May 2014 ABOG List Page 1

ABOG Reading List: May 2014

The following ABOG Maintenance of Certification reading list is provided to you by the Mercer

University Medical Library. This list contains citations followed by the abstracts and

commentaries of articles when available. To access the full-text of library-subscribed content,

click the icon. If you are accessing from off campus, you will be

prompted to login with your library username and password. If you do not know your library

login, have issues accessing an article, or wish to request an article via ILL, please email the

library at reference.ill@gain.mercer.edu.

Gynecology:

1) Am J Obstet Gynecol. 2013 Nov;209(5):490.e1-9. doi: 10.1016/j.ajog.2013.06.018. Epub 2013

Jun 13.

Surgical site infection after hysterectomy.

Lake AG1, McPencow AM, Dick-Biascoechea MA, Martin DK, Erekson EA. Author information Abstract OBJECTIVE: Our objective was to estimate the occurrence of surgical site infections (SSI) after hysterectomy and the associated risk factors.

STUDY DESIGN: We conducted a cross-sectional analysis of the 2005-2009 American College of Surgeons National Surgical Quality Improvement Program participant use data files to analyze hysterectomies. Different routes of hysterectomy were compared. The primary outcome was to identify the occurrence of 30-day superficial SSI (cellulitis) after hysterectomy. Secondary outcomes were the occurrence of deep and organ-space SSI after hysterectomy. Logistic regression models were conducted to further explore the associations of risks factors with SSI after hysterectomy.

RESULTS: A total of 13,822 women were included in our final analysis. The occurrence of postoperative cellulitis after hysterectomy was 1.6% (n = 221 women). Risk factors that were associated with cellulitis were route of hysterectomy with an adjusted odds ratio (AOR) of 3.74 (95% confidence interval [CI], 2.26-6.22) for laparotomy compared with the vaginal approach, operative time >75th percentile (AOR, 1.84; 95% CI, 1.40-2.44), American Society of Anesthesia class ≥ 3 (AOR, 1.79; 95% CI, 1.31-2.43), body mass index ≥40 kg/m(2) (AOR, 2.65; 95% CI, 1.85-3.80), and

May 2014 ABOG List Page 2

diabetes mellitus (AOR, 1.54; 95% CI, 1.06-2.24) The occurrence of deep and organ-space SSI was 1.1% (n = 154 women) after hysterectomy.

CONCLUSION: Our finding of the decreased occurrence of superficial SSI after the vaginal approach for hysterectomy reaffirms the role for vaginal hysterectomy as the route of choice for hysterectomy.

KEYWORDS:

hysterectomy, outcome, postoperative complication, surgical site infection

PMID: 23770467 [PubMed - indexed for MEDLINE]

2) Obstet Gynecol. 2014 Jan;123(1):96-103. doi: 10.1097/AOG.0000000000000024.

Oral antibiotics to prevent postoperative urinary tract infection: a randomized controlled trial.

Dieter AA1, Amundsen CL, Edenfield AL, Kawasaki A, Levin PJ, Visco AG, Siddiqui NY. Author information

Erratum in

Obstet Gynecol. 2014 Mar;123(3):669.

Abstract OBJECTIVE: To evaluate whether nitrofurantoin prophylaxis prevents postoperative urinary tract infection (UTI) in patients receiving transurethral catheterization after pelvic reconstructive surgery.

METHODS: In a randomized, double-blind, placebo-controlled trial, participants undergoing pelvic reconstructive surgery were randomized to 100 mg nitrofurantoin or placebo once daily during catheterization if they were: 1) discharged with a transurethral Foley or performing intermittent self-catheterization; or 2) hospitalized overnight with a transurethral Foley. Our primary outcome was treatment for clinically suspected or culture-proven UTI within 3 weeks of surgery. Statistical analysis was performed by χ2 and logistic regression. Assuming 80% power at a P value of .05, 156 participants were needed to demonstrate a two-thirds reduction in UTI.

RESULTS: Of 159 participants, 81 (51%) received nitrofurantoin and 78 (49%) received placebo. There were no significant differences in baseline demographics, intraoperative characteristics,

May 2014 ABOG List Page 3

duration and type of catheterization, or postoperative hospitalization, except a lower rate of hysterectomy in the nitrofurantoin group. Nitrofurantoin prophylaxis did not reduce the risk of UTI treatment within 3 weeks of surgery (22% UTI with nitrofurantoin compared with 13% UTI with placebo, relative risk 1.73, 95% confidence interval 0.85-3.52, P=.12). Urinary tract infection treatment was higher in premenopausal women, lower in diabetics, and increased with longer duration of catheterization. In logistic regression adjusting for menopause, diabetes, preoperative postvoid residual volume, creatinine clearance, hysterectomy, and duration of catheterization, there was still no difference in UTI with nitrofurantoin as compared with placebo.

CONCLUSION: Prophylaxis with daily nitrofurantoin during catheterization does not reduce the risk of postoperative UTI in patients receiving short-term transurethral catheterization after pelvic reconstructive surgery.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01450800.

LEVEL OF EVIDENCE: I.

PMID: 24463669 [PubMed - indexed for MEDLINE]

3) Obstet Gynecol. 2014 Jan;123(1):57-64. doi: 10.1097/AOG.0000000000000056.

High-risk and low-risk human papillomavirus and the absolute risk of cervical intraepithelial

neoplasia or cancer.

Thomsen LT1, Frederiksen K, Munk C, Junge J, Castle PE, Iftner T, Kjaer SK.

Author information Abstract OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test.

METHODS: In this prospective cohort study, consecutive liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up to 10.5 years for development of CIN 3 or worse.

RESULTS:

May 2014 ABOG List Page 4

The 8-year absolute risk of CIN 3 or worse was 1.1% (95% confidence interval [CI] 1.0-1.3%) for HPV-negative women; 1.7% (0.8-2.6%) for low-risk HPV-positive women without concurrent high-risk HPV; 17.4% (16.4-18.5%) for high-risk HPV-positive women without concurrent low-risk HPV; and 15.9% (13.5-18.3%) for women with concurrent high-risk and low-risk HPV. The 8-year absolute risk of CIN 3 or worse after a negative high-risk HPV test (irrespective of low-risk HPV status) was lower than after a normal cytology result among women aged younger than 30 years (3.5% [95% CI, 2.9-4.0%] compared with 6.9% [6.2-7.5%], P<.001) and women aged 30 years or older (0.7% [95% CI, 0.6-0.9%] compared with 1.8% [95% CI, 1.6-2.0%], P<.001).

CONCLUSION: A negative high-risk HPV test provides greater long-term reassurance against CIN 3 or worse than normal cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types.

LEVEL OF EVIDENCE: II.

PMID: 24463664 [PubMed - indexed for MEDLINE]

4) Obstet Gynecol. 2014 Mar;123(3):585-92. doi: 10.1097/AOG.0000000000000144.

Effects of age, parity, and device type on complications and discontinuation of intrauterine devices.

Aoun J1, Dines VA, Stovall DW, Mete M, Nelson CB, Gomez-Lobo V. Author information Abstract OBJECTIVE: To conduct an analysis of intrauterine device (IUD)-related outcomes including expulsion, contraceptive failure, and early discontinuation and to compare these outcomes in regard to age, parity, and IUD type.

METHODS: This was a multicenter retrospective chart review of adolescents and women aged 13-35 years who had an IUD inserted for contraception between June 2008 and June 2011.

RESULTS: A total of 2,523 patients' charts were reviewed. Of these, 2,138 patients were included in our analysis. After a mean follow-up of 37±11 months, the overall rates of IUD expulsion and pregnancy were 6% and 1%, respectively, and were not significantly different by age or parity. Intrauterine device discontinuation rates were 19% at 12 months and 41% after a mean follow-up of 37 months. Despite similar rates of IUD discontinuation between age groups at 12 months of use, teenagers and young women aged 13-19 years were more likely to request early discontinuation at the end of the total follow-up period. No significant difference was noted in pelvic inflammatory disease rates (2%) based on age. After adjusting for age and parity, we

May 2014 ABOG List Page 5

found that copper IUD users were more likely to experience expulsion and contraception failure compared with levonorgestrel intrauterine system users (hazard ratios 1.62, 95% confidence interval [CI] 1.06-2.50 and hazard ratios 4.89, 95% CI 2.02-11.80, respectively).

CONCLUSION: Similar to adults, IUD use in adolescents and nulliparous women is effective and associated with low rates of serious complications. Health practitioners should therefore consider IUDs for contraception in all females. Teenagers and young women are more likely to request premature discontinuation of their IUDs and may benefit from additional counseling.

PMID: 24499755 [PubMed - indexed for MEDLINE]

5) Am J Obstet Gynecol. 2014 May;210(5):480.e1-8. doi: 10.1016/j.ajog.2013.12.040. Epub 2013

Dec 28.

Findings of universal cystoscopy at incontinence surgery and their sequelae.

Zyczynski HM1, Sirls LT2, Greer WJ3, Rahn DD4, Casiano E5, Norton P6, Kim HY7, Brubaker

L8; Urinary Incontinence Treatment Network.

Author information Abstract OBJECTIVE: The purpose of this study was to report the frequency of abnormal cystoscopy at incontinence surgery and to identify risk factors and sequelae of injury.

STUDY DESIGN: Findings of cystoscopy were collected prospectively in 3 multicenter surgical trials. Clinical, demographic, and procedure characteristics and surgeon experience were analyzed for association with iatrogenic injury and noninjury abnormalities. Impact of abnormalities on continence outcomes and adverse events during 12 months after the procedure were assessed.

RESULTS: Abnormal findings in the bladder or urethra were identified in 95 of 1830 women (5.2%). Most injuries (75.8%) were iatrogenic. Lower urinary tract (LUT) injury was most common at retropubic urethropexy and retropubic midurethral sling (MUS) procedures (6.4% each), followed by autologous pubovaginal sling procedures (1.7%) and transobturator MUS (0.4%). Increasing age (56.9 vs 51.9 years; P = .04), vaginal deliveries (3.2 vs 2.6; P = .04), and blood loss (393 vs 218 mL; P = .01) were associated with LUT injury during retropubic urethropexy; however, only age (62.9 vs 51.4 years; P = .02) and smoking history (P = .04) were associated for pubovaginal sling procedures. No factors correlated with increased risk of injury at retropubic and transobturator MUS. Notably, previous incontinence surgery, concomitant procedures, anesthesia type, and trainee participation did not increase LUT injury frequency. Although

May 2014 ABOG List Page 6

discharge with an indwelling catheter was more common after trocar perforation compared with the noninjury group (55.6% vs 18.5%; P < .001), they did not differ in overall success, voiding dysfunction, recurrent urinary tract infections, or urge urinary incontinence.

CONCLUSION: Universal cystoscopy at incontinence surgery detects abnormalities in 1 in 20 women. Urinary trocar perforations that are addressed intraoperatively have no long-term adverse sequelae.

KEYWORDS:

cystoscopy, iatrogenic bladder injury, incontinence surgery

PMID: 24380742 [PubMed - in process]

Obstetrics:

6) Obstet Gynecol. 2014 Apr;123(4):737-44. doi: 10.1097/AOG.0000000000000177. Association of Maternal Body Mass Index, Excessive Weight Gain, and Gestational Diabetes Mellitus With Large-for-Gestational-Age Births.

Kim SY1, Sharma AJ, Sappenfield W, Wilson HG, Salihu HM. Author information Abstract OBJECTIVE: To estimate the percentage of large-for-gestational age (LGA) neonates associated with maternal overweight and obesity, excessive gestational weight gain, and gestational diabetes mellitus (GDM)-both individually and in combination-by race or ethnicity.

METHODS: We analyzed 2004-2008 linked birth certificate and maternal hospital discharge data of live, singleton deliveries in Florida. We used multivariable logistic regression to assess the independent contributions of mother's prepregnancy body mass index (BMI), gestational weight gain, and GDM status on LGA (birth weight-for-gestational age 90 percentile or greater) risk by race and ethnicity while controlling for maternal age, nativity, and parity. We then calculated the adjusted population-attributable fraction of LGA neonates to each of these exposures.

RESULTS: Large-for-gestational age prevalence was 5.7% among normal-weight women with adequate gestational weight gain and no GDM and 12.6%, 13.5% and 17.3% among women with BMIs of 25 or higher, excess gestational weight gain, and GDM, respectively. A reduction ranging between 46.8% in Asian and Pacific Islanders and 61.0% in non-Hispanic black women in LGA

May 2014 ABOG List Page 7

prevalence might result if women had none of the three exposures. For all race or ethnic groups, GDM contributed the least (2.0-8.0%), whereas excessive gestational weight gain contributed the most (33.3-37.7%) to LGA.

CONCLUSION: Overweight and obesity, excessive gestational weight gain, and GDM all are associated with LGA; however, preventing excessive gestational weight gain has the greatest potential to reduce LGA risk.

LEVEL OF EVIDENCE: III.

PMID: 24785599 [PubMed - in process]

7) Obstet Gynecol. 2014 Feb;123(2 Pt 1):372-9. doi: 10.1097/01.AOG.0000443276.68274.cc.

ACOG Practice Bulletin No.142: Cerclage for the management of cervical insufficiency.

American College of Obstetricians and Gynecologists. Abstract The inability of the uterine cervix to retain a pregnancy in the second trimester is referred to as cervical insufficiency. Controversy exists in the medical literature pertaining to issues of pathophysiology, screening, diagnosis, and management of cervical insufficiency. The purpose of this document is to provide a review of current evidence of cervical insufficiency, including screening of asymptomatic at-risk women, and to offer guidelines on the use of cerclage for management. The diagnosis and management of other cervical issues during pregnancy, such as short cervical length, are discussed more in-depth in other publications of the American College of Obstetricians and Gynecologists.

PMID: 24451674 [PubMed - indexed for MEDLINE]

8) N Engl J Med. 2014 Jan 16;370(3):254-61. doi: 10.1056/NEJMcp1103640.

Clinical practice. Prevention of preterm parturition.

Iams JD.

May 2014 ABOG List Page 8

PMID: 24428470 [PubMed - indexed for MEDLINE]

9) Am J Obstet Gynecol. 2014 Apr;210(4):319.e1-4. doi: 10.1016/j.ajog.2014.01.018. Epub 2014

Feb 20.

The relationship between primary cesarean delivery skin incision type and wound complications in women with morbid obesity.

Marrs CC1, Moussa HN2, Sibai BM2, Blackwell SC2. Author information Abstract OBJECTIVE: We sought to evaluate the relationship between skin incision, transverse or vertical, and the development of wound complications in women with morbid obesity requiring primary cesarean delivery (CD).

STUDY DESIGN: Morbidly obese women (body mass index ≥40 kg/m(2)) undergoing primary CD at ≥24 weeks' gestation were studied in a secondary analysis of a multicenter registry. Clinical characteristics and outcomes were compared between women who had transverse vs vertical skin incision. The primary outcome was composite wound complication (infection, seroma, hematoma, evisceration, fascial dehiscence) and composite adverse maternal outcome (transfusion, hysterectomy, organ injury, coagulopathy, thromboembolic event, pulmonary edema, death). Multivariable logistic regression analyses were performed to adjust for confounding factors.

RESULTS: In all, 3200 women were studied: 2603 (81%) had a transverse incision and 597 (19%) had a vertical incision. Vertical skin incision was associated with lower risk for wound complications (adjusted odds ratio, 0.32; 95% confidence interval, 0.17-0.62; P < .001) but not with composite adverse maternal outcome (adjusted odds ratio, 0.72; 95% confidence interval, 0.41-1.25; P = .24).

CONCLUSION: In morbidly obese women undergoing a primary CD, vertical skin incision was associated with a lower wound complication rate. Due to the selection bias associated with utilization of skin incision type and the observational nature of this study, a randomized controlled trial is necessary to answer this clinical question.

KEYWORDS:

cesarean delivery, morbid obesity, obesity, skin incision, wound complication

PMID: 24560557 [PubMed - in process]

May 2014 ABOG List Page 9

10) Am J Obstet Gynecol. 2014 Mar;210(3):219.e1-6. doi: 10.1016/j.ajog.2013.10.006. Epub 2013

Oct 5.

Acute pyelonephritis in pregnancy: an 18-year retrospective analysis.

Wing DA1, Fassett MJ2, Getahun D3. Author information

1Department of Obstetrics and Gynecology, University of California, Irvine, School of Medicine, Orange, CA.

2Department of Obstetrics and Gynecology, Kaiser Permanente Southern California Medical Group, West Los Angeles, CA.

3Department of Research and Evaluation, Kaiser Permanente Southern California Medical Group, Pasadena, CA; Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ.

Abstract OBJECTIVE: We sought to describe the incidence of acute pyelonephritis in pregnancy, and to assess its association with perinatal outcomes in an integrated health care system.

STUDY DESIGN: A retrospective cohort study was performed using medical records on 546,092 singleton pregnancies delivered in all Kaiser Permanente Southern California hospitals from 1993 through 2010. These medical records include the perinatal service system along with inpatient and outpatient encounter files. Adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were used to estimate associations.

RESULTS: The incidence of acute antepartum pyelonephritis was 0.5% (2894/543,430). Women with pyelonephritis in pregnancy were more likely to be black or Hispanic, young, less educated, nulliparous, initiate prenatal care late, and smoke during pregnancy. Pregnancies of women with pyelonephritis compared to those without were more likely to be complicated by anemia (26.3% vs 11.4%; OR, 2.6; 95% CI, 2.4-2.9), septicemia (1.9% vs 0.03%; OR, 56.5; 95% CI, 41.3-77.4), acute pulmonary insufficiency (0.5% vs 0.04%; OR, 12.5; 95% CI, 7.2-21.6), acute renal dysfunction (0.4% vs 0.03%; OR, 16.5; 95% CI, 8.8-30.7), and spontaneous preterm birth (10.3% vs 7.9%; OR, 1.3; 95% CI, 1.2-1.5). Most of the preterm births occurred between 33-36 weeks (9.1%).

CONCLUSION:

May 2014 ABOG List Page 10

We characterize the incidence of pyelonephritis in an integrated health care system where routine prenatal screening for asymptomatic bacteriuria is employed. Maternal complications are commonly encountered and the risk of preterm birth is higher than the baseline obstetric population.

KEYWORDS:

perinatal outcomes, pregnancy, preterm labor, pyelonephritis

PMID: 24100227 [PubMed - indexed for MEDLINE]

Office Practice (includes Cross Content & Primary Care):

11) Obstet Gynecol. 2014 Jan;123(1):202-16. doi: 10.1097/01.AOG.0000441353.20693.78.

ACOG Practice Bulletin No. 141: management of menopausal symptoms.

[No authors listed] Abstract Vasomotor and vaginal symptoms are cardinal symptoms of menopause. Vasomotor symptoms can be particularly troubling to women and are the most commonly reported menopausal symptoms, with a reported prevalence of 50-82% among U.S. women who experience natural menopause (1, 2). The occurrence of vasomotor symptoms increases during the transition to menopause and peaks approximately 1 year after the final menstrual period (3-5). The purpose of this document is to provide evidence-based guidelines for the treatment of vasomotor and vaginal symptoms related to natural and surgical menopause. (Treatment of menopausal symptoms in cancer survivors is discussed in the American College of Obstetricians and Gynecologists' Practice Bulletin Number 126, Management of Gynecologic Issues in Women With Breast Cancer.).

PMID: 24463691 [PubMed - indexed for MEDLINE]

12) JAMA. 2012 Aug 15;308(7):681-9. doi: 10.1001/jama.2012.6434.

Effect of screening for partner violence on women's quality of life: a randomized controlled trial.

May 2014 ABOG List Page 11

Klevens J1, Kee R, Trick W, Garcia D, Angulo FR, Jones R, Sadowski LS. Author information Abstract CONTEXT: Although partner violence screening has been endorsed by many health organizations, there is insufficient evidence that it has beneficial health outcomes.

OBJECTIVE: To determine the effect of computerized screening for partner violence plus provision of a partner violence resource list vs provision of a partner violence list only on women's health in primary care settings, compared with a control group.

DESIGN, SETTING, AND PARTICIPANTS: A 3-group blinded randomized controlled trial at 10 primary health care centers in Cook County, Illinois. Participants were enrolled from May 2009-April 2010 and reinterviewed 1 year (range, 48-56 weeks) later. Participants were English- or Spanish-speaking women meeting specific inclusion criteria and seeking clinical services at study sites. Of 3537 women approached, 2727 were eligible, 2708 were randomized (99%), and 2364 (87%) were recontacted 1 year later. Mean age of participants was 39 years. Participants were predominantly non-Latina African American (55%) or Latina (37%), had a high school education or less (57%), and were uninsured (57%).

INTERVENTION: Randomization into 3 intervention groups: (1) partner violence screen (using the Partner Violence Screen instrument) plus a list of local partner violence resources if screening was positive (n = 909); (2) partner violence resource list only without screen (n = 893); and (3) no-screen, no-partner violence list control group (n=898).

MAIN OUTCOME MEASURES: Quality of life (QOL, physical and mental health components) was the primary outcome, measured on the 12-item Short Form (scale range 0-100, mean of 50 for US population).

RESULTS: At 1-year follow-up, there were no significant differences in the QOL physical health component between the screen plus partner violence resource list group (n = 801; mean score, 46.8; 95% CI, 46.1-47.4), the partner violence resource list only group (n = 772; mean score, 46.4; 95% CI, 45.8-47.1), and the control group (n = 791; mean score, 47.2; 95% CI, 46.5-47.8), or in the mental health component (screen plus partner violence resource list group [mean score, 48.3; 95% CI, 47.5-49.1], the partner violence resource list only group [mean score, 48.0; 95% CI, 47.2-48.9], and the control group [mean score, 47.8; 95% CI, 47.0-48.6]). There were also no differences between groups in days unable to work or complete housework; number of hospitalizations, emergency department, or ambulatory care visits; proportion who contacted a partner violence agency; or recurrence of partner violence.

CONCLUSIONS: Among women receiving care in primary care clinics, providing a partner violence resource list with or without screening did not result in improved health.

May 2014 ABOG List Page 12

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00526994.

Comment in

Health care's response to women exposed to partner violence: moving beyond universal screening. [JAMA. 2012]

Partner violence screening and women's quality of life. [JAMA. 2012]

Partner violence screening and women's quality of life. [JAMA. 2012]

PMID: 22893165 [PubMed - indexed for MEDLINE]

13) N Engl J Med. 2014 Mar 31. [Epub ahead of print]

Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 3-Year Outcomes.

Schauer PR1, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier

CE,Kim ES, Nissen SE, Kashyap SR; the STAMPEDE Investigators.

Author information Abstract Background In short-term randomized trials (duration, 1 to 2 years), bariatric surgery has been associated with improvement in type 2 diabetes mellitus. Methods We assessed outcomes 3 years after the randomization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0% or less. Results The mean (±SD) age of the patients at baseline was 48±8 years, 68% were women, the mean baseline glycated hemoglobin level was 9.3±1.5%, and the mean baseline body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.0±3.5. A total of 91% of the patients completed 36 months of follow-up. At 3 years, the criterion for the primary end point was met by 5% of the patients in the medical-therapy group, as compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering medications, including insulin, was lower in the surgical groups than in the medical-therapy group. Patients in the surgical groups had greater mean percentage reductions in weight from baseline, with reductions of 24.5±9.1% in the gastric-bypass group and 21.1±8.9% in the sleeve-gastrectomy group, as compared with a reduction of 4.2±8.3% in the medical-therapy group (P<0.001 for both comparisons). Quality-of-life measures were significantly better in the two surgical groups than

May 2014 ABOG List Page 13

in the medical-therapy group. There were no major late surgical complications. Conclusions Among obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. Analyses of secondary end points, including body weight, use of glucose-lowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number, NCT00432809 .).

PMID: 24679060 [PubMed - as supplied by publisher]

14) N Engl J Med. 2014 Apr 3;370(14):1287-97. doi: 10.1056/NEJMoa1311194. Epub 2014 Mar 19.

Multitarget stool DNA testing for colorectal-cancer screening.

Imperiale TF1, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, Ahlquist DA, Berger BM. Author information Abstract BACKGROUND: An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening.

METHODS: We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings.

RESULTS: Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative

May 2014 ABOG List Page 14

results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT.

CONCLUSIONS: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).

Comment in

Stool DNA and colorectal-cancer screening. [N Engl J Med. 2014]

PMID: 24645800 [PubMed - indexed for MEDLINE]

15) N Engl J Med. 2014 Jan 16;370(3):233-44. doi: 10.1056/NEJMoa1304501.

Body-mass index and mortality among adults with incident type 2 diabetes.

Tobias DK1, Pan A, Jackson CL, O'Reilly EJ, Ding EL, Willett WC, Manson JE, Hu FB. Author information

Erratum in

N Engl J Med. 2014 Apr 3;370(14):1368.

Abstract BACKGROUND: The relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an "obesity paradox").

METHODS: We studied participants with incident diabetes from the Nurses' Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories.

RESULTS: There were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to

May 2014 ABOG List Page 15

27.4, 27.5 to 29.9, 30.0 to 34.9, and ≥35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction).

CONCLUSIONS: We observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox. (Funded by the National Institutes of Health and the American Diabetes Association.).

Comment in

BMI and mortality among adults with incident type 2 diabetes. [N Engl J Med. 2014] BMI and mortality among adults with incident type 2 diabetes. [N Engl J Med. 2014] BMI and mortality among adults with incident type 2 diabetes. [N Engl J Med. 2014] BMI and mortality among adults with incident type 2 diabetes. [N Engl J Med. 2014] BMI and mortality among adults with incident type 2 diabetes. [N Engl J Med. 2014]

PMID: 24428469 [PubMed - indexed for MEDLINE]

Female Pelvic Medicine & Reconstructive Surgery:

May 2014 ABOG List Page 16

16) Am J Obstet Gynecol. 2014 Feb;210(2):163.e1-8. doi: 10.1016/j.ajog.2013.10.012. Epub 2013

Oct 11.

Evaluation and management of complications from synthetic mesh after pelvic reconstructive surgery: a multicenter study.

Abbott S1, Unger CA1, Evans JM2, Jallad K3, Mishra K4, Karram MM2, Iglesia CB3, Rardin CR4, Barber MD5. Author information Abstract OBJECTIVE: The purpose of this study was to describe the evaluation and management of synthetic mesh-related complications after surgery for stress urinary incontinence (SUI) and/or pelvic organ prolapse (POP).

STUDY DESIGN: We conducted a multicenter, retrospective analysis of women who attended 4 US tertiary referral centers for evaluation of mesh-related complications after surgery for SUI and/or POP from January 2006 to December 2010. Demographic, clinical, and surgical data were abstracted from the medical record, and complications were classified according to the Expanded Accordion Severity Classification.

RESULTS: Three hundred forty-seven patients sought management of synthetic mesh-related complications over the study period. Index surgeries were performed for the following indications: SUI (sling only), 49.9%; POP (transvaginal mesh [TVM] or sacrocolpopexy only), 25.6%; and SUI + POP (sling + TVM or sacrocolpopexy), 24.2%. Median time to evaluation was 5.8 months (range, 0-65.2). Thirty percent of the patients had dyspareunia; 42.7% of the patients had mesh erosion; and 34.6% of the patients had pelvic pain. Seventy-seven percent of the patients had a grade 3 or 4 (severe) complication. Patients with TVM or sacrocolpopexy were more likely to have mesh erosion and vaginal symptoms compared with sling only. The median number of treatments for mesh complications was 2 (range, 1-9); 60% of the women required ≥2 interventions. Initial treatment intervention was surgical for 49% of subjects. Of those treatments that initially were managed nonsurgically, 59.3% went on to surgical intervention.

CONCLUSION: Most of the women who seek management of synthetic mesh complication after POP or SUI surgery have severe complications that require surgical intervention; a significant proportion require >1 surgical procedure. The pattern of complaints differs by index procedure.

KEYWORDS:

mesh excision, mesh-related complication, sling, synthetic mesh

PMID: 24126300 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 17

17) Am J Obstet Gynecol. 2013 Dec;209(6):584.e1-5. doi: 10.1016/j.ajog.2013.09.011. Epub 2013

Sep 11.

An update on the current and future demand for care of pelvic floor disorders in the United States.

Kirby AC1, Luber KM, Menefee SA. Author information Abstract OBJECTIVE: In 2001, we predicted a 45% increase in the demand for care of women with pelvic floor disorders (PFDs) between 2000 and 2030. However, in 2010, we observed that in our clinic demand for care had increased substantially more than expected. Using updated data, we sought to provide more accurate projections of future demand for care of pelvic floor disorders in the United States.

STUDY DESIGN: Demographic data on all new female patients between 30 and 89 years of age seen for pelvic floor disorders in our Urogynecology Clinic between 2009 and 2011 were analyzed. These data were combined with United States Census Bureau projections for 2010 and 2030 stratified by 10-year age blocks.

RESULTS: In 2010, our clinic saw a 116% increase in new patients per year compared with 2000. There was an 85% increase in new patient visits per 1000 women per year compared with 2000. We estimate that 1,218,371 new patient visits took place in the United States in 2010 and predict 1,644,804 visits will occur in 2030.

CONCLUSION: If the United States population increases 24% by 2030 as projected by the United States Census Bureau, we predict the demand for care for pelvic floor disorders will increase by 35% between 2010 and 2030. This new, more accurate projection for 2030 is based on improved baseline data from 2010 and is 72% higher than we predicted in 2000. Accurately quantifying this growing demand for care of pelvic floor disorders is important for public health planning and physician training.

KEYWORDS:

demographics, health care policy, pelvic organ prolapse, urinary incontinence

PMID: 24036399 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 18

18) Am J Obstet Gynecol. 2013 Nov;209(5):470.e1-6. doi: 10.1016/j.ajog.2013.08.003. Epub 2013

Aug 3.

Patient preferences for uterine preservation and hysterectomy in women with pelvic organ prolapse.

Korbly NB1, Kassis NC, Good MM, Richardson ML, Book NM, Yip S, Saguan D, Gross C, Evans J, Lopes VV, Harvie HS, Sung VW. Author information Abstract OBJECTIVE: The purpose of this study was to describe patient preferences for uterine preservation and hysterectomy in women with pelvic organ prolapse symptoms and to describe predictors of preference for uterine preservation.

STUDY DESIGN: This multicenter, cross-sectional study evaluated patient preferences for uterine preservation vs hysterectomy in women with prolapse symptoms who were being examined for initial urogynecologic evaluation. Before meeting the physician, the women completed a questionnaire that asked them to indicate their prolapse treatment preference (uterine preservation vs hysterectomy) for scenarios in which the efficacy of treatment varied. Patient characteristics that were associated with preferences were determined, and predictors for uterine preservation preference were identified with multivariable logistic regression.

RESULTS: Two hundred thirteen women participated. Assuming outcomes were equal between hysterectomy and uterine preservation, 36% of the women preferred uterine preservation; 20% of the women preferred hysterectomy, and 44% of the women had no strong preference. If uterine preservation was superior, 46% of the women preferred uterine preservation, and 11% of the women preferred hysterectomy. If hysterectomy was superior, 21% of the women still preferred uterine preservation, despite inferior efficacy. On multivariable logistic regression, women in the South had decreased odds of preferring uterine preservation compared with women in the Northeast (odds ratio [OR], 0.17; 95% CI, 0.05-0.66). Women with at least some college education (OR, 2.87; 95% CI, 1.08-7.62) and those who believed that the uterus is important for their sense of self (OR, 28.2; 95% CI, 5.00-158.7) had increased odds for preferring uterine preservation.

CONCLUSION: A higher proportion of women with prolapse symptoms who were examined for urogynecologic evaluation preferred uterine preservation, compared with hysterectomy. Geographic region, education level, and belief that the uterus is important for a sense of self were predictors of preference for uterine preservation.

KEYWORDS:

hysterectomy, patient preference, prolapse, uterine preservation

May 2014 ABOG List Page 19

PMID: 23921090 [PubMed - indexed for MEDLINE]

19) Obstet Gynecol. 2014 Feb;123(2 Pt 1):232-8. doi: 10.1097/AOG.0000000000000081.

Bowel preparation before vaginal prolapse surgery: a randomized controlled trial.

Ballard AC1, Parker-Autry CY, Markland AD, Varner RE, Huisingh C, Richter HE. Author information Abstract OBJECTIVE: To compare surgeons' intraoperative surgeon acceptability or assessment of the operative field regarding bowel contents and patients' satisfaction with or without a mechanical bowel preparation before reconstructive vaginal prolapse surgery.

METHODS: In this single-blind, randomized trial, women scheduled to undergo vaginal prolapse surgery with a planned apical suspension and posterior colporrhaphy were allocated using block randomization to an intervention or control group. Surgeons were blinded to patient allocation. One day before surgery, mechanical bowel preparation instructions consisted of a clear liquid diet and two self-administered saline enemas; the participants in the control group sustained a regular diet and nothing by mouth after midnight. The primary outcome was surgeons' intraoperative assessment of the surgical field regarding bowel content as measured on a 4-point Likert scale (1, excellent; 4, poor). Secondary outcomes included participant satisfaction and bowel symptoms. The primary outcome was determined by intention-to-treat analysis and other analyses were per protocol.

RESULTS: Of the 150 women randomized (75 women to intervention and control group), 145 completed the study. No differences existed in the demographic, clinical, and intraoperative characteristics between groups (P>.05). Surgeons' intraoperative assessment rating was 85% "excellent or good" with bowel preparation compared with 90% for participants in the control group (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.21-1.61; P=.30). The bowel preparation group was less likely to report "complete" satisfaction compared with the participants in the control group (OR 0.11, 95% CI 0.04-0.35; P<.001). Abdominal fullness and cramping, fatigue, anal irritation, and hunger pains were greater in the bowel preparation group (all P<.01).

CONCLUSION: Before reconstructive vaginal surgery, mechanical bowel preparation conferred no benefit regarding surgeons' intraoperative assessment of the operative field, reflected decreased patient satisfaction, and had increased abdominal symptoms.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01431040.

May 2014 ABOG List Page 20

LEVEL OF EVIDENCE: I.

PMID: 24402594 [PubMed - indexed for MEDLINE]

20) Obstet Gynecol. 2014 Jan;123(1):5-12. doi: 10.1097/AOG.0000000000000006.

Robotic compared with laparoscopic sacrocolpopexy: a randomized controlled trial.

Anger JT1, Mueller ER, Tarnay C, Smith B, Stroupe K, Rosenman A, Brubaker L, Bresee C, Kenton K. Author information Abstract OBJECTIVE: Laparoscopic and robotic sacrocolpopexy are widely used for pelvic organ prolapse (POP) treatment. Evidence comparing outcomes and costs is lacking. We compared costs and clinically relevant outcomes in women randomized to laparoscopic sacrocolpopexy compared with robotic sacrocolpopexy.

METHODS: Participants with symptomatic stage POP II or greater, including significant apical support loss, were randomized to either laparoscopic or robotic sacrocolpopexy. We compared surgical costs (including costs for robot, initial hospitalization) and rehospitalization within 6 weeks. Secondary outcomes included postoperative pain, POP quantification, symptom severity and quality of life, and adverse events.

RESULTS: We randomized 78 women (mean age 59 years): laparoscopic (n=38) and robotic (n=40). The robotic sacrocolpopexy group had higher initial hospital costs ($19,616 compared with $11,573, P<.001) and over 6 weeks, hospital costs remained higher for robotic sacrocolpopexy ($20,898 compared with $12,170, P<.001). When we excluded costs of robot purchase and maintenance, we did not detect a statistical difference in initial day of surgery costs of robotic compared with laparoscopic ($12,586 compared with $11,573; P=.160) or hospital costs over 6 weeks ($13,867 compared with $12,170; P=.060). The robotic group had longer operating room times (202.8 minutes compared with 178.4 minutes, P=.030) and higher pain scores 1 week after surgery (3.5±2.1 compared with 2.6±2.2; P=.044). There were no group differences in symptom bother by Pelvic Floor Distress Inventory, POP stage, or rate of adverse events.

CONCLUSION: Costs of robotic sacrocolpopexy are higher than laparoscopic, whereas short-term outcomes and complications are similar. Primary cost differences resulted from robot maintenance and purchase costs.

CLINICAL TRIAL REGISTRATION:

May 2014 ABOG List Page 21

Clinicaltrials.gov, www.clinicaltrials.gov, NCT01124916.

LEVEL OF EVIDENCE: I.

Comment in

Robotics in gynecology: is the glass half empty or half full? [Obstet Gynecol. 2014]

PMID: 24463657 [PubMed - indexed for MEDLINE]

21) Obstet Gynecol. 2014 Mar;123(3):553-61. doi: 10.1097/AOG.0000000000000148.

Transobturator sling compared with single-incision mini-sling for the treatment of stress urinary incontinence: a randomized controlled trial.

Djehdian LM1, Araujo MP, Takano CC, Del-Roy CA, Sartori MG, Girão MJ, Castro RA. Author information Abstract OBJECTIVE: To determine the efficacy and safety of a single-incision mini-sling compared with a transobturator midurethral sling for stress urinary incontinence (SUI) treatment.

METHODS: This prospective single-center randomized controlled trial involved 130 women with a diagnosis of SUI. Primary outcomes were the objective and subjective cure rates, defined as negative cough stress and pad tests, and satisfaction rates. Quality of life assessed by the Incontinence Quality of Life Questionnaire and the Urogenital Distress Inventory Short Form, operation time, complications, and reoperation rates were also recorded. The efficacy was analyzed using a noninferiority test with a margin of 15%. For the noninferiority test, a P value >.05 rejects the noninferiority hypothesis of the mini-sling.

RESULTS: Sixty-four patients in the mini-sling group and 56 in the transobturator group completed the 12-month follow-up. The objective cure rates for the mini-sling and the transobturator sling were 68.1% and 81.9% (absolute difference 13.8; 90% confidence interval [CI] 1.5-26.1; P=.439) and the subjective cure rates were 81.1% and 88.5% (absolute difference 7.4%; 90% CI 2.8-17.6; P=.110), respectively. There was a significant improvement in quality of life in both groups. Thigh pain was greater after the transobturator sling, four patients (7.1%) compared with zero (P=.045). The mean operation time was 5 minutes shorter for the mini-sling procedure (P=.000). Five patients (7.8%) in the mini-sling group and one patient (1.8%) in the transobturator group underwent surgical reintervention for persistent SUI (P=.213).

CONCLUSION:

May 2014 ABOG List Page 22

The noninferiority of the mini-sling could not be demonstrated in this study at the 12-month follow-up. The mini-sling was associated with shorter operative time and less postoperative thigh pain.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01094353.

PMID: 24499750 [PubMed - indexed for MEDLINE]

Gynecologic Oncology:

22) Ann Oncol. 2012 Oct;23(10):2605-12. Epub 2012 Aug 21.

The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy.

Hanker LC1, Loibl S, Burchardi N, Pfisterer J, Meier W, Pujade-Lauraine E, Ray-Coquard I, Sehouli J,Harter P, du Bois A; AGO and GINECO study group. Author information Abstract BACKGROUND: Despite recent progress in the treatment of ovarian cancer, the majority of patients eventually relapse. There is little information on the effectiveness of chemotherapy in higher treatment lines.

PATIENTS AND METHODS: Characterization of the second to sixth line therapy and its effects on survival was carried out, based on data of n = 1620 patients from three large randomized phase III trials investigating primary therapy.

RESULTS: Median progression-free survival (PFS) after the first, second, third, fourth and fifth relapse was 10.2 [95% confidence interval (CI) 9.6-10.7], 6.4 (5.9-7.0), 5.6 (4.8-6.2), 4.4 (3.7-4.9) and 4.1 (3.0-5.1) months, respectively. Median overall survival (OS) after the first, second, third, fourth and fifth relapse was 17.6 (95% CI 16.4-18.6), 11.3 (10.4-12.9), 8.9 (7.8-9.9), 6.2 (5.1-7.7) and 5.0 (3.8-10.4) months, respectively. The most frequent second and third line chemotherapy was platinum combination (n = 313, 24.5%) and topotecan (n = 118, 23.6%), respectively. Relapse treatment improved PFS and OS at the second to fourth recurrence, although frequently not performed according to the standard of care. In multivariate analysis, platinum sensitivity and optimal primary tumor debulking were revealed as independent prognostic factors for PFS up to third relapse.

May 2014 ABOG List Page 23

CONCLUSION: A maximum of three lines of subsequent relapse treatment seems to be beneficial for patients with recurrent ovarian cancer. Optimal primary tumor debulking and platinum sensitivity remain independent prognostic factors even after more frequent relapses.

PMID: 22910840 [PubMed - indexed for MEDLINE]

23) Gynecol Oncol. 2013 Jun;129(3):580-5. doi: 10.1016/j.ygyno.2013.02.024. Epub 2013 Feb 26.

Postoperative outcomes after continent versus incontinent urinary diversion at the time of pelvic exenteration for gynecologic malignancies.

Urh A1, Soliman PT, Schmeler KM, Westin S, Frumovitz M, Nick AM, Fellman B, Urbauer

DL, Ramirez PT.

Author information Abstract OBJECTIVE: To compare outcomes of patients undergoing continent or incontinent urinary diversion after pelvic exenteration for gynecologic malignancies.

METHODS: Data on patients who underwent pelvic exenteration for gynecologic malignancies at The University of Texas MD Anderson Cancer Center between January 1993 and December 2010 were collected. A multivariate logistic regression model was used and statistical significance was P<0.05.

RESULTS: A total of 133 patients were included in this study. The mean age at exenteration was 47.6 (range, 30-73) years in the continent urinary diversion group and 57.2 (range, 27-86) years in the incontinent urinary diversion group (P<0.0001). Forty-six patients (34.6%) had continent urinary diversion, and 87 patients (65.4%) had incontinent urinary diversion. The rates of postoperative complications in patients with continent and incontinent urinary diversion, respectively, were as follows: pyelonephritis, 32.6% versus 37.9% (P=0.58); urinary stone formation, 34.8% versus 2.3% (P<0.001); renal insufficiency, 4.4% versus 14.9% (P=0.09); urostomy stricture, 13.0% versus 1.2% (P=0.007); ureteral (anastomotic) leak, 4.4% versus 6.9% (P=0.71); ureteral (anastomotic) stricture, 13.0% versus 23% (P=0.25); fistula formation, 21.7% versus 19.5% (P=0.82); and reoperation because of complications of urinary diversion, 6.5% versus 2.3% (P=0.34). Among patients with continent urinary diversion, the incidence of incontinence was 28.3%, and 15.2% had difficulty with self-catheterization.

CONCLUSION:

May 2014 ABOG List Page 24

There were no differences in postoperative complications between patients with continent and incontinent conduits except that stone formation was more common in patients with continent conduits.

PMID: 23480870 [PubMed - indexed for MEDLINE]

24) Nature. 2013 May 2;497(7447):67-73. doi: 10.1038/nature12113.

Integrated genomic characterization of endometrial carcinoma.

Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H,Robertson AG, Pashtan I, Shen R, Benz CC, Yau C, Laird PW, Ding L, Zhang W, Mills GB, Kucherlapati R, Mardis ER, Levine DA. Collaborators (313)

Erratum in

Nature. 2013 Aug 8;500(7461):242.

Abstract We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Comment in

Genetics: new classification for endometrial cancer puts genes in POLE position. [Nat Rev Clin Oncol. 2013]

PMID: 23636398 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 25

25) Gynecol Oncol. 2013 Aug;130(2):264-8. doi: 10.1016/j.ygyno.2013.04.050. Epub 2013 Apr 26.

Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)?

Kang WD1, Choi HS, Kim SM. Author information Abstract OBJECTIVES: This study was conducted to determine whether vaccination with the quadrivalent human papillomavirus (HPV) vaccine after loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2-3) is effective in preventing recurrence of CIN2-3.

METHODS: Between August 2007 and July 2010, 737 patients aged 20-45 years who were diagnosed with CIN2-3 were treated by LEEP and followed. Three hundred and sixty patients were vaccinated with the quadrivalent HPV vaccine after LEEP (vaccination group), and 377 patients were followed without vaccination (non-vaccination group). The vaccination group received the first dose at 1 week after LEEP and the remaining two doses two and six months later. Post-LEEP follow-up was performed at 3, 6, 9, 12, 18, and 24 months during the first 2 years and yearly thereafter.

RESULTS: Irrespective of causal HPV type, 36 (4.9%) patients developed recurrence. In the vaccination group (360 patients), 9 patients (2.5%) developed recurrence, whereas 27 patients (7.2%) in the non-vaccination group (377 patients) developed recurrence. In patients infected with HPV of 16 and/or 18 type, 5 patients (2.5%) in the vaccination group (197 patients) and 18 patients (8.5%) in the non-vaccination group (211 patients) developed recurrent disease related to vaccine HPV types (HPV 16 or 18 types) after LEEP (P<0.01). Multivariate analysis showed that no vaccination after LEEP was an independent risk factor for recurrent CIN2-3 (HR=2.840; 95% confidence interval, 1.335-6.042; P<0.01).

CONCLUSIONS: Vaccination with the quadrivalent HPV vaccine after treatment may be considered in preventing recurrence of CIN2-3.

KEYWORDS:

HPV, High grade CIN, LEEP, Vaccine

PMID: 23623831 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 26

26) JAMA. 2013 May 1;309(17):1793-802. doi: 10.1001/jama.2013.1625.

Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.

Dobson SR1, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW,Kollmann TR, Halperin SA, Langley JM, Bettinger JA, Singer J, Money D, Miller D, Naus M, Marra F,Young E. Author information Abstract IMPORTANCE: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible.

OBJECTIVE: To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses.

DESIGN, SETTING, AND PATIENTS: Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%).

INTERVENTION: Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months.

MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months.

RESULTS: The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all

May 2014 ABOG List Page 27

genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36.

CONCLUSIONS AND RELEVANCE: Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00501137.

Comment in

HPV vaccination: too soon for 2 doses? [JAMA. 2013]

PMID: 23632723 [PubMed - indexed for MEDLINE]

27) J Clin Oncol. 2013 Jul 1;31(19):2500-10. doi: 10.1200/JCO.2013.49.2678. Epub 2013 May

Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update.

Loren AW1, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, Quinn G, Wallace WH,Oktay K; American Society of Clinical Oncology.

Author information Abstract PURPOSE: To update guidance for health care providers about fertility preservation for adults and children with cancer.

METHODS: A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language.

RESULTS: There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions

May 2014 ABOG List Page 28

to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added.

RECOMMENDATIONS: As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.

PMID: 23715580 [PubMed - indexed for MEDLINE]

Maternal & Fetal Medicine:

28) Obstet Gynecol. 2013 Dec;122(6):1160-7. doi: 10.1097/AOG.0000000000000015.

Accuracy of ultrasonography at 11-14 weeks of gestation for detection of fetal structural anomalies: a systematic review.

Rossi AC1, Prefumo F.

Author information Abstract OBJECTIVE: To review the literature concerning the efficacy of early ultrasonography (at 11-14 weeks of gestation) to identify fetal malformations.

DATA SOURCES: A search in PubMed, MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov was performed (January 2000 to December 2012). Keywords were: fetal anatomy, fetal echocardiography, nuchal translucency, fetal structural anomalies, fetal malformations, prenatal diagnosis, prenatal screening, and first-trimester ultrasonography.

May 2014 ABOG List Page 29

METHODS OF STUDY SELECTION: Inclusion criteria were: fetal anatomy examination at early ultrasonography and diagnosis of fetal malformations confirmed by postnatal or postmortem examination. Data abstracted were: sample size, location of structural defect, ultrasound modality, presence of multiple defects, and study population. Pooled detection rate was calculated for each malformation and compared with χ. Differences were considered statistically significant if P<.05.

TABULATION, INTEGRATION, AND RESULTS: From 1,203 articles, 19 were included. Overall, we pooled 78,002 fetuses undergoing ultrasonography at 11-14 weeks, of which 996 were malformed, leading to prevalence of malformation of 12 per 1,000. The overall detection rate was 472 of 957 (51%). The highest detection rate was achieved for neck anomalies (92%), whereas limbs (34%), face (34%), and genitourinary anomalies (34%) were associated with the lowest detection rate. At 14 weeks of gestation or less, fetal echocardiography detected 53% of congenital heart disease compared with 43% by complete scan (P=.040). The use of Doppler did not improve the detection rate for congenital heart defects (52% compared with 44%, respectively; P=.11). Multiple defects were identified more frequently than isolated malformations (60% compared with 44%; P=.005). The detection rate was higher combining transabdominal and transvaginal techniques (62%) than either abdominal (51%) or transvaginal (34%; P<.001). Detection rate was higher in women at high risk (65%) than unselected population (50% P=.001).

CONCLUSION: Because of the natural history of fetal defects and the late development of some organ systems, a number of fetal malformations remain undetected by early ultrasonography.

PMID: 24201688 [PubMed - indexed for MEDLINE]

29) Ultrasound Obstet Gynecol. 2013 Oct;42(4):400-8. doi: 10.1002/uog.13190.

Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE).

Lees C1, Marlow N, Arabin B, Bilardo CM, Brezinka C, Derks JB, Duvekot J, Frusca T, Diemert A,Ferrazzi E, Ganzevoort W, Hecher K, Martinelli P, Ostermayer E, Papageorghiou AT, Schlembach D,Schneider KT, Thilaganathan B, Todros T, van Wassenaer-Leemhuis A, Valcamonico A, Visser GH, Wolf H; TRUFFLE Group. Collaborators (14) Author information Abstract OBJECTIVES:

May 2014 ABOG List Page 30

Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery.

METHODS: We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26-32 weeks of gestation, with abdominal circumference < 10(th) percentile and umbilical artery Doppler pulsatility index > 95(th) percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis.

RESULTS: Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to gestational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome.

CONCLUSIONS: Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions.

KEYWORDS:

CTG, Doppler, ductus venosus, fetal heart, neonatal, outcome, perinatal, short-term variation

Comment in

Reply. [Ultrasound Obstet Gynecol. 2014]

Critical umbilical artery Doppler abnormalities in early fetal growth restriction and the timing of delivery: an overestimated clinical challenge in daily obstetric practice? [Ultrasound Obstet Gynecol. 2014]

May 2014 ABOG List Page 31

PMID: 24078432 [PubMed - indexed for MEDLINE]

30) Obstet Gynecol. 2013 Dec;122(6):1271-8. doi: 10.1097/AOG.0000000000000010.

Safety of influenza A (H1N1) 2009 live attenuated monovalent vaccine in pregnant women.

Moro PL1, Museru OI, Broder K, Cragan J, Zheteyeva Y, Tepper N, Revzina N, Lewis P, Arana J, Barash F, Kissin D, Vellozzi C. Author information Abstract OBJECTIVE: To characterize maternal and infant outcomes for pregnant women who received live H1N1 influenza vaccine and had no reported adverse events.

METHODS: We identified Vaccine Adverse Event Reporting System reports, which described receipt of live H1N1 vaccine during pregnancy without an indication of an adverse event at the time of the report during October 2009 to June 2010. We reviewed the initial reports and obtained pregnancy outcome and infant data through 6 months of age from medical records. We reviewed the numbers and characteristics of pregnancy complications and infant outcomes including major birth defects and medically important infant conditions. Rates of spontaneous abortion, preterm birth, and major birth defects and their 95% confidence intervals were calculated.

RESULTS: The Vaccine Adverse Event Reporting System received 113 reports stating receipt of live H1N1 vaccine during pregnancy with no adverse events reported. We obtained follow-up maternal records on 95 of the 113 (84%) live H1N1 reports (40.2% were vaccinated in the first trimester) and found: 87 live births (two twin pregnancies) and no maternal deaths occurred. Number and rates of pregnancy-specific adverse events included: 10 (10.5%, 5.8-18.3) spontaneous abortions; four (4.7%, 1.8-11.4) preterm deliveries at 35-36 weeks of gestation; three (3.4%, 1.2-9.7) infants had one or more major birth defects noted at birth: one cleft palate, one cleft lip, and one microtia (underdeveloped or absent external ear). Seven neonates and infants were hospitalized for medically important conditions. One infant death occurred in a 2.5-month-old boy as a result of pertussis.

CONCLUSION: Rates of spontaneous abortion, preterm birth, and major birth defects in pregnant women who received live H1N1 vaccine were similar to or lower than published background rates. No concerning patterns of medical conditions in infants were identified.

LEVEL OF EVIDENCE: III.

May 2014 ABOG List Page 32

Comment in

Safety of influenza A (H1N1) 2009 live attenuated monovalent vaccine in pregnant women.[Obstet Gynecol. 2014]

In reply. [Obstet Gynecol. 2014]

PMID: 24201689 [PubMed - indexed for MEDLINE]

31) BMJ. 2013 Nov 12;347:f6460. doi: 10.1136/bmj.f6460.

Perinatal outcomes after bariatric surgery: nationwide population based matched cohort

study.

Roos N1, Neovius M, Cnattingius S, Trolle Lagerros Y, Sääf M, Granath F, Stephansson O. Author information Abstract OBJECTIVE: To compare perinatal outcomes in births of women with versus without a history of bariatric surgery.

DESIGN: Population based matched cohort study.

SETTING: Swedish national health service.

PARTICIPANTS: 1,742,702 singleton births identified in the Swedish medical birth register between 1992 and 2009. For each birth to a mother with a history of bariatric surgery (n=2562), up to five control births were matched by maternal age, parity, early pregnancy body mass index, early pregnancy smoking status, educational level, and year of delivery. Secondary control cohorts, including women eligible for bariatric surgery (body mass index ≥ 35 or ≥ 40), were matched for the same factors except body mass index. History of maternal bariatric surgery was ascertained through the Swedish national patient register from 1980 to 2009.

MAIN OUTCOME MEASURES: Preterm birth (<37 weeks), small for gestational age birth, large for gestational age birth, stillbirth (≥ 28 weeks), and neonatal death (0-27 days).

RESULTS: Post-surgery births were more often preterm than in matched controls (9.7% (243/2511) v 6.1% (750/12,379); odds ratio 1.7, 95% confidence interval 1.4 to 2.0; P<0.001). Body mass index

May 2014 ABOG List Page 33

seemed to be an effect modifier (P=0.01), and the increased risk of preterm birth was only observed in women with a body mass index <35. A history of bariatric surgery was associated with increased risks of both spontaneous (5.2% (130/2511) v 3.6% (441/12,379); odds ratio 1.5, 1.2 to 1.9; P<0.001) and medically indicated preterm birth (4.5% (113/2511) v 2.5% (309/12,379); odds ratio 1.8, 1.4 to 2.3; P<0.001). A history of bariatric surgery was also associated with an increased risk of a small for gestational age birth (5.2% (131/2507) v 3.0% (369/12,338); odds ratio 2.0, 1.5 to 2.5; P<0.001) and lower risk of a large for gestational age birth (4.2% (105/2507) v 7.3% (895/12,338); odds ratio 0.6, 0.4 to 0.7; P<0.001). No differences were detected for stillbirth or neonatal death. The increased risks for preterm and small for gestational age birth, as well as the decreased risk for large for gestational age birth, remained when post-surgery births were compared with births of women eligible for bariatric surgery.

CONCLUSION: Women with a history of bariatric surgery were at increased risk of preterm and small for gestational age births and should be regarded as a risk group during pregnancy.

PMID: 24222480 [PubMed - indexed for MEDLINE]

32) BMJ. 2013 Nov 7;347:f6099. doi: 10.1136/bmj.f6099.

Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England.

Abdul Sultan A1, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Author information Abstract OBJECTIVE: To examine the potential for preventing venous thromboembolism during and after antepartum hospital admissions in pregnant women.

DESIGN: Cohort study using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records.

SETTING: Primary and secondary care centres, England.

PARTICIPANTS: 206,785 women aged 15-44 who had one or more pregnancies from 1997 up to 2010.

MAIN OUTCOME MEASURE: Risk of first venous thromboembolism in pregnant women admitted to hospital for one or more days for reasons other than delivery or venous thromboembolism. Risk was assessed by calculating the absolute rate of venous thromboembolism and comparing these rates with

May 2014 ABOG List Page 34

those observed during follow-up time not associated with hospital admission using a Poisson regression model to estimate incidence rate ratios.

RESULTS: Admission to hospital in pregnancy was associated with an increased risk of venous thromboembolism (absolute rate 1752/100,000 person years; incidence rate ratio 17.5, 95% confidence interval 7.69 to 40.0) compared with time outside hospital. The rate of venous thromboembolism was also high during the 28 days after discharge (absolute rate 676; 6.27, 3.74 to 10.5). The rate during and after admission combined was highest in the third trimester (961; 5.57, 3.32 to 9.34) and in those aged ≥ 35 years (1756; 21.7, 9.62 to 49.0). While the absolute rate in the combined period was highest for those with three or more days in hospital (1511; 12.2, 6.65 to 22.7), there was also a fourfold increase (558; 4.05, 2.23 to 7.38) in the risk of venous thromboembolism for those admitted to hospital for less than three days.

CONCLUSION: The overall risk of first venous thromboembolism in pregnant women increased during admissions to hospital not related to delivery, and remained significantly higher in the 28 days after discharge. During these periods need for thromboprophylaxis should receive careful consideration.

Comment in

Risk of venous thromboembolism in pregnancy and risks from unnecessary investigations must both be minimised. [BMJ. 2013]

PMID: 24201164 [PubMed - indexed for MEDLINE]

33) Ultrasound Obstet Gynecol. 2013 Nov;42(5):518-24. doi: 10.1002/uog.12451. Epub 2013 Oct 9.

Prenatal sonography can predict degree of placental invasion.

Chalubinski KM1, Pils S, Klein K, Seemann R, Speiser P, Langer M, Ott J. Author information Abstract OBJECTIVE: To evaluate whether the maximum degree of placental invasion (placenta accreta, increta or percreta) can be predicted with ultrasound imaging, using criteria developed in our department.

METHODS: This was a retrospective study of all 232 patients at risk for placental invasion who were part of a routine screening program for placental invasion from January 2001 to January 2011. The

May 2014 ABOG List Page 35

whole placenta was scanned in a systematic manner using both gray-scale ultrasound and color-flow mapping. Sonographic findings were compared with the clinical outcome during and after delivery and the histomorphological examination of the placenta.

RESULTS: Placental invasion was suspected by ultrasound in 40 (17.2%) patients and was clinically/histopathologically confirmed in a total of 35 (15.1%) patients. The sensitivity, specificity and positive and negative predictive values of ultrasound for placental invasion were 91.4% (95% CI, 77.6-97.0%), 95.9% (95% CI, 92.2-97.9%), 80.0% (95% CI, 65.2-89.5%) and 98.4% (95% CI, 95.5-99.5%), respectively. No case of placenta increta (n = 7) or percreta (n = 17) was diagnosed as showing normal placentation or placenta accreta on ultrasound, giving an overall accuracy for the differentiation between normal placentation/placenta accreta and placenta increta/percreta of 100%.

CONCLUSION: Our data suggest that prediction of the degree of placental invasion is possible using prenatal ultrasound, with high overall accuracy.

KEYWORDS:

antenatal, placenta accreta, placental invasion, predictive value, ultrasound

PMID: 23471888 [PubMed - in process]

Reproductive Endocrinology & Infertility:

34) Fertil Steril. 2014 Feb;101(2):420-6. doi: 10.1016/j.fertnstert.2013.10.056. Epub 2013 Dec 12.

Pregnancies of unknown location after in vitro fertilization: minimally invasive management with Karman cannula aspiration.

Brady P1, Imudia AN2, Awonuga AO3, Wright DL4, Styer AK4, Toth TL4. Author information

May 2014 ABOG List Page 36

Abstract OBJECTIVE: To describe a standardized protocol for the assessment of asymptomatic patients with pregnancies of unknown location (PUL) after IVF.

DESIGN: Retrospective cohort study.

SETTING: University-based infertility clinic.

PATIENT(S): Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 2005 and 2011.

INTERVENTION(S): Endometrial sampling using Karman suction cannula in patients with PUL and abnormal β-hCG trend (increase <53% or decrease <15% in 2 days) and a pelvic ultrasound unremarkable for an intrauterine pregnancy (IUP) or an ectopic pregnancy (EP).

MAIN OUTCOME MEASURE(S): Proportion of patients spared methotrexate (MTX) administration.

RESULT(S): Endometrial sampling was performed in 45 patients. Of these, 31 (68.9%) were diagnosed with failed IUP by either a sampling after the β-hCG decline (≥15%) and/or the presence of villi on final pathology. No further intervention was required. Fourteen patients (31.1%) were diagnosed with presumed EP by persistent β-hCG level after negative pathology. Ten of these patients (71%) were successfully treated with a single dose of MTX; three required an additional dose, and one required laparoscopy for a ruptured EP.

CONCLUSION(S): In asymptomatic patients with PUL and abnormal β-hCG trends after IVF, the utility of Karman aspiration to confirm an IUP may obviate treatment with MTX in more than two-thirds of patients.

KEYWORDS:

Beta-human chorionic gonadotropin, IVF/ICSI, early pregnancy, ectopic pregnancy, pregnancy of unknown location

PMID: 24331836 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 37

35) J Clin Endocrinol Metab. 2014 Feb 11:jc20131569. [Epub ahead of print]

Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54.

Jayasena CN1, Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, Nijher GM, Ganiyu-Dada Z, Mehta A, Todd C, Ghatei MA, Bloom SR, Dhillo WS. Author information Abstract BACKGROUND: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age, and is associated with deficient LH pulsatility. High dose kisspeptin-54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitisation. GnRH has paradoxical effects on reproductive activity; we therefore hypothesised that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH / LH pulsatility in women with HA.

AIM: Determine whether constant intravenous infusion of kisspeptin 54 temporarily increases pulsatile LH secretion in women with HA.

METHODS: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous intravenous infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30 or 1.00nmol/kg/h) was administered. LH pulses were detected using blinded deconvolution.

RESULTS: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8h: 1.6±0.4, vehicle; 5.0±0.5, kisspeptin-54, P<0.01 vs. vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in iU/l: 3.92±2.31, vehicle; 23.44±12.59, kisspeptin-54; P<0.05 vs. vehicle).

CONCLUSIONS: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore we have determined the dose-range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

PMID: 24517142 [PubMed - as supplied by publisher]

May 2014 ABOG List Page 38

36) N Engl J Med. 2013 Dec 5;369(23):2218-25. doi: 10.1056/NEJMoa1301467.

Fertility treatments and multiple births in the United States.

Kulkarni AD1, Jamieson DJ, Jones HW Jr, Kissin DM, Gallo MF, Macaluso M, Adashi EY. Author information Abstract BACKGROUND: The advent of fertility treatments has led to an increase in the rate of multiple births in the United States. However, the trends in and magnitude of the contribution of fertility treatments to the increase are uncertain.

METHODS: We derived the rates of multiple births after natural conception from data on distributions of all births from 1962 through 1966 (before fertility treatments were available). Publicly available data on births from 1971 through 2011 were used to determine national multiple birth rates, and data on in vitro fertilization (IVF) from 1997 through 2011 were used to estimate the annual proportion of multiple births that were attributable to IVF and to non-IVF fertility treatments, after adjustment for maternal age. Trends in multiple births were examined starting from 1998, the year when clinical practice guidelines for IVF were developed with an aim toward reducing the incidence of multiple births.

RESULTS: We estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during IVF (P<0.001) and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF (P<0.001).

CONCLUSIONS: Over the past four decades, the increased use of fertility treatments in the United States has been associated with a substantial rise in the rate of multiple births. The rate of triplet and higher-order births has declined over the past decade in the context of a reduction in the transfer of three or more embryos during IVF. (Funded by the Centers for Disease Control and Prevention.).

Comment in

Fertility treatments and multiple births in the United States. [N Engl J Med. 2014]

Fertility treatments and multiple births in the United States. [N Engl J Med. 2014]

Fertility treatments and multiple births in the United States. [N Engl J Med. 2014]

PMID: 24304051 [PubMed - indexed for MEDLINE]

May 2014 ABOG List Page 39

37) N Engl J Med. 2014 Jan 30;370(5):412-20. doi: 10.1056/NEJMoa1305224. Epub 2014 Jan 1.

Romosozumab in postmenopausal women with low bone mineral density.

McClung MR1, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY,Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG. Author information Abstract BACKGROUND: Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation.

METHODS: In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover.

RESULTS: All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups.

CONCLUSIONS: In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).

Comment in

May 2014 ABOG List Page 40

Sclerostin inhibition for osteoporosis--a new approach. [N Engl J Med. 2014] Pharmacotherapy: Novel antibody therapy demonstrates potential for building bone in

osteoporosis. [Nat Rev Endocrinol. 2014] Romosozumab in postmenopausal women with osteopenia. [N Engl J Med. 2014] Romosozumab in postmenopausal women with osteopenia. [N Engl J Med. 2014] Osteoporosis: Novel antibody therapy shows potential for building bone. [Nat Rev Rheumatol.

2014]

PMID: 24382002 [PubMed - indexed for MEDLINE]

38) Fertil Steril. 2014 Jan;101(1):64-9. doi: 10.1016/j.fertnstert.2013.09.003. Epub 2013 Oct 2.

Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters.

Samplaski MK1, Loai Y1, Wong K1, Lo KC2, Grober ED1, Jarvi KA3. Author information Abstract OBJECTIVE: To analyze how frequently and why men presenting with infertility take testosterone (T) and if negative effects of T on semen parameters are reversed following cessation.

DESIGN: Analysis of a prospectively collected database.

SETTING: Male Infertility clinic.

PATIENT(S): Men presenting for fertility evaluation from 2008 to 2012.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The frequency and reason for T use in the infertile male population, and semen and hormonal parameters while on T and following discontinuation.

RESULT(S): A total of 59/4,400 men (1.3%) reported taking T. T was prescribed by a variety of physicians, including endocrinologists (24%), general practitioners (17%), urologists (15%), gynecologists (5%), and reproductive endocrinologists (3%). Only one of the men admitted that he had obtained T from an illicit source. More than 82% of men were prescribed T for the treatment of

May 2014 ABOG List Page 41

hypogonadism, but surprisingly, 12% (7/59) were prescribed T to treat their infertility. While on T, 88.4% of men were azoospermic, but by 6 months after T cessation, 65% of the men without other known causes for azoospermia recovered spermatogenesis.

CONCLUSION(S): In Canada, T was not commonly used by men presenting for fertility investigation (1.3%). Close to 2/3 of infertile men using T recovered spermatogenesis within 6 months of T discontinuation.

KEYWORDS:

Testosterone, hormones, male infertility, semen, testosterone replacement therapy

PMID: 24094422 [PubMed - indexed for MEDLINE]

39) J Clin Endocrinol Metab. 2014 Apr;99(4):1314-21. doi: 10.1210/jc.2013-4086. Epub 2014 Jan 29.

Pharmacokinetics of human chorionic gonadotropin injection in obese and normal-weight

women.

Shah DK1, Missmer SA, Correia KF, Ginsburg ES. Author information Abstract Context: Obese women have poorer in vitro fertilization outcomes, but underlying mechanisms remain unclear. Objective: The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin (hCG) and ovarian steroid hormone production, after subcutaneous (sc) and intramuscular (im) injection of hCG in obese and normal-weight women. Design and Setting: This was a randomized, experimental study. Patients or Other Participants: Twenty-two women aged 18-42 years with body mass index of 18.5-24.9 (normal) or 30-40 kg/m(2) (obese). Interventions: Participants received im urinary hCG or sc recombinant hCG and returned for a second injection type after a 4-week washout. Intramuscular injections were performed under ultrasound guidance. Blood was taken 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 36 hours after injection. Main Outcome Measures: hCG was measured at each time point; estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), testosterone (T), dehydroepiandrosterone, and SHBG were measured at 0 and 36 hours. Results: Twenty-two women completed the study. In both normal-weight and obese women, peak serum concentration (Cmax), area under the curve (AUC), and average hCG concentration were higher after im injection as compared with sc injection (all P < .003). Obese women had markedly lower Cmax, AUC, and average hCG concentration after sc injection as compared with normal-weight women (P = .02, P = .009, and P = .008, respectively). After im injection, Cmax, AUC, and average concentration were similar for normal-weight and obese women (P = .31, P = .25, and P = .18, respectively). Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle. hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an

May 2014 ABOG List Page 42

increase in T in obese but not normal-weight women (all P < .04). Conclusions: Subcutaneous injection yields lower hCG levels in obese women. Standard-length needles are insufficient to administer im injections in many obese women.

PMID: 24476082 [PubMed - in process]