American Journal of Obstetrics & Gynecology - Articles in Press

Comprehensive Analysis Of LAMC1 Genetic Variants In Advanced Pelvic Organ Prolapse - Accepted Manuscript

2012-02-10

Abstract: Objective: We sought to comprehensively evaluate the association of laminin gamma-1 ( LAMC1) and advance pelvic organ prolapse. Study Design: We conducted a candidate gene association of cases (n=239) with stage III-IV prolapse and controls (n=197) with stage 0-I prolapse. We employed a linkage disequilibrium (LD) tagged approach to identify SNPs inLAMC1and focused on non-Hispanic white women to minimize population stratification. Additive and dominant multivariable logistic regression models were used to test for association between individual SNPs and advanced prolapse. Results: 14 SNPs representing 99% coverage ofLAMC1were genotyped. There was no association between SNP rs10911193 and advanced prolapse (p=0.34). However, there was a trend towards significance for rs1413390 (p=0.11), rs20563 (p=0.11), and rs20558 (p=0.12). Conclusion: While we found that the previously reportedLAMC1 SNP rs10911193 was not associated with non-familial prolapse, our results support further investigation of this candidate gene in the pathophysiology of prolapse.

Symptomatic and anatomic 1-year outcomes after robotic and abdominal sacrocolpopexy - Accepted Manuscript

Nazema Y. Siddiqui, Elizabeth J. Geller, Anthony G. Visco — 2012-02-10

Abstract: Objectives: To compare symptomatic and anatomic outcomes one year after robotic versus abdominal sacrocolpopexy. Study Design: A retrospective cohort study comparing women undergoing robotic sacrocolpopexy (RSC) with one surgeon to those who underwent abdominal sacrocolpopexy (ASC) as part of the Colpopexy And urinary Reduction Efforts (CARE) trial. Our primary outcome was a composite measure of vaginal bulge symptoms or repeat surgery for prolapse. Results: We studied 447 women (125 RSC and 322 ASC). Baseline characteristics were similar. There were no significant differences in failures one year after surgery based on our primary composite outcome [7/86 (8%) vs. 12/304 (4%), p=0.16]. When considering anatomic failure, there were also no significant differences between RSC and ASC [4/70 (6%) vs. 16/289 (6%), p=0.57]. Conclusions: One year after sacrocolpopexy, women undergoing RSC have similar symptomatic and anatomic success compared to those undergoing ASC.

Effect of surgical approach on physical activity and pain control after sacral colpopexy - Accepted Manuscript

Sarah A. Collins, Paul K. Tulikangas, David M. O’sullivan — 2012-02-10

Abstract: Objective: To compare recovery of activity and pain control after robotic versus abdominal sacral colpopexy. Study Design: Women undergoing robotic (ROB) and abdominal (ABD) sacral colpopexy wore accelerometers for 7 days preoperatively and the first 10 days postoperatively. They completed postoperative pain diaries and Short Form 36 (SF-36) questionnaires before and after surgery. Results: At 5 days postoperatively, 0/14 subjects in the ABD group and 4/28 (14.3%) in the ROB group achieved 50% total baseline activity counts (p=0.283). At 10 days, 5/14 (35.7%) in the ABD group and 8/26 (30.8%) in the ROB group (p=0.972) achieved 50%. Postoperative pain was similar in both groups. SF-36 Vitality (VT) scores were lower (p=0.017) after surgery in the ABD group, but not in the ROB group. Conclusion: Women undergoing robotic versus abdominal sacral colpopexy do not recover physical activity faster, and pain control is not improved.

Cardiovascular risk and combined oral contraceptives: Clinical decisions in Settings of uncertainty - Accepted Manuscript

Jennifer P. Beller, Christopher R. Mccartney — 2012-02-10

Abstract: While generally safe, combined oral contraceptives (COCs) are associated with risks, including an estimated two-fold increased relative risk of cardiovascular events. For most women taking COCs for contraception, absolute cardiovascular risks are very low, and the overall risks of COCs are outweighed by the risks of unwanted pregnancy. Nonetheless, risks of COCs may be excessive in some women, and both ACOG and WHO have offered contraindications for COC use. Complicating this issue, COCs are commonly used for reasons other than contraception (e.g., polycystic ovary syndrome, which is associated with subfertility and cardiovascular risk factors). Thus, in some clinical scenarios, ACOG and WHO guidelines may offer incomplete guidance regarding whether COC use would be associated with an unacceptable risk-benefit ratio.We propose that cardiovascular risk calculators may be helpful in some patients—as an adjunct to ACOG and WHO guidelines—by allowing physicians to estimate attributable risk of COC-related cardiovascular events.

Methicillin-Resistant Staphylococcus Aureus Colonization among Women Admitted for Preterm Delivery - Accepted Manuscript

Gweneth B. Lazenby, David E. Soper, Wanda Beardsley, Cassandra D. Salgado — 2012-02-10

Abstract: Objective: Methicillin-Resistant Staphylococcus aureus (MRSA) infection is associated with morbidity in the neonatal intensive care unit (NICU). The purpose of this study was to determine the relationship between preterm maternal MRSA colonization and subsequent colonization and infection in premature neonates. Study Design: We conducted a prospective cohort study of 422 women admitted for preterm delivery. MRSA cultures were collected from mothers and their neonates admitted to NICU. We determined the proportion of women and neonates colonized with MRSA and examined possible factors associated with colonization and infection. Results: 15/422 (3.6%) women were found to be colonized with MRSA. 13/212 (6.1%) neonates admitted to NICU were MRSA colonized and 3/13(23.1%) developed an MRSA infection. We identified one MRSA colonized maternal-neonatal pair. The infant became MRSA positive 30 days after admission and did not develop an MRSA infection. Conclusions: These findings suggest that maternal MRSA colonization is not a significant risk factor for vertical transmission of neonatal MRSA colonization.

Outcomes and Predictors of Failure of Trocar-guided Vaginal Mesh Surgery for Pelvic Organ Prolapse - Accepted Manuscript

Alfredo L. Milani, Mariella I.J. Withagen, Mark E. Vierhout — 2012-02-10

Abstract: Objectives: To compare one-year conventional and composite outcomes of trocar-guided vaginal mesh surgery and identification of predictors of failure. Study design: Prospective observational Cohort study. Failure outcome definitions were: I; prolapse stage ≥ II in mesh treated compartments, II; overall prolapse stage ≥ II, III; composite outcome of overall prolapse > hymen and presence of bulge symptoms or re-surgery. Logistic regression to identify predictors of failure. Results: One-year follow-up of 433 patients. Treated compartment failure (I): 15% (95% CI 12-19). Overall prolapse failure(II): 41% (95% CI 36-45). Composite failure (III): 9% (95% CI 7-13). Predictor of failure in all outcomes: combined anterior/posterior mesh with the uterus in situ. Conclusion: Outcome of prolapse surgery depends on outcome definition. The mesh treated compartment failure outcome (I) and the composite failure outcome (III) appeared not to be statistically different. Consistent factor for failure in all outcomes was the combined anterior/posterior mesh insertion with the uterus in situ.

Lymphadenectomy in Endometrial Cancer: What’s the Right Question ? - Accepted Manuscript

Stefano Basile, Maria Giovanna Salerno, Pierluigi Benedetti Panici — 2012-02-10

Lymphadenectomy Influences the Utilization of Adjuvant Radiation Treatment for Endometrial Cancer - Accepted Manuscript

Charu Sharma, Israel Deutsch, Thomas J. Herzog, Jason D. Wright — 2012-02-10

The Satisfaction Survey That Matters - Accepted Manuscript

Jack A. Lucas — 2012-02-10

Simulation of Robotic Hysterectomy Utilizing the Porcine Model - Accepted Manuscript

Mitchel S. Hoffman — 2012-02-10

Abstract: Purpose: This paper describes simulation of robotically-assisted hysterectomy utilizing the porcine model. Materials and Methods: Utilizing 3 domestic pigs a technique for robotically-assisted hysterectomy was developed. An edited video clip of the model was assessed by 6 gynecologic surgeons. Results: The steps of the operation are described in detail and shown in a video clip. Overall the procedure simulated that done in the human both anatomically and surgically. Some of the evaluators rated identification of the cervicovesical junction to be more difficult and division of the paracervical ligaments to be relatively easier in the model. Conclusion: Reported here is a technique for robotically-assisted hysterectomy in the domestic pig that may be useful for training purposes.

The FIGO Systems for Nomenclature and Classification of Causes of Abnormal Uterine Bleeding in the Reproductive Years…Who needs them? - Accepted Manuscript

Malcolm G. Munro, Hilary O.D. Critchley, Ian S. Fraser — 2012-02-10

Abstract: In November of 2010, FIGO formally accepted a new classification system for causes of abnormal uterine bleeding (AUB) in the reproductive years. The system, based on the acronym “PALM-COEIN”, (Polyps, Adenomyosis, Leiomyoma, Malignancy and hyperplasia – Coagulopathy, Ovulatory disorders, Endometrial causes, Iatrogenic, Not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation relating to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding, and the various symptoms that comprise abnormal bleeding has also been included. This manuscript describes the rationale, the structured methodology involving stakeholders worldwide, and the suggested use of the FIGO system for research, education and clinical care. Investigators in the field are encouraged to use the system in the design of their AUB-related research, an approach that should improve our understanding and management of this often-perplexing clinical condition.

In the nick of time: Despite 2 treatments a cervical ectopic pregnancy continued to advance - Accepted Manuscript

Emily S. Miller, Kathryn Marko, Leeber Cohen, Jeffrey S. Dungan, Lee P. Shulman — 2012-01-30

A hard cervix: Microscopic examination revealed that a rare transformation had occurred - Accepted Manuscript

2012-01-30

First 100 early endometrial cancer cases treated with laparo-endoscopic single-site surgery: A multicentric retrospective study - Accepted Manuscript

2012-01-30

Abstract: Objective: To assess feasibility and perioperative outcomes for Laparo-Endoscopic-Single-Site (LESS) surgery in early endometrial cancer. Study Design: Retrospective multicentric study of 100 early endometrial cancer cases undergoing LESS surgery between July 2009 and July 2011. Results: All patients underwent total hysterectomy and bilateral salpingo-oophorectomy by LESS. Pelvic and paraaortic lymphadenectomy were performed in 48 and 27 patients respectively. A median of 16 pelvic lymph nodes (Range: 1-33) and 7 paraaortic lymph nodes (Range: 2-28) were retrieved. Both median operative time (129 minutes;range 45-321). and estimated blood loss (70 ml;range 10-500) were greater when staging lymphadenectomy were performed (p values=0.001). Four intra operative and 4 post-operative complications were observed. Conversion to standard laparoscopy and laparotomy were necessary for completion of one case each. Patients responded positively regarding cosmetic result and minimal postoperative pain control. Conclusion: LESS further minimizes the invasive nature of surgery and is feasible for treatment of early-stage endometrial cancer.

The Adipokine Apelin and Human Uterine Contractility - Accepted Manuscript

Mark P. Hehir, John J. Morrison — 2012-01-30

Abstract: Objective: Obesity is an increasing problem in obstetric practice. Apelin, secreted by adipocytes, is present in increased serum concentrations in an obese state. Our group has previously highlighted that the adipokines leptin and ghrelin have a potential role in metabolic modulation of uterine contractility in obese women. The aim of this study was to evaluate the effects of apelin on human uterine contractility in vitro. Method: Biopsies of human myometrium were obtained at elective cesarean section. Myometrial strips suspended under isometric conditions, undergoing spontaneous and oxytocin-induced contractions, were exposed to cumulative additions of apelin in the concentration range of 1nmol/L to 1µmol/L. Control experiments were performed simultaneously. Results: Apelin exerted an inhibitory effect on spontaneous and oxytocin induced contractions in human myometrium. The mean maximal inhibition values were: 36.8±6.4% for spontaneous (n=6;P=0.002), and 30.4±4.6% for oxytocin-induced contractions (n=6;P<0.0001). Conclusion: Apelin inhibits human uterine contractility in vitro, raising the possibility that such metabolic modulation may play a physiological role in obese parturients.

Chromosome-selective sequencing of maternal plasma cell-free DNA for first-trimester detection of trisomy 21 and trisomy 18 - Accepted Manuscript

2012-01-27

Abstract: Objective: To assess the prenatal detection rate of trisomies 21 and 18 and false positive rate by chromosome-selective sequencing of maternal plasma cell-free DNA (cfDNA). Study design: Nested case-control study of cfDNA was examined in plasma obtained before chorionic villous sampling from 300 euploid, 50 trisomy 21 and 50 trisomy 18 pregnancies at 11-13 weeks. Laboratory personnel were blinded to fetal karyotype. Results: Risk scores for trisomy 21 and trisomy 18 were given for 397 of the 400 samples that were analyzed. In all 50 cases of trisomy 21 the risk score for trisomy 21 was ≥99% and the risk score for trisomy 18 was ≤0.01%. In all 50 cases of trisomy 18 the risk score for trisomy 21 was ≤0.01% and the risk score for trisomy 18 was ≥99% in 47 cases, 98.8% in one, 88.5% in one and 0.11% in one. In 3 (1%) of the 300 euploid pregnancies no risk score was provided because there was failed amplification and sequencing. In the remaining 297 the risk score for trisomy 21 was ≤0.01% and the risk score for trisomy 18 was ≤0.01% in 295 cases, 0.04% in one and 0.23% in one. Therefore, the sensitivity for detecting trisomy 21 was 100% (50/50), the sensitivity for trisomy 18 was 98% (49/50) and the specificity was 100% (297/297). Conclusion: In this study, chromosome-selective sequencing of cfDNA separated all cases of trisomy 21 and 98% of trisomy 18 from euploid pregnancies.

Non-invasive Prenatal Detection and Selective Analysis of Cell-free DNA Obtained from Maternal Blood: Evaluation for Trisomy 21 and Trisomy 18 - Accepted Manuscript

Andrew B. Sparks, Craig A. Struble, Eric T. Wang, Ken Song, Arnold Oliphant — 2012-01-27

Abstract: Objective: To develop a novel biochemical assay and algorithm for the prenatal evaluation of risk for fetal trisomy 21 and 18 using cell-free DNA obtained from maternal blood. Study Design: We assayed cfDNA from a training set and a blinded validation set of pregnant women, comprising 250 disomy, 72 trisomy 21 (T21), and 16 trisomy 18 (T18) pregnancies. We used Digital ANalysis of Selected Regions (DANSR) in combination with a novel algorithm, Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE) to determine trisomy risk for each subject. Results: 163/171 subjects in the training set passed quality control (QC) criteria. Using a Z statistic, 35/35 T21 cases and 7/7 T18 cases had Z statistic >3 and 120/121 disomic cases had Z statistic <3. FORTE produced an individualized trisomy risk score for each subject, and correctly discriminated all T21 and T18 cases from disomic cases. All 167 subjects in the blinded validation set passed QC and FORTE performance matched that observed in the training set correctly discriminating 36/36 T21 cases and 8/8 T18 cases from 123/123 disomic cases. Conclusions: DANSR and FORTE enable accurate, scalable non-invasive fetal aneuploidy detection.

Is comprehensive surgical staging needed for thorough evaluation of early stage ovarian carcinoma? (Journal Club article for discussion March 2012 re: W11-0302) - Accepted Manuscript

Linda Van Le, George A. Macones — 2012-01-25

Is comprehensive surgical staging needed for thorough evaluation of early stage ovarian carcinoma? (Journal Club article for discussion March 2012 re: W11-0302) - Accepted Manuscript

George A. Macones — 2012-01-24

Impact of fetal gender on the labor curve - Corrected Proof

2012-01-24

Objective: We sought to estimate the association between fetal gender and first-stage labor curve at term. Study Design: Within a large, retrospective cohort study of consecutive, singleton term labor patients who delivered in the second stage, we compared the active phase of first-stage labor by fetal gender. The primary outcome was length of active stage 1. Interval-censored regression was used to estimate the effect of fetal gender on the duration of active first stage (4-10 cm) and was adjusted for relevant covariates. Results: Of 2400 women, 2373 women had complete labor information and were available for this analysis. Male gender was associated with both a statistically significantly longer active first stage of labor (4.6 vs 4.0 hours; P = .002) and stratified analyses by parity and labor type. Conclusion: Male fetuses are associated with longer active phase of the first stage of labor and, specifically, may need to be considered in the setting of arrest diagnoses.

Outcomes of Late Preterm Birth: Who is at Risk and for What? - Accepted Manuscript

H. Gerry Taylor — 2012-01-24

Intrauterine transfusion for Parvovirus B19 infection: Long-term neurodevelopmental outcome - Accepted Manuscript

2012-01-19

Abstract: Objective: To evaluate long-term neurodevelopmental outcome of children treated with intrauterine transfusions for fetal anemia due to parvovirus B19 infection. Study design: Children treated with intrauterine transfusions for fetal anemia due to parvovirus B19 infection underwent standardized age-appropriate neurodevelopmental testing. Main outcome was the incidence of neurodevelopmental impairment. Results: Twenty-eight children were evaluated at a median age of 5 years (range 1.5-13 years). Neurodevelopmental impairment was diagnosed in 3/28 (11%) children, including one child with combined cerebral palsy and severe developmental delay and two children with isolated severe developmental delay. Conclusion: Neurodevelopmental impairment in children treated with intrauterine transfusion for parvovirus B19 infection is increased compared to the general population. Large long-term follow-up studies are required to determine potential risk factors.

Robotic surgical staging for obese patients with endometrial cancer - Accepted Manuscript

2012-01-16

Abstract: Objective: To compare surgical outcomes for robotic versus laparotomy staging in obese endometrial cancer patients. Study design: This was a retrospective cohort study of patients with body mass index ≥ 30 kg/m2 staged in a community gynecologic oncology practice. Patients undergoing robotic staging were compared with historic laparotomy controls. Results: 129 patients underwent robotic staging, compared with 110 laparotomy patients. The robotic cohort had fewer abdominal wound complications (13.9% vs 32.7%, p < .001), but more vaginal cuff complications (4.7% vs 0, p = .032). Blood loss was lower in the robotic group (p <.001), as was length of stay (p <.001). Surgical times were longer in the robotic group (p <.001). There was no difference in terms of percentage of patients undergoing pelvic or para-aortic lymph node dissection. Conclusions: Robotic staging for endometrial cancer is feasible in obese women, with fewer abdominal wound complications, but more vaginal cuff complications.

Unintended Consequences: The Story of Healthcare in the United States - Accepted Manuscript

Robert P. Prins — 2012-01-16

The microbial burden of genital mycoplasmas and intensity of intraamniotic inflammation - Accepted Manuscript

2012-01-16

Abstract: Objective: To determine whether the bacterial load of genital mycoplasmas and gestation age are related to intraamniotic inflammatory response using the amniotic fluid levels of 18 inflammatory mediators. Study design: A prospective study of 145 women with singleton pregnancies complicated by preterm prelabor rupture of membranes between 240/7 and 366/7 weeks was conducted. Amniotic fluid was obtained from all women by transabdominal amniocentesis. The amounts of genital mycoplasmas DNA were determined using the threshold cycle value, relative and absolute quantification techniques. A panel of multiple proteins was analyzed simultaneously using multiplex technology. Results: Twenty-four women with the presence of genital mycoplasmas in amniotic fluid were included in the final analyses. The concentrations of 9 of the 18 evaluated proteins in the amniotic fluid correlated with bacterial load of genital mycoplasmas independent of the quantification technique employed. Conclusions: The intensity of intraamniotic inflammatory response to genital mycoplasmas decreased with gestational age.

Presidential Address: Obesity and Implications for Future Generations - Accepted Manuscript

Gayle Olson — 2012-01-16

The natural history of pelvic vein thrombosis on magnetic resonance venography after vaginal delivery - Corrected Proof

Hisham Khalil, Leonard Avruch, Andre Olivier, Mark Walker, Marc Rodger — 2012-01-16

Objective: Venous thromboembolism constitutes the leading cause of direct maternal mortality in the developed world. To date, there are no studies using magnetic resonance venography (MRV) to delineate the incidence and natural history of intraluminal filling defects in the postpartum period in patients with low thrombosis risk. Study design: This was a prospective cohort study of women at low thrombosis risk postvaginal delivery undergoing MRV in the early postpartum period. Results: In 30 eligible and consenting participants, independently adjudicated MRV, conducted on a median of postpartum day 1, identified definite thrombosis in 30% (95% confidence interval [CI], 13.6–46.4%) of study participants. All episodes of definite thrombosis were identified in the iliac and ovarian veins. Probable thrombosis was identified in an additional 27% of study participants (95% CI, 10.3–41.7%), and possible thrombosis in an additional 10% (95% CI, 0–20.7%). Conclusion: In this group of low-risk postpartum patients, we identified a high prevalence of definite pelvic vein intraluminal filling defects of uncertain clinical significance. This study suggests that some degree of pelvic vein intraluminal filling defect may be a normal finding after uncomplicated vaginal delivery.

Early detection of placental inflammation by MRI enabling protection by clinically relevant IL-1Ra administration - Corrected Proof

Sylvie Girard, Luc Tremblay, Martin Lepage, Guillaume Sebire — 2012-01-16

Objective: We studied whether magnetic resonance imaging (MRI) could be used to detect placental inflammation before the detection of irreversible tissue damage. Next, we tested whether this early detection would enable the administration of treatment (ie, interleukin-1 receptor antagonist [IL-1Ra]) in a realistic clinical time after diagnosis. Study Design: Pregnant rats were injected intraperitoneally with lipopolysaccharide with/without delayed IL-1Ra. MRI was performed at different time after the injection, and placentas were collected for comparison. Placental inflammation was assessed by determination of the levels of inflammatory cytokines. Results: Placental inflammation was detected by MRI as early as 3 hours after maternal administration of lipopolysaccharide, concomitantly to IL-1β up-regulation. This was observed before any tissue damage, which appeared only at 24 hours after the administration of lipopolysaccharide. Delayed IL-1Ra administration (after MRI diagnosis) protected the placenta, as seen by the preserved tissue integrity and limited macrophages infiltration in the placental parenchyma. Conclusion: These findings established a noninvasive diagnostic method for early in utero detection of placental inflammation that would allow the administration of placentoprotective intervention within a clinically relevant delay after diagnosis.

Haptoglobin Phenotype, Angiogenic Factors and Preeclampsia Risk - Accepted Manuscript

2012-01-16

Abstract: Objectives:: To determine whether haptolgobin phenotype is related to preeclampsia risk, or to plasma concentrations of soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF). Study Design:: Haptoglobin phenotype was retrospectively determined in primiparous women with uncomplicated pregnancies (n=309), gestational hypertension (n=215) and preeclampsia (n=249). Phenotype was assessed by peroxidase staining following native polyacrylamide gel electrophoresis of hemoglobin-supplemented serum. Results:: Compared to haptoglobin 1-1, haptoglobin 2-1 was associated with a significantly increased risk of preeclampsia (odds ratio (95% confidence interval) 2.11 (1.07, 4.18)) and term preeclampsia (2.45 (1.07, 5.83)) in Caucasian women. Haptoglobin phenotype was not associated with preeclampsia risk in African Americans. Preeclamptic women had higher plasma sEng and sFlt-1, and lower PlGF, than controls. sEng, sFlt-1 and PlGF did not differ among women of different haptoglobin phenotypes. Conclusion:: Haptoglobin 2-1 is associated with higher preeclampsia risk in primiparous Caucasian women.

Safety of laparoscopy versus laparotomy in the surgical staging of endometrial cancer: A systematic review and meta-analysis of randomized controlled trials - Accepted Manuscript

Fulvio Zullo, Angela Falbo, Stefano Palomba — 2012-01-16

Abstract: The aim of the current study was to compare the safety of the laparoscopic versus abdominal approach to staging endometrial cancer. A search was conducted for randomized controlled trials (RCTs) that reported data from women with histologically confirmed endometrial cancer who underwent laparoscopic or abdominal surgery. An additional meta-analysis was performed. The primary end-points were the rates of intraoperative and postoperative complications. A total of eight original RCTs were included in the final analysis. No significant difference was observed in the relative risk (RR) for intraoperative complications between laparoscopy and laparotomy (RR=1.25, 95% CI 0.99 to 1.56, P =0.062). In contrast, a significant advantage of laparoscopy over laparotomy was obtained in terms of postoperative complications (RR=0.71, 95% CI 0.63 to 0.79, P=0.016). In comparison with abdominal surgery, the safety of the laparoscopic approach for surgical staging of endometrial cancer is similar in terms of intraoperative complications but results in fewer postoperative complications.

Human birth observed in real-time open magnetic resonance imaging - Accepted Manuscript

2012-01-16

Abstract: Objective:: Knowledge about the mechanism of labor is based on assumptions and radiographic studies performed decades ago. The goal of this study was to describe the relationship between the fetus and the pelvis as the fetus travels through the birth canal, using an open Magnetic Resonance Imaging (MRI) scanner. Study design:: Real-time MRI series during delivery of the fetal head. Results:: Delivery occurred by progressive head extension. However, extension was a very late movement that was observed when the occiput was in close contact with the inferior margin of the symphysis pubis, occuring simultaneously with gliding downward of the fetal head. Conclusion:: This observational study shows, for the first time, that birth can be analyzed with real-time MRI. MRI technology allows assessment of maternal and fetal anatomy during labor and delivery.

Re: Levator avulsion using a tomographic ultrasound and magnetic resonance-based model - Accepted Manuscript

Kim W.M. Van Delft, Ranee Thakar, Abdul H. Sultan — 2012-01-16

The Natural History of Pelvic Vein Thrombosis – The Natural History of Involution? - Accepted Manuscript

Andra H. James — 2012-01-16

Neonatal morbidity after induction versus expectant monitoring in intrauterine growth restriction at term – a subanalysis of the DIGITAT RCT - Accepted Manuscript

2012-01-16

Abstract: Objective: The DIGITAT-trial compared induction of labor and expectant management in suspected intrauterine growth restriction (IUGR) at term. In this sub-analysis, we report neonatal morbidity between the policies based on the morbidity assessment index for newborns (MAIN). Study design: We used data from the DIGITAT-trial, For each neonate, we calculated the MAIN score, a validated outcome scale. Results: There were no differences in mean MAIN scores, nor in MAIN morbidity categories. We found that neonatal admissions are lower after 38 weeks gestational age compared to 36 and 37 weeks in both groups. Conclusions: The incidence of neonatal morbidity in IUGR at term is comparable and relatively mild either after induction or after an expectant policy. However, neonatal admissions are lower after 38 weeks of pregnancy, so if induction to pre-empt possible stillbirth is considered, it is reasonable to delay until 38 weeks, provided watchful monitoring.

A novel training model for the loop electrosurgical excision procedure - Accepted Manuscript

2012-01-16

The Expression of Antioxidant Enzymes in a Mouse Model of Fetal Alcohol Syndrome - Accepted Manuscript

2012-01-16

Abstract: Objective: Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) prevent cellular damage produced by free radicals. Our objective was to evaluate if prenatal alcohol exposure decreased the expression of antioxidant enzymes in the brain, liver or placenta of fetal mice. Study Design: Timed, pregnant C57BL6/J mice were treated on gestational day 8 (E8) with intraperitoneal injection of alcohol (0.03 ml/g) or saline (control). Fetuses were harvested on E18. Fetal brain, liver and placenta were analyzed for mRNA expression of SOD, GPx and CAT by real-time PCR, with 18S RNA used as reference. Results: SOD, GPx and CAT expression was lower in fetal brains exposed to alcohol with no differences detected in the liver or placenta between the two groups. Conclusion: Maternal alcohol consumption causes a decrease in SOD, GPx and CAT expression in the fetal brain. This may explain the long term neurologic findings in fetal alcohol syndrome.

Is comprehensive surgical staging needed for thorough evaluation of early stage ovarian carcinoma? (Journal Club article for discussion March 2012 re: W11-0302) - Accepted Manuscript

George A. Macones — 2012-01-16

Rapid Progression Of Pelvic Organ Prolapse After High Dose Glucocorticoid Initiation - Accepted Manuscript

Emily S. Zoulek, Deborah R. Karp, G. Willy Davila — 2012-01-06

Decreased brachial plexus palsy after institution of shoulder dystocia protocol - Corrected Proof

Russ Jelsema — 2012-01-05

In the recent study evaluating outcomes after instituting a shoulder dystocia protocol that included 5 components, the authors describe a “reduced frequency of brachial plexus palsy when a shoulder dystocia occurred.” I have several questions for the authors:

Reply - Corrected Proof

William A. Grobman — 2012-01-05

We would like to thank Dr Jelsema for his interest in our article as well as the questions he has asked. During time periods A, B, and C of the study, the cesarean rates were 27.1%, 28.2%, and 29%, respectively. This change in the point estimate was not statistically significant (P = .12). Even if statistical significance had been reached, we do not believe this would explain a decrease in the frequency of brachial plexus palsy documented given the denominator for the frequency was “per shoulder dystocia,” and that the frequency of shoulder dystocia per delivery did not change over time. The protocol itself was focused upon the team response to the shoulder dystocia and did not convey specific maneuvers, or order of maneuvers, that should be employed in the management of the shoulder dystocia. Thus, providers' judgment was relied upon to determine what maneuvers and traction were employed.

2009 H1N1 vaccination by pregnant women during the 2009-10 H1N1 influenza pandemic - Corrected Proof

2012-01-03

Objective: Pregnant women were identified at greater risk and given priority for 2009 H1N1 vaccination during the 2009 through 2010 H1N1 pandemic. We identified factors associated with acceptance or refusal of 2009 H1N1 vaccination during pregnancy. Study design: We conducted an in-person survey of postpartum women on the labor and delivery service from June 17 through Aug. 13, 2010, at 4 New York hospitals. Results: Of 1325 survey respondents, 34.2% received 2009 H1N1 vaccination during pregnancy. A provider recommendation was most strongly associated with vaccine acceptance (odds ratio [OR], 19.4; 95% confidence interval [CI], 12.7–31.1). Also more likely to take vaccine were women indicating the vaccine was safe for the fetus (OR, 12.4; 95% CI, 8.3–19.0) and those who previously took seasonal flu vaccination (OR, 7.9; 95% CI, 5.8–10.7). Race, education, income, and age were less important in accepting vaccine. Conclusion: Greater emphasis on vaccine safety and provider recommendation is needed to increase the number of women vaccinated during pregnancy.

Serum levels of the ovarian cancer biomarker HE4 are decreased in pregnancy and increase with age - Corrected Proof

2012-01-03

Objective: The purpose of this study was to establish normal ranges for human epididymis protein 4 (HE4) serum levels in healthy women. Study Design: HE4 levels were measured in healthy women and analyzed by age, menopausal status, and pregnancy status. Upper 95th percentiles were determined for normal ranges. Results: Serum samples from 1101 healthy women and 67 pregnant women were analyzed. Above the age of 40 years significant elevations in HE4 concentrations emerged with advancing age. The upper 95th percentile for HE4 levels was 89 pmol/L for premenopausal women, 128 pmol/L for postmenopausal women, and 115 pmol/L for all women. There was a significant difference in the median serum HE4 levels in premenopausal women (46.6 pmol/L) compared with postmenopausal women (57.6 pmol/L; P < .001). In pregnant women, median HE4 concentrations were significantly lower than their premenopausal counterparts (P < .001). Conclusion: HE4 serum concentrations vary significantly on the basis of age. These variations must be considered when the upper limit of normal for HE4 is determined.

Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders - Corrected Proof

2012-01-03

Objective: The human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancer. This study measured the HE4 and CA125 levels in women with benign gynecological disorders. Study Design: Sera were obtained from women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with elevated biomarker levels were compared. Results: There were 1042 women with benign disease. HE4 levels were less often elevated than CA125 (8% vs 29%, P < .001). A marked difference was observed in patients with endometriosis in which HE4 was elevated in 3% of patients and CA125 in 67% (P < .0001). Serous ovarian tumors were associated with elevated levels of HE4 in 8% of patients and CA125 in 20% (P = .0002); uterine fibroids in 8% vs 26% (P = .0083); dermoids in 1% vs 21% (P = .0004); and inflammatory disease in 10% vs 37% (P = .014). Conclusion: HE4 is elevated less frequently than CA125 in benign disease, particularly in premenopausal patients.

Occupational exposures among nurses and risk of spontaneous abortion - Corrected Proof

2012-01-03

Objective: We investigated self-reported occupational exposure to antineoplastic drugs, anesthetic gases, antiviral drugs, sterilizing agents (disinfectants), and X-rays and the risk of spontaneous abortion in US nurses. Study Design: Pregnancy outcome and occupational exposures were collected retrospectively from 8461 participants of the Nurses' Health Study II. Of these, 7482 were eligible for analysis using logistic regression. Results: Participants reported 6707 live births, and 775 (10%) spontaneous abortions (<20 weeks). After adjusting for age, parity, shift work, and hours worked, antineoplastic drug exposure was associated with a 2-fold increased risk of spontaneous abortion, particularly with early spontaneous abortion before the 12th week, and 3.5-fold increased risk among nulliparous women. Exposure to sterilizing agents was associated with a 2-fold increased risk of late spontaneous abortion (12-20 weeks), but not with early spontaneous abortion. Conclusion: This study suggests that certain occupational exposures common to nurses are related to risks of spontaneous abortion.

Care of the human immunodeficiency virus–infected menopausal woman - Corrected Proof

Helen Elizabeth Cejtin — 2012-01-03

More women than ever before are both human immunodeficiency virus infected and menopausal, because of increased survival and more frequent diagnosis in older women. Such a woman has the combined burden of her infection, its treatment, comorbid conditions, and aging. Thus, she is at risk for a variety of problems, such as disorders of bone mineral density and deficiencies in cognitive functioning. In addition to this, she experiences menopause in a unique fashion, with more symptoms and perhaps at an earlier age. The clinician caring for her must take a proactive approach to this multitude of factors that may affect her health and well-being.

Adenosine plasma levels in the fetoplacental circulation in preeclampsia - Corrected Proof

Carlos Escudero, Luis Sobrevia — 2012-01-03

We have read with much interest the article by Espinoza et al in which they reanalyzed data regarding high umbilical adenosine plasma level in fetuses from pregnancies coursing with preeclampsia that were presented in this Journal by the same group in 2 different articles in 1994 and 1996. We here intend to contribute to the discussion by incorporating ideas into the complex regulatory scenario that modulates the human umbilical adenosine level. In consequence with the proposal of Espinoza et al, the high extracellular level of adenosine that results from reduced expression and activity of human equilibrative nucleoside transporters 1 were described, for the first time, by our groups in primary cultures of human placental microvascular endothelial cells (hPMEC) from preeclampsia. We then hypothesized an abnormal adenosine handling by the fetoplacental circulation in this syndrome. However, this possibility raises the question of where adenosine is coming from? Accordingly, in hPMEC from preeclampsia, we recently have found altered adenosine-nucleotides catabolism compared with normal pregnancies (Escudero C, Sobrevia L, unpublished data). Nevertheless, whether these purines cross the placental barrier towards the maternal circulation and participate in the pathophysiologic condition of preeclampsia is unclear. However, it is intriguing that adenosine and purine metabolism is associated with high uric acid plasma levels in women who are given a diagnosis of preeclampsia; and adenosine triphosphate infusion generates a preeclampsia-like disease in rats. Another emerging question is what is adenosine controlling in the fetoplacental circulation? Since adenosine induces vasodilatation or vasoconstriction in several vascular beds (including the human placenta) and regulates angiogenesis, it is likely that a high adenosine level in the fetoplacental circulation in preeclampsia is an adaptive response that courses with placental angiogenesis in coordination with changes in maternal blood flow. This was proposed by our group in a review in 2009 and agrees with the study of Espinoza et al. However, because there is no literature that demonstrates a direct relationship among those effects, further studies to characterize the involved mechanisms are required. Thus, we certainly reinforce the importance of addressing adenosine roles in the pathophysiologic condition of maternal and fetal vascular dysfunction in preeclampsia and aim to encourage informed discussion in the field retouched by Espinoza et in their recent review in this Journal.

Reply - Corrected Proof

Jimmy Espinoza, Andres F. Espinoza, Gordon G. Power — 2012-01-03

We thank Drs Escudero and Sobrevia for their interest in our article regarding high fetal plasma adenosine levels in patients with preeclampsia. There is accumulating evidence that adenosine may be implicated in the mechanisms of disease in preeclampsia. This includes our work in the 1990s, the more recent work of Dr Escudero et al, and contributions from others. Our recent article specifically focuses on the potential role of the fetus in preeclampsia and not on the role of the placenta. In this regard, we quoted relevant contributions that included an elegant in vitro study that suggested that reduced placental blood flow is associated with increased concentrations of circulating fetal adenosine and a more recent report that indicated that adenosine signaling may be important in the placental release of sFlt-1, which is an antiangiogenic factor that is implicated in preeclampsia. In the letter to the editor Drs Escudero and Sobrevia quote their 2009 review in which they wrote “umbilical and maternal blood levels of adenosine are higher in mild and severe preeclampsia compared with normal pregnancies.” However, none of the articles quoted, including several from our group, specifically compare the fetal plasma adenosine in normal pregnancies with that from patients with preeclampsia. This is precisely 1 of the novelties of our recent report. Furthermore, we indicated that it is the subset of patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia that account for the observed differences. Thus, we have not “retouched” the relevance of adenosine in preeclampsia, but using teleologic reasoning, we have reanalyzed our old data to provide a new conceptual framework whereby the fetus may play a central role in the pathophysiologic condition of preeclampsia. We agree strongly with the need for additional studies to further characterize the nature of fetal signaling in patients with preeclampsia, in particular in those without sonographic evidence of chronic uteroplacental ischemia.

Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus–associated birth defects - Corrected Proof

2011-12-29

Objective: The purpose of this study was to examine the risk of birth defects in relation to diabetes mellitus and the lack of use of periconceptional vitamins or supplements that contain folic acid. Study Design: The National Birth Defects Prevention Study (1997-2004) is a multicenter, population-based case-control study of birth defects (14,721 cases and 5437 control infants). Cases were categorized into 18 types of heart defects and 26 noncardiac birth defects. We estimated odds ratios for independent and joint effects of preexisting diabetes mellitus and a lack of periconceptional use of vitamins or supplements that contain folic acid. Results: The pattern of odds ratios suggested an increased risk of defects that are associated with diabetes mellitus in the absence vs the presence of the periconceptional use of vitamins or supplements that contain folic acid. Conclusion: The lack of periconceptional use of vitamins or supplements that contain folic acid may be associated with an excess risk for birth defects due to diabetes mellitus.

Failing To Prevent Birth Defects Caused by Maternal Diabetes - Accepted Manuscript

Godfrey P. Oakley — 2011-12-29

Successful frozen blastocyst transfers after failed fresh transfers in assisted reproductive technologies patients with hydrosalpinx - Corrected Proof

Carolina M. Sueldo, Amin A. Milki, Ruth B. Lathi — 2011-12-29

Untreated hydrosalpinx is known to decrease in vitro fertilization success. We report on 4 patients with hydrosalpinx for whom fresh transfers of 11 good quality embryos did not produce a pregnancy; however, frozen blastocyst transfers in natural cycles resulted in several successful pregnancies, with an implantation rate of 60% (9/15 blastocysts implanted).