American Journal of Obstetrics & Gynecology - Articles in Press

Fetoplacental biometry and umbilical artery Doppler velocimetry in the overnourished adolescent model of fetal growth restriction - Accepted Manuscript

2012-05-16

Abstract: Objectives: To evaluate ultrasonographically fetal growth trajectories, placental biometry and umbilical artery (UA) Dopplers in growth-restricted pregnancies of overnourished adolescent ewes and normally-developing pregnancies of control-fed ewes. Study Design: Singleton pregnancies were established using embryo transfer in 42 adolescent ewes, which were overnourished (n=27) or control-fed (n=15), scanned at weekly intervals from 83–126d and necropsied at 131d gestation (term=145d). Results: Ultrasonographic placental measurements were reduced and UA Doppler indices increased from 83d, whilst measurements of fetal abdominal circumference and femur length, renal volume and tibia length, and biparietal diameter were reduced from 98d, 105d and 112d, respectively, in overnourished versus control-intake pregnancies. Conclusions: Overnourishment of adolescent sheep dams produced late-onset asymmetrical fetal growth restriction, commensurate with brain sparing. Ultrasonographic placental biometry was already reduced and UA Doppler indices increased by mid-gestation in overnourished pregnancies, preceding reduced fetal growth velocity and indicative of an early nutritionally-mediated insult on placental development.

Adverse event reports after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines in pregnant women - Accepted Manuscript

2012-05-14

Abstract: Objective: To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap). Study design: We searched VAERS for reports of pregnant women who received Tdap vaccine from 1/1/2005-6/30/2010. We conducted clinical review of reports and available medical records. Results: We identified 132 reports after Tdap vaccine administered to pregnant women; 55 (42%) described no adverse events (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified. Conclusions: During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant or fetal outcomes.

Effects of Alcohol, Lithium, and Homocysteine on Nonmuscle Myosin-II in the Mouse Placenta and Human Trophoblasts - Accepted Manuscript

2012-05-14

Abstract: Mouse embryonic exposure to alcohol, lithium, and homocysteine results in intrauterine growth restriction (IUGR) and cardiac defects. Our present study focuses on the placental effects. Objectives: We analyzed the hypothesis that expression of nonmuscle myosin (NMM)-II isoforms involved in cell motility, mechanosensing, and extracellular matrix assembly, are altered by the three factors in human trophoblast (HTR8/SVneo) cells in vitro and in the mouse placenta in vivo. Study Design: After exposure during gastrulation to alcohol, homocysteine, or lithium, ultrasonography defined embryos exhibiting abnormal placental blood flow. Results: NMM-IIA /NMM-IIB are differentially expressed in trophoblasts and in mouse placental vascular endothelial cells under pathological conditions. Misexpression of NMM-IIA/ NMM-IIB in the affected placentas continued stably to mid-gestation, but can be prevented by folate and myo-inositol supplementation. Conclusions: It is concluded that folate and myo-inositol initiated early in mouse pregnancy can restore NMM-II expression, permit normal placentation/embryogenesis, and prevent IUGR induced by alcohol, lithium, and homocysteine.

Pharmacokinetics of the Etonogestrel Contraceptive Implant in Obese Women - Accepted Manuscript

2012-05-10

Abstract: Objectives: To examine the pharmacokinetics and acceptability of the etonogestrel contraceptive implant in obese women. Study Design: We developed and validated a plasma etonogestrel concentration assay and enrolled 13 obese (BMI≥30) women and 4 normal-weight (BMI<25) women, who ensured comparability with historical controls. Etonogestrel concentrations were measured at 50-hour intervals through 300 hours post-insertion, then at 3 and 6 months to establish a pharmacokinetic curve. Results: All obese participants were African American, while all normal-weight participants were white. Across time, the plasma etonogestrel concentrations in obese women were lower than published values for normal-weight women and 31-63% lower than in the normal-weight study cohort, although these differences were not statistically significant. The implant device was found highly acceptable among obese women. Conclusion: Obese women have lower plasma etonogestrel concentration than normal-weight women in the first six months after implant insertion. These findings should not be interpreted as decreased contraceptive effectiveness without additional considerations.

Molecular pathways regulating contractility in rat uterus through late gestation and parturition - Accepted Manuscript

Michael J. Taggart, Patrice Arthur, Barbara Zielnik, Bryan F. Mitchell — 2012-05-10

Abstract: Objective: Endogenous uterine agonists can activate numerous signaling pathways to effect increased force. Our objective was to assess expression of key constituents of these pathways, in alliance with contractile function, through late gestation and during term and preterm labor. Study Design: Using myography, we measured the response to three agonists compared to depolarization alone (K+, 124 mM) and calculated agonist/depolarization ratio (ADR). We measured gene expression using qRT-PCR. Results: Contractile responsiveness to depolarization alone, oxytocin or endothelin-1 increased during pregnancy compared to non-pregnant animals. ADR did not change during uterine activation or parturition. Inhibition of ROK decreased responses to OT in all tissues but significantly more during uterine activation. Expression of rhoA and ROK was increased significantly in active labor at term or preterm. Conclusions: The rhoA/ROK pathway is a key regulator of uterine activation during labor and may be a useful target for prevention of spontaneous preterm birth.

Examining the correlation between placental and serum placenta growth factor in preeclampsia - Accepted Manuscript

2012-05-10

Abstract: Objective: Decreased levels of serum placenta growth factor (PlGF) are associated with preeclampsia. We sought to determine whether serum and placental levels of PlGF (sPlGF, pPlGF) are associated with preeclampsia, and whether there is a correlation between serum and placental PlGF levels. Study Design: These analyses were part of a larger, prospective, case-control study. Cases were women with preeclampsia. Controls were women without preeclampsia who delivered at term. Analyses included non-parametric tests to compare medians, logistic regression to estimate odds, and calculation of correlation coefficients. Results: 24 cases (10 preterm, 14 term) were compared to 14 controls. Median levels of PlGF were significantly lower in cases than controls (pPlGF: 232.6 vs. 363.4 pg/mL, p=0.02; sPlGF: 85.5 vs. 274.4 pg/mL, p<0.001). Serum and placental PlGF were correlated (overall: 39%, p=0.006; cases with preterm preeclampsia and growth restriction: 87%, p=0.02). Conclusion: Serum and placental PlGF are independently associated with preeclampsia and correlated with each other.

Antenatal corticosteroids: too much of anything is bad ? - Accepted Manuscript

Sushree Samiksha Naik, Rashmi Ranjan Das — 2012-05-10

Reply to Letter # E12-014AR1 - Accepted Manuscript

C.J.D. McKinlay, C.A. Crowther, P. Middleton, J.E. Harding — 2012-05-10

Lactation and maternal subclinical cardiovascular disease among premenopausal women - Accepted Manuscript

Candace K. McClure, Janet M. Catov, Roberta B. Ness, Eleanor Bimla Schwarz — 2012-05-04

Abstract: Objective: Examine the association between lactation and maternal subclinical cardiovascular disease (sCVD). Study Design: The Women and Infants Study of Healthy Hearts enrolled 607 mothers who delivered a singleton between 1997 and 2002. In 2007, participating mothers underwent measurements of carotid intima-media thickness, lumen diameter (LD), adventitial diameter (AD), and carotid-femoral pulse wave velocity. Multivariable linear and logistic regression were used to estimate the associations between lactation and sCVD. Results: Compared with mothers who breastfed for ≥3 months after every birth, mothers who never breastfed exhibited a 0.13mm larger LD (95%CI 0.04,0.22) and a 0.12mm larger AD (95%CI 0.02,0.22) in models adjusting for age, parity, birth outcome, sociodemographic variables, health-related behaviors, family history, gestational weight gain, early adult BMI, current BMI, CRP, blood pressure, cholesterol, triglyceride, HDL, glucose and insulin levels. Conclusions: Mothers who do not breastfeed have vascular characteristics associated with a greater risk of cardiovascular disease.

Changes in vaginal breech delivery rates in a single large metropolitan area - Accepted Manuscript

Mary Sheridan, Debra Bick, Susan Bewley — 2012-05-04

Changes in vaginal breech delivery rates in a single large metropolitan area - Accepted Manuscript

Mark P. Hehir, Hugh D. O’Connor, Fergal D. Malone — 2012-05-04

Decision-to-Incision Time: How to accomplish this calculation - Accepted Manuscript

Elliot M. Levine — 2012-05-04

Response to Letter #E12-013AR1, Decision to Incision: Time to Reconsider - Accepted Manuscript

Frank H. Boehm — 2012-05-04

Maternal BMI, glucose tolerance, and adverse pregnancy outcomes - Accepted Manuscript

2012-05-04

Abstract: Objectives: To estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome. Study Design: In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, defined as 50g glucose loading test between 135 and 199 mg/dL and fasting glucose <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity. Results: Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI was also positively associated with LGA, and both maternal BMI and fasting glucose were associated with birth-weight z-score and neonatal fat mass. Conclusions: Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birth weight and neonatal fat mass, independent of OGTT values.

Prenatal Retinoic Acid Improves Lung Vascularization And VEGF Expression In CDH Rat - Accepted Manuscript

2012-05-02

Abstract: Objective: Investigate the effects of antenatal retinoic acid on the pulmonary vasculature and VEGF expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. Study Design: Rat fetuses were exposed to nitrofen at gestational day (GD) 9.5 and/or all-trans retinoic acid (ATRA) at GD 18.5 through 20.5. We assessed lung growth, airway and vascular morphometry. VEGF, VEGFR1, VEGFR2 expression was analyzed by western blotting and immunohistochemistry. Continuous data were analyzed by ANOVA and Kruskal-Wallis test. Results: CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors which were reduced in CDH. Conclusions: Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH.

The Risk of Diagnostic Hysteroscopy in Women with Endometrial Cancer - Accepted Manuscript

Jennifer E. Soucie, Pamela A. Chu, Sue Ross, Tom Snodgrass, Stephen L. Wood — 2012-05-02

Abstract: Objective: To evaluate whether hysteroscopy in patients with endometrial cancer had an effect on disease stage or mortality. Study Design: Retrospective cohort analysis of data linked between a registry of women diagnosed with endometrial cancer and physician billing data on hysteroscopy. Results: A 99.8% match rate was obtained. Eighty-five percent of these cases had complete data on staging. Of 1972 cases, 672 (34.1%) had had a hysteroscopy performed. There was no difference in stage III disease between the hysteroscopy (7.1%) vs no hysteroscopy (6.5%) group (p=0.38). There was also no difference in death rates, 13.2% vs 15.2% (p=0.25), or in the proportion of women dying of “female genital organ” cancer, 46.1% vs 42.1% (p=0.53), respectively. Conclusion: Hysteroscopy is not associated with a higher rate of stage III disease or mortality. It allows for accurate diagnosis with direct visualization and biopsy, and should be considered a safe diagnostic tool.

Chlamydial and Gonococcal Testing during Pregnancy in the United States - Accepted Manuscript

Amy J. Blatt, Jay M. Lieberman, Donald R. Hoover, Harvey W. Kaufman — 2012-05-02

Abstract: Objective: To estimate rates of testing, prevalence and follow-up testing for chlamydial and gonococcal infection in a nationally-based population that is comparable to the U.S. pregnant population in terms of age and race. Study Design: We extracted laboratory results for 1,293,423 pregnant women tested over a three-year period. Results: During pregnancy, 59% (761,315/1,293,423) and 57% (730,796/1,293,423) women were tested at least once forC. trachomatis or for N. gonorrhoeae, respectively. Of those women tested, 3.5% (26,437/761,315) and 0.6% (4,605/730,796) tested positive for chlamydial and gonococcal infection, respectively, at least once during pregnancy. Of those women initially positive for the given infection, 78.3% (16,039/20,489) and 75.6% (2,610/3,435) were retested, of whom 6.0% (969/16,039) and 3.8% (100/2,610) were positive on their last prenatal test for C. trachomatis and N. gonorrhoeae, respectively. Conclusion: Many pregnant women are not tested forChlamydia trachomatis andNeisseria gonorrhoeae despite recommendations to test. Follow-up testing to monitor the effectiveness of treatment is also not always performed.

Maternal antidepressant use and adverse outcomes: a cohort study of 228,876 pregnancies - Accepted Manuscript

2012-05-02

Abstract: Objective: Describe antidepressant medication use patterns during pregnancy and pregnancy outcomes. Study Design: Cohort of 228,876 singleton pregnancies covered by Tennessee Medicaid, 1995-2007. Results: Of 23,280 pregnant women with antidepressant prescriptions prior to pregnancy, 75% filled none in the second or third trimesters of pregnancy and 10.7% used antidepressants throughout pregnancy. Filling 1, 2, and 3+ antidepressants during second trimester was associated with shortened gestational age by 1.7 (1.2- 2.3), 3.7 (2.8- 4.6), and 4.9 (3.9- 5.8) days, controlling for measured confounders. Third trimester selective serotonin reuptake inhibitor (SSRI) use was associated with infant convulsions; adjusted odds ratios were 1.4 (0.7-2.8); 2.8 (1.9- 5.5); and 4.9 (2.6-9.5) for filling 1, 2, and 3 prescriptions respectively. Conclusions: Most women discontinue antidepressant medications prior or during the first trimester of pregnancy. Second trimester antidepressant use is associated with preterm birth, and third trimester SSRI use is associated with infant convulsions.

In vitro anti-HIV-1 activity in cervicovaginal secretions from pregnant and non-pregnant women - Accepted Manuscript

2012-05-02

Abstract: Objective: To evaluate whether cervicovaginal secretions inhibit HIV-1 infectivity in an in vitro model, and estimate concentration of immune mediators. Study design: We enrolled mid-trimester pregnant and regularly menstruating (non-pregnant) women. Cervicovaginal lavage (CVL) was collected at 2 visits and incubated with HIV-1 and TZM-bl cells. Infectivity was compared to positive controls. Concentrations of immune mediators were compared between groups. Results: At enrollment, CVL inhibited IIIB virus 88.2% and 82.4%, and BaL virus 72.8% and 77.9%, among pregnant (n=13) and non-pregnant women (n=9), respectively. At second visit, CVL inhibited IIIB 89.7% and 82.5%, and BaL 77.4% and 69.9% among pregnant (n=15) and non-pregnant women (n=8), respectively (all P ≤ 0.04). Adjusting for body mass index, race, and protein content of CVL, antimicrobials were suppressed but cytokines and chemokines were not markedly different in pregnancy. Conclusion: Cervicovaginal secretions significantly suppress HIV-1 infectivity in this model. Concentrations of certain immune mediators are altered in pregnancy.

Universal maternal cervical length screening during the second trimester: pros and cons of a strategy to identify women at risk of spontaneous preterm delivery - Accepted Manuscript

Samuel Parry, Hyagriv Simhan, Michal Elovitz, Jay Iams — 2012-04-30

Abstract: Three large randomized controlled trials investigating the efficacy of universal cervical length screening and treatment with vaginal progesterone or cervical cerclage to prevent preterm delivery have been published over the past several years.1-3 None of these trials demonstrate proven efficacy for universal cervical length screening and cerclage placement in women with short cervical length. However, universal cervical length screening and treatment with daily vaginal progesterone in women with short cervical length reduces the risk of preterm birth, but large numbers of women must be screened to prevent a relatively small number of preterm deliveries. Issues that should be considered while implementing universal cervical length screening include: 1) the standards of quality and reproducibility for transvaginal ultrasound cervical length ascertainment; 2) the implications of screening on the application of therapeutic strategies to populations not known to benefit (so-called “indication creep”); and 3) the willingness of obstetricians to prescribe vaginal progesterone formulations that are not approved by the US Food and Drug Administration for preterm birth prevention. Optimal strategies to employ cervical ultrasound and progesterone treatment might be revealed by additional studies investigating cervical length cut-offs, frequency of screening, selective screening in higher-risk groups, and the use of transabdominal cervical length screening as a surrogate for transvaginal cervical length screening.

Pharmacokinetics and ovarian suppression during use of a contraceptive vaginal ring in normal-weight and obese women - Accepted Manuscript

2012-04-30

Abstract: Background:: Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiological studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring (CVR) performance in obese women are needed. Methods:: 20 normal weight (BMI 19.0-24.9, median 21.65) and 20 obese (BMI 30.0-39.9, median 33.7) women enrolled in a prospective study of ethinyl estradiol (EE) and etonorgestrel (ENG) pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of CVR use. Results:: Thirty-seven women completed follow-up. Mean day 0-21 EE concentrations were lower among obese versus normal weight women (15.0 versus 22.0 pg/mL, respectively. p = 0.004), while ENG concentrations were similar (1138 versus 1256 pg/mL, respectively. p = 0.39). Follicular development was minimal in both groups, with only five women achieving a maximum follicle diameter > 13mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels < 1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 versus 1.4 days, respectively. p = 0.01). Conclusions:: While obese women had lower EE levels during CVR use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that CVR effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE levels in the obese women may explain the greater reported bleeding or spotting days.

Obstetrician–gynecologists, religious institutions, and conflicts regarding patient care policies - Accepted Manuscript

Debra B. Stulberg, Annie M. Dude, Irma Dahlquist, Farr A. Curlin — 2012-04-30

Abstract: Objective:: To assess how common it is for obstetrician-gynecologists working in religiously-affiliated hospitals or practices to experience conflict with those institutions over religiously-based policies for patient care, and to identify the proportion of obstetrician-gynecologists who report that their hospitals restrict their options for treating ectopic pregnancy. Study Design:: Mailed survey, nationally representative sample of 1,800 practicing obstetrician–gynecologists. Results:: The response rate was 66%. Among obstetrician–gynecologists who practice in religiously affiliated institutions, 37% have had a conflict with their institution over religiously-based policies. These conflicts are most common in Catholic institutions (52%, adjusted Odds Ratio 8.7, 95% Confidence Interval 1.7-46.2). Few report that their options for treating ectopic pregnancy are limited by their hospitals (2.5% at non-Catholic institutions vs. 5.5% at Catholic, p=0.07). Conclusion:: Many obstetrician-gynecologists who practice in religiously-affiliated institutions have had conflicts over religiously-based policies. The effects of these conflicts on patient care and outcomes are an important area for future research.

The prediction of recurrent preterm birth in patients on 17-alpha-hydroxyprogesterone caproate using serial fetal fibronectin and cervical length - Accepted Manuscript

2012-04-30

Abstract: Objective:: To estimate the predictive value of cervical length (CL) and fetal fibronectin (fFN) in patients being treated with 17-alpha-hydroxyprogesterone caproate (17P). Methods:: Retrospective cohort of 176 patients with a prior spontaneous preterm birth being treated with weekly injections of 17P who underwent serial CL and fFN screening. Results:: A short CL (=25mm) was significantly associated with an earlier gestational age at delivery and with recurrent preterm birth <37, <35, <34 , and <32 weeks. A positive fFN was not significantly associated with recurrent preterm birth. As a screening test for recurrent preterm birth, the positive and negative likelihood ratios for CL were 2.04 and 0.35, respectively, whereas for fFN they were 1.22 and 0.98, respectively, indicating that fFN did not offer any additional predictive value. Conclusion:: In patients being treated with 17P, cervical length at 22-32 weeks is predictive of recurrent preterm birth, but fetal fibronectin is not.

Referral to telephonic nurse management improves outcomes in women with gestational diabetes - Accepted Manuscript

2012-04-26

Abstract: Objective: To determine whether, among women with gestational diabetes (GDM), referral to a telephonic nurse management program was associated with lower risk of macrosomia and increased postpartum glucose testing. Study Design: There was medical center-level variation in the percent of patients referred to a telephonic nurse management program at 12 Kaiser Permanente medical centers, allowing to examine in a quasi-experimental design the associations between referral and outcomes. Results: Compared with women from centers where the annual proportion of referral nurse management was <30%, women who delivered from centers with an annual referral proportion >70% were less likely to have a macrosomic infant and more likely to have postpartum glucose testing [multiple-adjusted OR (95%CI): 0.75 (0.57-0.98) and 22.96 (2.56-3.42), respectively]. Conclusion: Receiving care at the centers with higher referral frequency to a telephonic nurse management for GDM was associated with decreased risk of macrosomic infant and increased postpartum glucose testing.

Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecological outpatient service (Journal Club article for discussion June 2012 re: W11-0787) - Accepted Manuscript

George A. Macones — 2012-04-26

Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecological outpatient service (Journal Club article for discussion June 2012 re: W11-0787) - Accepted Manuscript

George A. Macones — 2012-04-23

Geriatric Gynecology: Promoting Health and Avoiding Harm - Accepted Manuscript

Karen L. Miller, Carole A. Baraldi — 2012-04-18

Abstract: Age increases vulnerability, commonly accompanied by greater reliance on others and susceptibility to maltreatment. Physiologic processes become less resilient; the potential for harm from medical care increases. Awareness of frailty, functional, social, and potential maltreatment issues enables early referrals to help the patient maintain her independence. Health issues that may impede both gynecologic care and self sufficiency include sensory deficits, physical disability, and cognitive impairment. Speaking slowly and providing contextual information enhance patient comprehension. Cancer screening depends on life expectancy. Osteoporosis treatment requires managing fall risk. Gynecologic complaints more likely have multiple contributing factors than one etiology. Incontinence is a particularly complex issue, but invariably includes bladder diary assessment and pelvic floor muscle training. Function and frailty measures best predict perioperative morbidity. Communication with the patient, her family, other providers, and healthcare organizations is an important frontier in avoiding errors and adverse outcomes.

Rapid repeat pregnancy in adolescents: do immediate postpartum contraceptive implants make a difference? - Accepted Manuscript

Kristina M. Tocce, Jeanelle L. Sheeder, Stephanie B. Teal — 2012-04-18

Abstract: Objectives: Determine contraceptive continuation and repeat pregnancy rates in adolescents offered immediate postpartum etonogestrel implant insertion. Study Design: Participants in an adolescent prenatal-postnatal program were enrolled in a prospective observational study of immediate postpartum implant insertion (IPI group; n=171) versus other methods (control group; n=225). Contraceptive continuation and repeat pregnancies were determined. Results: Implant continuation at 6 months was 96.9% (156/161); at 12 months, 86.3% (132/153). At 6 months, 9.9% of controls were pregnant (21/213); there were no IPI pregnancies. By 12 months, 18.6% (38/204) of controls experienced pregnancy versus 2.6% (4/153) of IPI recipients (RR 5.0, 95% CI 1.9-12.7). Repeat pregnancy at 12 months was predicted by not receiving immediate postpartum implant insertion (OR 8.0, 95% CI 2.8-23.0) and having more than one child (OR 2.1, p=0.03, 95% CI 1.1-4.3). Conclusion: Immediate postpartum etonogestrel implant placement in adolescents has excellent continuation one year post-delivery; rapid repeat pregnancy is significantly decreased compared to controls.

Urinary Incontinence, Depression and Post-traumatic Stress Disorder in Women Veterans - Accepted Manuscript

2012-04-18

Abstract: Objective: To study associations between urinary incontinence (UI) symptoms, depression and post-traumatic stress disorder (PTSD) in women veterans. Study Design: This cross-sectional study enrolled women 20 to 52 years of age registered at two Midwestern U.S. Veterans Affairs Medical Centers or outlying clinics within five years preceding study interview. Participants completed a computer-assisted telephone interview assessing urogynecologic, medical and mental health. Multivariable analyses studied independent associations between stress and urgency UI and depression and PTSD. Results: 968 women mean age 38.7 ± 8.7 years were included. 191 (19.7%) reported urgency/mixed UI and 183 (18.9%) stress UI. PTSD (OR [95%CI] = 1.8 [1.0, 3.1]) but not depression (OR [95%CI] = 1.2 [0.73, 2.0]) was associated with urgency/mixed UI. Stress UI was not associated with PTSD or depression. Conclusion: In women veterans, urgency/mixed UI was associated with PTSD but not depression.

Smoking during pregnancy influences the maternal immune response in mice and humans - Accepted Manuscript

2012-04-18

Abstract: Objective: During pregnancy the maternal immune system has to adapt its response to accommodate the fetus. The objective of this study was to analyze the effects of smoking on the maternal immune system. Study design: First-trimester decidual tissue, and peripheral blood of smoking and nonsmoking women was analyzed by real time RT-PCR and flow cytometry. A mouse-model was used to further analyze the effects of smoking. Murine tissue was analyzed by flow cytometry, real time RT-PCR, and immunohistochemistry. Results: Smoking caused lower percentages of viable pups in mice and lower birth weights in humans. Smoking mothers, both mice and human, had more NK cells and inflammatory macrophages locally, whereas systemically they had lower percentages of regulatory T cells than nonsmoking controls. Conclusion: Maternal smoke exposure during pregnancy influences local and systemic immune responses in both women and mice. Such changes may be involved in adverse pregnancy outcomes in smoking individuals.

The Diagnosis, Treatment and Follow-Up of Cesarean Scar Pregnancy - Accepted Manuscript

2012-04-18

Abstract: Objective: The diagnosis and treatment of cesarean scar pregnancy is challenging. The objective of this study was to evaluate the diagnostic method, treatments and long-term follow-up of cesarean scar pregnancy. Materials & Methods: This is a retrospective case series of 26 patients between 6 and 14 postmenstrual weeks suspected to have cesarean section scar pregnancies who were referred for diagnosis and treatment. The diagnosis was confirmed with transvaginal ultrasound. In 19 of the 26 patients the gestational sac was injected with 50 mg methotrexate: 25mg into the area of the embryo/fetus and 25 mg into the placental area; and an additional 25 mg was administered intramuscularly. Serial serum hCG determinations were obtained. Gestational sac volumes and vascularization were assessed by 3D ultrasound and used to monitor resolution of the injected site and outcome. Results: The 19 treated pregnancies were followed for 24 to 177 days. No complications were observed. After the treatment, typically, there was an initial increase in the hCG serum concentrations as well as in the volume of the gestational sac and their vascularization. After a variable time period mentioned elsewhere the values decreased, as expected. Conclusion: Combined intramuscular and intragestational methotrexate injection treatment was successful in treating these cesarean scar pregnancies.

Source of 17-hydroxyprogesterone caproate in clinical trials - Corrected Proof

C. Andrew Combs, Kimberly Maurel, Thomas J. Garite — 2012-04-09

Rozenberg and colleagues reported that 17-hydroxyprogesterone caproate (17Pc) (500 mg twice/wk) did not significantly increase time to delivery or improve neonatal outcome when used as maintenance therapy after an episode of preterm labor. We would ask the authors to disclose the source of the drug and to clarify whether there was any testing to assure its quality. This is critical because of questions about the purity and potency of some 17Pc preparations available on the global market.

Reply - Corrected Proof

Patrick Rozenberg — 2012-04-09

We would like to thank Dr Combs and colleagues for their comments regarding our recent article entitled “Prevention of preterm delivery after successful tocolysis in preterm labor by 17 alpha-hydroxyprogesterone caproate: a randomized controlled trial.”

Cost minimization minilaparotomy vs laparoscopic sacral colpopexy - Corrected Proof

Daniel A. Tsin — 2012-04-09

I read with interest the paper entitled “Cost minimization analysis of laparoscopic sacral colpopexy and total vaginal mesh” by Drs Christopher F. Maher and Luke B. Connelly. The paper focused on cost containment for the treatment of uterine prolapse. I noticed that the authors considered laparoscopy vs the total mesh vaginal approach. This very well-done study did not mention the inexpensive minilaparotomy approach.

Reply - Corrected Proof

Christopher F. Maher, Luke B. Connelly — 2012-04-09

We thank Dr Tsin for his letter to the editor outlining the surgical technique of the minilaparotomy approach to sacral cervicopexy for uterine procidentia. Clearly, uterine procidentia is an important and fertile area of research; however, our trial evaluated only those with posthysterectomy vaginal vault prolapse.

Ovulation induction in women with polycystic ovarian syndrome: still steps to take - Corrected Proof

Charalampos Siristatidis, Nikolaos Vrachnis, Charalampos Chrelias — 2012-04-09

We read with interest the clinical opinion paper on ovulation induction in women with polycystic ovarian syndrome (PCOS). PCOS remains an enigma in which the abnormalities in extra- and intra-ovarian factors exert a negative impact on the level of oocyte and embryo. We wish to highlight some points on the topic.

Reply - Corrected Proof

Balasubramanian Bhagavath, Sandra A. Carson — 2012-04-09

We thank Dr Siristatidis and colleagues for their interest in our clinical opinion on ovulation induction in polycystic ovary syndrome and for taking the time to raise interesting questions. This opinion was specifically directed at helping general obstetricians and gynecologists and not at the specialist reproductive endocrinology and infertility specialist. However, we have highlighted the potential complication and strategies to reduce multiple pregnancies under “Complications of ovulation induction.” The opinion is focused on ovulation induction in women with polycystic ovary syndrome; therefore, we did not include management of other factors such as male factor infertility that may coexist in couples struggling with infertility. We have mentioned in the last paragraph of the introduction that consideration be given to evaluating the male partner as well as the uterine cavity and fallopian tubes.

Effectiveness of timing strategies for delivery of monochorionic diamniotic twins - Corrected Proof

Barrett K. Robinson, Russell S. Miller, Mary E. D'Alton, William A. Grobman — 2012-04-09

Objective: The purpose of this study was to compare strategies for delivery timing of uncomplicated monochorionic diamniotic twin pregnancies. Study Design: A decision tree compared 9 strategies that included scheduled delivery between 32 and 38 weeks' gestation, with or without confirmation of fetal lung maturity. Outcomes in the model included fetal death, infant death, respiratory distress syndrome, mental retardation, and cerebral palsy. Results: A scheduled delivery at 38 weeks' gestation was the preferred strategy, which resulted in the highest quality adjusted life years under base-case assumptions. Decreased, but comparable, quality adjusted life years estimates resulted from scheduled deliveries at 36 and 37 weeks' gestation, with or without amniocentesis. Sensitivity analyses demonstrated that the optimal gestational age for delivery was always ≥36 weeks' gestation. Conclusion: This decision analysis suggests that, for women with uncomplicated monochorionic twins, delivery between 36 and 38 weeks' gestation is the preferred strategy for timing of delivery.

Successful in utero treatment of an oral teratoma via operative fetoscopy: case report and review of the literature - Corrected Proof

Eftichia V. Kontopoulos, Marc Gualtieri, Rubén A. Quintero — 2012-04-09

The prenatal diagnosis of a nasopharyngeal teratoma carries a very grave prognosis. Although these tumors constitute only 9% of all teratomas, all previous cases diagnosed antenatally have been associated with either fetal demise or emergent surgery at birth. Of the fetuses that survive to birth, delivery can be associated with airway obstruction and multiple postnatal surgeries. These complications could be averted if the tumor could be safely treated in utero. We hereby report the successful treatment of an oral teratoma via operative fetoscopy, with the birth of a healthy infant at term.

Does route of delivery affect maternal and perinatal outcome in women with eclampsia? A randomized controlled pilot study - Corrected Proof

2012-04-09

Objective: The route of delivery in eclampsia is controversial. We hypothesized that adverse maternal and perinatal outcomes may not be improved by early cesarean delivery. Study design: This was a randomized controlled exploratory trial carried out in a rural teaching institution. In all, 200 eclampsia cases, carrying ≥34 weeks, were allocated to either cesarean or vaginal delivery. Composite maternal and perinatal event rates (death and severe morbidity) were compared by intention-to-treat principle. Results: Groups were comparable at baseline with respect to age and key clinical parameters. Maternal event rate was similar: 10.89% in the cesarean arm vs 7.07% for vaginal delivery (relative risk, 1.54; 95% confidence interval, 0.62–3.81). Although the neonatal event rate was less in cesarean delivery–9.90% vs 19.19% (relative risk, 0.52; 95% confidence interval, 0.25–1.05)–the difference was not significant statistically. Conclusion: A policy of early cesarean delivery in eclampsia, carrying ≥34 weeks, is not associated with better outcomes.

Temporal alterations in vascular angiotensin receptors and vasomotor responses in offspring of protein-restricted rat dams - Corrected Proof

2012-04-09

Objective: Examine temporal alterations in vascular angiotensin II receptors (AT1R and AT2R) and determine vascular response to angiotensin II in growth-restricted offspring. Study Design: Offspring of pregnant rats fed low-protein (6%) and control (20%) diet were compared. Results: Prenatal protein restriction reprogrammed AT1aR messenger RNA expression in male rats' mesenteric arteries to cause 1.7- and 2.3-fold increases at 3 and 6 months of age associated with arterial pressure increases of 10 and 33 mm Hg, respectively; however, in female rats, increased AT1aR expression (2-fold) and arterial pressure (15 mm Hg) occurred only at 6 months. Prenatal protein restriction did not affect AT2R expression. Losartan abolished hypertension, suggesting that AT1aR plays a primary role in arterial pressure elevation. Vasoconstriction to angiotensin II was exaggerated in all protein-restricted offspring, with greater potency and efficacy in male rats. Conclusion: Prenatal protein restriction increased vascular AT1R expression and vasoconstriction to angiotensin II, possibly contributing to programmed hypertension.

Endometrial ablation: postoperative complications - Corrected Proof

Howard T. Sharp — 2012-04-09

Endometrial ablation as a treatment for abnormal uterine bleeding has evolved considerably over the past several decades. Postoperative complications include the following: (1) pregnancy after endometrial ablation; (2) pain-related obstructed menses (hematometra, postablation tubal sterilization syndrome); (3) failure to control menses (repeat ablation, hysterectomy); (4) risk from preexisting conditions (endometrial neoplasia, cesarean section); and (5) infection. Physicians performing endometrial ablation should be aware of postoperative complications and be able to diagnose and provide treatment for these conditions.

Knowledge of contraceptive effectiveness - Corrected Proof

2012-04-09

Objective: The purpose of this study was to determine women's knowledge of contraceptive effectiveness. Study Design: We performed a cross-sectional analysis of a contraceptive knowledge questionnaire that had been completed by 4144 women who were enrolled in the Contraceptive CHOICE Project before they received comprehensive contraceptive counseling and chose their method. For each contraceptive method, women were asked “what percentage would get pregnant in a year: <1%, 1-5%, 6-10%, >10%, don't know.” Results: Overall, 86% of subjects knew that the annual risk of pregnancy is >10% if no contraception is used. More than 45% of women overestimate the effectiveness of depo-medroxyprogesterone acetate, pills, the patch, the ring, and condoms. After adjustment for age, education, and contraceptive history, the data showed that women who chose the intrauterine device (adjusted relative risk, 6.9; 95% confidence interval, 5.6–8.5) or implant (adjusted relative risk, 5.9; 95% confidence interval, 4.7–7.3) were significantly more likely to identify the effectiveness of their method accurately compared with women who chose either the pill, patch, or ring. Conclusion: This cohort demonstrated significant knowledge gaps regarding contraceptive effectiveness and over-estimated the effectiveness of pills, the patch, the ring, depo-medroxyprogesterone acetate, and condoms.

An unusual way to give birth: The patient's son was delivered paravaginally while she was en route to the hospital - Corrected Proof

Renée J. Detollenaere, Harm H. de Haan — 2012-04-01

A 33-year-old pregnant woman (gravida 2, para 1) was referred because she sustained vaginal wall rupture during home birth. Her first delivery was complicated by a third-degree perineal tear from which she fully recovered after surgery. During transfer in the ambulance, she delivered an 8.6 lb (3.9 kg) male infant. On admission to our hospital, a complex rupture was evident ().

Clustering of maternal/fetal clinical conditions and outcomes and placental lesions - Corrected Proof

Jerzy Stanek, Jacek Biesiada — 2012-04-01

Objective: To identify by an inductive statistical analysis mutually similar and clinically relevant clinicoplacental clusters. Study Design: Twenty-nine maternofetal and 49 placental variables have been retrospectively analyzed in a 3382 case clinicoplacental database using a hierarchical agglomerative Ward dendrogram and multidimensional scaling. Results: The exploratory cluster analysis identified 9 clinicoplacental (macerated stillbirth, fetal growth restriction, placenta creta, acute fetal distress, uterine hypoxia, severe ascending infection, placental abruption, and mixed etiology [2 clusters]), 5 purely placental (regressive placental changes, excessive extravillous trophoblasts, placental hydrops, fetal thrombotic vasculopathy, stem obliterative endarteritis), and 1 purely clinical (fetal congenital malformations) statistically significant clusters/subclusters. The clusters of such variables like clinical umbilical cord compromise, preuterine and postuterine hypoxia, gross umbilical cord or gross chorionic disk abnormalities did not reveal statistically significant stability. Conclusion: Although clinical usefulness of several well-established placental lesions has been confirmed, claims about high predictability of others have not.

The utility of endocervical curettage: does routine ECC at the time of colposcopy for low-grade cytologic abnormalities improve diagnosis of high-grade disease? - Corrected Proof

Joseph D. Rose, Sharon Y. Byun, Shireen Madani Sims, John D. Davis — 2012-04-01

Objective: To determine the use of endocervical curettage at the time of colposcopy for low-grade cytologic abnormalities. Study Design: We conducted a retrospective chart review of women with low-grade Papanicolaou smears who had undergone satisfactory colposcopic examinations with identifiable lesions. We evaluated results during a 2-year period thereafter to determine whether endocervical curettage increased the diagnosis of high-grade dysplasia. Results: The study group consisted of 374 patients. Of these patients, 16 had endocervical curettages suggestive of high-grade dysplasia. Of these 16 patients, 4 did not have concomitant high-grade dysplasia identified on ectocervical biopsy. Therefore, 93 to 94 endocervical curettages needed to be performed to detect 1 case of high-grade dysplasia that would not have been identified otherwise. Conclusion: Routine endocervical curettage at the time of satisfactory colposcopy for low-grade cytologic abnormalities with a visible lesion does not significantly improve the diagnosis of high-grade dysplasia.

The survival impact of systematic lymphadenectomy in endometrial cancer with the use of propensity score matching analysis - Corrected Proof

2012-04-01

Objective: We sought to evaluate whether patients with endometrial cancer in the Surveillance, Epidemiology, and End Results database who underwent lymphadenectomy demonstrate improved survival. Study design: The study population comprised 50,969 patients. The 3-year cause-specific survival was tested by using propensity score matching (PSM) analysis. Results: The PSM analysis generated a balanced, matched cohort in which baseline characteristics were not significantly different. The benefit of systematic lymphadenectomy appears to be significant for presumed stage I International Federation of Gynecology and Obstetrics grade 3 cancers and presumed stages II-III cancer. The omission of lymphadenectomy in stage I did not appear to show a deleterious survival consequence if the differentiation grade was moderate (grade 2) or well (grade 1). Conclusion: Using PSM analysis, our results show no evidence of benefit in terms of survival for systematic lymphadenectomy in women with stage I endometrial cancer, except for grade 3 cancers.

Merkel cell carcinoma in a patient with noninvasive vulvar Paget's disease - Corrected Proof

Ira S. Winer, Fulvio Lonardo, Samuel C. Johnson, Gunter Deppe — 2012-04-01

We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis.

Changes in vaginal breech delivery rates in a single large metropolitan area - Corrected Proof

2012-04-01

Objective: Vaginal breech delivery rates have been accepted widely to be in decline and the Term Breech Trial (TBT) has recommended delivery of a breech-presenting infant by elective cesarean section delivery. Our aim was to examine the rate of vaginal delivery of term breech pregnancies in the 8 years before and after the publication of the TBT. Study Design: We retrospectively examined vaginal delivery rates of breech presentations over a 16-year period in 3 large tertiary maternity hospitals that serve a single large metropolitan population. All 3 hospitals are of similar size and serve a population with similar risk profile. We also examined rates of perinatal mortality in the 3 hospitals over the study period. Results: During the 16-year study period, there were 344,259 deliveries among the 3 hospitals; 11,913 of which were breech deliveries. There were 5655 breech deliveries in the 8 years before the publication of the TBT, with a cesarean delivery rate of 76.9%. There were 6258 breech deliveries in the 8 years since publication of the TBT, and the cesarean delivery rate increased to 89.7% (P < .0001). During the 8 years since publication, the rate of vaginal delivery in nulliparous women decreased from 15.3-7.2% (P < .0001). The vaginal breech delivery rate in multiparous women decreased from 32.6-14.8% (P < .0001). The rates of corrected perinatal mortality showed a significant decrease in the last 4 years of the study. Conclusion: Our study demonstrates that the results and recommendations of the TBT have contributed to decreasing vaginal breech delivery rates, which were already in decline before its publication.

Risk factors for abnormal anal cytology over time in HIV-infected women - Corrected Proof

2012-04-01

Objective: The objective of the study was to assess the incidence of, and risk factors for, abnormal anal cytology and anal intraepithelial neoplasia (AIN) 2-3 in human immunodeficiency virus (HIV)–infected women. Study Design: This prospective study assessed 100 HIV-infected women with anal and cervical specimens for cytology and high-risk human papillomavirus (HPV) testing over 3 semiannual visits. Results: Thirty-three women were diagnosed with an anal cytologic abnormality at least once. Anal cytology abnormality was associated with current CD4 count less than 200 cells/mm3, anal HPV infection, and a history of other sexually transmitted infections (STIs). Twelve subjects were diagnosed with AIN2-3: 4 after AIN1 diagnosis and 4 after 1 or more negative anal cytology. AIN2-3 trended toward an association with history of cervical cytologic abnormality and history of STI. Conclusion: Repeated annual anal cytology screening for HIV-infected women, particularly for those with increased immunosuppression, anal and/or cervical HPV, a history of other STIs, or abnormal cervical cytology, will increase the likelihood of detecting AIN2-3.