Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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.
Oxytocin induction not associated with autism (August 2016)
A possible association between oxytocin induction of labor and development of autism in offspring has been widely publicized in the lay press, based on findings from a single epidemiological study. Recently, a nationwide epidemiologic study in Sweden found no association between labor induction and autism in offspring when adjustments were made for environmental and genetic factors shared by siblings . A strength of this study was that comparison of exposure-discordant births to the same woman allowed control for all unmeasured factors shared by siblings. We believe an association between oxytocin induction and autism is unlikely. (See "Induction of labor", section on 'Other'.)
Low-dose aspirin for preeclampsia prophylaxis (August 2016)
In July 2016, the American College of Obstetricians and Gynecologists (ACOG) endorsed the United States Preventive Services Task Force (USPSTF) recommendation for use of low-dose aspirin prophylaxis in women at high risk of developing preeclampsia, and identified these women based on the same criteria designated by the USPSTF . Prior to July 2016, ACOG defined high risk more narrowly: history of early-onset preeclampsia and preterm delivery <34 weeks of gestation or more than one prior pregnancy complicated by preeclampsia. The broader USPSTF criteria included multifetal gestation, chronic hypertension, pregestational diabetes, renal disease, and some autoimmune diseases. We continue to suggest low-dose aspirin prophylaxis for women included under the broader criteria, as well as some women with multiple moderate risk factors for preeclampsia. (See "Preeclampsia: Prevention", section on 'Guidelines from selected organizations'.)
Mosquito-borne transmission of Zika virus in the continental United States (August 2016)
Zika virus is a mosquito-borne infection associated with congenital microcephaly and other birth defects among babies born to women infected during pregnancy. Mosquito-borne transmission of Zika virus was detected in Florida in July 2016, and in August 2016 the United States Centers for Disease Control and Prevention (CDC) issued an advisory recommending that pregnant women avoid travel to affected areas . Updates regarding areas with Zika may be found on the CDC website (http://www.cdc.gov/zika/). (See "Zika virus infection: An overview", section on 'Travel advisories for pregnant women'.)
Testing for Zika virus infection in pregnant women (July 2016)
The approach to testing for Zika virus infection is different for pregnant versus nonpregnant individuals because Zika virus RNA persists longer in pregnant women’s serum and because pregnant women may transmit the infection to the fetus, even if the mother is asymptomatic. Congenital Zika virus infection can result in serious sequelae. The United States Centers for Disease Control and Prevention recently revised their algorithm for the diagnosis of Zika virus infection in pregnancy to reflect these principles . (See "Zika virus infection: Pregnancy and congenital infection", section on 'Clinical approach'.)
Pharmacotherapy for smoking cessation during pregnancy (July 2016)
Pregnant women are strongly encouraged to stop smoking, but the efficacy of pharmacotherapy for smoking cessation during pregnancy has been debated. In a prospective questionnaire study of over 1200 pregnant smokers, use of either nicotine replacement therapy (NRT) or bupropion in the first trimester of pregnancy was associated with smoking cessation rates of approximately 80 percent compared with a 0 percent cessation rate for smokers not using either medication . Over 60 percent of NRT and bupropion users who discontinued the medication did not resume smoking during or up to one year after pregnancy. In an adjusted analysis, both medications reduced the risk of prematurity and NRT was also associated with a nearly 40 percent reduced risk for small-for-gestational-age infants compared with continued smoking, although the sample sizes were small. We offer pharmacotherapy to pregnant women as we believe the benefits of quitting with pharmacotherapy outweigh the potential risks. (See "Cigarette smoking: Impact on pregnancy and the neonate", section on 'Nicotine replacement'.)
Safety of intranasal triamcinolone for allergic rhinitis in pregnancy (July 2016)
Intranasal glucocorticoid sprays are highly effective for treatment of allergic rhinitis, but concerns remain about their use in pregnancy. The overall safety of intranasal glucocorticoids in pregnancy was supported by an observational cohort study of over 140,000 pregnant women, of whom 2502 were exposed to these medications during the first trimester . Exposure was not associated with increased rates of miscarriage or overall rates of major congenital malformations compared with non-exposure. Triamcinolone was the only intranasal glucocorticoid of potential concern; first trimester use was associated with abnormalities of the respiratory system and choanal atresia. Although these findings are not conclusive, we prefer to use other intranasal glucocorticoids in the first trimester, such as intranasal mometasone, fluticasone, or budesonide, pending further data . (See "Recognition and management of allergic disease during pregnancy", section on 'Glucocorticoid nasal sprays'.)
WHO recommendations for infant prophylaxis to prevent mother-to-child HIV transmission (July 2016)
The World Health Organization (WHO) has updated its guidelines on the use of antiretroviral agents to manage and prevent HIV infection . One major change from previous WHO statements involves post-exposure prophylaxis of infants born to HIV-infected mothers. The recommended regimen for infant prophylaxis now takes into account the infant's risk of infection, as determined by the timing of maternal infection and maternal antiretroviral treatment, in addition to the type of infant feeding; a two-drug regimen is recommended for high-risk infants. This recommendation was based, in part, on earlier data that demonstrated a lower HIV transmission rate with dual-agent rather than single-agent prophylaxis among infants born to mothers who had not received antiretroviral agents during pregnancy. (See "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Infant antiretroviral use'.)
Induction of labor in women with low Bishop scores (June 2016)
Previously, the HYPITAT randomized trial demonstrated that routine induction of labor in women with mild preeclampsia or gestational hypertension at >360/7 weeks resulted in lower rates of adverse maternal outcome and cesarean delivery compared with expectant management with maternal/fetal monitoring. However, the outcome of women with unfavorable cervixes was not analyzed separately. In a secondary analysis of data from this trial and DIGITAT (pregnancies complicated by fetal growth restriction), induction of labor at term in women with a median Bishop score of 3 (range 1 to 6) was not associated with a higher rate of cesarean delivery than expectant management, and approximately 85 percent of women in both groups achieved a vaginal delivery . Thus, an unfavorable cervix does not alter the decision to induce labor in women with pregnancy-induced hypertension at term. (See "Preeclampsia: Management and prognosis", section on 'Preeclampsia without features of severe disease'.)
Polyhydramnios due to X-linked Bartter syndrome (May 2016)
The most common type of Bartter syndrome presenting in utero is an autosomal recessive disorder that results in fetal polyuria and subsequent polyhydramnios between 24 and 30 weeks of gestation. Persistent postnatal renal salt wasting requires life-long treatment. Recently, a severe but transient type of antenatal Bartter's syndrome was attributed to mutations in the MAGED2 gene, which maps to the X-chromosome and appears to be essential for fetal renal salt reabsorption and maintenance of normal amniotic fluid homeostasis . This X-linked disorder has very early onset of severe polyhydramnios (median 19 to 20 weeks of gestation), often resulting in preterm birth (median gestational age 22 to 34 weeks), but symptoms disappear spontaneously in infants who survive. Prenatal or early postnatal genetic diagnosis can avoid potentially harmful therapeutic interventions. (See "Polyhydramnios", section on 'Etiology'.)
Weight loss and infertility (May 2016)
Obesity is associated with increased risks for infertility and adverse pregnancy outcome. For this reason, obese women are encouraged to lose weight prior to attempting to conceive. However, the effectiveness of lifestyle-intervention programs in this population had not been evaluated by a large randomized trial. Recently, a multicenter trial randomly assigned 577 infertile women with BMI ≥29 kg/m2 to either a six-month structured weight-loss program preceding infertility treatment or prompt infertility treatment . The intervention group achieved a higher rate of natural conception (26 versus 16 percent); however, the primary outcome, term births of vaginally delivered healthy singletons, was similar in both groups. Only 38 percent of women achieved the target weight loss (5 to 10 percent of the original body weight) and 22 percent dropped out of the program, which limited interpretation of the effectiveness of the intervention. We continue to advise weight loss for infertile obese women because it is an inexpensive, low-risk intervention for improving the likelihood of natural conception and it has long-term benefits for overall health. (See "Overview of treatment of female infertility", section on 'High body weight'.)
Platelet counts in neonatal alloimmune thrombocytopenia (April 2016)
In pregnancies with human platelet antigen (HPA)-1a incompatibility, data from retrospective studies suggest that fetal/neonatal platelet counts are lower in the second affected pregnancy. However, the only prospective study of neonatal platelet counts in 29 subsequent untreated pregnancies did not confirm this finding . When the index pregnancy was complicated by neonatal alloimmune thrombocytopenia (NAIT), neonatal platelet counts in the subsequent pregnancy were the same or higher in two-thirds of cases. When the index pregnancy was complicated by NAIT with severe thrombocytopenia, neonatal platelet counts in the subsequent pregnancy were the same or higher in 29 percent of cases. These findings, if confirmed in larger studies, suggest that the severity of NAIT does not consistently worsen in subsequent pregnancies. (See "Neonatal alloimmune thrombocytopenia: Parental evaluation and pregnancy management", section on 'Background'.)
Artemisinin combination therapy for uncomplicated falciparum malaria in pregnancy (March 2016)
An artemisinin combination therapy (ACT) is the regimen of choice for treatment of pregnant women with uncomplicated chloroquine-resistant P. falciparum malaria during the second or third trimesters. This approach is supported by a recent large trial including 3428 pregnant women in four African countries (Burkina Faso, Ghana, Malawi and Zambia) randomly assigned to treatment with one of four ACT regimens (artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate, or dihydroartemisinin-piperaquine) with cure rates of 95 to 99 percent . Dihydroartemisinin-piperaquine had the best efficacy and an acceptable safety profile, with the benefit of a longer post-treatment prophylactic effect. Artemether-lumefantrine was associated with the fewest adverse effects and acceptable cure rates, but had the shortest post-treatment prophylactic effect; this may be particularly important in high-transmission settings where a prolonged post-treatment prophylactic effect can reduce morbidity by decreasing the frequency of new infections. (See "Prevention and treatment of malaria in pregnant women", section on 'Second and third trimesters'.)
Pessary use for reduction of preterm birth (March 2016)
The efficacy of using a vaginal pessary to improve pregnancy outcome in women with a short cervix is controversial. Recently, the largest randomized trial of pessary use in pregnant women with a short cervix (n = 932 participants) reported no differences between the pessary and control (no pessary) groups in rates of spontaneous delivery <34 weeks, perinatal death, adverse neonatal events, or need for neonatal special care . We believe the body of evidence does not support pessary use for pregnant women with a short cervix. However, further study is warranted as the available evidence is limited by differences in use of progesterone prophylaxis and the low number of preterm births and neonatal complications in published trials. (See "Cervical insufficiency", section on 'Pessary'.)
Vaginal progesterone and risk for preterm birth (March 2016)
Progesterone (intramuscular or vaginal) is administered to pregnant women with a history of preterm birth or a short cervix in the current pregnancy to reduce the risk of preterm birth. However, a recent large trial did not observe a benefit for vaginal progesterone. In the OPPTIMUM trial, over 1200 women at high risk for preterm birth by various criteria were randomly assigned to receive either vaginal progesterone or a placebo daily, beginning at 22 to 24 weeks of gestation and ending at 34 weeks . Progesterone supplementation did not reduce any of the primary study outcomes: fetal death or birth before 34 weeks; neonatal death, brain injury, or bronchopulmonary dysplasia; cognitive score at two years of age.
We continue to suggest hydroxyprogesterone caproate injections for women with a previous preterm birth because this drug was effective in previous trials and not evaluated by this trial. We continue to suggest vaginal progesterone for women with a short cervix since this population was not the focus of this trial. An updated meta-analysis addressing vaginal progesterone supplementation for women with a short cervix that includes data from this new trial would be helpful. (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on 'OPPTIMUM (progesterone capsules vaginally)'.)
Induction of labor in women 35 years and older (March 2016)
The risk of stillbirth at term rises with increasing maternal age. Term induction of labor for older mothers may reduce the risk of stillbirth but has raised concerns for potentially increasing cesarean and operative vaginal delivery rates. However, in a trial of over 600 women aged 35 years or older, cesarean and operative vaginal delivery rates were similar among women induced in the 39th week of pregnancy or expectantly managed . This study adds to the body of literature indicating that induction of labor at term does not increase the rates of cesarean or operative vaginal delivery. (See "Management of infertility and pregnancy in women of advanced age", section on 'Risk of stillbirth versus delivery'.)
Hypertensive disorders of pregnancy and future risk of cardiomyopathy (March 2016)
The American Heart Association considers a history of preeclampsia or pregnancy-induced hypertension a major risk factor for development of ischemic heart disease and stroke later in life. A recent retrospective population-based cohort study reported the new finding that women with a hypertensive disorder of pregnancy were also at increased risk for cardiomyopathy >5 months after delivery compared with women without this history, although the absolute risk of cardiomyopathy was small . Only about 50 percent of cases were associated with chronic hypertension after delivery, suggesting other factors were responsible for cardiomyopathy. This study supports current recommendations to include hypertensive disorders of pregnancy as a major risk factor for future cardiovascular disease, including cardiomyopathy. (See "Preeclampsia: Management and prognosis", section on 'Cardiovascular disease'.)
Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy (March 2016, Modified March 2016)
For pregnant women who live in areas with medium and high malaria transmission, we agree with the World Health Organization (WHO) strategy to provide intermittent preventive treatment during pregnancy (IPTp). Sulfadoxine-pyrimethamine (SP) has been an effective drug for IPT, although its benefit may be limited given the emergence of drug resistance. Two trials in Kenya and Uganda (where SP resistance is widespread) have evaluated the efficacy of dihydroartemisinin-piperaquine (DP) for IPTp:
●In a trial including over 1500 Kenyan women randomly assigned to receive IPT with SP or DP, IPT with DP resulted in a lower prevalence of malaria infection at delivery (3 versus 10 percent) and fewer episodes of clinical malaria during pregnancy (38 versus 6 episodes) compared with IPT with SP . The trial was not powered to detect small differences in neonatal outcomes.
●In a trial including 300 pregnant adolescents and women in Uganda randomly assigned to receive IPT with SP (three doses), DP (three doses), or DP (monthly treatments starting as early as 16 weeks of gestation) , the prevalence of histopathologically confirmed placental malaria was lower among those who received monthly DP (27 percent) than among those who received three doses of DP (34 percent) or IPT with SP (50 percent). In addition, monthly DP treatment was superior to three-dose DP with regard to several outcomes, including adverse birth outcomes and the incidence of symptomatic malaria.
DP is a promising alternative agent for IPTp; further study of DP dosing in pregnancy is needed. (See "Prevention and treatment of malaria in pregnant women", section on 'Intermittent preventive treatment during pregnancy'.)
Pessary placement and twin pregnancies with a short cervix (February 2016)
Whether pessary placement prolongs the length of gestation in pregnancies with a short cervical length is controversial. In a multi-center randomized trial in Spain, placement of a pessary in twin pregnancies with a short cervix at 18 to 22 weeks significantly reduced the rate of spontaneous preterm birth <34 weeks, the primary study outcome . However, there was no difference in a composite neonatal morbidity outcome for pessary use compared with no pessary use. Pending confirmatory data from additional studies and demonstration of improvement in neonatal outcome, we do not currently advise this intervention. (See "Twin pregnancy: Prenatal issues", section on 'Unproven interventions to prevent or delay preterm labor'.)
Antenatal steroids at 34 to 37 weeks for pregnancies at high risk of preterm birth (February 2016)
Antenatal corticosteroid therapy at 23 to 34 weeks of gestation for women at risk for preterm delivery reduces the incidence and severity of respiratory distress syndrome in offspring delivered within seven days of administration. Steroids have not been administered after 34 weeks because studies have not demonstrated a benefit, although data have been sparse. Recently, the Antenatal Late Preterm Steroids (ALPS) Trial randomly assigned women at 340/7ths to 365/7ths weeks of gestation at high risk for late preterm birth to receive a first course of antenatal betamethasone or placebo and found that the frequency of a composite outcome of neonatal respiratory problems was reduced in the betamethasone group . Based on these data, we believe offering a first course of antenatal corticosteroids to patients scheduled for cesarean delivery at 340/7ths to 366/7ths weeks is reasonable. We would not administer a first course of steroids to women at 340/7ths to 366/7ths weeks planning vaginal delivery as transient tachypnea of the newborn is less common after labor and vaginal birth. For women in whom delivery at 340/7ths to 366/7ths is uncertain (eg, threatened preterm labor), we would not administer a course of steroids because of the potential for long-term harm with no benefit if the patient does not deliver preterm. For women at 340/7ths to 366/7ths weeks who received a course of antenatal corticosteroids earlier in pregnancy, we would not administer a second course as the benefits and risks have not been studied in this population. This approach limits late preterm in utero steroid exposure to pregnancies certain to deliver preterm and with neonates at most risk for experiencing serious respiratory problems from transient tachypnea of the newborn. We do not administer steroids to women undergoing scheduled cesarean delivery at ≥37 weeks: the overall risk of respiratory illness at this gestational age is low and rarely serious. (See "Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality from preterm delivery", section on 'After 34 weeks'.)
Metformin use in nondiabetic obese pregnant women does not improve neonatal outcome (February 2016)
It has been hypothesized that administering metformin to nondiabetic obese pregnant women might reduce gestational weight gain and, in turn, pregnancy complications associated with obesity. In the Metformin in Obese Nondiabetic Pregnant Women randomized trial, metformin use in the second and third trimesters reduced gestational weight gain compared with placebo (4.6 versus 6.3 kg) and the rate of preeclampsia (3 versus 11.3 percent), but did not reduce the frequency of large for gestational age neonates or adverse neonatal outcomes . Based on these and other recent data , we believe use of metformin in pregnancy should be limited to management of hyperglycemia. (See "Weight gain and loss in pregnancy", section on 'Metformin'.)
Sleep disorders in the menopausal transition: Telephone-based cognitive behavioral therapy (August 2016)
New-onset sleep disturbances are common in perimenopausal and menopausal women, occurring most often in women with hot flashes, but also in women without hot flashes. Midlife women with insomnia are usually treated with pharmacologic therapies (estrogen or hypnotic agents), but effective behavioral therapies are also available, including in-person cognitive behavioral training (CBT) for insomnia. In-person CBT, while effective, has practical limitations (availability, cost, and scheduling challenges), so alternative CBT strategies have been explored. In one trial, 106 peri- and postmenopausal women with insomnia and hot flashes were randomly assigned to an eight-week intervention with telephone-based cognitive behavioral therapy for insomnia (CBT-I) versus standard menopause education control (MEC) (also telephone-based) . After eight weeks, CBT-I, but not MEC, resulted in a clinically meaningful insomnia score reduction. The percentage of women who achieved Insomnia Index Severity scores in the “no insomnia” range was 70 and 24 percent for CBT-I and MEC, respectively. CBT-I reduced hot flash “bother” but not frequency. (See "Menopausal hot flashes", section on 'Promising therapies: Need further study'.)
Treatment failure of pharyngeal gonorrhea following combination antimicrobial therapy (July 2016)
Because of concerns about the decreasing susceptibility of Neisseria gonorrhoeae to several classes of antibiotics, combination antimicrobial therapy with ceftriaxone plus a second agent, preferably azithromycin, is the recommended treatment for uncomplicated gonorrhea. However, treatment failure following combination therapy has now been reported, in a heterosexual man from the United Kingdom who presented with both urogenital and pharyngeal infection . Although the urogenital infection was successfully treated with ceftriaxone plus azithromycin, the pharyngeal infection persisted, and decreased susceptibility to both agents was detected in the post-treatment isolate. This report, in addition to surveillance reports suggesting increasing rates of decreased susceptibility to azithromycin in N. gonorrhoeae isolates in the United States , highlights the need for novel treatment strategies for gonorrhea in the face of rising antimicrobial resistance. (See "Treatment of uncomplicated gonococcal infections", section on 'Monitoring for and managing treatment failure' and "Treatment of uncomplicated gonococcal infections", section on 'Rationale for dual therapy'.)
Shortage of benzathine penicillin G (Bicillin L-A) (May 2016)
In May 2016, the United States Centers for Disease Control and Prevention reported a manufacturing delay of benzathine penicillin G (Bicillin L-A), which is the treatment of choice for all stages of syphilis . In light of potential shortages of this agent, it is important for clinicians to note that only a single dose of benzathine penicillin G is warranted for early syphilis. Pregnant women with syphilis should be prioritized for benzathine penicillin G, and so alternative regimens, such as doxycycline, may need to be used for nonpregnant adults if supplies are limited. Bicillin C-R (equal concentrations of procaine and benzathine penicillin G) should not be used to treat syphilis. (See "Syphilis: Treatment and monitoring", section on 'Penicillin as the treatment of choice'.)
Efficacy and safety of flibanserin for low sexual desire in women (May 2016)
Flibanserin, the only drug approved by the US Food and Drug Administration (FDA) for female sexual dysfunction, results in modest increases in sexual desire in women with decreased desire associated with distress. A recent meta-analysis of eight placebo-controlled randomized trials provided the best available evidence of the safety and efficacy of flibanserin . Use of flibanserin resulted in small but significant increases in sexual desire and the number of sexually satisfying events per month, but also increased the risk for mild adverse events, such as dizziness, somnolence, nausea, and fatigue. More severe effects, such as hypotension or syncope, also occur and are magnified with concurrent alcohol use. We believe the clinical role of flibanserin may be limited by the daily dosing regimen, low efficacy, risk of adverse effects, and safety concerns if alcohol is consumed or the woman is taking certain medications (eg, fluconazole, antidepressants). (See "Sexual dysfunction in women: Management", section on 'Flibanserin'.)
Revised FDA labeling for mifepristone for first trimester abortion (April 2016)
The US Food and Drug Administration has revised labeling for mifepristone as used for first trimester abortion . In the new mifepristone/misoprostol protocol, the gestational age has been extended from 49 days to 70 days, the mifepristone dose has been reduced from 600 mg orally to 200 mg orally, the misoprostol dose has been increased from 400 mcg orally to 800 mcg buccally, and misoprostol can be self-administration instead of by a clinician. The dosing changes are consistent with a protocol called the “evidence-based regimen” that UpToDate recommends and already used by many clinicians. (See "First-trimester medication abortion (termination of pregnancy)", section on 'Medication regimen'.)
Pregnancy risk with progestin-releasing implants in HIV-infected women using efavirenz (March 2016)
Potential drug interactions are important considerations when choosing hormonal contraception for HIV-infected women on antiretroviral therapy (ART). Two recent observational studies from Africa have suggested that drug interactions between the non-nucleoside reverse transcriptase inhibitor efavirenz and progestin-releasing implants (both levonorgestrel and etonogestrel) are associated with decreased contraceptive efficacy [30,31]. In one of these studies, the adjusted pregnancy incidence among over 6000 women using progestin-releasing implants was three times higher in those using an efavirenz- versus a nevirapine-based regimen . If a progestin-releasing implant is the preferred contraceptive method for a women taking an efavirenz-based ART regimen, a second form of contraception should also be used. (See "HIV and women", section on 'Drug interactions'.)
Effects of hormonal contraceptives on libido (March 2016)
Available data on the effect of hormonal contraceptives on female sexuality are inconsistent. In the largest study to address this issue, a prospective cohort study found that women who used the copper intrauterine device (IUD) reported lower rates of lack of interest in sex than women using depot medroxyprogesterone, the progestin implant, and the estrogen-progestin vaginal ring, but rates similar to users of the progestin IUD, estrogen-progestin oral contraceptive, and estrogen-progestin patch . In a subset of participants who were using no contraceptive method or withdrawal at baseline, lack of interest in sex at six months was less than at baseline (24 versus 42 percent). Further study is needed to understand whether and how hormonal contraceptives impact sexual function. (See "Sexual dysfunction in women: Epidemiology, risk factors, and evaluation", section on 'Hormonal contraceptives'.)
Screening for ovarian cancer in average risk women (March 2016)
The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is the largest randomized trial evaluating the use of serum testing for CA 125 and transvaginal ultrasound (TVUS) for ovarian cancer screening in average risk women . The trial compared three arms: no screening; screening with annual transvaginal ultrasound; and multimodal screening (MMS, consisting of annual CA 125 testing, followed by TVUS if the CA 125 was abnormal, using an algorithmic guideline). After a median of 11 years, cancers were detected in 0.7 percent of women in the MMS group and 0.6 percent of women in the control and TVUS-only groups. Compared with no screening, MMS detected cancer at an earlier stage and the primary analysis showed a nonsignificant trend toward a 15 percent reduction (95% CI -3 to 30) in mortality from ovarian cancer for MMS. When prevalent ovarian cancer cases were excluded, the mortality reduction with MMS was significant. The results of the UKCTOCS trial are not consistent with results from another randomized trial that did not show decreased mortality with MMS. Based on the available data, it is not clear that the benefits of screening for ovarian cancer outweigh the harms related to the adverse effects associated with false positive findings. UpToDate suggests not screening average risk women for ovarian cancer. (See "Screening for ovarian cancer", section on 'Multimodal screening'.)
In-bag morcellation (August 2016)
Use of contained tissue extraction during power morcellation of uterine tissue has been hypothesized to reduce the risk of disseminating cells from an unsuspected malignancy. A new tissue containment system (PneumoLiner) for use with certain laparoscopic power morcellators was approved by the US Food and Drug Administration (FDA) in April 2016 . However, this device has not been proven to reduce the risk of spreading cancer.
A recent multicenter prospective study of women who underwent hysterectomy or myomectomy using a contained power morcellation technique (not the PneumoLiner) reported spillage of tissue or dye in 9.2 percent of cases, even though containment bags were intact . The only randomized trial of in-bag manual versus uncontained power morcellation in women undergoing laparoscopic myomectomy found no differences in total procedure time, morcellation time, simplicity of morcellation, or operative complications . Further study is needed to evaluate the safety of in-bag morcellation and the efficacy in containing cells. (See "Uterine tissue extraction by morcellation: Techniques and clinical issues", section on 'Containment systems'.)
Ovary-sparing hysterectomy reduces ovarian reserve (April 2016)
Hysterectomy with ovarian conservation has been associated with earlier menopause, but the reason is unclear. One theory is that the procedure hastens follicular depletion, and another theory is that women with underlying follicular depletion are at risk for having symptoms that prompt hysterectomy. Anti-Mullerian hormone (AMH) is a marker for the size of the ovarian follicle pool. A study including nearly 150 women who underwent ovary-sparing hysterectomy found that at one year post-hysterectomy, hysterectomized women had AMH levels that were on average 77 percent of the levels in a control group of similar age and baseline AMH levels who did not undergo hysterectomy . This finding supports the hypothesis that the surgical procedure itself hastens follicular depletion and thus increases the risk for early menopause. (See "Choosing a route of hysterectomy for benign disease", section on 'Earlier menopause or decreased ovarian reserve'.)
Showering after uncomplicated surgery (April 2016)
When a patient can resume bathing/showering after uncomplicated surgery is not well defined. A recent trial randomly assigned 444 patients undergoing procedures classified as clean or clean-contaminated to showering with the wound undressed 48 hours after surgery or no showering until stitches were removed (median time 10 days) . The rate of surgical site infection was not significantly different between the groups, suggesting that showering is safe following an initial period of wound coverage (48 hours). (See "Basic principles of wound management", section on 'Acute wounds'.)
Outcome of myomectomy with morcellation in unsuspected uterine sarcoma (August 2016)
Uterine morcellation and myomectomy in women with unsuspected uterine cancer can potentially spread malignant cells, but few data are available about the frequency of tumor dissemination and prognosis. A retrospective cohort study of 59 women with a postoperative diagnosis of previously unsuspected uterine sarcoma compared outcomes of those who underwent myomectomy with morcellation (n = 30) with those who underwent total hysterectomy (n = 29) . At five years, myomectomy with morcellation was associated with significantly lower overall survival rate (38 versus 43 percent) and a trend toward lower recurrence-free survival (24 versus 46 percent). These data illustrate the potential effects of myomectomy with morcellation in women with uterine sarcoma. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Myomectomy'.)
Role of endometrial sampling in preoperative diagnosis of uterine sarcoma (August 2016)
Uterine sarcoma is a rare and aggressive malignancy, with few reliable methods for preoperative diagnosis. In a recent study including 68 women with leiomyosarcoma who underwent endometrial sampling before surgery, the sensitivity of the test for diagnosis of features of a smooth muscle malignancy was 52 percent (leiomyosarcoma: 35 percent, spindle cell or other features suspicious for malignancy: 16 percent) . There was no significant difference in test performance between office endometrial biopsy and dilation and curettage. We suggest endometrial sampling for women with a uterine mass and signs, symptoms, risk factors, or other findings that raise suspicion of uterine sarcoma or endometrial carcinoma or for women in whom planned surgical treatment includes intraperitoneal morcellation. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Endometrial sampling'.)
Guidelines for vulvar cancer treatment from the NCCN (June 2016)
The National Comprehensive Cancer Network (NCCN) has released guidelines for the first time on the treatment of squamous cell vulvar carcinoma . The guidelines address surgery, chemotherapy, and radiation. Key sections regarding surgical resection include use of a ≥1 cm margin for surgical resection and, for women with positive margins, consideration of nodal status in deciding whether to perform a repeat resection. These guidelines are consistent with established practice in gynecologic oncology. Their publication adds an important tumor site to existing NCCN guidelines on cervical, uterine, and ovarian cancers. (See "Squamous cell carcinoma of the vulva: Staging and surgical treatment", section on 'Treatment of positive or narrow margins'.)
Menopausal hormone therapy in ovarian cancer survivors (May 2016)
Menopausal hormone therapy (HT) is generally considered safe in survivors of epithelial ovarian cancer (EOC), but data are limited. A meta-analysis of six comparative studies (including two randomized trials) of women with EOC found that those treated with menopausal HT compared with no HT had no difference in EOC recurrence . They also found lower rates of cancer death in the women who were treated with HT, but this might reflect underlying better health status among women in the nonrandomized studies who were prescribed HT treatment. HT does not appear to increase the risk of epithelial ovarian cancer recurrence or mortality. (See "Overview of the approach to survivors of epithelial ovarian, fallopian tube, or peritoneal carcinoma", section on 'Menopause'.)
Management of vaginal cytology results (May 2016)
Vaginal cancer is a rare disease, and screening with vaginal cytology is advised only for selected women at high risk (eg, prior hysterectomy and history of high-grade cervical intraepithelial neoplasia). The American Society for Colposcopy and Cervical Pathology (ASCCP) has published new guidance regarding the management of vaginal cytology results . Indications for vaginal colposcopy were provided and included: high-grade squamous intraepithelial lesion (HSIL), atypical squamous cells cannot exclude high-grade lesion (ASC-H), or atypical glandular cells (AGC); atypical squamous cells of undetermined significance (ASC-US) with human papillomavirus (HPV) 16/18-positive; and follow-up testing for ≥ASC-US or HPV-positive. This is the first guideline to address management of vaginal cytology results. (See "Cervical and vaginal cytology: Interpretation of results (Pap test report)", section on 'Management of results'.)
Atypical glandular cells on cervical cytology associated with immediate and long-term risks of cervical cancer (March 2016)
Women with atypical glandular cells (AGC) on cervical cytology appear to be at increased risk for cervical cancer in both the short and long term. A recent study used data from Swedish national registries to analyze outcomes of over 14,000 women with AGC on their first recorded cervical cancer screening test . Immediately following an AGC result, adenocarcinoma was identified in 0.99 percent of women and squamous carcinoma in 0.30 percent. Compared with women with normal cytology at their first recorded cervical cancer screening test, women with AGC continued to be at higher risk of cervical cancer for up to 15.5 years. The highest risk of cervical cancer was in the first 3.5 years, and then decreased over time. (See "Cervical cytology: Evaluation of atypical and malignant glandular cells", section on 'Histology and site of lesion'.)
Dose-dense IV chemotherapy for epithelial ovarian cancer (March 2016)
For patients receiving intravenous chemotherapy for epithelial ovarian cancer (EOC), dose-dense chemotherapy (weekly paclitaxel with carboplatin every three weeks) had previously been found to prolong progression-free survival (PFS) and overall survival (OS) relative to conventional dosing (paclitaxel and carboplatin every three weeks). By contrast, in the recent Gynecologic Oncology Group (GOG) 262 trial, dose-dense therapy did not improve outcomes in women with stage II to IV EOC (PFS of 15 versus 14 months with conventional dosing) . However, unlike previous studies, adjunctive bevacizumab was used by 84 percent of the patients in this study which may have affected the results or introduced other unmeasured confounders. Given previous data and the unknown effect that bevacizumab may have had on PFS in this study, we continue to utilize dose-dense treatment for patients treated with intravenous combination chemotherapy for advanced ovarian cancer. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer".)
Toxicity outweighs benefit of adjunctive cediranib for relapsed platinum-sensitive ovarian cancer (March 2016)
For women with relapsed platinum-sensitive epithelial ovarian cancer, there has been interest in adjunctive therapy with angiogenesis inhibitors. Cediranib is an investigational oral inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3. In the randomized International Collaborative Ovarian Neoplasms (ICON6) trial of over 450 patients, chemotherapy plus cediranib (given concurrently and for an additional 18 months after completion of chemotherapy) resulted in a longer progression-free survival (PFS) compared with chemotherapy alone (11 versus 8.7 months) . However, cediranib was also associated with an excess of substantial adverse effects. Given the imbalance between the PFS benefit and the additional 18 months of treatment-associated toxicities, we continue to use platinum-based combination chemotherapy without cediranib for patients with relapsed platinum-sensitive disease. We await final reporting of overall survival data from this study before altering our approach. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease", section on 'Cediranib'.)
Tubal ligation and stage of endometrial carcinoma (February 2016)
The mechanisms for spread of endometrial cancer cells are not well defined. In a case-control study of women with endometrial carcinoma, a prior tubal ligation was associated with lower odds of stage III or IV disease at presentation . This suggests that transtubal spread is a mechanism for metastasis of endometrial carcinoma and is impeded by prior tubal ligation. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Tubal ligation'.)
Obesity is a risk factor for endometrial cancer in black women (February 2016)
Obesity is a risk factor for endometrial carcinoma in white women. A recent study also found a strong positive association between obesity and endometrial cancer in black women. In this large prospective study of black women in the United States, the risk of endometrial carcinoma was 1.88-fold higher in black women with body mass index (BMI) ≥30 kg/m2 than in those with a BMI <25 kg/m2 . Obesity appears to play a similar role as a risk factor for endometrial carcinoma in both white and black women. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Obesity'.)
Frozen versus fresh embryo transfer for women with polycystic ovary syndrome (August 2016)
Traditionally, fresh embryos are transferred at the initial in-vitro fertilization (IVF) cycle and excess embryos are frozen for future use. However, women with polycystic ovary syndrome (PCOS) may have improved outcomes with transfer of frozen embryos. In a recent trial of 1500 subfertile women with PCOS in China randomly assigned to fresh or frozen embryo transfer, frozen embryo transfer resulted in a higher frequency of live birth and lower frequencies of pregnancy loss and ovarian hyperstimulation syndrome (OHSS), but the frequency of preeclampsia was increased . Of note, the study protocol differed from standard IVF protocols in the United States (US) and the mean body mass index (BMI) of the subjects was much lower than the BMI of women with PCOS in the US. Given these concerns and the higher risk for preeclampsia, we do not recommend routine transfer of frozen rather than fresh embryos in women with PCOS undergoing IVF in the US. (See "In vitro fertilization", section on 'Women with polycystic ovary syndrome (PCOS)'.)
IVF and risk of breast cancer (July 2016)
The body of evidence suggests that breast cancer risk is not increased after in vitro fertilization (IVF), but is limited by lack of long-term follow-up data. In a recent Dutch cohort study of over 19,000 women treated with IVF between 1983 and 1995 and followed for a median of 21 years, the risk of breast cancer was similar to that in subfertile women not treated with IVF and in the general population, adjusted for parity and age at first birth . These data are reassuring, but difficult to generalize to women undergoing contemporary IVF treatment since IVF drug regimens have changed over time and improved success rates have reduced the number of cycles women are exposed to these regimens. Additionally, only 14 percent of the cohort was age >60 years, so the risk of postmenopausal breast cancer was not well defined. (See "In vitro fertilization", section on 'Breast cancer risk'.)
Polycystic ovary syndrome: Weight loss before ovulation induction improves live birth rates (July 2016)
For anovulatory women with polycystic ovary syndrome (PCOS) who are overweight or obese, we suggest weight loss prior to initiating ovulation induction therapy. Modest weight loss of 5 to 10 percent has been associated with an improvement in metabolic status, a reduction in serum androgen concentrations, and resumption of ovulation in some studies, but data on pregnancy rates have been limited. In a post hoc comparison of two multicenter, concurrent trials in overweight/obese women with PCOS undergoing ovulation induction with four cycles of clomiphene citrate, a 16-week pretreatment lifestyle intervention (diet, exercise, medication) before starting clomiphene resulted in an approximate 6.5 percent weight loss from baseline and cumulative per-cycle ovulatory and live birth rates of 62 and 25 percent, respectively . In contrast, in women who underwent immediate clomiphene therapy, ovulatory and live birth rates were lower (45 and 10.2 percent, respectively). (See "Treatment of polycystic ovary syndrome in adults", section on 'Weight loss'.)
Hysteroscopy before IVF (May 2016)
Hysteroscopy is often performed to evaluate the uterine cavity before in-vitro fertilization (IVF). In a 2008 meta-analysis of two small randomized trials and three nonrandomized studies, hysteroscopy appeared to improve pregnancy rates in the following IVF cycle despite previous performance of imaging studies of the uterine cavity. However, the added value of hysteroscopy remained unclear due to methodological concerns about the included studies. Recently, a large multicenter randomized trial revaluated this issue in women <38 years of age with two to four prior unsuccessful IVF cycles and a normal ultrasound of the uterine cavity . The live birth rate was the same whether or not precycle hysteroscopy was performed, which suggests that any intrauterine pathology not identified by ultrasound was clinically insignificant. Based on these findings, we believe hysteroscopy is not routinely indicated before IVF, but may be preferable to ultrasound in areas where high-quality uterine ultrasound is unavailable. (See "In vitro fertilization", section on 'Reasons for failure'.)
Cardiovascular effects of early versus late menopausal hormone therapy (April 2016)
The Women's Health Initiative reported that menopausal hormone therapy is associated with an excess risk of coronary heart disease, but accumulating data suggest that estrogen therapy started soon after menopause does not increase risk. In The Early versus Late Intervention Trial with Estradiol (ELITE), 643 postmenopausal women, stratified according to time since menopause (<6 or >10 years; early versus late, respectively), received oral estradiol (with progesterone for women with a uterus) or placebo for a median of five years . Progression of subclinical atherosclerosis (measured as carotid intima-medial thickness) was slower with hormone therapy than with placebo in the early intervention group, while rates of progression were similar to placebo in the late intervention group. Estradiol had no effect on computed tomography measures of coronary artery calcium in either the early or late intervention group. (See "Menopausal hormone therapy: Benefits and risks", section on 'Younger postmenopausal women'.)
Endocrine Society Statement: Bioidentical hormone therapy (April 2016)
The Endocrine Society has issued a Scientific Statement warning against the use of custom compounded "bioidentical hormone therapy" for managing menopausal symptoms . This term refers to the use of custom-compounded, multi-hormone regimens (pills, gels, sublingual tablets, or suppositories) with dose adjustments based upon serial hormone monitoring. Compounded preparations typically include estradiol, estrone, estriol, progesterone, testosterone, and dehydroepiandrosterone (DHEA). Included among the key points were the absence of randomized trials demonstrating either efficacy or safety of compounded bioidentical hormone therapy for treating menopausal symptoms and the absence of regulatory oversight. When tested, potencies and patterns of absorption of compounded estrogens have been highly variable. Women who choose to take menopausal hormone therapy should be encouraged to use approved and regulated preparations of bioidentical hormones (for example, 17-beta estradiol and micronized progesterone). (See "Treatment of menopausal symptoms with hormone therapy", section on 'Bioidentical hormone therapy'.)
Zika virus and tissue/gamete donation (March 2016)
Zika virus has been detected in a number of tissues and body fluids. To avoid possible transmission of Zika virus infection, the US Food and Drug Administration (FDA) has issued donor deferral recommendations for hematopoietic stem cells, tissues, and donor sperm or eggs; the recommendations do not apply to solid organs . Living donors with Zika virus infection or relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported, or unprotected sexual contact with a person who meets these criteria) should be considered ineligible for donation for six months. Deceased donors with Zika virus infection in the preceding six months should also be considered ineligible. The deferral period recommended by the FDA for blood donors with risk factors for Zika virus infection remains at four weeks. (See "Zika virus infection: An overview", section on 'Blood/tissue donation'.)
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