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What's new in obstetrics and gynecology

Disclosures: Kristen Eckler, MD, FACOG Nothing to disclose. Sandy J Falk, MD, FACOG Employee of UpToDate, Inc. Vanessa A Barss, MD, FACOG Employee of UpToDate, Inc. Equity Ownership/Stock Options: Merck; Pfizer; Abbvie.

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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2014. | This topic last updated: Oct 20, 2014.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Anticoagulation and placenta-mediated complications (October 2014)

Placenta-mediated pregnancy complications include pregnancy loss, severe/early-onset preeclampsia, and birth of small for gestational age infant. Anticoagulation has been recommended to prevent placenta-mediated pregnancy complications in women with thrombophilia, but the effectiveness of this approach is controversial. In a multinational randomized trial (TIPPS), prophylactic use of dalteparin in women with thrombophilia and a history of previous placenta-mediated pregnancy complications did not reduce the occurrence of the composite outcome (pregnancy loss, severe/early-onset preeclampsia, birth of small for gestational age infant, major venous thromboembolism) compared with women who did not receive dalteparin [1]. We believe the available evidence supports not prescribing anticoagulants to prevent adverse obstetrical outcomes in pregnant women with thrombophilia. (See "Inherited thrombophilias in pregnancy", section on 'Prevention of pregnancy complications'.)

Aspirin for preventing preeclampsia (September 2014)

For women at high risk of developing preeclampsia, the US Preventive Services Task Force (USPSTF) now recommends use of low dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia, preterm birth, and fetal growth restriction [2]. Low dose aspirin prophylaxis results in potentially substantial benefit and no more than minimally harmful effects. This recommendation is consistent with recommendations of other professional organizations. The USPSTF also offered a pragmatic approach for selecting a high risk population, while acknowledging that there are no validated methods for identifying these women. (See "Preeclampsia: Prevention", section on 'Approach to therapy'.)

Maternal mortality among women with epilepsy (August 2014)

Individuals with chronic epilepsy are at increased risk for sudden death, and a new study suggests that this risk may contribute to increased maternal mortality among women with epilepsy. A study that examined all epilepsy-related deaths in a United Kingdom population-based registry of over two million pregnancies found 14 deaths in women with epilepsy over a two-year period; 80 percent of these were attributed to sudden unexpected death in epilepsy (SUDEP) [3]. The estimated maternal death rate, 1 in 1000 among women with epilepsy, was 10-fold higher than the rate in the general population of pregnant women but similar to estimates of SUDEP risk in the chronic epilepsy population. Additional studies are needed to confirm this finding and to determine whether there are modifiable risk factors for SUDEP during pregnancy. (See "Risks associated with epilepsy and pregnancy", section on 'Maternal mortality'.)

Antidepressants and risk of congenital cardiac defects (August 2014)

A large population-based study has provided reassuring results suggesting that treatment with antidepressants during pregnancy is not associated with congenital cardiac defects [4]. The study used an administrative claims database to compare infants of depressed mothers who were either treated with antidepressants during the first trimester or not treated with antidepressants. After adjusting for confounding, there was no significant difference in risk of congenital cardiac malformations among exposed versus unexposed infants. Seven other analyses examined specific exposure to selective serotonin reuptake inhibitors (as a class), fluoxetine, paroxetine, sertraline, serotonin-norepinephrine reuptake inhibitors, tricyclics, and bupropion; in each analysis, exposure was not associated with an increased risk of cardiac defects. (See "Risks of antidepressants during pregnancy", section on 'Antidepressant composite data'.)

Additional benefits of delayed cord clamping (August 2014)

Delayed cord clamping raises neonatal hemoglobin levels. In addition, delaying cord clamping until spontaneous respirations are established appears to improve cardiopulmonary hemodynamics during the fetal to neonatal transition. In an observational study performed in a hospital in rural Tanzania, healthy self-breathing neonates were more likely to die or be admitted to a neonatal care unit if cord clamping occurred before or immediately after onset of spontaneous respirations, but not when cord clamping was delayed [5]. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

Value of placental examination in stillbirth (August 2014)

In a 2014 systematic review that investigated the likelihood of diagnosing a cause of stillbirth from placental examination, histopathological examination provided useful information about the cause of death or contributing factors in 11 to 84 percent of cases [6]. Although certain placental abnormalities are more common in stillbirths, determination of causality in an individual case is difficult because the same abnormalities also occur in uncomplicated pregnancies. Nevertheless, microscopic examination of the placenta is commonly performed as part of the perinatal autopsy. (See "Evaluation of stillbirth", section on 'Components of the perinatal autopsy'.)

Physical activity reduces risk of type 2 diabetes after gestational diabetes (July 2014)

Increasing evidence suggests that an active lifestyle reduces the risk of developing type 2 diabetes in women with gestational diabetes. In a 16-year prospective observational study, 14 percent of women with a history of gestational diabetes self-reported the development of type 2 diabetes [7]. Women with a total physical activity level equivalent to 150 minutes per week of moderate-intensity physical activity or 75 minutes per week of vigorous-intensity physical activity had a 30 to 50 percent lower risk of developing type 2 diabetes than women with lower levels of physical activity. (See "Gestational diabetes mellitus: Glycemic control and maternal prognosis", section on 'Follow-up and prevention of type 2 diabetes'.)

Benefits of controlled cord traction (June 2014)

We suggest controlled cord traction to facilitate separation and delivery of the placenta. In a 2014 meta-analysis of randomized trials comparing controlled cord traction with a hands-off approach, controlled cord traction resulted in a 30 percent reduction in need for manual removal of the placenta, as well as small reductions in the duration of the third stage (three minutes), mean blood loss (10 mL), and incidence of postpartum hemorrhage (11.8 versus 12.7 percent); the rates of severe postpartum hemorrhage, need for additional uterotonics, and blood transfusion were similar [8]. Although the benefits of controlled cord traction are small, there are no significant harms from the maneuver if performed without excessive traction. (See "Management of normal labor and delivery", section on 'Delivery of the placenta'.)

Fish consumption advisory (June 2014)

Because of the potential fetal benefits of maternal docosahexaenoic acid (DHA) intake, the US Food and Drug Administration and the US Environmental Protection Agency now advise women who might become pregnant, pregnant women, and breastfeeding women to consume 8 to 12 ounces of a variety of fish lower in mercury each week (table 1), rather than "up to 12 ounces" as previously recommended [9]. This is consistent with two to three servings of fish per week. We suggest that pregnant and breastfeeding women try to achieve fish consumption resulting in at least 200 mg/day DHA intake instead of relying on the number of servings of fish, since fish vary widely in DHA content. (See "Fish consumption during pregnancy", section on 'Diet and supplements'.)

Risk of perinatal transmission of HBV in the United States (June 2014)

Administration of hepatitis B virus (HBV) vaccination and hepatitis B immune globulin (HBIG) to newborns of women with chronic HBV infection significantly reduces the risk of perinatal HBV transmission but does not eradicate it. In an observational study of over 4000 infants born to HBV-infected mothers in the United States between 1997 and 2010, over 95 percent received HBV vaccination and HBIG [10]. Perinatal transmission occurred in 3.40 percent of births to hepatitis B e antigen (HBeAg) positive mothers and 0.04 percent of births to HBeAg negative mothers. Among women whose HBV DNA results and HBeAg status were known, no HBV transmission occurred with a viral load less than 5 x107 IU/mL, regardless of the HBeAg status. (See "Hepatitis B and pregnancy", section on 'HBV DNA level'.)

Antidepressants and risk of preterm delivery (May 2014)

Use of antidepressants during pregnancy may be associated with preterm delivery, and a new study suggests that this effect may be related to the timing of exposure. In a meta-analysis of 41 observational studies, third trimester exposure to antidepressants was associated with an approximately twofold higher risk of preterm birth compared with no exposure, whereas first trimester exposure was not associated with increased risk [11]. Management of depression during pregnancy requires that these and other potential risks of medications be weighed against the maternal and fetal risks of untreated illness. (See "Risks of antidepressants during pregnancy", section on 'Antidepressant composite data'.)

Effect of gravity on placental transfusion (April 2014)

The length of time a mother can safely hold her newborn before the umbilical cord is clamped is controversial because of concerns that gravity may decrease the volume of placental transfusion. In the first randomized trial evaluating this issue, the location of the newborn above or below the level of the placenta for two minutes before cord clamping did not affect the volume of placental transfusion (as assessed by change in newborn weight) [12]. This finding suggests that placing the newborn on the maternal abdomen or chest before cord clamping does not adversely affect the volume of placental transfusion. (See "Management of normal labor and delivery", section on 'Cord clamping'.)

Hyperimmune globulin does not prevent congenital CMV infection (April 2014)

Although prospective observational studies have reported that administration of hyperimmune globulin to pregnant women with primary cytomegalovirus (CMV) infection reduced maternal-to-fetal transmission and the severity of congenital infection, a recent randomized trial did not demonstrate a significant benefit. The Congenital Human CMV Infection Prevention (CHIP) trial randomly assigned pregnant women at 5 to 26 weeks of gestation with recent onset primary CMV infection to receive hyperimmune globulin or placebo every four weeks [13]. The overall rate of congenital infection and the proportion of infected infants symptomatic at birth was similar for both groups. (See "Cytomegalovirus infection in pregnancy", section on 'Hyperimmunoglobulin'.)

Vancomycin dose for intrapartum GBS chemoprophylaxis (April 2014)

A study has found that vancomycin dosing recommendations from a 2010 guideline from the US Centers for Disease Control (CDC) regarding intrapartum chemoprophylaxis of neonatal early-onset Group B Streptococcus may provide subtherapeutic levels in neonates. The CDC guidelines recommend vancomycin 1 gram every 12 hours for penicillin allergic women if GBS isolates are resistant to clindamycin or susceptibility results are not available. However, a 2014 study of vancomycin levels in neonatal cord blood noted that therapeutic levels were infrequently achieved in neonates whose mothers received this dose, but usually were achieved with maternal weight-based dosing (20 mg/kg every 8 hours; maximum dose 2 grams) [14]. We now suggest weight-based dosing for vancomycin intrapartum GBS chemoprophylaxis. (See "Neonatal group B streptococcal disease: Prevention", section on 'Patients with penicillin allergy'.)


Long-acting reversible contraception for adolescents (October 2014)

The intrauterine device and etonogestrel implant are two types of long-acting reversible contraception (LARC). Although LARC is more effective than other methods, few adolescents choose LARC. Lack of access to services, lack of information, and increased cost may be barriers to LARC for adolescents. Removal of these barriers appears to be associated with increased use of LARC and decreased rates of pregnancy. In a prospective study, 1404 urban adolescents 15 to 19 years of age were educated about reversible contraception (emphasizing the benefits of LARC), provided with their choice of reversible contraception at no cost, and followed for two to three years [15]. Nearly three-quarters of participants chose LARC. The pregnancy rate among participants was nearly five times less than that in a contemporaneous cohort of sexually active teenagers in the United States (34.0 versus 158.5 per 1000). The American Academy of Pediatrics now recommends the etonogestrel implant and intrauterine device as first-line contraceptive options for adolescents [16]. (See "Contraception: Overview of issues specific to adolescents", section on 'Overcoming barriers'.)

Levonorgestrel IUD in endometrial carcinoma prevention (September 2014)

The levonorgestrel-releasing intrauterine device (LNg-IUD) is a popular option for both contraception and treatment of abnormal uterine bleeding (AUB). It also appears to have a preventive effect on endometrial carcinoma, at least in women with AUB. One of the largest studies of this issue was a national registry study from Finland that reported that women using the LNg-IUD for treatment of menorrhagia had one-half the expected incidence of endometrial carcinoma [17]. The results of this study support a potential preventive, as well as therapeutic, role of the LNg-IUD in women with AUB. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Hormonal contraceptives'.)

KEEPS hormone therapy trial in newly menopausal women (September 2014)

The Women's Health Initiative (WHI), a set of menopausal hormone therapy (MHT) trials in older postmenopausal women (average age 63 years) reported an excess risk of coronary heart disease (CHD) with MHT. Emerging data, including secondary analyses from the WHI, now suggest that use of MHT in the early menopausal years is not associated with excess CHD risk. The Kronos Early Estrogen Prevention Study (KEEPS) is the first randomized trial of MHT in younger menopausal women (727 women ages 45 to 54 years) [18]. When combined with cyclical monthly oral progesterone, low dose oral conjugated estrogen (0.45 mg daily) or transdermal estradiol (50 mcg daily) for four years relieved menopausal symptoms. While several markers of cardiovascular risk improved in the MHT group, there was no significant effect on surrogate markers of atherosclerosis progression (coronary artery calcium and carotid intima-medial thickness) when compared to placebo. This trial provides additional reassurance that early use of MHT is safe for the treatment of menopausal symptoms, though it does not support a role for MHT in prevention. (See "Menopausal hormone therapy and cardiovascular risk", section on 'Timing of exposure'.)

Injectable progestins and risk of venous thrombosis (September 2014)

In contrast to other progestin-only contraceptives, depot medroxyprogesterone acetate (DMPA) use may be associated with an increased risk of venous thrombosis and embolism (VTE). In a case-control study, women with a first episode of VTE were twice as likely to be DMPA users than were controls in the general population [19]. In this study, VTE was not associated with use of progestin-only pills, the levonorgestrel-releasing intrauterine device, or the progestin-only contraceptive implant. However, in the absence of data about absolute risk of VTE in DMPA users, we continue to think that the advantages of using DMPA generally outweigh the risks for women with a history of VTE. (See "Depot medroxyprogesterone acetate for contraception", section on 'Cardiovascular risk'.)

Oral emergency contraception in overweight women (August 2014)

In Europe, product labeling for levonorgestrel-based emergency contraception (NorLevo) was updated in February 2014 to indicate that it may be less effective in women ≥75 kg (165 pounds). In July 2014, the European Medicines Association concluded that the available data were not robust enough to be certain the contraceptive efficacy of levonorgestrel emergency contraception is reduced with increased bodyweight and that the benefits of taking the medication outweighed any risks [20]. We counsel overweight and obese women of potentially reduced efficacy of levonorgestrel emergency contraception as BMI increases above the normal range (25 kg/m2) or at weights ≥75 kg (165 pounds), and offer them a copper-releasing IUD as first-line therapy to prevent pregnancy. If the IUD is not an option, ulipristal is more likely to be effective than levonorgestrel. (See "Emergency contraception", section on 'Overweight and obese women'.)

Pelvic examination in asymptomatic women (July 2014)

Routine pelvic examinations in asymptomatic women are controversial. The American College of Physicians has issued guidelines that advise against performing screening pelvic examinations in asymptomatic, nonpregnant, adult women [21]. The American College of Obstetricians and Gynecologists continues to recommend annual pelvic examination for nonpregnant women age 21 years and older, but suggests that asymptomatic women participate in the decision [22]. We believe the decision whether or not to perform a complete pelvic examination at the time of the periodic health examination for the asymptomatic patient should be a shared decision after a discussion between the patient and her healthcare provider. (See "The gynecologic history and pelvic examination", section on 'Indications and frequency for examination'.)

Topical lidocaine for dyspareunia after treatment for breast cancer (May 2014)

Dyspareunia is a frequent issue for women after treatment for breast cancer. For women with dyspareunia isolated to tenderness in the vulvar vestibule, topical lidocaine appears to provide effective relief. This was shown in a small trial that included 49 women randomly assigned to local treatment with topical lidocaine or normal saline [23]. Compared with normal saline, topical lidocaine resulted in a significant reduction in coital pain scores. While these data suggest that topical lidocaine can effectively treat dyspareunia in women with vulvar vestibule discomfort, its effectiveness for women who have findings of intravaginal or pelvic floor pain is not known. (See "Approach to the patient following treatment for breast cancer", section on 'Sexual health'.)

Cobas HPV test and cervical cancer screening (May 2014)

The cobas HPV test for cervical cancer screening detects the presence of HPV types 16 and 18 with a pooled result for 12 additional high-risk types. HPV types 16 and 18 confer the highest risk for cervical cancer among HPV types. The cobas HPV test was approved by the US Food and Drug Administration (FDA) in April 2014 for use alone as primary screening in women 25 years of age and older [24]. Evidence regarding use of the cobas HPV test as stand-alone testing is not yet publicly available. Awaiting review of this evidence, we continue to recommend cytological (Pap smear) screening for cervical cancer in women 21 to 30 years of age, and either Pap smear alone or co-testing with Pap and HPV testing in women age 30 and older. (See "Screening for cervical cancer: Rationale and recommendations", section on 'HPV testing'.)


Risk of dissemination of gynecologic tumors with power morcellation (April 2014, MODIFIED August 2014)

Unsuspected gynecologic malignancy is detected postoperatively in a small proportion of women who undergo laparoscopic hysterectomy or myomectomy with power morcellation (cutting the uterus into small pieces to facilitate removal). In such cases, power morcellation may disseminate malignant cells and potentially worsen the survival outcome. In April 2014, the US Food and Drug Association (FDA) issued a safety communication that discouraged power morcellation during laparoscopic hysterectomy or myomectomy in women with uterine fibroids and stated that morcellation should not be used in women with known or suspected uterine cancer [25]. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Professional society and FDA statements'.)

Accurate estimates of the prevalence of malignancy at the time of laparoscopic hysterectomy with power morcellation are lacking. In the largest study to date, among 36,370 women who underwent laparoscopic or robotic hysterectomy with power morcellation, there were 99 cases of uterine cancer (0.27 percent) and 26 cases of other gynecologic malignancies (0.07 percent) [26]. The prevalence of gynecologic malignancy increased with age. Compared with women younger than 40 years, the prevalence of gynecologic malignancy was approximately 5-fold higher for women 50 to 54 and 19-fold higher for women 55 to 59 years. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Prevalence of sarcoma after surgery for presumed leiomyomas'.) 

Power morcellation should be avoided in women with known or suspected uterine or other gynecologic cancer or significant risk factors for uterine sarcoma (eg, postmenopausal status; ≥2 years of tamoxifen therapy; history of pelvic radiation, childhood retinoblastoma, or hereditary leiomyomatosis and renal cell carcinoma syndrome). Patients should be counseled about the risk of tumor dissemination if an unsuspected malignancy is present. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Do morcellation, myomectomy, or supracervical hysterectomy worsen prognosis?'.)

Salpingostomy versus salpingectomy for tubal ectopic pregnancy (May 2014, MODIFIED July 2014)

Tubal pregnancy may be treated surgically with salpingostomy or salpingectomy. A randomized trial comparing salpingostomy and salpingectomy in 446 women found similar rates of spontaneous intrauterine pregnancy at 36 months (61 and 56 percent) [27]. The rate of repeat ectopic pregnancy in the ipsilateral tube was also similar (3 versus 1 percent). Based on the comparable reproductive outcomes in this and other studies, salpingostomy is preferred for most women because the fallopian tube is conserved. Salpingectomy is required for women with or at high risk of tubal rupture or with severe tubal damage. (See "Surgical treatment of ectopic pregnancy", section on 'Salpingostomy versus salpingectomy'.)


FDA approval for bevacizumab for cervical cancer (August 2014)

For women with advanced, recurrent, or metastatic cervical cancer, a Gynecologic Oncology Group randomized trial (GOG 240) showed that chemotherapy plus bevacizumab significantly improved outcomes, including a prolongation of overall survival, compared with the administration of chemotherapy alone. Based on these results, the US Food and Drug Administration approved the use of bevacizumab in combination with chemotherapy for these patients in August 2104 [28]. Despite these developments, issues related to costs of therapy may need to be considered, especially in underdeveloped areas. (See "Management of recurrent or metastatic cervical cancer", section on 'Chemotherapy plus bevacizumab as first-line treatment'.)

Opportunistic salpingectomy and operative outcomes (August 2014)

Opportunistic salpingectomy (the removal of the fallopian tubes in a woman undergoing pelvic surgery for another indication) is a new strategy for the primary prevention of ovarian, fallopian tube, or peritoneal carcinoma in average-risk women. Adoption rates are high in Canada, where it was first proposed, and the first large study found no increase in operative morbidity. This retrospective population-based cohort study found an increase in the rate of salpingectomy performed at the time of hysterectomy (from 5 to 35 percent) or sterilization (from <1 to 33 percent) between 2008 and 2011 [29]. Opportunistic salpingectomy was associated with a modest increase in operative duration (10 to 16 minutes), but no increase in the rate of blood transfusion or readmission. Although opportunistic salpingectomy appears to be safe, further study is necessary to determine the impact on gynecologic cancer risk. (See "Opportunistic salpingectomy for ovarian, fallopian tubal, and peritoneal carcinoma risk reduction", section on 'Outcome'.)

Tubal ligation and risk of ovarian cancer (June 2014)

Tubal ligation is associated with a decreased risk of ovarian cancer. The Nurses’ Health Study and Nurses’ Health Study II, two large prospective cohort studies, found that tubal ligation was associated with a 24 percent decrease in the risk of ovarian cancer [30]. The effect was stronger for endometrioid, clear cell, and mucinous carcinomas than for serous carcinomas. This finding provides support for the role of the fallopian tube in the pathogenesis of ovarian cancer. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Tubal ligation'.)


Letrozole versus clomiphene citrate for ovulation induction in PCOS (October 2014)

Clomiphene citrate (CC) has been the first line ovulation induction drug for women with polycystic ovary syndrome (PCOS) for many years. However, a multicenter trial in 750 women with PCOS suggests that letrozole results in higher cumulative birth rates (over five cycles) when compared to CC (27.5 percent and 19.1 percent, respectively) [31]. Body mass index (BMI) had a significant impact on live birth rates. For women with a BMI ≤30.3, the cumulative live birth rate (approximately 30 percent) was similar in the CC and letrozole groups. For women with a BMI ≥30.3, the cumulative live birth rates were significantly higher with letrozole when compared to CC (20 versus 10 percent). The possible advantage of letrozole was supported by a meta-analysis of six trials, including this multicenter trial, comparing letrozole and CC, which found higher birth rates with letrozole although BMI data were not provided [32].

Safety data suggest that letrozole is not associated with an increased risk of congenital malformations, but the evidence is based upon a relatively small number of pregnancies. Unlike CC, letrozole is not approved in any country for ovulation induction. However, based upon available data, for women with PCOS pursuing ovulation induction, we now suggest letrozole for those with a BMI >30 kg/m2, while we still suggest CC for those with a BMI ≤30 kg/m2.

(See "Ovulation induction with letrozole", section on 'Ovulation induction in PCOS'.)


Transobturator versus retropubic slings for stress urinary incontinence (July 2014)

Midurethral slings are the most common surgical treatment for stress urinary incontinence in women. The two techniques for this procedure are the retropubic and the newer transobturator sling routes. Growing data have suggested that they are comparably effective treatments for stress urinary incontinence. A meta-analysis of 21 randomized trials found no significant difference between these two techniques in subjective and objective cure rates [33]. The distinct perioperative complications associated with each technique are important factors in deciding between the two. (See "Stress urinary incontinence in women: Choosing a type of midurethral sling", section on 'Transobturator versus retropubic midurethral slings'.)

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