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What's new in obstetrics and gynecology
Official reprint from UpToDate® ©2016 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
What's new in obstetrics and gynecology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2016. | This topic last updated: May 24, 2016.

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.


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 [1]. 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 [2]. 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 [3]. 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 [4]. 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 [5]. 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 [6]. 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 [7]. 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 [8]. 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) [9], 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 [10]. 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 [11]. 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 [12]. Based on these and other recent data [13], we believe use of metformin in pregnancy should be limited to management of hyperglycemia. (See "Weight gain and loss in pregnancy", section on 'Metformin'.)

Chlorhexidine-alcohol for skin prep before cesarean delivery (February 2016)

Either chlorhexidine-alcohol or iodine-alcohol is used for skin preparation before cesarean delivery. In a recent randomized trial comparing these agents for prevention of surgical-site infection (SSI) in over 11,000 women undergoing cesarean delivery, use of chlorhexidine-alcohol reduced the overall rate of SSIs and the frequency of postoperative office visits for wound concerns by about 40 percent [14]. We recommend preparing the abdominal surgical site with a chlorhexidine-alcohol scrub before cesarean delivery, based on these data and previous data from adults undergoing clean-contaminated surgery [15]. (See "Cesarean delivery: Preoperative issues", section on 'Skin preparation'.)

Screening for perinatal depression (February 2016)

Up to 15 percent of pregnant women experience depression either during pregnancy or in the postpartum period. Perinatal depression is under-recognized and associated with adverse outcomes including preterm birth, impaired fetal growth, lower birth weight, and impaired maternal-infant bonding. A systematic review, comparing usual care with a program for depression screening during pregnancy (one trial) or postpartum (four trials), found that screening reduced the prevalence of depression at three- to five-month follow-up (absolute reduction 2.1 to 9.1 percent) [16,17]. We suggest routine screening for depression during pregnancy and at the six-week postpartum visit, with services available to ensure follow-up for diagnosis and treatment. The most widely used screening instrument is the 10-item Edinburgh Postnatal Depression Scale (figure 1A-B), which also can be used for prenatal depression. This approach is consistent with practice guidelines issued by the US Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the United Kingdom National Institute for Health and Care Excellence. (See "Unipolar major depression in pregnant women: Clinical features, consequences, assessment, and diagnosis" and "Postpartum blues and unipolar depression: Epidemiology, clinical features, assessment, and diagnosis".)

Postpartum psychosis associated with high recurrence risk (February 2016)

Postpartum psychosis is characterized by the emergence of psychotic symptoms, such as delusions and hallucinations, typically within the first weeks after delivery. Small studies have suggested that women with a history of postpartum psychosis are at increased risk of recurrence following a subsequent pregnancy. A meta-analysis of studies describing more than 5000 deliveries found that 35 percent of women with prior postpartum psychosis experienced recurrence following a subsequent pregnancy [18]. Thus, women with a history of postpartum psychosis should be educated about the increased risk of recurrence following childbirth and monitored closely in the first few weeks postpartum for early indications of psychosis. (See "Postpartum psychosis: Epidemiology, clinical manifestations, assessment, and diagnosis", section on 'Course'.)

Serum test for prediction of preeclampsia (January 2016)

The ratio of soluble fms–like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is increased in the serum of women with preeclampsia; however, the clinical application for this observation remains unclear. A prospective international observational study (PROGNOSIS) attempted to derive and validate a serum sFlt-1:PlGF ratio that would predict the absence or presence of preeclampsia in women who had signs suggestive of the disease, but who did not meet standard criteria for preeclampsia [19]. An sFlt-1:PlGF ratio cutoff of 38 using a specific automated commercial assay had a negative predictive value (no preeclampsia in the next seven days) of 99.3 percent. Few women in the cohort ultimately developed preeclampsia, resulting in a positive predictive value of only 36.7 percent for preeclampsia diagnosis in the next four weeks. Further study is warranted, including determining whether the cut-off varies among laboratories and patient populations, the best interval for repeat testing, and how this information affects clinical decisions, outcomes and costs. (See "Preeclampsia: Clinical features and diagnosis", section on 'Measurement of angiogenic factors'.)

Conception after miscarriage (January 2016)

Although data support the benefits of delaying conception after a live birth, it is not clear if such a delay benefits women after miscarriage. In a study of nearly 1100 women who had a miscarriage at less than 20 weeks of gestation, women who attempted conception within 0 to 3 months of the loss were more likely to achieve a live birth, had a faster time to pregnancy that resulted in a live birth, and had similar pregnancy complications compared with women who waited greater than 3 months to try to conceive [20]. We advise women who have completed a miscarriage that they may attempt conception as soon as they are psychologically ready. (See "Spontaneous abortion: Management", section on 'Interval to conception'.)

Zika virus infection in the Americas (January 2016)

Zika virus is a member of the flavivirus family that is spread via mosquito bites. Outbreaks have occurred in Africa, Southeast Asia, and the Pacific Islands; more recently Zika virus has spread to the Americas. More than 20 countries in Latin America have confirmed circulation; cases of Zika virus infection in the United States have occurred among returning travelers. The illness is usually mild; typical symptoms include fever, rash, joint pain, and conjunctivitis. However, Zika virus infection has also been associated with perinatal complications (congenital microcephaly and fetal losses) and Guillain-Barre syndrome [21]. In 2015-2016, more than 5000 cases of microcephaly were reported among newborns in Brazil; this represents a >20-fold increase in the number of cases compared with years prior to the circulation of Zika virus [22]. A number of authorities have advised that pregnant women consider postponing travel to areas below 6500 feet (2000 meters) where mosquito transmission of Zika virus is ongoing [23]. Sexual transmission have been described [24]. It is prudent for individuals with Zika virus infection/exposure to abstain from sexual activity (vaginal, anal, and oral sex) or use barrier protection; men who have a pregnant partner should follow such guidance for the duration of the pregnancy. Zika virus is also transmissible via blood products; deferral of blood donors for one month following Zika virus infection/exposure is advised [25]. (See "Zika virus infection: An overview", section on 'Geographic distribution'.)

Membrane sweeping in GBS-colonized women (January 2016)

Some practitioners choose not to sweep/strip fetal membranes to induce labor in group B Streptococcus (GBS)-colonized women because of theoretical concerns of bacterial seeding during the procedure. The first prospective study to compare maternal and neonatal outcomes following membrane sweeping among GBS-positive (n = 135), GBS-negative (n = 361), and GBS-unknown (n = 46) women found no significant difference in adverse maternal or neonatal outcomes between groups [26]. There was no difference in the rate of possible early-onset neonatal infection between the GBS-positive and GBS-negative groups and no cases of neonatal sepsis in the entire cohort. Most GBS-positive women received intrapartum GBS antibiotic prophylaxis. Although these results are reassuring about the safety of membrane sweeping in GBS-positive women, the study did not have adequate power to detect modest differences in outcome and is subject to the limitations of an observational design. We believe GBS colonization is not a contraindication to membrane sweeping as there is no direct evidence of harm, but given the paucity of safety data for the procedure in known GBS carriers, we weigh the potential risks and benefits before performing the procedure in known carriers. (See "Induction of labor", section on 'Membrane stripping'.)

Miscarriage risk with oral fluconazole (January 2016)

The pregnancy effects of oral azoles for treatment of vulvovaginal candidiasis is unclear. Studies have reported an increased risk of birth defects after exposure to high-dose azole therapy (400 to 800 mg/day), but not for the low dose therapy used to treat vulvovaginal infections (eg, fluconazole 150 mg). Prior studies have not reported an increased risk of miscarriage with oral fluconazole. However, a recent cohort study of over 3300 women who received 150 to 300 mg of oral fluconazole between 7 and 22 weeks of pregnancy reported an approximately 50 percent increased risk of miscarriage in exposed women compared with either unexposed women or with women treated with vaginal azole therapy [27]. We continue to offer topical azole treatment during pregnancy and prefer to avoid oral therapy until more data on reproductive outcomes are available. (See "Candida vulvovaginitis", section on 'Pregnancy'.)

Neonatal and maternal outcomes for planned out-of-hospital birth (January 2016)

In the United States (US), the safety of non-hospital births is unclear. Several studies have reported that women who deliver at home or at a birth center have equal or improved neonatal and maternal outcomes compared with those who deliver in a hospital; however, outcomes of women transferred to the hospital intrapartum or postpartum because of complications were often included with the hospital delivery group, which could have impacted results. In a US study that analyzed birth outcomes by planned birth location rather than actual delivery site, approximately 16 percent of women planning out-of-hospital births (combined home births and freestanding birth centers) required hospital transfer and their infants had higher rates of perinatal death, neonatal seizures, and neonatal ventilator support compared with infants of planned in-hospital births [28]. Mothers who planned out-of-hospital births but delivered in a hospital had fewer obstetric interventions and a higher rate of blood transfusion. For women in the United States, this study provides a more accurate understanding of the outcomes associated with planned out-of-hospital versus planned in-hospital birth. (See "Planned home birth", section on 'Retrospective studies'.)

Progesterone to prevent recurrent preterm birth in obese women (December 2015)

Progesterone supplementation during pregnancy can reduce the risk of recurrent preterm birth. However, a secondary analysis of data from the Maternal-Fetal Medicine Units Network Trial of hydroxyprogesterone caproate for prevention of recurrent preterm birth reported that this drug may not be effective in women with a pre-pregnancy body mass index (BMI) >30 kg/m2 [29]. The threshold for efficacy appeared to be <165 pounds (74.8 kg). This finding requires further study since the analysis was an unplanned post hoc analysis, pre-pregnancy weights were self-reported, and no data were available on weight gain during pregnancy or hydroxyprogesterone caproate serum levels. We suggest not using any BMI or weight criteria to limit use of hydroxyprogesterone caproate supplementation for prevention of recurrent preterm birth until confirmatory data are available. (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on 'Maternal obesity'.)

Maternal hypertension and risk of congenital heart disease in offspring (November 2015)

Women with chronic hypertension, either treated or untreated, may be at increased risk of having offspring with congenital heart disease (CHD) compared with normotensive women. In a recent systematic review including 16 studies and five million subjects, the frequency of CHD in offspring of hypertensive pregnant women who received or did not receive treatment increased by 100 percent and 40 percent, respectively, compared with normotensive pregnant women [30]. The magnitude of effect was generally similar across subtypes of CHD and across the range of antihypertensive therapies. These results should be interpreted with caution, as neither a dose-response relationship between maternal hypertension medication and CHDs nor some potentially important characteristics of the population (eg, severity of hypertension) could be ascertained. We suggest avoiding antihypertensive therapy for mild hypertension in pregnancy as there is no clear maternal or fetal benefit and it may be harmful. Severe hypertension should be treated to reduce the risk of maternal stroke. (See "Management of hypertension in pregnant and postpartum women", section on 'Antihypertensive therapy'.)

Universal versus selective ultrasound screening for fetal growth restriction (November 2015)

Early identification of fetal growth restriction allows for closer surveillance and earlier intervention in case of fetal decompensation. However, the value of universal rather than selective ultrasound examination in late pregnancy to screen for fetal growth restriction is unclear. A recent prospective cohort study (Pregnancy Outcome Prediction study) addressed this issue in unselected nulliparous women with singleton gestations who underwent routine early ultrasonography for pregnancy dating [31]. These women were scheduled to undergo serial ultrasound examinations at about 20, 28, and 36 weeks of gestation, but findings were masked from the women and their providers. Universal sonography in the third trimester almost tripled the detection of infants subsequently born small for gestational age compared with clinically indicated sonography, but also misdiagnosed many normal infants as small. Among fetuses with estimated fetal weight <10th percentile, only those with abdominal circumference growth velocity at the lowest decile were at increased risk for neonatal morbidity. UpToDate continues to recommend selective use of ultrasound in patients with risk factors for growth restriction rather than universal third trimester screening. (See "Routine prenatal ultrasonography as a screening tool", section on 'Better diagnosis of deficient growth and improvement in perinatal outcome'.)

Timing of delivery in late preterm membrane rupture (November 2015)

Optimum timing of delivery for pregnancies with late preterm premature rupture of membranes (PPROM) is unclear. This issue was recently addressed by a multicenter, international, randomized trial (PPROMT) that randomly assigned over 1800 women with PPROM between 34 and 366/7ths weeks of gestation to immediate delivery or expectant management [32]. The rate of neonatal sepsis (primary outcome) did not differ significantly between the two groups, but infants in the immediate delivery group were more likely to develop respiratory distress syndrome, require mechanical ventilation, and spend more time in the neonatal intensive care unit. Mothers assigned to expectant management were more likely to develop antepartum or intrapartum bleeding and intrapartum fever and had a longer hospital stay, but they also had a lower cesarean delivery rate.

Several limitations of this trial preclude extrapolating the findings to women in the United States. International facilities had different levels of resources; some patients were managed as outpatients; there were no clear criteria for determining the timing of delivery in the expectantly managed group; protocols for administration of prophylactic antibiotics were variable and use of corticosteroids was inconsistent. We continue to recommend delivery rather than expectant management for late preterm PPROM (algorithm 1). (See "Preterm premature (prelabor) rupture of membranes", section on 'Initial approach'.)


Efficacy and safety of flibanserin for low sexual desire (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 [33]. 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 [34]. 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 [35,36]. 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 [36]. 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 [37]. 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 [38]. 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'.)

Acupuncture ineffective for menopausal hot flashes (January 2016)

It is estimated that up to 75 percent of postmenopausal women use complementary therapies to treat their menopausal symptoms, despite little evidence of efficacy. Acupuncture is among the most frequently used, but results from clinical trials have been conflicting. The best evidence to date that acupuncture is no more effective than placebo (sham-acupuncture) comes from a trial in 327 peri- or postmenopausal women with moderate to severe hot flashes who were randomly assigned to 10 traditional Chinese acupuncture or noninsertive sham acupuncture treatments over eight weeks [39]. Hot flash (HF) scores, a calculated score based upon HF frequency and severity, were no different between the groups at the end of treatment (both showed approximately 40 percent improvement). Thus, like other nonhormonal and complementary therapies for hot flashes, acupuncture has an important placebo effect, but it has no additional benefit over sham acupuncture. (See "Menopausal hot flashes", section on 'Inconsistent evidence of efficacy'.)

2016 ACOG guidelines for cervical cancer screening (January 2016)

The 2016 American College of Obstetricians and Gynecologists (ACOG) guidelines for cervical cancer screening have been released [40]. ACOG continues to recommend screening for cervical cancer beginning at age 21 with cervical cytology, and co-testing (cervical cytology plus human papillomavirus [HPV] testing) for women age 30 and older. However, in agreement with the 2015 American Society for Colposcopy and Cervical Pathology guidelines, ACOG now also considers primary HPV testing as an option for screening in women age 25 years and older. Because HPV tests may be transiently positive in many younger women, UpToDate authors suggest that women age <30 years be screened with cervical cytology (Pap smear). (See "Screening for cervical cancer", section on 'Primary HPV testing'.)

Azithromycin versus doxycycline for uncomplicated chlamydia (January 2016)

The first-line regimens for uncomplicated urogenital chlamydial infection are azithromycin administered as a single dose or a seven-day course of doxycycline administered twice daily. There is emerging evidence that the efficacy of doxycycline may be marginally greater than that of azithromycin, although the reasons for this are unknown. In a trial of 310 adolescents and young adults who screened positive for urogenital Chlamydia trachomatis upon entrance into a correctional facility, microbial cure rates at 28 days were high for both doxycycline and azithromycin (each administered as directly-observed therapy), but were numerically higher for doxycycline (100 versus 97 percent) [41]. Adherence is the main challenge with the doxycycline regimen, and direct observation of the full course is unrealistic in most situations; thus, it is uncertain that doxycycline would achieve a similarly superior cure rate in the community. Given the very high efficacy of azithromycin, we continue to favor directly-observed single-dose azithromycin for treatment of uncomplicated urogenital C. trachomatis infection. (See "Treatment of Chlamydia trachomatis infection", section on 'First-line agents'.)


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 [42]. 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'.)

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) [43]. 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'.)

Surgical outcomes of in-bag uterine morcellation (March 2016)

The possibility of disseminating tumor cells during uterine morcellation has led to development of contained morcellation systems for gynecologic surgery. The only randomized trial of in-bag manual versus uncontained power morcellation found no differences in total procedure time, morcellation time, simplicity of morcellation, or operative complications in 104 women undergoing laparoscopic myomectomy [44]. Further study is needed to evaluate the safety of in-bag morcellation and the efficacy in containing cells. (See "Differentiating uterine leiomyomas (fibroids) from uterine sarcomas", section on 'Alternatives or modifications to morcellation'.)

Synthetic mesh for vaginal prolapse repair (January 2016)

The safety of synthetic mesh in the surgical repair of pelvic organ prolapse (POP) is controversial. In response to increased reporting of adverse events, the US Food and Drug Administration (FDA) reclassified surgical mesh for transvaginal POP repair from a class II (moderate risk) to a class III (high risk) device [45]. This reclassification applies only to transvaginal POP repair, not to transabdominal POP repair or surgical treatment of stress urinary incontinence. For women undergoing transvaginal POP surgery, we limit the use of synthetic mesh to women who have failed prior reconstruction or have a high future risk of failure. (See "Overview of transvaginal placement of mesh for prolapse and stress urinary incontinence", section on 'Guidelines for mesh use'.)


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 [46]. 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'.)

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) [47]. 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 [48]. 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 [49]. 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'.)


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 [50]. 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 [51]. 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 [52]. 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'.)

Novel genetic mutations identified as cause of female infertility (January 2016)

The genetic events that disrupt normal human oocyte maturation are unknown. In a recent study, seven novel mutations in the gene TUBB8 were identified in women with primary infertility [53]. TUBB8 mutations impact only oocytes and result in oocyte meiosis I arrest, which leads to fertilization failure. Although a clinical test is not available, identification of these gene mutations opens new pathways for fertility research and diagnosis for women with primary infertility. (See "Causes of female infertility", section on 'Genetic causes'.)

Conception after miscarriage (January 2016)

Although data support the benefits of delaying conception after a live birth, it is not clear if such a delay benefits women after miscarriage. In a study of nearly 1100 women who had a miscarriage at less than 20 weeks of gestation, women who attempted conception within 0 to 3 months of the loss were more likely to achieve a live birth, had a faster time to pregnancy that resulted in a live birth, and had similar pregnancy complications compared with women who waited greater than 3 months to try to conceive [20]. We advise women who have completed a miscarriage that they may attempt conception as soon as they are psychologically ready. (See "Spontaneous abortion: Management", section on 'Interval to conception'.)

Vaginal progesterone does not reduce recurrent pregnancy loss (December 2015)

Progesterone produced by the corpus luteum is essential to achieve and maintain pregnancy during most of the first trimester. Vaginal progesterone supplements have been prescribed for women with unexplained recurrent pregnancy loss (RPL) in an attempt to improve outcome, but the benefit has been unclear. In a recent trial that randomly assigned over 800 women with unexplained RPL (defined as three or more consecutive or non-consecutive unexplained first trimester miscarriages) to vaginal progesterone or placebo therapy from diagnosis of pregnancy through 12 weeks of gestation, approximately two-thirds of women in both groups delivered a live infant after 24 weeks of gestation [54]. This trial provides the best evidence to date that vaginal progesterone therapy does not improve live birth rates once a pregnancy has been established. We recommend not using supplemental vaginal progesterone for women with unexplained RPL. (See "Management of couples with recurrent pregnancy loss", section on 'Progesterone'.)


Synthetic mesh for vaginal prolapse repair (January 2016)

The safety of synthetic mesh in the surgical repair of pelvic organ prolapse (POP) is controversial. In response to increased reporting of adverse events, the US Food and Drug Administration (FDA) reclassified surgical mesh for transvaginal POP repair from a class II (moderate risk) to a class III (high risk) device [45]. This reclassification applies only to transvaginal POP repair, not to transabdominal POP repair or surgical treatment of stress urinary incontinence. For women undergoing transvaginal POP surgery, we limit the use of synthetic mesh to women who have failed prior reconstruction or have a high future risk of failure. (See "Overview of transvaginal placement of mesh for prolapse and stress urinary incontinence", section on 'Guidelines for mesh use'.)

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