The following represent additions to UpToDate since the last version of What’s New that were considered by the authors and editors to be of particular interest.
OBSTETRICS
Pessary for short cervix — A multicenter trial randomly assigned 385 pregnant women with cervical length ≤25 mm at 20 to 23 weeks to use of a cervical pessary or expectant management (no pessary) [1]. The majority of these patients (89 percent) had no history of previous preterm birth and none were treated with progesterone or cerclage. The pessary group had a significantly lower rate of spontaneous preterm birth <28 and <34 weeks than the expectant management group. Although promising, we do not recommend implementation of this approach instead of vaginal progesterone until these data are confirmed by additional randomized trials. (See "Transvaginal ultrasound assessment of the cervix and prediction of spontaneous preterm birth", section on 'Singleton, no prior preterm birth'.)
Progesterone for short cervix — In a meta-analysis of individual patient data from five placebo-controlled randomized trials of progesterone supplementation of women with asymptomatic midtrimester sonographic short cervix, progesterone supplementation was associated with a 30 to 50 percent reduction in preterm birth <28, <33, and <35 weeks and a 40 percent reduction in composite neonatal morbidity and mortality [2]. These benefits were similar at progesterone doses of 90, 100, and 200 mg daily and for women with and without a history of prior preterm birth. Beneficial effects were noted at cervical lengths <10 mm, 10 to 20 mm, and 21 to 25 mm, but only the 10 to 20 mm group reached statistical significance. (See "Progesterone supplementation to reduce the risk of spontaneous preterm birth", section on 'Short cervix in current pregnancy'.)
Hypothyroidism during pregnancy — A randomized trial compared neurocognitive outcomes in children of women with subclinical hypothyroidism who were or were not treated with levothyroxine during pregnancy [3]. Twenty-one thousand eight hundred and forty-six pregnant women (gestational age <15 weeks), without known thyroid disease, were randomly assigned to a screening or control group. All women had blood drawn for thyrotropin (TSH) and free T4, but only serum samples from the screening group were immediately assayed. Serum samples from the control group were stored and assayed after delivery. Patients in the screening group who had TSH above the 97.5th percentile (>3.65 mU/L), serum free T4 below the 2.5th percentile, or both were treated with levothyroxine to achieve a TSH between 0.1 and 1.0 mU/L. IQ testing was performed in the children of mothers in the screening and control groups who had tested positive for thyroid dysfunction. There was no difference in the IQ of the children at three years of age or in the proportion of children with IQ score <85. (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Cognitive impairment'.)
Minimum gestational age for betamethasone administration — Meta-analyses of trials of betamethasone administration prior to 26 weeks of gestation have not demonstrated significant neonatal benefits; however, recent data support administration as early as 23 weeks of gestation. In a multicenter prospective cohort study including almost 5000 infants with or without in-utero betamethasone exposure, the composite outcome ‘death or neurodevelopmental impairment at 18 to 22 months of age’ was significantly lower for betamethasone-exposed fetuses born at 23, 24, or 25 weeks of gestation, but not for those infants born at 22 weeks of gestation [4]. (See "Antenatal use of corticosteroids in women at risk for preterm delivery", section on '23 to 34 weeks'.)
Pregnancy risks in mild to moderate kidney disease — Women with mild to moderate chronic kidney disease have worse maternal and fetal outcomes. In a meta-analysis of 13 cohort studies, pregnant women with preexisting renal impairment were significantly more likely than women with normal renal function to develop gestational hypertension, preeclampsia, eclampsia, or to die (12 versus 2 percent) [5]. Maternal mortality was more frequent in those with chronic kidney disease (4 versus 1 percent), although this was not statistically significant. Preterm birth was significantly increased among women with renal impairment (13 versus 6 percent), while nonsignificantly higher rates were noted for intrauterine growth restriction, small for gestational age infants, and stillbirth. (See "Pregnancy in women with underlying renal disease", section on 'Pregnancy in mild to moderate CKD'.)
Breastfeeding not protective against the development of eczema — In the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two study, the association between breastfeeding and eczema was examined in over 50,000 children aged 8 to 12 years from both high and low income countries [6]. A slight but significant increased risk of ever having eczema was found in children ever breastfed; when the duration of breastfeeding was taken into account, a small increased risk was found for children who had been breastfed <6 months, but no association was noted in children breastfed for ≥6 months. Allergen sensitization and parental atopy did not modify these results. These results are consistent with a 2009 meta-analysis of studies that were performed almost exclusively in developed, high-income countries. (See "The impact of breastfeeding on the development of allergic disease", section on 'Breastfeeding and atopic dermatitis (eczema)'.)
Prenatal SSRI exposure and PPHN — In a population-based study that included more than 1.6 million live births from five Nordic countries, filling a prescription for selective serotonin reuptake (SSRI) use after 20 weeks of gestation was associated with a two-fold increase in persistent pulmonary hypertension of the newborn (PPHN) [7]. This resulted in a small absolute increase of PPHN (1.2 per 1000 births for the unexposed population to 2.9 per 1000 births for late prenatal exposure to SSRI).
In a 2011 review of their 2006 public health advisory regarding the possibility of an increased risk of PPHN in infants with late prenatal exposure to SSRIs, the US Food and Drug Administration (FDA) concluded that it was not yet possible to establish a link between SSRI use in pregnancy and PPHN and recommended that health care professionals not alter their clinical management of depression during pregnancy based on a concern of PPHN in the offspring [8]. Of note, the FDA report did not include the Nordic study, as it was published after the FDA review. However, the reported absolute increase in the incidence of PPHN is so small that we continue to suggest following the 2011 FDA recommendation of not altering effective SSRI therapy during pregnancy. (See "Infants with antenatal exposure to serotonin reuptake inhibitors", section on 'Persistent pulmonary hypertension'.)
OFFICE GYNECOLOGY
Revised guidelines for cervical cancer screening — New guidelines for screening for cervical cancer have been issued by the U.S. Preventive Services Task Force (USPSTF) [9]and by a combined group representing the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology (ACS/ASCCP/ASCP) [10]. The two sets of guidelines, developed independently, overlap in their major recommendations (table 1). The American College of Obstetricians and Gynecologists (ACOG) is currently reviewing guidelines they last issued in 2009, and ACOG members were involved in the development of the ACS/ASCCP/ASCP guidelines [11]. The two new guidelines advise initiating cervical cancer screening for average-risk women at age 21 and discontinuing screening at age 65 for women who have had adequate negative prior screening. Average-risk women have no history of cervical cancer, DES in utero exposure, or significant immunocompromise (such as HIV infection). Women aged 21 to 29 should be screened every three years with cytology only, and women aged 30 to 65 should be screened by either cytology alone every three years or co-testing (HPV test plus cytology) every five years. The ACS/ASCCP/ASCP prefers the co-testing strategy, while the USPSTF suggests co-testing as an alternative for those women who wish to lengthen their screening interval while accepting an increased risk that colposcopy would be needed. All guidelines advise that cervical cancer screening is not indicated for women who have had a hysterectomy, in the absence of a history of cervical cancer or high-grade cervical cancer precursor. (See "Screening for cervical cancer: Rationale and recommendations", section on 'Recommendations of professional organizations'.)
Progestin therapy for complex endometrial hyperplasia — Complex atypical endometrial hyperplasia is generally treated with hysterectomy, with the exception of women who desire future pregnancy and thus are treated medically with progestins. The effectiveness of progestin therapy (in a variety of formulations, eg, oral, depot injection, intrauterine device) was illustrated by a meta-analysis of observational studies that found a 66 percent complete response rate, with persistent disease in 14 percent and recurrent disease in 23 percent [12]. (See "Management of endometrial hyperplasia", section on 'Progestin therapy'.)
Ulipristal acetate for uterine fibroids — Ulipristal acetate, a selective progesterone receptor modulator, was evaluated for treatment of symptomatic uterine fibroids in two randomized trials. One trial found that ulipristal acetate was significantly more effective than placebo for treatment of menorrhagia [13]. In the other trial, ulipristal acetate resulted in a comparable rate of resolution of menorrhagia compared with leuprolide acetate, and patients in the ulipristal acetate group had a significantly lower rate of hot flashes [14]. However, the reduction in uterine size was significantly lower for the ulipristal than leuprolide. (See "Overview of treatment of uterine leiomyomas (fibroids)", section on 'Ulipristal acetate'.)
Progestins for threatened abortion — The use of oral or intravaginal progestin therapy to prevent miscarriage in women with threatened abortion was supported by a meta-analysis of four randomized trials that found that for women with vaginal bleeding at ≤23 weeks of gestation, the rate of spontaneous abortion was significantly lower with progestin treatment compared with placebo or no treatment (14 versus 26 percent) [15]. (See "Spontaneous abortion: Management", section on 'Threatened abortion'.)
Progestins in combination hormonal contraceptives associated with an increased risk of thrombosis — In a study that assessed the risk of cardiovascular events in 835,826 combined hormonal contraceptives users, use of combined contraceptives containing drospirenone, norelgestromin, or etonogestrel was associated with a significantly increased risk of venous thrombosis compared with use of standard low-estrogen combined hormonal contraceptives [16]. However, when the analysis was restricted to new users, only drospirenone was associated with a significantly increased risk of thrombosis. (See "Risks and side effects associated with estrogen-progestin contraceptives", section on 'Venous thromboembolic disease'.)
Intermittent hormonal contraception — No hormonal contraceptive method is approved for use only at the time of intercourse (ie, intermittent rather than continuous use), but this approach may be effective. In a systematic review of mostly prospective observational studies of precoital and postcoital use of levonorgestrel as a method of contraception in women who had infrequent intercourse, intermittent use of levonorgestrel was safe and moderately effective as a contraceptive [17]. For the most commonly used regimen (0.75 mg of levonorgestrel within one hour after coitus), the pooled Pearl index was 5.1 pregnancies per 100 woman-years. Pearl indices for standard contraceptive methods are shown in the table (table 2). (See "Overview of contraception", section on 'Intermittent hormonal contraception'.)
Gynecologic and obstetric care of women with hereditary angioedema — An international expert panel produced guidelines on the gynecologic and obstetric care of women with hereditary angioedema [18]. The guideline reviews the impact of menstruation, pregnancy, lactation, and menopause on disease activity. Options for contraception are summarized and information regarding treatment of infertility and hormonal treatments for breast and cervical cancers are reviewed. (See "Prevention of attacks in hereditary angioedema", section on 'Gynecologic and obstetric care'.)
REPRODUCTIVE ENDOCRINOLOGY
Ovarian cancer risk after IVF — Whether there is an association between in vitro fertilization (IVF) and subsequent diagnosis of borderline or malignant ovarian tumors is controversial. In a large retrospective cohort study of ovarian cancer risk in women who underwent IVF and subfertile women who did not undergo IVF, the risk of ovarian neoplasia was significantly increased in the IVF group [19]. There was no dose-response relationship between the number of IVF cycles or the number of oocytes harvested and risk of ovarian neoplasia. Because of limitations in design, this study cannot be considered definitive proof of a cause and effect relationship between IVF and ovarian malignancy. (See "In vitro fertilization".)
GYNECOLOGIC SURGERY
Postoperative treatment of endometriosis — Hormonal suppression following surgical treatment of endometriosis has been found to decrease recurrence rates, but a beneficial effect on pain and pregnancy rates remains unproven. A randomized trial found that postoperative insertion of the levonorgestrel-releasing intrauterine device, compared with expectant management, resulted in decreased dysmenorrhea and pelvic pain at one-year follow-up [20]. (See "Overview of the treatment of endometriosis", section on 'Postoperative medical therapy'.)
Maneuvers to displace trapped carbon dioxide after laparoscopy — Trapped carbon dioxide gas used in laparoscopy may cause abdominal or shoulder pain after surgery. A trial to assess the most effective strategy for displacing the gas randomly assigned women undergoing gynecologic laparoscopic surgery to one of three arms: instillation of normal saline after release of the pneumoperitoneum; pulmonary maneuvers in which the anesthesiologist manually inflates the thorax to increase intra-abdominal pressure; or no maneuvers (control) [21]. The incidence of postoperative shoulder pain was significantly lower in the saline group 24 hours after surgery and upper abdominal pain was improved for both treatment groups compared with the control group. (See "Abdominal access techniques used in laparoscopic surgery", section on 'Access-related pain'.)
Early menopause after hysterectomy — Hysterectomy is associated with earlier age at menopause. A prospective cohort study found that menopause occurred 1.9 years earlier in women who had a hysterectomy while premenopausal than those who did not [22]. Among women who underwent hysterectomy, the rate of early menopause was significantly higher in those who also underwent unilateral oophorectomy than those who had both ovaries conserved. (See "Overview of hysterectomy", section on 'Earlier menopause'.)
Bipolar sealing devices for vaginal hysterectomy — Bipolar vessel sealing devices may be used as an alternative to suturing for ligation of the uterine vessels during vaginal hysterectomy. A meta-analysis of seven randomized trials of women undergoing vaginal hysterectomy found that use of an energy-based vessel sealing devices (eg, LigaSure™, BiClamp®) decreased blood loss by an average of 48 mL and operative duration by an average of 17 minutes compared with suturing [23]. (See "Vaginal hysterectomy", section on 'Ligating the uterine vessels'.)
GYNECOLOGIC ONCOLOGY
Ovarian cancer symptoms and complete cytoreduction — Symptoms associated with ovarian cancer have been identified (eg, abdominal bloating, early satiety, pelvic or abdominal pain), but the impact on ovarian cancer survival of actively eliciting these symptoms is unknown. One potential role for identification of symptoms is to diagnose ovarian cancer when optimal cytoreduction is possible. A prospective study identified 11 women with ovarian, fallopian tube, or primary peritoneal cancer among 1455 who were found to have ovarian cancer symptoms using targeted questioning at routine medical visits and a public health campaign [24]. These women were more likely than those who presented with these malignancies through standard care to have completely resectable disease (72 versus 23 percent). However, 239 women required investigation to identify the 11 ovarian cancers, with a prevalence of one per 132 women (0.76 percent) who had symptoms. (See "Early detection of epithelial ovarian cancer: Role of symptom recognition", section on 'Role of early detection'.)
Expectant management of hydatidiform mole — Women with hydatidiform mole are typically treated with chemotherapy for presumed malignant gestational disease if the serum human chorionic gonadotropin (hCG) level remains elevated at six months after uterine evacuation. However, some data suggest that continued surveillance is reasonable in some women. A retrospective study including over 12,000 women with hydatidiform mole followed with serial hCG measurements found that the level normalized in 99 percent within six months after uterine evacuation [25]. hCG levels remained elevated in 76 women; ten of these patients received chemotherapy and 66 women were managed with continued hCG surveillance. The hCG level normalized within six to 12 months after evacuation in 45 of the 66 patients (89 percent). (See "Gestational trophoblastic disease: Management of hydatidiform mole", section on 'Diagnosis of persistent disease'.)
BRCA mutations and ovarian cancer prognosis — A meta-analysis of 26 observational studies found that BRCA gene mutation carriers with ovarian cancer, particularly BRCA2 mutation carriers, have a significantly better prognosis than noncarriers [26]. The five-year all-cause mortality rate for noncarriers was 47 percent compared with 45 percent for BRCA1 mutation carriers and 36 percent for BRCA2 mutation carriers.
Self-collected HPV testing for cervical cancer screening in resource-limited settings — Self-collected human papilloma virus (HPV) testing was compared with clinic-based cervical cytology in a randomized trial of over 12,000 women in Mexico [27]. Acceptability of self-collected HPV testing was high; nearly all women in this group performed the testing. Sensitivity of HPV testing was 2.9-fold higher for detection of a high-grade cervical intraepithelial lesion (CIN) or more severe disease and 3.6-fold higher for detection of invasive cervical cancer. The disadvantage of HPV testing was that many more women underwent unnecessary colposcopy. For a diagnosis of high-grade CIN or more severe disease, the positive predictive value of HPV testing was 12.2 percent compared with 90.5 percent for cytology. (See "Screening for cervical cancer in resource-limited settings", section on 'Self-collected samples'.)
Ultrasound for ovarian cancer screening — A large prospective study with follow-up to 20 years evaluated annual transvaginal ultrasonography for the detection of ovarian cancer in over 37,000 asymptomatic women (aged 50 and older or aged 25 and older with a documented family history of ovarian cancer) [28]. The specificity and positive predictive value for primary invasive epithelial ovarian cancer were 98.5 and 8.9 percent, respectively; 11.1 operations were performed per primary ovarian cancer detected. Seventy percent of the 47 screen-detected invasive cancers were stage I or II. The five-year survival rate for women with screen-detected invasive ovarian cancer was higher than for ovarian cancers in unscreened women at the same institution; whether this difference reflects a true mortality difference or biases related to nonrandomized studies (lead time, length time, and healthy volunteer effects) cannot be determined. Additionally, these results reflect findings from a center with high expertise in ultrasound and are not likely to be reproducible in the general community. UpToDate does not recommend screening average risk women for ovarian cancer. (See "Screening for ovarian cancer", section on 'Pelvic ultrasonography'.)
Bevacizumab plus chemotherapy for newly diagnosed epithelial ovarian cancer — Most women with newly diagnosed epithelial ovarian cancer (EOC) are treated with surgery followed by platinum- and taxane-based chemotherapy. Despite this, the majority will relapse within three years. The Gynecologic Oncology Group trial 218 (GOG 218) and the Gynecologic InterGroup trial (ICON7) randomly assigned women with newly diagnosed EOC to treatment using standard chemotherapy with or without the angiogenesis inhibitor bevacizumab [29,30]. Both studies showed that incorporation of bevacizumab significantly improved progression free survival, but did not impact overall survival. Despite this improvement in progression free survival, we continue to suggest not adding bevacizumab routinely until there is longer follow-up on quality of life and overall survival outcomes. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, or peritoneal cancer", section on 'Incorporation of angiogenesis inhibitors'.)
UROGYNECOLOGY
ACOG and AUGS recommendations regarding transvaginal mesh for pelvic organ prolapse repair — The American College of Obstetricians and Gynecologists and the American Urogynecologic Society issued a joint statement in response to the US Food and Drug Administration warning (September, 2011) regarding use of transvaginal mesh for pelvic organ prolapse repair [31]. The recommendations included: limiting vaginal mesh repair to women for whom the benefit of mesh use outweighs the risks (eg, recurrent prolapse or comorbidities precluding more invasive procedures), device-specific training for surgeons, and reporting of outcome data for transvaginal mesh procedures. (See "Reconstructive materials in urogynecology: Clinical applications".)
Complications of retropubic versus transobturator midurethral slings — The Trial of Midurethral Slings study (TOMUS), a randomized trial comparing retropubic and transobturator midurethral slings, reported two-year follow-up data regarding complications [32]. Adverse events, comprised mostly of bladder perforation and postoperative bleeding, were significantly more likely with retropubic procedures. Neurologic symptoms (eg, numbness, weakness) were the only type of adverse event that was significantly more likely to occur with transobturator procedures. (See "Stress urinary incontinence in women: Choosing a type of midurethral sling", section on 'Transobturator versus retropubic midurethral slings'.)
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.
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