Mild obesity does not affect perinatal outcome in gestational carrier cycles.

STUDY QUESTION: Does BMI of gestational carriers (GCs) affect perinatal outcomes after embryo transfer? SUMMARY ANSWER: Overweight and class I obesity in GCs does not affect the rate of good perinatal outcomes. WHAT IS KNOWN ALREADY: The use of GCs is increasing, but uniform guidance regarding optimal BMI for GCs is lacking. Women with obesity who conceive without fertility treatment or through autologous or donor in vitro fertilization are at higher risk of adverse maternal and fetal outcomes, but data on obesity in GCs are very limited. STUDY DESIGN, SIZE, DURATION: We performed a retrospective cohort study of 1121 GC cycles from January 2015 to December 2020 at US Fertility, the largest national partnership of fertility practices in the USA. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: All GC cycles performed at a large network of fertility practices were reviewed. Same-sex partners undergoing co-IVF were excluded. The primary outcome was good perinatal outcome from the first embryo transfer, defined as a singleton live birth at ≥37 weeks of gestation with birth weight between 2500 and 4000 g. Secondary outcome measures included frequencies of live birth, clinical pregnancy, miscarriage, full-term birth, low birth weight, large for gestational age, and cesarean delivery. A generalized linear model (log-binomial) was used for each to compare outcomes across BMI groups using normal BMI (20-24.9 kg/m2) as the reference group. Risk ratios and 95% CIs were estimated for each category group relative to normal BMI. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 1121 cycles in which GCs underwent first embryo transfer, of which 263 (23.5%) were in GCs with BMI >30. Demographics and reproductive history for GCs did not differ by BMI groups. The age of intended parents, use of frozen eggs, and fresh embryo transfers were higher with increasing BMI group. There were no statistically significant associations between BMI and good perinatal outcomes, live birth, clinical pregnancy, biochemical, spontaneous abortion, or low birth weight. However, among live births, higher BMI was significantly associated with birth by cesarean (P = 0.015) and large for gestational age infants (P = 0.023). LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study, and there may be unmeasured confounders. The number of patients with BMI <20 or ≥35 was small, limiting the power for these groups. We were not able to assess all maternal and fetal outcomes. WIDER IMPLICATIONS OF THE FINDINGS: In this study, we did not identify any significant impact of BMI on the chances of having a good perinatal outcome. Prior research studies have been inconsistent and this is the largest study to date. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this work. The authors do not have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Ectopic pregnancy prediction in women with a pregnancy of unknown location: data beyond 48 h are necessary.

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.

Randomized controlled trial of benzocaine versus placebo spray for pain relief at hysterosalpingogram.

Many women experience pain during hysterosalpingogram (HSG). This prospective, randomized, double-blinded, placebo-controlled study assessed whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, parity, pre-procedure oral analgesic use and history of dysmenorrhoea and/or chronic pelvic pain. Median change in pain score from baseline to procedure was 50.6mm (-7.4 to 98.8mm) in the benzocaine group and 70.4mm (19.8 to 100mm) in the placebo group. There was no difference between groups after adjusting for history of dysmenorrhoea. There was no difference in resolution of pain in benzocaine versus placebo groups at 5 min post procedure--median pain score difference -11.1 (-90.1 to 18.5) versus -37.0 (-100 to 1.2)--or at 30 min post procedure. Satisfaction scores did not differ by treatment and did not correlate with pain score during the procedure (rho=0.005). The use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain. Many women experience pain during hysterosalpingogram (HSG), which is a test used to evaluate the uterine cavity and fallopian tube. We conducted a prospective, randomized, double-blinded, placebo-controlled study to assess whether the use of benzocaine spray during HSG is associated with reduced pain as compared with placebo. Thirty women presenting for HSG were enrolled and randomized to either benzocaine or saline spray. Treatment groups were similar in age, race, previous pregnancies, pre-procedure oral analgesic use and history of dysmenorrhoea (painful periods) and/or chronic pelvic pain. There was no difference in pain scores or resolution of pain between the two groups. Satisfaction scores did not differ by treatment group and did not correlate with the pain score during the procedure. We conclude that the use of benzocaine spray does not significantly improve pain relief during HSG nor does it hasten resolution of pain post HSG. Of interest, patient satisfaction was not correlated with pain.

Hormone variations associated with quantitative fat measures in the menopausal transition.

OBJECTIVE: Reproductive hormone levels are associated with body size, and the association between estradiol and body size varies over the menopausal transition. This study aims to delineate these relationships using quantitative measures of visceral and subcutaneous fat. METHODS: Early follicular hormones (follicle stimulating hormone (FSH), estradiol, luteinizing hormone, dehydroepiandrosterone sulfate, testosterone) and T-1 weighted abdominal MRI images were obtained in a cross-sectional assessment of 77 women in the Penn Ovarian Aging Study. Fat volume (cm(3)) was quantified using validated software (Amira) and divided into tertiles of visceral and subcutaneous fat volume for analysis. Multivariable linear regression models compared hormone values between tertiles adjusting for race, age, and menopausal status. RESULTS: In adjusted models, estradiol was positively associated with visceral fat tertiles (geometric mean (GM) estradiol (pg/ml): Low 13.0, Mid 17.5, High 26.7, p = 0.006) while FSH was inversely associated with visceral fat tertiles (GM FSH (mIU/ml): Low 42.8, Mid 43.2, High 30.8, p = 0.03). The association of estradiol with visceral and subcutaneous fat tertiles varied by menopausal status (p < 0.001). In the early transition, estradiol was similar across tertiles of fat; postmenopause, estradiol was positively associated with visceral fat. Other hormones were not associated with fat measures. CONCLUSIONS: Estradiol was associated with quantitative measures of visceral fat and varies by menopausal status. This finding suggests that visceral fat may be an important mediator in hormone changes over the menopausal transition.

A decrease in serum estradiol levels after human chorionic gonadotrophin administration predicts significantly lower clinical pregnancy and live birth rates in in vitro fertilization cycles.

BACKGROUND: Although close observation of serum estradiol (E2) levels remains a mainstay of assessing clinical response to controlled ovarian stimulation, the prognostic value of any change in E2 levels after administration of hCG remains unclear. The objective of this study is to evaluate the relationship between serum E2 response after hCG administration and the clinical pregnancy and live birth rates in fresh IVF cycles. METHODS: We conducted a retrospective cohort study of women aged 21-45 years undergoing their first IVF cycle from 1999 to 2008 at a single practice. We compared the post-hCG serum E2 level with values on the day of hCG trigger. IVF cycles were stratified by post-hCG E2 response and appropriate parametric and non-parametric statistics were performed. Clinical intrauterine pregnancy and live births were the primary outcomes of interest. Multivariable logistic regression models were created to identify predictive factors associated with outcomes while adjusting for potential confounders. RESULTS: Among the 1712 IVF cycles, 1065 exhibited a >10% increase (Group A), 525 had a plateau (± 10%, Group B) and 122 showed a >10% decrease (Group C) in post-hCG E2 levels. While the E2 levels on the day of hCG were similar across groups, Group C had more patients with diminished ovarian reserve, required higher gonadotrophin doses and had the lowest implantation rates. After adjusting for age, total gonadotrophin dose, infertility diagnosis, number of oocytes and number of transferred embryos, the associations between post-hCG E2 decline (Group C) and clinical pregnancy [adjusted odds ratio (aOR): 0.53; 95% confidence interval (CI): 0.33-0.84, P= 0.007] and live birth (aOR: 0.40; 95% CI: 0.22-0.71, P= 0.002) were significant. We also found significant associations between E2 plateau (Group B) and clinical pregnancy (aOR: 0.73; 95% CI: 0.57-0.94, P= 0.013) and live birth (aOR: 0.74; 95% CI: 0.56-0.97, P= 0.032) when adjusting for the same factors. CONCLUSIONS: In our study, >10% decrease in E2 levels after hCG administration was associated with 40-50% reduction in clinical pregnancy and live birth rates. Similarly, post-hCG E2 plateau (± 10%) lowered the clinical pregnancy and live birth rates by >25%. Our study suggests that the change in the post-hCG E2 level is another parameter that can be used by clinicians to counsel patients regarding their likelihood of success with assisted reproductive technologies prior to oocyte retrieval.

Periodontal infection and preterm birth: successful periodontal therapy reduces the risk of preterm birth.

OBJECTIVE: This study tested the hypothesis that successful periodontal treatment was associated with a reduction in the incidence of spontaneous preterm birth (PTB). DESIGN: This was a randomised, controlled, blinded clinical trial. SETTING: Hospital outpatient clinic. POPULATION: Pregnant women of 6-20 weeks of gestation were eligible. METHODS: Of 322 pregnant women with periodontal disease, 160 were randomly assigned to receive scaling and root planing (SRP, cleaning above and below the gum line), plus oral hygiene instruction, whereas the remaining 162 received only oral hygiene instruction and served as an untreated control group. Subjects received periodontal examinations before and 20 weeks after SRP, and were classified blindly according to the results of treatment into two groups: successful ('non-exposure') and unsuccessful ('exposure') treatment. Groups were compared using standard inferential statistics; dichotomous variables were compared using the chi-square test or logistic regression. Results are presented in terms of odds ratios. MAIN OUTCOME MEASURE: The main outcome measure was spontaneous preterm birth before 35 weeks of gestation. RESULTS: No significant difference was found between the incidence of PTB in the control group (52.4%; n = 162) and the periodontal treatment group (45.6%; n = 160) (P < 0.13, Fisher's exact test). The incidence of PTB was compared within the periodontal treatment group, considering the success of therapy. A logistic regression analysis showed a strong and significant relationship between successful periodontal treatment and full-term birth (adjusted odds ratio 6.02; 95% CI 2.57-14.03). Subjects refractory to periodontal treatment were significantly more likely to have PTB. CONCLUSIONS: A beneficial effect on PTB may be dependent on the success of periodontal treatment.

Does a prediction model for pregnancy of unknown location developed in the UK validate on a US population?

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.

Adverse reproductive outcomes in urban women with adeno-associated virus-2 infections in early pregnancy.

BACKGROUND: We demonstrated recently that adeno-associated virus-2 (AAV-2) DNA was detected significantly more frequently in placental trophoblast cells from cases of severe pre-eclampsia than from normal term deliveries. Here, we sought to determine if maternal AAV-2 infection early in pregnancy preceded adverse outcomes resulting from placental dysfunction. METHODS: We collected first trimester maternal serum samples and compared anti-AAV-2 IgM antibody levels (indicating primary infection or reactivation of latent AAV-2) between controls delivered at term (n = 106) and three groups of cases: spontaneous abortions (n = 34), spontaneous preterm deliveries (n = 24) and women with at least one outcome usually attributed to placental dysfunction, including pre-eclampsia, intrauterine growth restriction (IUGR) or stillbirth (n = 20). The seroprevalence of immunoglobulin G (IgG) antibodies against AAV-2 and IgM antibodies against viruses that promote AAV-2 replication [adenovirus and cytomegalovirus (CMV)] were also determined. RESULTS: First trimester maternal IgM seropositivity was 5.6 times more prevalent among pre-eclampsia/IUGR/stillbirth cases (P = 0.0004) and 7.6 times more prevalent among preterm deliveries (P < 0.0001) than among controls. CMV and adenovirus IgM antibodies and chronic AAV-2 infections (IgG seropositivity) were not associated with adverse pregnancy outcomes. CONCLUSIONS: Primary or reactivated AAV-2 infection (maternal IgM seropositivity) early in pregnancy was associated with adverse reproductive outcomes associated with placental dysfunction, including pre-eclampsia, stillbirth and spontaneous preterm delivery.

Does AMH relate to timing of menopause? Results of an Individual Patient Data meta- analysis.

CONTEXT: Anti-Müllerian hormone based (AMH) age at menopause predictions remain cumbersome due to predictive inaccuracy. OBJECTIVE: To perform an Individual Patient Data (IPD) meta-analysis, regarding AMH based menopause prediction. DATA SOURCES: A systematic literature search was performed using PubMed, Embase and Cochrane databases. STUDY SELECTION: Prospective cohort studies regarding menopause prediction using serum AMH levels were selected by consensus discussion. DATA SELECTION: Individual cases were included if experiencing a regular cycle at baseline. Exclusion criteria were hormone use and gynecological surgery. DATA SYNTHESIS: 2596 women were included, 1077 experienced menopause. A multivariable Cox regression analysis assessed time to menopause (TTM) using age and AMH. AMH predicted TTM, however, added value on top of age was poor (age alone C-statistic 84%; age + AMH HR 0.66 95% CI 0.61-0.71, C-statistic 86%). Moreover, the capacity of AMH to predict early (≤45 years) and late menopause (≥55 years) was assessed. An added effect of AMH was demonstrated for early menopause (age alone C-statistic 52%; age + AMH HR 0.33, 95% CI 0.24-0.45, C-statistic 80%). A Weibull regression model calculating individual age at menopause revealed that predictive inaccuracy remained present and increased with decreasing age at menopause. Lastly, a check of non-proportionality of the predictive effect of AMH demonstrated a reduced predictive effect with increasing age. CONCLUSION: AMH was a significant predictor of TTM and especially of time to early menopause. However, individual predictions of age at menopause demonstrated a limited precision, particularly when concerning early age at menopause, making clinical application troublesome.

Induction, labor length and mode of delivery: the impact on preeclampsia-related adverse maternal outcomes.

OBJECTIVE: The objectives were to evaluate whether induction, specifically prolonged labor, was associated with adverse maternal outcomes related to preeclampsia with severe features (PEC-S) and whether cesarean affected the rate. STUDY DESIGN: This was a retrospective cohort study of women with PEC-S ⩾34 weeks who were diagnosed either before planned cesarean or before induction/latent labor. The primary outcome was a composite adverse maternal outcome related to PEC-S. RESULTS: The final cohort comprised 193 women (n=172 with labor and n=21 with planned cesarean). The prevalence of the outcome was 15.5%. Women exposed to labor did not have a higher rate compared with planned cesarean (16.3% vs 9.5%, P=0.4). Adjusting for confounders, women with a cesarean after prolonged labor had a 10-fold higher adverse outcome risk compared with women with a planned cesarean (adjusted odds ratio (aOR) 9.7 (1.2 to 78.6), P=0.03) or with a vaginal delivery <24 h (aOR 9.7 (1.4 to 67.4), P=0.02). CONCLUSION: Prolonged labor and cesarean in labor were both associated with an increase in our outcome.

Follicular phase hormone levels and menstrual bleeding status in the approach to menopause.

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.

The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.

Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.

DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years.

BACKGROUND: The objective of this study was to elucidate the associations of dehydroepiandrosterone sulfate (DHEA-S) levels and depressive symptoms in African American and Caucasian women in the late reproductive years, a transitional age zone preceding the perimenopause, in which ovarian aging and associated endocrine changes begin. We had hypothesized that lower levels of DHEA-S would be associated with depressive symptoms and that, because DHEA-S levels decline with increasing age, older women would have an increased prevalence of depressive symptoms. METHODS: This cross-sectional study used a population-based urban sample recruited through random digit telephone dialing. The sample was 338 women between the ages of 35 and 47 years with regular menses. Half the sample was African American and half was Caucasian. RESULTS: Higher DHEA-S levels were associated with depressive symptoms in women in the younger half of this cohort. Lower DHEA-S levels were associated with depressive symptoms in the women in the older half of this cohort. The direction of the relationship of DHEA-S and depressive symptoms changes with age, being a positive relationship in younger women and an inverse relationship in the older women in this cohort. This change in the direction of the relationship appears to occur at a younger age in African American women. CONCLUSIONS: Our hypothesis of a relationship between low DHEA-S levels and elevated depressive symptoms was supported only in the older women in this cohort. Unexpectedly, younger women in this cohort demonstrated a positive association between DHEA-S levels and depressive symptoms. Changes in DHEA-S levels, depressive symptoms, and the relationship of other hormones in the hypothalamic-pituitary-adrenal axis need to be better understood in premenopausal women approaching perimenopause.

Response to first drug trial predicts outcome in childhood temporal lobe epilepsy.

OBJECTIVE: To construct a clinical prediction model for the early identification of children destined to develop refractory temporal lobe epilepsy (TLE) 2 years after epilepsy onset. METHODS: Patients with TLE between 1 and 18 years old seen in the Division of Neurology at Children's Hospital of Philadelphia during 1999 were identified through billing records and chart review. Data were abstracted independently on 5 candidate predictor variables for refractory TLE and on seizure frequency outcome at 2 years after epilepsy onset. RESULTS: One hundred twenty patients met inclusion criteria and had at least 2 years of follow-up. Forty-five of 120 patients (37.5%) had refractory TLE at 2 years after onset, and 75 of 120 (62.5%) were seizure free. Three significant predictors of refractory TLE were found on bivariate analysis: an early risk factor for epilepsy (risk ratio = 3.5 [95% CI 2.2, 5.6]), temporal lobe abnormality on MRI scan (2.9 [95% CI 1.9, 4.6]), and failure of the first antiepileptic drug (AED) trial (16.5 [95% CI 6.3, 43.9]). Logistic regression indicated that the best model to predict refractory TLE contained only the variable "failure of first AED trial," with a positive predictive value of 0.89 (95% CI 0.76, 0.96) and negative predictive value of 0.95 (95% CI 0.87, 0.99) to predict "refractory TLE" at 2 years. CONCLUSIONS: Failure of first AED trial accurately predicts refractory TLE at 2 years after onset, based on retrospective cohort data in children. If verified prospectively and with longer follow-up, this finding should support earlier consideration of surgical options.

Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota.

Although several studies have reported on valve abnormalities among users of fenfluramine or dexfenfluramine, detailed information on these subjects has not been provided, limiting the ability to understand who may be at risk for valve abnormalities and to generate hypotheses about the etiology and pathogenesis of these abnormalities. This study was a detailed medical record review of 18 previously reported users of fenfluramine and phentermine, all with valve abnormalities on echocardiogram and 2 with surgical pathology. Both clinical characteristics and medication use were recorded by trained abstracters using a standardized data collection form. Two subjects (11%) had other possible etiologies of valve disease: a history of rheumatic fever and prescribed ergotamine. Three subjects (17%) had a history of migraine headaches and 4 (22%) had murmurs noted before using fenfluramine. Use of medications that may affect serotonin receptors was common: ergotamine (1 subject, 5%), selective serotonin reuptake inhibitors (6, 33%), sumatriptan (2, 11%), and mirtazapine (1, 5%). Prior medication and nonmedication allergies were recorded in 6 (33%) and 3 (17%) subjects, respectively. All subjects had symptoms possibly due to fenfluramine or phentermine side effects. This study raises the hypotheses that valvular heart disease among fenfluramine users may be less common than previously estimated, that serotonin excess may play a role in valve pathology, and that a patient's response to anorexigens and other medications may serve as a marker for increased risk. Further study is needed to test these hypotheses.

Symptom reports from a cohort of African American and white women in the late reproductive years.

OBJECTIVE: To identify symptoms experienced in a cohort of healthy women in the late reproductive years; to compare symptom reports between African American and Caucasian women; and to determine the extent to which other factors in reproductive health, mood and behavior, lifestyle, and demographic background are associated with the reported symptoms. DESIGN: A cohort of women aged 35 to 47 years (mean age, 41 years) was identified through random digit dialing. This study is a cross-sectional analysis of data collected at enrollment from a subset of 308 women who completed daily symptom reports (DSR) for one menstrual cycle. Data were obtained in structured interviews and self-administered standard questionnaires. The associations of the study variables with symptoms as assessed by the DSR were examined using analysis of variance and general linear models. RESULTS: The African American women were significantly more likely to report in interview that they experienced menopausal symptoms (46% vs. 30%; p < 0.001) and had significantly higher ratings on the physiological symptom factor of the DSR, which included hot flashes, dizziness, poor coordination/clumsiness, urine leaks, and vaginal dryness. The DSR yielded two other factors of psychological and somatic symptoms. Race was associated only with the physiological symptom factor in the multivariable analyses. Neither race nor age were associated with psychological symptoms, which were predicted by current or past mood problems. CONCLUSIONS: Symptoms commonly associated with the menopause are experienced in the late reproductive years before observable changes in menstrual cycles. African American women reported more physiological symptoms than white women. These data provide an essential baseline for longitudinal study of symptoms associated with the ovarian decline in the perimenopausal years.

A serum proteomics approach to the diagnosis of ectopic pregnancy.

An ectopic pregnancy (EP) occurs when implantation of the embryo occurs outside of the uterus. If left untreated, the developing fetus will continue to grow, leading to life-threatening consequences for the mother. A major difficulty with the diagnosis of ectopic pregnancy is that methods of detection are limited, and some, such as ultrasound, are not very reliable in the earliest days of gestation. Currently, no effective serum test exists to distinguish an ectopic pregnancy from a normal intrauterine pregnancy. The incidence of ectopic pregnancy is increasing and has doubled in the last 20 years. It is now the second most common cause of maternal death in the first trimester of pregnancy. To address this issue, we initiated a project to identify serum markers of ectopic pregnancy. The subjects for these studies presented at the Hospital of the University of Pennsylvania. We obtained over 140 serum samples from women with suspected ectopic pregnancy: women presenting with pain and/or bleeding in the first trimester of pregnancy. The approximate racial breakdown of the subjects is as follows: African American, 36%; Caucasian, 3%; Asian, 2%; Hispanic, 1%; unknown, 58%. Serum samples from 139 women (62 with ectopic pregnancy and 77 with a normal intrauterine pregnancy) were applied to WCX2 (weak ion exchange) protein chip surfaces and analyzed for serum markers using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Several proteins in the 7500-18,000 Da mass range were identified that may discriminate an ectopic pregnancy from an intrauterine pregnancy. The most promising markers were analyzed using classification and regression tree analysis (CART) with and without clinical variables (serum hCG value, length of amenorrhea). Two different algorithms were developed that classify the patients on the basis of sensitivity (number of EPs who screen positive/# of EPs) or specificity (# of healthy patients who screen negative/# of healthy). Our current approach is to refine these two "rule sets" to segregate patients into three groups: those who need immediate intervention for a probable ectopic pregnancy, those who appear to have a normal pregnancy, and those who need further monitoring for diagnosis.

Premenstrual syndrome as a predictor of menopausal symptoms.

OBJECTIVE: To estimate whether premenstrual syndrome (PMS) predicts common menopausal symptoms assessed longitudinally for 5 years among women in the transition to menopause. METHODS: Data were obtained from a structured interview questionnaire, daily symptom ratings, and standard measures of depressive symptoms and sleep quality at 7 assessment periods in a population-based cohort of 436 women. Menstrual status was determined by menstrual bleeding dates. Hormones were measured in the early follicular phase, with a maximum of 14 measures per subject. Multivariate logistic regression models for repeated measures were used to estimate the effects of study variables. RESULTS: Premenstrual syndrome significantly decreased with age (P <.001) and with changes in menstrual bleeding status (P =.003). Women with PMS at enrollment were more likely over the 5-year period to report menopausal hot flushes (odds ratio [OR] 2.09; confidence interval [CI] 1.42, 3.08; P <.001); depressed mood (OR 2.34; CI 1.60. 3.43; P <.001); poor sleep (OR 1.72; CI 1.16, 2.53; P =.007), and decreased libido (OR 1.54; CI 1.06, 2.24; P =.024) after adjusting for age, race, diagnosis of major depression, and estradiol. Subjects' fluctuations in estradiol were significantly associated with hot flushes, depressive symptoms, and poor sleep. CONCLUSION: Premenstrual syndrome decreased in the transition to menopause. Women who reported PMS at baseline were at greater risk of menopausal hot flushes, depressed mood, poor sleep, and decreased libido. Further studies of the associations of symptoms and changes in ovarian function are needed to elucidate the underlying symptom physiology and aid in the development of effective treatments for women during the menopausal transition.

Sleep quality, estradiol levels, and behavioral factors in late reproductive age women.

OBJECTIVE: To estimate the prevalence of perceived poor sleep in women aged 35-49 years and to correlate sleep quality with levels of gonadal steroids and predictors of poor sleep. METHODS: A cohort of 218 black and 218 white women aged 35-47 years at enrollment (aged 37-49 at final follow-up) with regular menstrual cycles was identified through random digit dialing for a longitudinal study of ovarian aging correlates. Data obtained at four assessment periods, including enrollment, over a 2-year interval were collected between days 1 and 6 (mean = 3.9) of the menstrual cycle. The primary outcome measure was subjects' rating of sleep quality at each assessment period. Associations of sleep quality with hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, and dehydroepiandrosterone sulfate) and other clinical, behavioral, and demographic variables were examined in bivariable and multivariable analyses. RESULTS: Approximately 17% of subjects reported poor sleep at each assessment period. Significant independent associations with poor sleep included greater incidence of hot flashes (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.08, 2.12, P =.02), higher anxiety levels (OR 1.03; 95% CI 1.00, 1.06, P =.04), higher depression levels (OR 1.05; 95% CI 1.02, 1.07, P <.001), greater caffeine consumption (OR 1.25; 95% CI 1.04, 1.49, P =.02), and lower estradiol levels in women aged 45-49 (OR 0.53; 95% CI 0.34, 0.84, P =.006), after adjustment for current use of sleep medications. CONCLUSION: Both hormonal and behavioral factors were associated with sleep quality. Estradiol levels are an important factor in poor sleep reported by women in the 45-49 age group. Further evaluation of estrogen treatment for poor sleep of women 45 years and older is warranted.

Racial differences in sex hormone levels in women approaching the transition to menopause.

OBJECTIVE: Evaluate racial differences in reproducibility of hormone levels over time (estradiol, DHEAS, FSH, and testosterone) while adjusting for covariates previously identified as relevant in the study population. DESIGN: Longitudinal cohort study. SETTING: Healthy, late-reproductive-age women in a community-based sample. PATIENT(S): African American and Caucasian women identified by random digit dialing. INTERVENTION(S): Hormone levels measured in the early follicular phase of the menstrual cycle four times over 9 months. A multivariate, linear mixed model estimated effects on hormone levels of race, age at enrollment, age at menarche, number of pregnancies, current smoking, alcohol consumption, body mass index (BMI), waist/hip ratio (WHR), and menstrual cycle length. MAIN OUTCOME MEASURE(S): Follicular plasma levels of estradiol, FSH, DHEAS, and testosterone. RESULT(S): African American but not Caucasian women had significantly lower levels of estradiol and DHEAS with increasing age. African American but not Caucasian women had significantly decreased levels of estradiol and significantly increased levels of DHEAS with increasing BMI. No racial differences in reproducibility of hormone measures were found. CONCLUSION(S): There are racial differences in associations of hormone levels with age and BMI in late reproductive age women. Further study is needed to replicate these findings and to determine the relationships of these hormonal associations with menopausal symptoms.