly classified as potentially normal pregnancies. At 6 days after initial hCG, only seven ectopic pregnancies (12.1%) and 25 early pregnancy losses (5.6%) were incorrectly classified as potentially normal pregnancies. In established models, up to nine intrauterine pregnancies (5.4%) were misclassified as abnormal pregnancies and up to 26 ectopic pregnancies (44.8%) and 58 early pregnancy losses (12.5%) were incorrectly classified as potentially normal pregnancies., Conclusion: The proposed new hCG threshold model optimizes a balance between identifying potentially viable intrauterine pregnancies and minimizing misdiagnosis of ectopic pregnancies and early pregnancy losses. External validation in other cohorts is needed before widespread clinical use., Competing Interests: Financial Disclosure: Danny J. Schust has stock options in Univfy, Inc. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Women with polycystic ovary syndrome are at a higher risk of cardiometabolic and psychiatric comorbidities and preconception and antepartum complications, but the impact of polycystic ovary syndrome during the postpartum period is unknown., Objective: This study aimed to investigate the risk of postpartum cardiovascular disease complications and perinatal and postpartum depression., Study Design: This was a retrospective cohort study conducted using a United States insurance claims database. Women with and without polycystic ovary syndrome aged 18 to 50 years enrolled continuously in a single health plan during the preconception, antepartum, and postpartum periods between 2000 and 2016 were included. The primary outcome was postpartum cardiovascular disease and depression (perinatal and postpartum). Multivariable logistic regression was used to adjust for covariates including age, geographic location, preterm delivery, assisted reproductive technology use, multiple births, prepregnancy depression, prepregnancy diabetes, prepregnancy hypertension, gestational diabetes, gestational hypertension, obesity, history of hyperlipidemia, smoking, and race., Results: We identified 42,391 unique women with polycystic ovary syndrome and 795,480 women without polycystic ovary syndrome. In multivariable models, women with polycystic ovary syndrome had significantly higher odds of cardiovascular disease complications, including postpartum preeclampsia (adjusted odds ratio, 1.30; 95% confidence interval, 1.17-1.45), eclampsia (adjusted odds ratio, 1.45; 95% confidence interval, 1.14-1.86) cardiomyopathy (adjusted odds ratio, 1.26; 95% confidence interval, 1.03-1.54), hypertensive heart disease (adjusted odds ratio, 1.32: 95% confidence interval, 1.07-1.64), thrombotic disease (adjusted odds ratio, 1.50; 95% confidence interval, 1.20-1.87), congestive heart failure (adjusted odds ratio, 1.35; 95% confidence interval, 1.13-1.61), and cerebrovascular accidents (adjusted odds ratio, 1.21; 95% confidence interval, 1.14-1.29), than those without polycystic ovary syndrome, as well as both perinatal (adjusted odds ratio, 1.27; 95% confidence interval, 1.22-1.33) and postpartum depression (adjusted odds ratio, 1.46; 95% confidence interval, 1.36-1.57). Nonobese women with polycystic ovary syndrome had higher odds of postpartum eclampsia (adjusted odds ratio 1.72; 95% confidence interval, 1.31-2.26), peripartum cardiomyopathy (adjusted odds ratio, 1.43; 95% confidence interval, 1.14-1.79), and cerebrovascular accidents (adjusted odds ratio, 1.28; 95% confidence interval, 1.19-1.38) than nonobese women without polycystic ovary syndrome. In the group of women without prepregnancy depression, the odds of perinatal depression (adjusted odds ratio, 1.32; 95% confidence interval, 1.26-1.39) and postpartum depression (adjusted odds ratio, 1.50; 95% confidence interval, 1.39-1.62) were higher in women with polycystic ovary syndrome than those without polycystic ovary syndrome., Conclusion: In a large United States cohort, our study found that women with polycystic ovary syndrome are at increased risk of both cardiovascular and psychiatric complications during the postpartum period. Polycystic ovary syndrome should be recognized as an at-risk condition; our findings underscore the need for routine screening and early interventions for these major comorbidities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess whether variation in serum human chorionic gonadotropin (hCG) measures, used to assess early gestation viability, are associated with differences in clinical presentation and patient factors., Method: This retrospective cohort study included 285 women with first-trimester pain and bleeding and a pregnancy of unknown location for whom a normal intrauterine pregnancy was ultimately confirmed. Serial samples were collected at three U.S. sites and hCG changes were analyzed for differences by race, ethnicity, and clinical factors. A nonlinear, mixed-effects regression model was used assuming a random subject shift in the time axis., Results: The hCG rise in symptomatic women with ongoing intrauterine pregnancy differs by patient factors and level at presentation. The 2-day minimum (first percentile) rise in hCG was faster when presenting hCG values were low and slower when presenting hCG value was high. African American women had a faster hCG rise (P<.001) compared with non-African American women. Variation in hCG curves was associated with prior miscarriage (P=.014), presentation of bleeding (P<.001), and pain (P=.002). For initial hCG values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and 33%, respectively., Conclusion: The rise of hCG levels in women with viable intrauterine pregnancies and symptoms of potential pregnancy failure varies significantly by initial value. Changes in hCG rise related to race should not affect clinical care. To limit interruption of a potential desired intrauterine pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values are high., Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate factors associated with accuracy of initial ultrasonography in patients with symptomatic first-trimester pregnancy., Methods: Ultrasound diagnosis in the emergency department was compared with an ultimate clinical diagnosis in women in need of a gynecologic consult. The sensitivity, specificity, positive predictive values, and accuracy of the initial ultrasound impression were calculated and stratified by criteria of diagnosis, serum human chorionic gonadotropin (hCG) levels, pain, and bleeding., Results: Eighteen hundred eighty women were evaluated. Overall accuracy of initial ultrasound diagnosis was 78%. A probable ultrasound diagnosis of ectopic pregnancy (adnexal mass without the presence of a yolk sac or embryo) resulted in a higher sensitivity (42.1% compared with 13.2%: P<.001) but a lower positive predictive value (82.7% compared with 98%: P<.01) compared with a definite diagnosis. A probable ultrasound diagnosis of intrauterine pregnancy (double decidual sign without yolk sac or embryo) resulted in a higher sensitivity (36.0% compared with 4.0%; P<.001) and lower positive predictive value (58.8% compared with 87.0%; P>.001) compared with a definite diagnosis. The sensitivity (34.3% compared with 75.9%; P<.01) and positive predictive value (80.4% compared with 91.5%; P=.02) were lower for diagnosis of ectopic pregnancy when serum hCG level was less than 2,000 milli-international units/mL. Ultrasonography was less accurate when bleeding was the chief complaint (72.7% compared with 84.8% P<.006) but not substantially altered by pain as a chief complaint (78.0 compared with 77.8% P>.99)., Conclusion: A substantial number of misdiagnoses can occur when initial ultrasound diagnosis of intrauterine pregnancy or ectopic pregnancy is made without evidence of a yolk sac or embryo, when hCG values are low, or when a patient has significant bleeding., Level of Evidence: II.

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy., Design: Nested case-control study., Setting: University medical center., Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999., Intervention(s): None., Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions., Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88-4.73] for one prior EP and 16.04 [5.39-47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11-2.05]), pain at presentation (1.42 [1.06-1.92]), vaginal bleeding at presentation (1.42 [1.04-1.93]), and hCG of 501-2,000 mIU/mL (1.73 [1.24-2.42]). Age younger than 25 years (0.59 [0.41-0.85]) and a history of abortion were protective from EP (0.58 [0.38-0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP., Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis.

Background: In early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP) is a major clinical challenge when ultrasound is not yet diagnostic. Clinical treatments for these outcomes are drastically different making early, accurate diagnosis imperative. Hence, a greater understanding of the biological mechanisms involved in these early pregnancy complications could lead to new molecular diagnostics. Methods: Trophoblast and endometrial tissue was collected from consenting women having an IUP (n = 4), EPL (n = 4), or EP (n = 2). Samples were analyzed by LC–MS/MS followed by a label-free proteomics analysis in an exploratory study. For each tissue type, pairwise comparisons of different pregnancy outcomes (EPL vs. IUP and EP vs. IUP) were performed, and protein changes having a fold change ≥ 3 and a Student's t-test p-value ≤ 0.05 were defined as significant. Pathway and network classification tools were used to group significantly changing proteins based on their functional similarities. Results: A total of 4792 and 4757 proteins were identified in decidua and trophoblast proteomes. For decidua, 125 protein levels (2.6% of the proteome) were significantly different between EP and IUP, whereas EPL and IUP decidua were more similar with only 68 (1.4%) differences. For trophoblasts, there were 66 (1.4%) differences between EPL and IUP. However, the largest group of 344 differences (7.2%) was observed between EP and IUP trophoblasts. In both tissues, proteins associated with ECM remodeling, cell adhesion and metabolic pathways showed decreases in EP specimens compared with IUP and EPL. In trophoblasts, EP showed elevation of inflammatory and immune response pathways. Conclusions: Overall, differences between an EP and IUP are greater than the changes observed when comparing ongoing IUP and nonviable intrauterine pregnancies (EPL) in both decidua and trophoblast proteomes. Furthermore, differences between EP and IUP were much higher in the trophoblast than in the decidua. This observation is true for the total number of protein changes as well as the extent of changes in upstream regulators and related pathways. This suggests that biomarkers and mechanisms of trophoblast function may be the best predictors of early pregnancy location and viability. [ABSTRACT FROM AUTHOR]

Importance: Women with an early nonviable pregnancy of unknown location are at high risk of ectopic pregnancy and its inherent morbidity and mortality. Successful and timely resolution of the gestation, while minimizing unscheduled interventions, are important priorities.Objective: To determine if active management is more effective in achieving pregnancy resolution than expectant management and whether the use of empirical methotrexate is noninferior to uterine evacuation followed by methotrexate if needed.Design, Setting, and Participants: This multicenter randomized clinical trial recruited 255 hemodynamically stable women with a diagnosed persisting pregnancy of unknown location between July 25, 2014, and June 4, 2019, in 12 medical centers in the United States (final follow up, August 19, 2019).Interventions: Eligible patients were randomized in a 1:1:1 ratio to expectant management (n = 86), active management with uterine evacuation followed by methotrexate if needed (n = 87), or active management with empirical methotrexate using a 2-dose protocol (n = 82).Main Outcomes and Measures: The primary outcome was successful resolution of the pregnancy without change from initial strategy. The primary hypothesis tested for superiority of the active groups combined vs expectant management, and a secondary hypothesis tested for noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed using a noninferiority margin of -12%.Results: Among 255 patients who were randomized (median age, 31 years; interquartile range, 27-36 years), 253 (99.2%) completed the trial. Ninety-nine patients (39%) declined their randomized allocation (26.7% declined expectant management, 48.3% declined uterine evacuation, and 41.5% declined empirical methotrexate) and crossed over to a different group. Compared with patients randomized to receive expectant management (n = 86), women randomized to receive active management (n = 169) were significantly more likely to experience successful pregnancy resolution without change in their initial management strategy (51.5% vs 36.0%; difference, 15.4% [95% CI, 2.8% to 28.1%]; rate ratio, 1.43 [95% CI, 1.04 to 1.96]). Among active management strategies, empirical methotrexate was noninferior to uterine evacuation followed by methotrexate if needed with regard to successful pregnancy resolution without change in management strategy (54.9% vs 48.3%; difference, 6.6% [1-sided 97.5% CI, -8.4% to ∞]). The most common adverse event was vaginal bleeding for all of the 3 management groups (44.2%-52.9%).Conclusions and Relevance: Among patients with a persisting pregnancy of unknown location, patients randomized to receive active management, compared with those randomized to receive expectant management, more frequently achieved successful pregnancy resolution without change from the initial management strategy. The substantial crossover between groups should be considered when interpreting the results.Trial Registration: ClinicalTrials.gov Identifier: NCT02152696. [ABSTRACT FROM AUTHOR]

Abstract Objective Pregnancy of unknown location (PUL) is not a diagnosis but a transient state used to classify a woman when she has a positive pregnancy test without definitive evidence of an intra-uterine or extra-uterine pregnancy on transvaginal ultrasonography. Management of a persisting PUL varies substantially, including expectant or active management. Active management can include uterine cavity evacuation or systemic administration of methotrexate. To date, no consensus has been reached on whether either management strategy is superior or non-inferior to the other. Design Randomized controlled trial. Setting Academic medical centers. Patients We plan to randomize 276 persisting PUL-diagnosed women who are 18 years or older from Reproductive Medicine Network clinics and additional interested sites, all patients will be followed for 2 years for fertility and patient satisfaction outcomes. Interventions Randomization will be 1:1:1 ratio between expectant management, uterine evacuation and empiric use of methotrexate. After randomization to initial management plan, all patients will be followed by their clinicians until resolution of the PUL. The clinician will determine whether there is a change in management, based on clinical symptoms, and/or serial human chorionic gonadotropin (hCG) concentrations and/or additional ultrasonography. Main outcome The primary outcome measure in each of the 3 treatment arms is the uneventful clinical resolution of a persistent PUL without change from the initial management strategy. Secondary outcome measures include: number of ruptured ectopic pregnancies, number and type of re-interventions (additional methotrexate injections or surgical procedures), treatment complications, adverse events, number of visits, time to resolution, patient satisfaction, and future fertility. Conclusion This multicenter randomized controlled trial will provide guidance for evidence-based management for women who have persisting pregnancy of unknown location. [ABSTRACT FROM AUTHOR]

Early pregnancy failure is the most common complication of pregnancy, and 1% to 2% of all pregnancies will be ectopic. As one of the leading causes of maternal morbidity and mortality, diagnosing ectopic pregnancy and determining the fate of a pregnancy of unknown location are of great clinical concern. Several serum and plasma biomarkers for ectopic pregnancy have been investigated independently and in combination. The following is a review of the state of biomarker discovery and development for ectopic pregnancy and pregnancy of unknown location. [ABSTRACT FROM AUTHOR]

Objective: To assess a scoring system to triage women with a pregnancy of unknown location. Design: Validation of prediction rule. Setting: Multicenter study. Patient(s): Women with a pregnancy of unknown location. Intervention(s): None. Main Outcome Measure(s): Scores assigned to factors identified at clinical presentation, total score calculated to assess risk of ectopic pregnancy (EP) in women with a pregnancy of unknown location, and a proposed three-tiered clinical action plan. Result(s): The cohort of 1,400 women (284 ectopic pregnancies, 759 miscarriages, and 357 intrauterine pregnancies) was more diverse than the original cohort used to develop the decision rule. The recommendations of the action plan were low risk, intermediate risk, and high risk; the recommendation based on the model score was compared with clinical diagnosis. A total of 29.4% intrauterine pregnancies were identified for less frequent follow-up observation, and 18.4% nonviable gestations were identified for more frequent follow-up observation (to rule out an ectopic pregnancy) compared with intermediate risk (i.e., monitor in current standard fashion). For a decision of possible less frequent monitoring, the specificity was 90.8% (89.0–92.6) with negative predictive value of 79.0% (76.7–81.3). For a decision of more intense follow-up observation, the specificity was 95.0% (92.7–97.2). Test characteristics using the scoring system were replicated in the diverse validation cohort. Conclusion(s): A scoring system based on symptoms at presentation has value to stratify risk and influence the intensity of outpatient surveillance for women with pregnancy of unknown location but does not serve as a diagnostic tool. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 29-year-old woman who had an ectopic pregnancy. The patient was taken to the hospital after experiencing vaginal spotting and abdominal pain. There are several factors that contribute to the risk of such pregnancy including a history of ectopic pregnancy, previous tubal surgery, and damage to the fallopian tubes. Various signs of shock are also experienced by patients with a ruptured ectopic pregnancy including rebound tenderness, tachycardia, and hypotension.

The article discusses the issues related to ectopic pregnancies. Damaged fallopian tubes from prior tubal surgery or pelvic infection, smoking, and conception using assisted reproduction are predisposing factors to ectopic pregnancies. Symptoms of and risk factors for ectopic pregnancies are enumerated. Diagnostic procedures for ectopic pregnancies are explained.

OBJECTIVE: To analyze the change in serial human chorionic gonadotropin (hCG) levels in women symptomatic with pain or bleeding who presented with nondiagnostic ultrasonography but were ultimately confirmed to have a viable intrauterine pregnancy. METHODS: The rise in serial hCG measures were modeled over time, with the start point defined in 2 ways: by last menstrual period and by date of presentation for care. Both semiparametric (spline) curves and linear random-effects models were explored. The slope and projected increase of hCG were calculated to define 99% of viable intrauterine pregnancies. RESULTS: A total of 287 subjects met inclusion criteria and contributed 861 measurements of hCG. On average, these subjects contributed 3.00 observations and were followed up for 5.25 days. A linear increase in log hCG best described the pattern of rise. Curves derived from last menstrual period and day of presentation do not differ substantially. The median slope for a rise of hCG after 1 day was 1.50, (or a 50% increase); 2.24 after 2 days (or a 124% rise), and 5.00 after 4 days. The fastest rise was 1.81 at 1 day, 3.28 at 2 days, and 10.76 at 4 days. The slowest or minimal rise for a normal viable intrauterine pregnancy was 24% at 1 day and 53% at 2 days. CONCLUSION: These data define the slowest rise in serial hCG values for a potentially viable gestation and will aid in distinguishing a viable early pregnancy from a miscarriage or ectopic pregnancy. The minimal rise in serial hCG values for women with a viable intrauterine pregnancy is ‘slower’ than previously reported, suggesting that intervention to diagnosis and treat an abnormal gestation should be more conservative. [ABSTRACT FROM AUTHOR]

The prophylactic use of Rh immune globulin has been a medical success, protecting women who could be at risk from exposure to the Rh(D) antigen. Thus, it is not surprising that Rh(D) immunoprophylaxis has been extended from women with term pregnancies to all women with miscarriages, abortions, and ectopic pregnancies. In this article we review the existing medical literature to assess the risks of fetomaternal hemorrhage and Rh isoimmunization after complications of a first-trimester pregnancy, induced abortion, or ectopic pregnancy. The evidence to support the use of Rh immune globulin in the first trimester is sparse, but there is theoretic evidence of its necessity. Despite weak evidence to support its use, there is little risk. [ABSTRACT FROM AUTHOR]

The majority of perinatal morbidity after in vitro fertilization (IVF) is due to multiple pregnancy; however, even singleton infants are at an increased risk for adverse outcomes. We have summarized data that evaluates adverse outcomes in IVF infants and recent attempts to delineate the underlying causes of this risk. We submit that practitioners of reproductive medicine should remain at the forefront of this investigation. [Copyright &y& Elsevier]

Objective: We sought to determine utility of uterine evacuation for diagnosis of nonviable pregnancy of unknown location (PUL). Study Design: We conducted a cohort study to assess the prevalence of ectopic pregnancy (EP), overall, and stratified by presenting signs and symptoms in women with a nonviable PUL. Results: Of the 173 women, 66 (38%) had miscarriage (spontaneous abortion [SAB]) and 107 (62%) had EP. When initial human chorionic gonadotropin (hCG) was <2000 mIU/mL, the odds of an EP were greater (odds ratio, 4.32; 95% confidence interval, 2.04–9.12). Demographic factors, obstetric history, and clinical presentation were not useful in distinguishing between EP and SAB. Pre-evacuation hCG increase had strong trend association with EP (odds ratio, 2.14; 95% confidence interval, 0.98–4.68). A >30% fall in postcurettage hCG was suggestive, but was not a diagnostic indicator of SAB. Conclusion: Uterine evacuation is a useful diagnostic aid for women with nonviable PUL. Nondiagnostic ultrasound findings and absolute and serial hCG values are associated with, but do not accurately predict final diagnosis. [ABSTRACT FROM AUTHOR]

Objective: Successful medical management of an ectopic pregnancy is inversely associated with initial hCG level. The purpose of this publication is to assess whether there is a level of hCG above which failure rate substantially increases. Design: A systematic review and summary analysis was performed, including studies reporting methotrexate treatment outcomes as stratified by various hCG ranges. Setting: Academic medical center. Patient(s): Review of published information regarding patients treated with methotrexate. Intervention(s): None. Main Outcome Measure(s): Success and failure rate of medical management. Result(s): Five observational studies, including 503 women, were found that reported successes in using single-dose methotrexate stratified by initial hCG concentration. Failure rates increase with increasing hCG levels. A substantial and statistically significant increase in failure rates is seen when comparing patients who have initial hCG levels of >5,000 mIU/mL with those who have initial levels of <5,000 mIU/mL (odds ratio: 5.45; 95% confidence interval: 3.04, 9.78). The failure rate for women who had an initial concentration between 5,000 and 9,999 mIU/mL was significantly higher than that for those who had initial levels between 2,000 and 4,999 mIU/mL (odds ratio: 3.76; 95% confidence interval: 1.16, 12.33). Conclusion(s): Results support a substantial increase in failure of medical management with single-dose methotrexate when the initial hCG is above 5,000 mIU/mL. Methotrexate should be used with caution in patients with ectopic pregnancy who present with hCG levels above this level. [Copyright &y& Elsevier]

Objective: To compare the cost and complication rate of two alternative strategies for the diagnosis and medical management of ectopic pregnancy when ultrasound is nondiagnostic. Design: A decision tree was constructed to compare [1] dilatation and curettage (D&C) followed by treatment of all ectopic pregnancies with methotrexate versus [2] empiric treatment of all patients with possible ectopic pregnancies with methotrexate without D&C. Setting: University setting. Patient(s): Ten thousand hypothetical women with nonviable pregnancies and a known incidence of ectopic pregnancy were entered into a computer model. Main outcome measure(s): The two approaches were compared with respect to the number of missed ectopic pregnancies, complications, procedures performed, admissions to the hospital, and cost. Result(s): The D&C group had 1% more failed managements of ectopic pregnancies and 13.4% fewer patients with a miscarriage undergo a second treatment for resolution. The D&C group had 13.7% fewer complications including 6.3% fewer hospitalizations. D&C costs $173 to $223 more than empiric use of methotrexate per patient. Conclusion(s): Empirically treating women at risk for ectopic pregnancy with methotrexate does not reduce complications or save money. In the absence of such savings, the desire to make an accurate and definitive diagnosis, allowing objective prognosis on future fertility and risk of repeat ectopic pregnancy, supports the need to distinguish a miscarriage from ectopic pregnancy before treatment with methotrexate. [Copyright &y& Elsevier]

Objective: To examine the impact of validation and temporal resolution of estimation of hCG increase, because patients' hCG values are not obtained at precise daily increments or always in the same laboratory.Design: Retrospective cohort study of women presenting with nondiagnosed symptomatic first-trimester pregnancies who had serial hCG level measurements over time.Setting: Not applicable.Patient(s): A total of 171 women presenting from September 2007 to February 2010 with first-trimester pregnancy pain and/or bleeding for whom a normal intrauterine pregnancy was ultimately confirmed.Interventions: None.Main Outcome Measure(s): Serial hCG values, time period between hCG measurements, hCG rise.Result(s): After data verification, 118 subjects contributing 327 values met inclusion criteria and passed data verification for analysis with improved temporal precision. The more precise data showed a steeper hCG rise, and the predicted 2-day hCG increase at the 1st percentile was slightly faster (1.68-fold vs. 1.56-fold) than the "raw" clinical data and previous models.Conclusion(s): Data verification and improved temporal precision suggested a faster hCG increase in early intrauterine gestation than previously demonstrated. Because laboratory variation and temporal imprecision are common, these data demonstrate that current modeling of the expected rise of hCG in a normal gestation is valid and appropriately conservative in the determination of a nonviable gestation. No change in the minimal threshold for potential viability is recommended. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate contraceptive efficacy, safety, acceptability, and fit of a single-size diaphragm used with contraceptive gel. METHODS: We conducted a multicenter trial in which 450 couples used the single-size diaphragm, 300 randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1, 3, and 6. Study outcomes included pregnancy probability, safety, acceptability, and fit. Pregnancy and safety were compared with an historical control group who used a standard diaphragm with these gels. RESULTS: Most (439/450 [98%]) women could be fitted with the single-size diaphragm. A total of 421 of 450 (94%) provided follow-up. The 35 study pregnancies yielded 6-month Kaplan-Meier cumulative typical use pregnancy probabilities per 100 women with 95% confidence intervals (CIs) of 10.4 (6.9-14.0) for all users and 9.6 (5.5-13.6) and 12.5 (5.4-19.5) with acid-buffering gel and nonoxynol-9, respectively. Historical control analysis yielded a propensity score-adjusted estimate of this pregnancy probability for the single-size diaphragm of 11.3 compared with 10.7 per 100 women for the standard diaphragm ([rounded] difference 0.7, 95% CI 23.6 to 4.9). Approximately half (51%) reported at least one urogenital event but compared favorably to the standard diaphragm in historical control analysis. Most (282/342 [82%]) liked the diaphragm. Results suggest that if provided by a clinician, 94% (95% CI 92-96%) could insert, correctly position, and remove the diaphragm. CONCLUSION: The single-size diaphragm was safe, as effective as a standard diaphragm, and acceptable when used with contraceptive gel. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To characterize the curve derived from serial human chorionic gonadotropin (hCG) values in women with spontaneous resolution of pregnancy of unknown location and to assess factors that modify the decline. METHODS: Data from three sites were extracted from a clinical database of women with a symptomatic pregnancy of unknown location that required follow-up with serial hCG levels. A nonlinear mixed-effects regression model was used to generate hCG elimination curves. RESULTS: Four hundred forty-three women presenting with a pregnancy of unknown location that resolved without intervention were studied between September 2007 and May 2009. Women older than 35 years had a slower hCG decline (P=.001) and those with pain had a steeper decline (P=.006), but these changes did not alter the curve in a clinically meaningful way. The decline in hCG is faster for those with a higher level at presentation. The average decline of hCG in women with spontaneous resolution is slower than previously reported. However, the minimal decline in hCG for women with spontaneous resolution of a pregnancy of unknown location ranged from 35% to 50% at 2 days of follow-up and from 66% to 87% at 7 days, which is more rapid than previously reported. CONCLUSION: In a diverse population, using updated statistical methods, it was observed that the minimal decline in hCG for women with spontaneous resolution is more rapid than previously reported. A decline slower than these thresholds may indicate the presence of retained trophoblastic tissue or ectopic pregnancy. [ABSTRACT FROM AUTHOR]

The article offers information about a study on the development of a multiple marker test for ectopic pregnancy. A case-control study was held with sera from 100 patients with ectopic pregnancy and 100 patients with intrauterine pregnancy who presented to three urban academic centers between September 2000 and April 2009 with first-trimester pain or bleeding. Conclusion revealed that most of the putative markers of ectopic pregnancy are not useful.

Objective: To summarize baseline characteristics from a large multicenter infertility clinical trial. Design: Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene). Setting: Academic Health Centers throughout the United States. Patient(s): Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study. Intervention(s): None. Main Outcome Measure(s): Historic, biometric, biochemical, and questionnaire parameters. Result(s): Females averaged 30 years and were obese (body mass index [BMI] 35) with ∼20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (∼2), and antimüllerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimüllerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters. Conclusion(s): The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. Clinical Trial Registration Number: NCT00719186. [ABSTRACT FROM AUTHOR]