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What's new in obstetrics and gynecology
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What's new in obstetrics and gynecology

Disclosures: Kristen Eckler, MD, FACOG Nothing to disclose. Sandy J Falk, MD, FACOG Nothing to disclose. Vanessa A Barss, MD, FACOG Nothing to disclose.

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.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2016. | This topic last updated: Feb 03, 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.

OBSTETRICS

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 [1]. 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 [2]. 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 [3]. In 2015, more than 3500 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 [4]. In January 2016, the United States and European Centers for Disease Control advised that pregnant women consider postponing travel to any area where Zika virus transmission is ongoing and also advised that healthcare providers ask all pregnant women about recent travel, with follow-up testing (ultrasound, laboratory testing, or both) depending on clinical circumstances [5]. Anecdotal reports of apparent sexual transmission have been described [6]. Although this appears to be an infrequent mechanism for Zika virus transmission, it may be prudent for men with symptoms of Zika virus infection who have female sexual partners of childbearing age to defer unprotected sex for at least a few weeks following resolution of symptoms. Zika virus is also transmissible via blood products; outside of areas with local mosquito-borne Zika virus transmission, self-deferral of blood donation for 28 days following potential Zika virus exposure has been advised [7]. (See "Zika virus infection", 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 [8]. 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 [9]. 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 [10]. 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 [11]. 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 [12]. 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 [13]. 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 [14]. 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'.)

Adverse pregnancy effects of improved control of malaria (November 2015)

Improvements in malaria control in some endemic areas have led to declines in malaria transmission and, in turn, immunity. A recent study from Mozambique illustrated an adverse consequence of a less immune population. In this study, a large reduction in malaria transmission in recent years was associated with a large reduction in maternal levels of antimalarial IgG antibodies against both pregnancy-specific parasite lines and more general parasite lines [15]. In addition, women who developed a malaria infection during pregnancy in recent years had greater reductions in hemoglobin level and newborn birth weight compared with pregnant women infected prior to the overall decline in malaria prevalence and reduced immunity. (See "Overview of malaria in pregnancy", section on 'Immunity'.)

n-3 LCPUFA supplementation in pregnancy and allergies in offspring (November 2015)

It has been hypothesized that maternal intake of long chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy may prevent development of allergies in offspring. However, a recent systematic review of randomized trials assessing the effect of n-3 LCPUFA supplementation during pregnancy and/or breastfeeding on allergy outcomes in offspring found supplementation did not significantly reduce childhood allergic disease (food allergy, atopic dermatitis, allergic rhinitis, asthma) at 36 months of age compared with no treatment/placebo [16]. (See "Fish consumption during pregnancy", section on 'Other outcomes'.)

Endotracheal suctioning does not benefit nonvigorous neonates with meconium-stained amniotic fluid (May 2015, Modified November 2015)

New American Heart Association, American Academy of Pediatrics, and International Liaison Committee on Resuscitation guidelines no longer recommend routine endotracheal suction for nonvigorous (depressed) newborns with meconium-stained amniotic fluid in the delivery room (ie, newborns with absent or depressed respirations, decreased muscle tone, or heart rate less than 100 beats/minute) [17,18]. This change was prompted by findings from a recent randomized clinical trial of endotracheal suctioning versus no suctioning in 122 nonvigorous term newborns with meconium-stained amniotic fluid [19]. No differences were observed between groups in meconium aspiration syndrome, need for mechanical ventilation, survival at nine months of age, and mental and motor developmental status at nine months of age. Our criteria for intervention for newborns with meconium-stained amniotic fluid are the same as those used for intervention in all neonates (algorithm 1). (See "Prevention and management of meconium aspiration syndrome", section on 'Neonatal care' and "Neonatal resuscitation in the delivery room", section on 'Next steps'.)

Maternal cancer during pregnancy and child development (October 2015)

Little is known about the effect of maternal cancer during pregnancy on subsequent child development. In a study of 129 children born to mothers diagnosed with cancer during pregnancy (over half of whom had breast cancer), cardiac, cognitive, and general development after a median of 22 months was equivalent to that in controls matched for gestational age at birth [20]. In a subgroup analysis, similar outcomes were also reported for children exposed to chemotherapy or radiation after the first trimester compared with gestational age-matched controls. Although these results are generally reassuring regarding early developmental outcomes among children born to mothers with cancer, the heterogeneity of cancers and treatments represented in this study should be taken into account when counseling individual patients. (See "Gestational breast cancer: Treatment", section on 'Pregnancy and infant outcome'.)

Increased maternal mortality and morbidity among women with epilepsy (October 2015)

Women with epilepsy are known to be at increased risk for a range of adverse outcomes during pregnancy compared with women without epilepsy. While the magnitude of the risk is relatively small for most outcomes, the risk of maternal death at the time of delivery may be higher than previously recognized. In a population-based study of delivery hospitalizations in >20 million pregnant women in the United States, including >69,000 women with epilepsy, the risk of maternal mortality was 10-fold higher among women with epilepsy (80 versus 6 deaths per 100,000 pregnancies) [21]. Most other adverse outcomes, including hemorrhage, preterm labor, and poor fetal growth, were increased by a factor less than two. Specific causes of death could not be determined by the study. These results emphasize the importance of close intrapartum care in women with epilepsy and the need for a better understanding of the causes of death in these patients. (See "Management of epilepsy and pregnancy" and "Risks associated with epilepsy and pregnancy", section on 'Perinatal morbidity and mortality'.)

Uterine exteriorization at cesarean delivery (October 2015)

A 2015 meta-analysis of randomized trials of extraabdominal (exteriorized) versus intraabdominal (in situ) hysterotomy repair at cesarean delivery found no clinically significant differences in blood loss, intraoperative nausea, vomiting, or pain between the two approaches [22]. Both personal preference and individual clinical circumstances should guide the choice of technique. (See "Cesarean delivery: Technique", section on 'Exteriorizing the uterus'.)

Chest compressions for cardiac arrest in pregnancy (October 2015)

Chest compressions are the cornerstone of resuscitation after cardiac arrest. The 2015 American Heart Association guideline on cardiac arrest in pregnancy recommends the same hand position for chest compressions in pregnant women and nonpregnant adults [23]. Previous guidelines suggested a more cephalad hand position in pregnancy to adjust for elevation of the diaphragm by the gravid uterus; however, a recent imaging study showed no significant vertical displacement of the heart in the third trimester relative to the nonpregnant state [24]. (See "Cardiopulmonary arrest in pregnancy", section on 'Chest compressions'.)

Preterm external cephalic version (October 2015)

The optimal gestational age to perform external cephalic version (ECV) of the breech fetus is unclear. A recent meta-analysis of randomized trials reported that ECV at 34 to 36 weeks was more likely than ECV at ≥37 weeks to decrease the rate of noncephalic presentation at the time of delivery (risk ratio [RR] 0.81); however, the decrease was not accompanied by a statistical reduction in the cesarean delivery rate [25]. The higher success rate when ECV is attempted at 34 to 36 weeks of gestation needs to be balanced with the possibility of rare complications necessitating preterm delivery and lack of convincing evidence of a substantial reduction in cesarean delivery. Women should be informed of the relative advantages and disadvantages of early initiation of ECV attempts to make an informed choice. (See "External cephalic version", section on 'Timing and outcome'.)

Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy (October 2015)

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) with sulfadoxine-pyrimethamine (SP). The optimal approach to IPTp is uncertain in areas of high SP resistance and malaria transmission, such as Kenya. In a recent trial including over 1500 Kenyan women randomly assigned to receive IPT with SP or dihydroartemisinin-piperaquine (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 [26]. The trial was not powered to detect small differences in neonatal outcomes. Before changing to IPT with DP, more data are needed to compare the effects of the two therapies on these outcomes. (See "Prevention and treatment of malaria in pregnant women", section on 'Intermittent preventive treatment during pregnancy'.)

Prescription medications during pregnancy (August 2015)

Concerns have been raised regarding the frequency with which medication is prescribed during pregnancy, especially for those drugs that may have adverse outcomes for the mother or her fetus. In a study of over one million pregnant women in the United States Medicaid program, nearly 40 percent were prescribed a potentially harmful medication (category D, most commonly codeine and hydrocodone) and 5 percent were prescribed a medication contraindicated during pregnancy (category X, most commonly hormonal contraceptives that were prescribed prior to the diagnosis of pregnancy) [27]. Overall, 83 percent were dispensed at least one medication of any kind (most commonly antibiotic or antifungal agents). While medication can be safely used in pregnancy, the lowest risk option is to avoid drug exposure if possible. When medication is to be taken, the risks and benefits must be discussed, particularly for medications with harmful potential, such as addiction. (See "Initial prenatal assessment and first-trimester prenatal care", section on 'Medications commonly used in pregnancy'.)

Limited value of fetal ST-segment analysis (August 2015)

The STAN S31 fetal heart monitor is a relatively new device used to monitor the fetal electrocardiogram during labor. Fetal ST-segment changes have been associated with hypoxemia and acidosis necessitating prompt delivery. The largest randomized trial of this approach to intrapartum fetal assessment assigned over 11,000 women to "open" or "masked" fetal ST-segment analysis and reported no significant between-group differences in the rate of cesarean delivery, any operative delivery, or the primary composite outcome (stillbirth, neonatal death, five-minute Apgar score ≤3, cord artery pH ≤7.05 and base deficit in extracellular fluid ≥12, intubation in the delivery room, seizures, neonatal encephalopathy) [28]. The results of this large, well-designed trial are important because previous small trials had suggested ST-segment analysis reduced the frequency of fetal scalp sampling, operative vaginal delivery, and neonatal metabolic acidosis. We do not perform fetal ST-segment analysis as there is no convincing evidence that it improves maternal or neonatal outcome. (See "Intrapartum fetal heart rate assessment", section on 'ST analysis'.)

OFFICE GYNECOLOGY

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 [29]. 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) [30]. 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'.)

Medication approved for low sexual desire in women (August 2015)

Flibanserin is the first and currently only drug approved by the US Food and Drug Administration (FDA) for female sexual dysfunction [31]. Daily use results in modest increases in the frequency of sexually satisfying events and sexual desire. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and by safety concerns or lack of safety data regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, CYP3A4 inhibitors, antidepressants). (See "Sexual dysfunction in women: Management", section on 'Flibanserin'.)

GYNECOLOGIC SURGERY

Short versus long suture width in the closure of abdominal incisions (October 2015)

When abdominal incisions are closed with a running suture, the needle is typically inserted at a distance of 10 mm from the fascia edge (ie, suture width). A reduction of that distance to 5 mm has been proposed in Europe based upon the result of a randomized trial [32]. In that trial, patients whose incisions were closed with a suture width of 5 mm developed significantly fewer incisional hernias at one year compared with patients whose incisions were closed with a 10 mm suture width (13 versus 21 percent). Further studies with longer follow-up periods are required before a suture width of less than 10 mm can be recommended for routine closure of all abdominal incisions. (See "Principles of abdominal wall closure", section on 'Technique'.)

Long-term mesh complication rates after anti-incontinence surgery (September 2015)

The risk of complications from transvaginal mesh used for urinary incontinence in women accumulates over time. In a cohort study that included nearly 60,000 women who underwent transvaginal mesh-based procedures for stress-urinary incontinence, the risk of a complication warranting surgical reintervention was 1.2 percent at one year and increased to a cumulative rate of 3.3 percent at 10 years [33]. This study highlights the need for a detailed preoperative discussion of the risks and benefits associated with transvaginal mesh and the importance of evaluation for mesh-related complications in any woman with a history of transvaginal mesh placement who develops a new urogynecologic complaint, regardless of the time elapsed since the original procedure. (See "Overview of transvaginal placement of mesh for prolapse and stress urinary incontinence", section on 'Complications'.)

Safety concerns and FDA panel meeting regarding hysteroscopic sterilization (July 2015, Modified September 2015)

Safety concerns have been raised about female sterilization via hysteroscopic placement of micro-inserts into the fallopian tubes. A prospective study of this procedure reported that, at five years, up to 38 percent of women reported recurrent menstrual irregularities and up to 5 percent reported recurrent pelvic pain [34]. Between 2002 and 2015, the US Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database received 5093 adverse event reports related to this device, including over 4700 related to menstrual abnormalities or pelvic pain [35]. In September 2015, the FDA convened a meeting of the Obstetrics and Gynecology Devices Panel to review the safety and effectiveness of hysteroscopic sterilization [36]. The panel discussed and made suggestions regarding a need for better patient information materials, a need for a review of existing and future data on adverse effects, and a need to better select candidates for the procedure. Less suitable candidates include those with hypersensitivity to metal or a history of pelvic inflammatory disease. (See "Hysteroscopic sterilization", section on 'FDA panel'.)

GYNECOLOGIC ONCOLOGY

Hormonal risk factors for endometrial cancer in women with Lynch syndrome (July 2015)

For women with Lynch syndrome, hormonal risk factors for the development of endometrial cancer appear to be the same as those in the general population. A multicenter international retrospective cohort study of a registry of 1128 women with a mismatch repair gene mutation included 133 women who developed endometrial cancer [37]. Later age at menarche (≥13 years), higher parity (≥1 live birth), and longer use of hormonal contraceptives (≥1 year) were associated with a decrease in the risk of endometrial cancer. The biologic behavior of endometrial cancer in Lynch syndrome in terms of hormonal risk factors appears similar to sporadic cases. (See "Endometrial and ovarian cancer screening and prevention in women with Lynch syndrome (hereditary nonpolyposis colorectal cancer)", section on 'Endometrial cancer'.)

REPRODUCTIVE ENDOCRINOLOGY

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 [38]. 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 [2]. 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 [39]. 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'.)

Letrozole treatment for women with unexplained infertility (December 2015)

For women with unexplained infertility, clomiphene citrate (CC) with intrauterine insemination (IUI) is typically first-line therapy; women who do not conceive are offered in vitro fertilization (IVF). When IVF is unsuccessful or not available, off-label treatment with the aromatase inhibitor letrozole appears to result in similar live birth and multiple gestation rates as CC/IUI. In a trial of 900 women with unexplained infertility randomly assigned to receive letrozole, CC, or gonadotropin therapy with IUI, the overall live birth rates were 19, 23, and 32 percent, respectively, and multiple gestation rates were 3, 1, and 13 percent, respectively [40]. For women who do not conceive with CC/IUI or IVF, we continue to suggest gonadotropin treatment rather than letrozole as it results in higher birth rates and is approved for ovulation induction. Women are counseled about the high risk of multiple gestation, particularly triplets. (See "Unexplained infertility", section on 'Our approach'.)

Frozen donor oocyte use impacts live birth rate (August 2015)

Use of donor oocytes (eggs) in assisted reproductive technology has allowed women unable to conceive with their own eggs the opportunity to achieve pregnancy. The use of frozen oocytes is more convenient and less costly compared with fresh oocytes because the donor and recipient don't have to be hormonally synchronized and frozen eggs can be shipped anywhere. Although initial studies reported equivalent pregnancy and live birth rates for donor egg transfers, a study of over 11,000 oocyte donation cycles, including 20 percent using frozen eggs, reported the live birth rate per transfer for frozen donor oocytes was lower than the live birth rate for fresh donor oocytes (47 versus 56 percent) [41]. Despite the possible discrepancy in live birth rate, the improved efficiency and lower cost of cryopreserved donor oocytes makes their use a reasonable and attractive option. (See "Management of infertility and pregnancy in women of advanced age", section on 'Oocyte or embryo donation'.)

OTHER GYNECOLOGY

New breast cancer screening guidelines from the American Cancer Society (October 2015)

The American Cancer Society (ACS) has issued revised guidelines for screening women for breast cancer [42]. Significant changes from previous ACS guidelines include recommendations to initiate mammographic screening in average risk women at age 45, to screen women aged 45 to 54 years annually and to screen women 55 years and older biennially as long as they are healthy and have a life expectancy of at least 10 years. Additionally, the guidelines recommend not performing a clinical breast examination. Multiple societies and agencies have developed guidelines with varying recommendations for age and frequency of mammogram screening (table 1). (See "Screening for breast cancer: Strategies and recommendations", section on 'Age to initiate'.)

Frequency of screening mammograms (October 2015)

An analysis of data from the Breast Cancer Surveillance Consortium compared annual and biennial mammogram screening among 15,440 women with breast cancer who were stratified by menopausal status and, if postmenopausal, use of menopausal hormone therapy (MHT) [43]. The proportion of cancers that were less favorable (stage IIB or higher) was higher for women who had biennial screening than for those who had annual screening. This was also the case for women taking MHT, but not for other postmenopausal women in whom tumor characteristics were similar for those screened annually or biennially. Although these data may suggest some benefit for more frequent (eg, annual) screening for premenopausal women, this benefit needs to be weighed against the increased risk of false positive mammogram findings in younger women. In general, for women aged 40 and older at average risk who opt to be screened for breast cancer after counseling and shared decision making, we suggest biennial screening. (See "Screening for breast cancer: Strategies and recommendations", section on 'Frequency of mammography'.)

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REFERENCES

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