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The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.

Objective: To evaluate efficacy in achieving vaginal delivery with a standardized vaginal compared with oral misoprostol regimen for labor induction at term., Methods: In this single-center, cluster randomized trial, we randomized induction method by week among individuals with gestational age of 37 weeks or more, cervical dilation of 2 cm or less, intact membranes, and indication for delivery to either oral (100 micrograms every 4 hours for up to two doses), or vaginal (25 micrograms every 3 hours for up to five doses) misoprostol regimens, followed by a standardized oxytocin protocol. Individuals with an antepartum stillbirth, major fetal anomalies, malpresentation, ruptured membranes, nonreassuring fetal status, or contraindication to prostaglandin were excluded. The primary outcome was vaginal delivery at first induction attempt. Secondary outcomes included time to delivery, need for oxytocin, chorioamnionitis, and adverse maternal and neonatal outcomes. Outcomes were recorded at the individual level and adjusted for clustering, with analysis by intention to treat., Results: Between May 24, 2021, to September 19, 2022, 1,322 women were randomized to vaginal misoprostol in 33 clusters and 1,224 to oral misoprostol in 37 clusters. Demographic characteristics or initial cervical dilation did not differ between groups. The primary outcome did not differ between induction regimens and occurred in 1,032 (78.1%) of the vaginal misoprostol arm and 945 (77.2%) of the oral misoprostol arm (adjusted relative risk [RR] 1.01, 95% CI, 0.97-1.05). Tachysystole with fetal heart rate changes occurred less frequently with vaginal compared with oral misoprostol (3.5% vs 5.9%, adjusted RR 0.59, 95% CI, 0.40-0.87). Time to delivery did not differ between groups. Oxytocin was less frequently required before delivery in the vaginal misoprostol group (68.8% vs 78.4%, adjusted RR 0.88, 95% CI, 0.84-0.92)., Conclusion: Induction of labor with vaginal compared with oral misoprostol protocols did not increase the frequency of vaginal delivery at term but did reduce the need for oxytocin use before delivery., Clinical Trial Registration: ClinicalTrials.gov, NCT04755218., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The U.S. Food and Drug Administration has recently withdrawn approval for 17-α hydroxyprogesterone caproate for prevention of recurrent preterm birth, and recent studies have called into question benefits of the pessary in the setting of a short cervix. Obstetric health care professionals are once again left with limited remaining options for preterm birth prevention. This narrative review summarizes the best current evidence on the use of vaginal progesterone, low-dose aspirin, and cerclage for the prevention of preterm birth; attempts to distill possible lessons learned from studies of progesterone and pessary, as well as their implementation into practice; and highlights areas where inroads into preterm birth prevention may be possible outside of the progesterone-aspirin-cerclage paradigm., Competing Interests: Financial Disclosure The author did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the use of cervical dilators concurrently with misoprostol to shorten labor in second-trimester medical termination of pregnancy., Methods: This multicenter randomized controlled trial compared the efficacy of cervical dilators inserted concurrently with misoprostol with that of misoprostol, alone, to shorten labor for women undergoing termination of pregnancy between 15 0/7 and 27 6/7 weeks of gestation. The primary outcome was the proportion of women with a duration of labor exceeding 12 hours. Secondary outcomes included median duration of labor, time to amniotomy, side effects, complications, NPRS (Numeric Pain Rating Scale) score, and women's distress as measured by the IES-R (Impact of Event Scale-Revised). These outcomes also were studied separately in the nulliparous subgroup. To demonstrate a reduction of 50% of the proportion of women with a duration of labor exceeding 12 hours in the dilator group, with a power of 80% and a 2-sided 0.05 significance level, a sample of 268 women (134 in each group) was required., Results: Between December 2017 and September 2019, this study enrolled and analyzed 347 women: 174 in the dilator group and 173 in the control group, including 87 and 93 nulliparous patients, respectively. Sociodemographic and obstetric characteristics were similar between groups. The proportion of women with labor exceeding 12 hours was not different between groups (49/174 [28.2%] in the dilator group vs 53/173 [30.6%] in the control group [ P =.61] for the whole population, and 37/87 [42.5%] vs 42/93 [45.2%] [ P =.72], respectively, among nulliparous patients). Median duration of labor was 8.5 hours in the dilator group compared with 9.2 hours in the control group ( P =.65) for the whole population, and 10.5 hours compared with 11.8 hours, respectively, among nulliparous patients ( P =.33). Median time to amniotomy was 3.6 hours in the dilator group compared with 5.0 hours in the control group ( P =.08) for the whole population, and 3.5 hours compared with 6.7 hours, respectively, among nulliparous patients ( P =.003). Side effects, complications, NPRS score, and IES-R score were similar between groups., Conclusion: Cervical dilators inserted concurrently with misoprostol did not reduce the proportion of women whose labor exceeded 12 hours compared with misoprostol alone., Clinical Trial Registration: ClinicalTrials.gov , NCT03194230., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Progesterone has been the standard of practice for the prevention of preterm birth for decades. The drug received expedited Food and Drug Administration approval, prior to the robust demonstration of scientific efficacy., Methods: Prospective research from the American Association of Birth Centers Perinatal Data Registry, 2007-2020. Two-tailed t tests, logistic regression, and propensity score matching were used., Results: Midwifery-led care was underutilized by groups most at risk for preterm birth and was shown to be effective at maintaining low preterm birth rates. The model did not demonstrate reliable access to progesterone. People of color are most at risk of preterm birth, yet were least likely to receiving progesterone treatment. Progesterone was not demonstrated to be effective at decreasing preterm birth when comparing the childbearing people with a history of preterm birth who used the medication and those who did not within this sample., Conclusions: This study adds to the body of research that demonstrates midwifery-led care and low preterm birth rates. The ineffectiveness of progesterone in the prevention of preterm birth among people at risk was demonstrated., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment., Methods: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed)., Results: Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis., Conclusion: A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry., Funding Source: The study was funded by Daré Bioscience, Inc., Clinical Trials Registration: ClinicalTrials.gov, NCT04370548., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate whether a synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening., Methods: In an open-label, noninferiority randomized trial, pregnant women undergoing induction of labor at 37 weeks of gestation or more with Bishop scores less than 6 were randomized to either mechanical cervical dilation or oral misoprostol. Participants in the mechanical dilation group underwent insertion of synthetic osmotic cervical dilator rods, and those in the misoprostol group received up to six doses of 25 micrograms orally every 2 hours. After 12 hours of ripening, oxytocin was initiated, with artificial rupture of membranes. Management of labor was at the physician's discretion. The primary outcome was the proportion of women achieving vaginal delivery within 36 hours of initiation of study intervention. Secondary outcomes included increase in Bishop score, mode of delivery, induction-to-delivery interval, total length of hospital stay, and patient satisfaction. On the basis of a noninferiority margin of 10%, an expected primary outcome frequency of 65% for misoprostol and 71% for mechanical methods, and 85% power, a sample size of 306 participants was needed., Results: From November 2018 through January 2021, 307 women were randomized, with 151 evaluable participants in the synthetic osmotic cervical dilator group and 152 in the misoprostol group (there were four early withdrawals). The proportion of women achieving vaginal delivery within 36 hours was higher with mechanical cervical dilation compared with misoprostol (61.6% vs 59.2%), with an absolute difference of 2.4% (95% CI -9% to 13%), indicating noninferiority for the prespecified margin. No differences were noted in the mode of delivery. Tachysystole was more frequent in the misoprostol group (70 [46.4%] vs 35 [23.3%]; P=.01). Participants in the synthetic osmotic cervical dilator group reported better sleep, less unpleasant abdominal sensations, and lower pain scores (P<.05)., Conclusion: Synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening. Advantages of synthetic osmotic cervical dilator include a better safety profile and patient satisfaction, less tachysystole, lower pain scores, and U.S. Food and Drug Administration approval., Clinical Trial Registration: ClinicalTrials.gov, NCT03670836., Funding Source: Medicem Technology s.r.o., Czech Republic., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To test the effectiveness of cervical pessary in addition to vaginal progesterone for the prevention of preterm birth in women with midpregnancy short cervixes., Methods: We performed a multicenter, open-label, randomized controlled trial in 17 perinatal centers. Asymptomatic women with singleton or twin pregnancies and cervical lengths of 30 mm or less, measured at 18 0/7-22 6/7 weeks of gestation, were randomized to cervical pessary plus vaginal progesterone (pessary plus progesterone group) or vaginal progesterone only (progesterone-only group) (200 mg/day). Treatments were used from randomization to 36 weeks of gestation or delivery. The primary outcome was a composite of neonatal mortality and morbidity. Secondary outcomes were delivery before 37 weeks and before 34 weeks of gestation. Analysis was performed according to intention to treat., Results: Between July 9, 2015, and March 29, 2019, 8,168 women were screened, of whom 475 were randomized to pessary and 461 to progesterone only. The composite perinatal outcome occurred in 19.2% (89/463) of the women in the pessary group compared with 20.9% (91/436) of the women in the progesterone-only group (adjusted risk ratio [aRR] 0.88, 95% CI 0.69-1.12). Delivery rates before 37 weeks of gestation were 29.1% compared with 31.4% (aRR 0.86, 95% CI 0.72-1.04); delivery rates before 34 weeks were 9.9% compared with 13.9% (aRR 0.66, 95% CI 0.47-0.93). Women in the pessary group had more vaginal discharge (51.6% [245/476] vs 25.4% [117/479] [P<.001]), pain (33.1% [157/476] vs 24.1% [111/479] [P=.002]), and vaginal bleeding (9.7% [46/476] vs 4.8% [22/479] [P=.004])., Conclusion: In asymptomatic women with short cervixes, the combination of pessary and progesterone did not decrease rates of neonatal morbidity or mortality when compared with progesterone only., Clinical Trial Registration: Brazilian Clinical Trial Registry (ReBec), UTN:U1111-1164-2636., Competing Interests: Financial Disclosure Ben W. Mol reports that money was paid to him from ObsEva. Money was paid to his institution from Guerbet, Merck, and Ferring. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This retrospective cohort study aims to determine the proportion of postmenopausal women with recurrent urinary tract infections (rUTIs) who improve with vaginal estrogen cream alone and to identify risk factors for those who go on to require additional therapies., Methods: Postmenopausal women presenting with rUTIs seen at a single institution over a 29-month period were identified. Patients who had not undergone previous treatment and were started on vaginal estrogen cream alone as first-line therapy were included in the study. Descriptive statistics were used to compare demographic and clinical characteristics between therapy groups. Log-binomial regression was used to explore the association between treatment failure (ie, the need for additional therapy for rUTIs) and patient sociodemographic and clinical characteristics., Results: During the study period, 167 patients with rUTIs met inclusion criteria. Of these, 67.7% noted improvement or resolution in their symptoms with vaginal estrogen cream alone. Women with a concomitant diagnosis of urinary incontinence, as defined as subjective report of bothersome stress or urgency urinary incontinence, were 2.3 times more likely to need additional therapy compared with women not reporting urinary incontinence (relative risk, 2.28; 95% confidence interval, 1.06-4.90)., Conclusions: Sixty-eight percent of postmenopausal women with rUTIs treated with vaginal estrogen alone did not go on to receive additional therapy. A risk factor for needing additional therapy in our study population is the presence of urinary incontinence., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2021 American Urogynecologic Society. All rights reserved.)

Objectives: We aimed to compare the efficacy of 2 commonly used contemporary vaginal estrogen administrations versus placebo for the prevention of urinary tract infection (UTI) in postmenopausal women with a clinical diagnosis of recurrent UTI (rUTI)., Methods: This was an investigator-initiated, multicenter, single-blind, randomized, placebo-controlled trial of vaginal estrogen (delivered via ring or cream) compared with placebo. Postmenopausal women with documented rUTI were randomized to receive either vaginal estrogen (via ring or cream) or placebo cream in a 1:1:1 fashion. The primary outcome was occurrence of UTI at 6 months. After 6 months, open-label use of ring or active cream was offered to all participants for an additional 6 months. Because of slower than expected recruitment, sample size calculations and block randomization schema were revised to combine estrogen groups (ring or cream) for statistical comparisons to placebo cream in a 1:1 fashion., Results: Thirty-five women were randomized with 9 dropouts (1 ring, 2 cream, and 6 placebo) prior to the 6 months. Intention-to-treat analysis (assuming dropouts as failures) revealed fewer women treated with vaginal estrogen had a UTI within 6 months versus placebo (11/18 vs 16/17, respectively; P = 0.041). Per-protocol analysis revealed fewer subjects treated with vaginal estrogen had a UTI at 6 months (8/15 vs 10/11, respectively; P = 0.036)., Conclusions: Commonly prescribed forms of vaginal estrogen with contemporary dosing schedules prevent UTIs in postmenopausal women with an active diagnosis of rUTI., (Copyright © 2019 American Urogynecologic Society. All rights reserved.)

Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of misoprostol use is withheld and the gross and histologic findings are sparse, as is often the case. One hundred thirty-two placentas with no vaginal misoprostol use, low-dose misoprostol use, and high-dose misoprostol use were reviewed for the presence, volume, and locations of microcrystalline cellulose and crospovidone, common tablet fillers in misoprostol tablets. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes. The presence of microcrystalline cellulose and/or crospovidone was associated with smaller placental weight (Mann-Whitney U, P = 0.019). These fillers have a reasonable sensitivity for high-dose vaginal tablet use and are very specific. Although they are not diagnostic for misoprostol administration, they provide a finding that may prompt additional investigation into the nature of the vaginal tablet administered and the circumstances surrounding birth.

The critical measures of importance in reducing the frequency of postcesarean infection are preoperative cleansing of the vagina with a povidone-iodine solution, administration of cefazolin plus azithromycin before surgery, preparation of the abdomen with a chlorhexidine solution, removal of the placenta by traction on the cord, closure of the deep part of the subcutaneous layer, and closure of the skin with sutures rather than staples.

Rationale: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles., Patient Concerns: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness., Diagnoses: Infertility undergoing FET cycles., Interventions: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy., Outcomes: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer., Lessons: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.

Objective: To evaluate whether cervical ripening with oral misoprostol increases cesarean delivery risk and prolongs time to vaginal delivery compared with vaginal misoprostol in a predominantly overweight population., Methods: This single center, retrospective cohort study was performed at a tertiary care academic medical center and compared labor induction outcomes with vaginal misoprostol to outcomes with oral misoprostol after a complete institutional shift to oral misoprostol. Labor induction using 25 micrograms vaginal misoprostol in 2013-2014 was compared with 50 micrograms oral misoprostol in 2014-2015. The primary outcome was cesarean delivery. Secondary outcomes included time to vaginal delivery, uterine tachysystole, maternal hemorrhage, and composite adverse neonatal outcomes. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios (aOR) as the measures of effect., Results: There were 138 women in the oral and 138 women in the vaginal misoprostol groups. In the overall cohort, the median (interquartile range) body mass index was 31.7 (28.2-36.8) and most women (72%) were of either black or Hispanic race or ethnicity. The frequency of cesarean delivery was higher in the oral than the vaginal misoprostol group (32% vs 21%; P=.04). The adjusted odds of cesarean was higher with oral misoprostol (aOR 2.01; 95% CI 1.07-3.76). Among nulliparous women, the frequency of cesarean delivery was 41% in the oral and 28% in the vaginal misoprostol groups (aOR 2.79; 95% CI 1.26-6.19). Women had a longer time to vaginal delivery in the oral compared with vaginal misoprostol group (41 vs 31 hours respectively, P=.01). Tachysystole occurred more frequently with vaginal misoprostol (20% vs 11%; P=.04)., Conclusion: Compared with vaginal misoprostol, oral misoprostol may be associated with increased risk of cesarean delivery and longer time to vaginal delivery.

Objective: To compare the effectiveness of cervical pessary to vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and short cervix., Methods: This randomized controlled trial was conducted at My Duc Hospital, Vietnam. Asymptomatic women with twin pregnancies and cervical length less than 38 mm were randomized to Arabin pessary or vaginal progesterone (400 mg once a day) group. The primary outcome was preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse maternal and perinatal complications. We planned a subgroup analysis according to quartile of cervical length. Analysis was conducted on an intention-to-treat basis. We estimated that the primary outcome would occur in 28.4% of women treated with progesterone. Thus a total sample size of 290 women divided equally into two groups was required to detect a 14% absolute risk difference in the primary outcome between the two groups (power 80%, alpha-error 5%, 10% loss to follow-up)., Results: Between March 2016 and June 2017, we randomized 300 women, 150 women in each group. Preterm birth at less than 34 weeks of gestation occurred in 24 (16%) women in the pessary group and 33 (22%) women in the progesterone group (relative risk [RR] 0.73, 95% CI 0.46-1.18). The use of pessary significantly reduced the composite of poor perinatal outcomes (19% vs 27%; RR 0.70, 95% CI 0.43-0.93). In women with cervical length of 28 mm or less (25th percentile), pessary significantly reduced the preterm birth rate at less than 34 weeks of gestation from 46% (16/35) to 21% (10/47) (RR 0.47, 95% CI 0.24-0.90) and significantly improved the composite of poor perinatal outcomes., Conclusion: Cervical pessary and 400 mg vaginal progesterone resulted in similar rates of preterm birth at less than 34 weeks of gestation in women with twin pregnancies and cervical length less than 38 mm., Clinical Trial Registration: ClinicalTrials.gov, NCT02623881.

Objectives: Pelvic floor hypertonic disorder is characterized by an involuntary spasm of the levator ani muscles and is associated with several clinical syndromes. Several treatment options have been described; however, treatment efficacy data are limited. The objective of this study was to determine the efficacy of intravaginal diazepam for the treatment of pelvic pain secondary to levator ani muscle spasm in comparison to placebo., Methods: Adult women with complaints of pelvic pain, who were noted to have levator ani muscle spasm on physical examination, were approached for enrollment in a double-blind, placebo-controlled, randomized clinical trial. Eligible participants were randomized to receive 10-mg diazepam capsules or identical-appearing placebo capsules. The primary outcome was the change in pain scores measured by a 100-mm visual analog scale at 4 weeks. Several validated questionnaires were similarly assessed as secondary outcomes., Results: In total, 49 women were randomized (25 in the diazepam arm and 24 in the placebo arm). At 4 weeks, 35 women returned for follow-up and had complete data available analysis. There was no difference in visual analog scale scores between the treatment groups after 4 weeks (50 vs 39 mm, for diazepam and placebo, respectively; P = 0.36). There were also no differences noted in the questionnaire scores., Conclusions: It is unlikely that self-administered intravaginal diazepam suppositories promote an improvement in the 100-mm visual analog scale of 20 mm or more or other substantial symptom improvement in women with pelvic floor hypertonic disorder.

Genitourinary syndrome of menopause (GSM) describes a collection of exam findings and bothersome symptoms associated with estrogen deficiency involving changes to the labia, introitus, clitoris, vagina, urethra, and bladder. Vulvovaginal atrophy is a component of GSM. GSM is a highly prevalent medical condition with adverse effects on the health and quality of life of midlife women. There are many effective treatment options, including nonhormonal lubricants and moisturizers, physical therapy, low-dose vaginal estrogen therapy, vaginal dehydroepiandrosterone, and oral ospemifene. Despite the availability of safe and effective therapies, GSM often remains unrecognized and untreated.

Women and health care providers are often fearful of using hormone therapy to deal with distressing menopausal symptoms in circumstances where there is a perceived or real increased risk of breast cancer. This paper examines the evidence for and against hormone therapy use in 3 common clinical situations: the woman with a positive family history in a first-degree relative, the woman who has undergone risk-reducing salpingo-oophorectomy due to a known genetic mutation, and the woman in whom treatment of breast cancer has induced premature menopause.

The goal of the 2017 North American Menopause Society Hormone Therapy (HT) Position Statement is to remove fear about HT and encourage individualized shared decision making, using best available evidence. Systemic HT is safe and effective for symptomatic menopausal women aged younger than 60 years and within 10 years of menopause. Special populations of early menopause, high risk for fracture, risk of breast or uterine cancer, and extended duration are discussed. With longer duration of use, periodic evaluation and reassessment of health risks are needed. Lowered doses, transdermal therapies or newer options may enhance the benefit:risk ratio for HT.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

Objective: To test the hypothesis that cervical ripening using a combination of misoprostol and a transcervical Foley bulb leads to delivery within a shorter time compared with misoprostol alone., Methods: This randomized controlled trial was offered to women admitted for cervical ripening. Inclusion criteria were gestational age 37 weeks or greater with intact membranes, singleton fetus, cephalic presentation, and Bishop score 6 or less. Exclusion criteria included, among others, prior uterine surgery, ruptured membranes, and any contraindication to vaginal delivery. Patients were randomized to cervical ripening using misoprostol and a transcervical Foley bulb simultaneously or misoprostol alone. Primary outcome was time from placement of the misoprostol to delivery. Secondary outcomes included time to active phase, time from active phase to delivery, cesarean delivery rate, uterine tachysystole, estimated blood loss, chorioamnionitis, cord pH, 5-minute Apgar score, and neonatal intensive care unit admission. Sample size calculation revealed that 94 participants were required in each group to detect a 3-hour difference with 80% power and α error of 0.05. Intention-to-treat analysis was performed., Results: From September 2015 to July 2016, a total of 200 patients were randomized, 100 to each group. There were no differences between groups with respect to parity, body mass index, gestational age, Bishop score, birth weight, or indication for induction. Time to delivery was significantly shorter in the combined misoprostol-transcervical Foley group: 15.0 (11.0-21.8) hours (median [interquartile range]) vs 19.0 (14.0-27.3) hours in the misoprostol-only group (P=.001). This time difference remained significant after subanalysis by parity or after excluding cesarean deliveries. There was no difference between groups with respect to the rate or indication for cesarean delivery, estimated blood loss, rate of tachysystole, chorioamnionitis, or neonatal outcomes., Conclusion: Cervical ripening using misoprostol in combination with a transcervical Foley bulb is an effective method to shorten the course of labor compared with misoprostol alone., Clinical Trial Registration: ClinicalTrials.gov, NCT02566005.

Objective: To examine success rates of 5-fluorouracil, excision, and laser ablation as the initial and secondary management strategies for women with high-grade vaginal intraepithelial neoplasia., Methods: We conducted a retrospective case series of women referred to a single center for management of biopsy-proven, high-grade vaginal intraepithelial neoplasia between April 1994 and May 2016. Data including demographic characteristics, human papillomavirus risk factors, antecedent Pap cytology, concurrent or prior cervical and vulvar dysplasia, and treatment outcome including follow-up Pap cytology were recorded. All women were counseled on options of excision, laser ablation, or 5-fluorouracil, which was administered intravaginally according to a standardized regimen. Recurrence was defined as a biopsy showing any vaginal intraepithelial neoplasia diagnosis after primary treatment., Results: Forty-seven patients were treated initially with 5-fluorouracil, 35 were treated with excision, and 22 were treated with laser ablation. Demographics were similar between groups. No recurrence was noted in 35 women treated with 5-fluorouracil (74%; 95% CI 62-87%), 20 treated with excision (57%; 95% CI 41-74%), and nine treated with laser ablation (41%; 95% CI 20-61%). Among 13 patients treated with 5-fluorouracil for recurrence, eight (62%) did not experience a second recurrence. Nine of 58 (16%) patients ever treated with 5-fluorouracil reported a side effect, most commonly irritation and dyspareunia., Conclusion: 5-fluorouracil was associated with a 74% success rate as the initial treatment modality for high-grade vaginal dysplasia. There is also a role for 5-fluorouracil in the management of recurrent or persistent high-grade vaginal intraepithelial neoplasia.

Objective: To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis., Data Sources: MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library were searched from their inception to January 2017., Methods of Study Selection: Selection criteria included all randomized controlled trials comparing vaginal cleansing (ie, intervention group) with a control group (ie, either placebo or no intervention) in women undergoing cesarean delivery. Any method of vaginal cleansing with any type of antiseptic solution was included. The primary outcome was the incidence of endometritis. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% CI., Tabulation, Integration, and Results: Sixteen trials (4,837 women) on vaginal cleansing immediately before cesarean delivery were identified as relevant and included in the review. In most of the included studies, 10% povidone-iodine was used as an intervention. The most common way to perform the vaginal cleansing was the use of a sponge stick for approximately 30 seconds. Women who received vaginal cleansing before cesarean delivery had a significantly lower incidence of endometritis (4.5% compared with 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and of postoperative fever (9.4% compared with 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants) compared with the control group. In the planned subgroup analyses, the reduction in the incidence of endometritis with vaginal cleansing was limited to women in labor before cesarean delivery (8.1% compared with 13.8%; RR 0.52, 95% CI 0.28-0.97; four studies, 440 participants) or those with ruptured membranes (4.3% compared with 20.1%; RR 0.23, 95% CI 0.10-0.52; three studies, 272 participants)., Conclusion: Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. Because it is generally inexpensive and a simple intervention, we recommend preoperative vaginal preparation before cesarean delivery in these women with sponge stick preparation of povidone-iodine 10% for at least 30 seconds. More data are needed to assess whether this intervention may be also useful for cesarean deliveries performed in women not in labor and for those without ruptured membranes., Systematic Review Registration: PROSPERO International prospective register of systematic reviews, https://www.crd.york.ac.uk/PROSPERO/, CRD42017054843.

Background and Purpose: Double-blind randomized studies on the effects of oral postmenopausal hormone therapies were stopped mainly because of increased risk of stroke. We aimed to assess the risk of all strokes and various subtypes associated with hormone therapy and explore the influence of regimens and routes of administration., Methods: A national historical cohort of women aged 51 to 70 years from 1995 to 2010 was established by linking 5 Danish registries. The National Registry of Medicinal Product Statistics provided information on hormone therapy exposure and the National Patient or Cause of Death Registries supplied data regarding stroke diagnoses (ischemic/hemorrhagic/subarachnoid hemorrhage). Multiply adjusted rate ratios with time-varying covariates were fitted in Poisson regression models., Results: Of the 980 003 included women, 20 199 suffered a stroke (78% ischemic, 12% hemorrhagic, and 10% subarachnoid hemorrhage). In total, 36% of women used hormone therapy. Current use conferred a relative rate of 1.16 (95% confidence interval, 1.12-1.22). Compared with never users, the increased rate ratio of all stroke with continuous, cyclic combined estrogen/progestin, and estrogen only oral therapies were 1.29 (95% confidence interval, 1.21-1.37), 1.11 (95% confidence interval, 1.04-1.20), and 1.18 (95% confidence interval, 1.10-1.26), respectively. The increased risk was because of ischemic stroke, but not hemorrhagic stroke. Transdermal application of hormone therapy was not associated with risk of stroke. Vaginal estrogen was associated with a decreased risk of stroke., Conclusions: In a national setting, we found an increased risk of stroke, based on ischemic stroke, with oral hormone therapies that was comparable to findings from randomized studies. We found no risk of stroke with transdermal application and a reduced risk with vaginal estrogen., (© 2017 American Heart Association, Inc.)

Objective: To assess the efficacy of progestogens for maintenance tocolysis in women undelivered after their first preterm labor episode., Methods: Women with singleton pregnancies between 22 0/7 and 31 6/7 weeks of gestation with arrested preterm labor and a cervical length 25 mm or less at hospital discharge were eligible. Patients with a previous preterm birth were excluded. In a randomized controlled trial conducted in five university hospitals, women were randomized to receive vaginal progesterone (200 mg per day) or intramuscular 17α-hydroxyprogesterone caproate (341 mg per week) or to an observation groups (control group). The primary outcome was the proportion of women with preterm birth at less than 37 weeks of gestation. A sample size of 160 per group (n=480) was planned to compare vaginal progesterone and 17α-hydroxyprogesterone caproate groups with those in the control group. The sample size estimation was based on the hypothesis that the risk of experiencing preterm birth in the control group would be 30% and that 17α-hydroxyprogesterone caproate or progesterone would decrease this risk to 15%. A P value of <.025 was defined as statistically significant. At planned interim analysis (n=254), the trial was stopped for futility., Results: Between July 2010 and June 2015, 257 women were eligible and 254 were subsequently randomly assigned to vaginal progesterone (n=86), 17α-hydroxyprogesterone caproate (n=87), or observation (n=81). Nineteen (8%) were excluded from the analysis because they either dropped out or information was missing, leaving 235 women available for analysis. Demographic characteristics were similar across groups. The preterm birth rate did not differ significantly between groups: 23% in the 17α-hydroxyprogesterone caproate group, 39% in the vaginal progesterone group, and 22% in the women in the control group (P=.949 for 17α-hydroxyprogesterone caproate compared with the women in the control group and P=.027 for vaginal progesterone compared with women in the control group)., Conclusion: The use of progestogens for maintenance tocolysis in women with a short cervix did not reduce the rate of preterm birth., Clinical Trial Registration: ClinicalTrials.gov, NCT01178788.

Objective: To estimate the effect of lidocaine-prilocaine cream on patient pain at the time of office pessary removal and reinsertion., Methods: In this double-blind, randomized placebo-controlled trial, participants undergoing routine pessary care in a urogynecology office at a tertiary referral center were randomized to application of 4 g of either lidocaine-prilocaine or placebo cream 5 minutes before pessary change. Visual analog scale pain scores were collected from the patient at baseline, after pessary removal, and after pessary reinsertion. Physicians also recorded their estimate of patient pain at pessary removal and reinsertion. The primary outcome was the participant-reported visual analog scale pain score at the time of pessary removal and reinsertion. A sample size of 26 per group (n=52) was planned to estimate an absolute mean difference in visual analog scale pain of 2.1 cm at the time of pessary removal. An analysis of covariance was used to evaluate pain at removal and reinsertion as a function of treatment assignment controlling for baseline pain., Results: From July 2015 through February 2016, 116 women were screened and 54 were recruited: 28 in the lidocaine-prilocaine cream group and 26 in the placebo group. One patient in the lidocaine-prilocaine cream group was later withdrawn owing to vaginal erosion. The participants were all postmenopausal women, with an average age of 77.8 years. Most characteristics were similar between groups. After adjusting for baseline pain, participants randomized to the lidocaine-prilocaine group had lower pain at pessary removal when compared with those assigned to placebo (mean difference=-2.05, 95% confidence interval -3.69 to -0.41; P=.015)., Conclusion: Lidocaine-prilocaine cream use at the time of office pessary removal reduces patient-reported pain. Clinicians may wish to include this simple intervention to optimize patient comfort and compliance., Clinical Trial Registration: ClinicalTrials.gov, NCT02380742.

Objective: To evaluate whether adding oxytocin to preinduction cervical ripening with a Foley catheter increases the rate of delivery within 24 hours., Methods: This was a randomized, multicenter, parallel trial of women with a singleton pregnancy at 24 weeks of gestation or greater undergoing labor induction. Women were randomly allocated to an intracervical Foley catheter followed by oxytocin or Foley with concurrent oxytocin infusion. Nulliparous and multiparous women were randomized and analyzed separately based on parallel design. The primary outcome was Foley placement to delivery at 24 hours or less. A sample size of 100 nulliparous women and 75 multiparous women per group would be required to detect a 20% increase in baseline 24-hour delivery rate with 80% power for each parity group., Results: From January 2015 through July 2016, 323 patients were enrolled: 184 nulliparous women and 139 multiparous women. Nulliparous women who received concurrent Foley and oxytocin delivered more frequently within 24 hours of Foley placement than did the Foley followed by oxytocin group (64% compared with 43%, P=.003, relative risk 1.51, 95% confidence interval [CI] 1.14-2.00). Multiparous women who received concurrent Foley and oxytocin delivered more frequently within 24 hours than the Foley followed by oxytocin group (87% compared with 72%, relative risk 1.22, 95% CI 1.02-1.45). Median time to delivery was shorter in both nulliparous women (20.9 compared with 26.1 hours, P<.001) and in multiparous women, (14.9 compared with 18.6 hours, P=.01) who received concurrent Foley and oxytocin compared with Foley followed by oxytocin. There were no significant differences in the rates of cesarean delivery, postpartum hemorrhage, chorioamnionitis, or neonatal intensive care unit admission between the randomization groups., Conclusion: Induction with concurrent oxytocin infusion added to Foley significantly increases the rate of delivery within 24 hours in both nulliparous and multiparous compared with Foley followed by oxytocin., Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02273115.

Objective: To assess whether a pH-balanced vaginal gel containing lactic acid is more effective than a placebo (lactate-free gel) in improving dyspareunia and sexual function among breast cancer survivors who were premenopausal at diagnosis and had dyspareunia after adjuvant chemotherapy., Methods: In a single-center, double-blind, randomized trial, a pH-balanced gel or placebo was administered three times per week at bedtime as well as during sexual intercourse for 8 weeks. The primary outcome was the improvement of dyspareunia measured by pain score of the Female Sexual Function Index after the treatment. Secondary outcomes included the total and individual domains of Female Sexual Function Index score, sexual dysfunction (a total Female Sexual Function Index score less than 25.0), vaginal pH, vaginal maturation index, and adverse events related to the intervention. A sample size of 47 per group was planned to achieve 80% power to detect a 19% difference in the primary outcome., Results: From October 2009 and March 2013, 167 women were screened and 136 were randomized: 69 to a pH-balanced gel and 67 to placebo. Baseline characteristics were similar in both groups. Although there was no difference between the two groups, both experienced a significant improvement of dyspareunia. The increase in median pain score from baseline was 1.2 in both groups (median [interquartile range] from 2.8 [2.0-4.0] to 4.0 [2.8-4.8] in the pH-balanced group and from 3.2 [2.0-4.0] to 4.4 [3.2-4.8] in the placebo group; all P<.01). Overall Female Sexual Function Index score and the frequency of sexual dysfunction also did not differ between the two groups although there was a significant improvement. On the other hand, vaginal pH and vaginal maturation index were slightly but significantly improved only in the pH-balanced group. There were no severe adverse events in either group., Conclusion: The pH-balanced vaginal gel is not superior to the placebo in improving dyspareunia and overall sexual function., Clinical Trial Registration: ClinicalTrials.gov, https://www.clinicaltrials.gov, NCT00981305.

Purpose of Review: The purpose of this review is to describe new terminology for vulvovaginal atrophy and female sexual dysfunction and to highlight recent findings related to vaginal moisturizers, lubricants and prescription estrogen preparations., Recent Findings: Sexual health is a marker for overall health. A minority (40%) of healthcare providers routinely ask about sexual problems and its impact on quality of life. New terminology by the American Psychiatric Association divides female sexual disorders into three categories: arousal/interest disorder, orgasmic disorder and genital pain and penetration disorder. First-line therapy for genitourinary syndrome of menopause includes over-the-counter vaginal lubricants and moisturizers, followed by topical estrogen formulations. Progesterones are generally not needed when topical low-dose estrogen is prescribed. A systemic selective estrogen receptor modulator, designed specifically for genitourinary menopausal symptoms, is an option for patients who do not tolerate local estrogen., Summary: Female sexual dysfunction is prevalent and causes distress, particularly among women at midlife. Although hypoactive sexual desire disorder may be the most prevalent dysfunction, dyspareunia and pain, particularly related to genitourinary and vulvovaginal atrophy, are also very common. Over-the-counter lubricants and prescription strength estrogen formulations are generally effective and well tolerated.

Objectives: The aims of this study were to compare 12-week outcomes of single-therapy tolterodine (Detrol LA) extended release to intravaginal estrogen (Estrace) for overactive bladder (OAB) symptoms and characterize 24- and 52-week outcomes in women undergoing combined therapy., Methods: A single-site randomized, open-label trial in women with urinary frequency, urgency, nocturia, and/or urgency urinary incontinence symptoms was performed. Fifty-eight participants were randomized to oral tolterodine extended release daily or intravaginal estradiol cream nightly for 6 weeks then twice per week. The primary outcome was change in Overactive Bladder Questionnaire (OAB-q) symptom bother score at 12 weeks. Secondary outcomes included the Health-Related Quality of Life Questionnaire (HRQL) of the OAB-q and a 3-day bladder diary. At 12 weeks, subjects were offered addition of the alternative therapy with follow-up at 24 and 52 weeks., Results: There was no difference in symptom bother score improvement between the tolterodine and intravaginal estradiol groups baseline to 12 weeks (20.6 ± 21.7, -15.8 ± 23.3, respectively, P = 0.45). There was a significant within-group decrease in symptom bother score from baseline to 12 weeks (tolterodine, P < 0.0001, and intravaginal estradiol, P = 0.002). Secondary outcome improvement within groups was noted in the HRQL total, urinary incontinence episodes, and median voiding frequency (all P ≤ 0.03) in the tolterodine group and in the HRQL total score (P = 0.03) in the intravaginal estradiol group, with no differences between groups. Combined therapy outcomes at 24 and 52 weeks compared with single therapy at 12 weeks revealed significant improvement in symptom bother score in the intravaginal estradiol + tolterodine group at 24 and 52 weeks (20.0 ± 23.9, P = 0.008; -16.7 ± 23.3, P = 0.02, respectively)., Conclusions: Significant within-group improvement in OAB-q symptom bother was noted in both the intravaginal estradiol and tolterodine groups for OAB symptoms, with no difference between groups. Greater improvement from 12-week single therapy to 24 and 52 weeks of combined therapy was noted in the group originally assigned to intravaginal estradiol. The role of combined medical therapy for OAB symptoms needs further investigation.

Background: The ex vivo challenge assay is a bio-indicator of drug efficacy and was utilized in this randomized, placebo controlled trial as one of the exploratory endpoints. Fresh and cryopreserved tissues were evaluated for human immunodeficiency virus (HIV) infection and pharmacokinetic (PK)/pharmacodynamic (PD) relationships., Methods: HIV-negative women used vaginal rings containing 25 mg dapivirine (DPV)/100 mg maraviroc (MVC) (n = 12), DPV only (n = 12), MVC only (n = 12), or placebo (n = 12) for 28 days. Blood plasma, cervicovaginal fluid (CVF), and cervical biopsies were collected for drug quantification and the ex vivo challenge assay; half (fresh) were exposed immediately to HIV while the other half were cryopreserved, thawed, then exposed to HIV. HIV replication was monitored by p24 enzyme-linked immunosorbent assay from culture supernatant. Data were log-transformed and analyzed by linear least squared regression, nonlinear Emax dose-response model and Satterthwaite t test., Results: HIV replication was greater in fresh compared to cryopreserved tissue (P = 0.04). DPV was detected in all compartments, while MVC was consistently detected only in CVF. Significant negative correlations between p24 and DPV levels were observed in fresh cervical tissue (P = 0.01) and CVF (P = 0.03), but not plasma. CVF MVC levels showed a significant negative correlation with p24 levels (P = 0.03); drug levels in plasma and tissue were not correlated with HIV suppression. p24 levels from cryopreserved tissue did not correlate to either drug from any compartment., Conclusion: Fresh tissue replicated HIV to greater levels and defined PK/PD relationships while cryopreserved tissue did not. The ex vivo challenge assay using fresh tissue could prioritize drugs being considered for HIV prevention.

Objective: To evaluate cervical pessary as an intervention to prevent preterm birth in twin pregnancies with a short cervix., Methods: This was a retrospective cohort study of twin pregnancies managed by a single maternal-fetal medicine practice from 2005 to 2015. We included patients at 28 weeks of gestation or less who were diagnosed with a cervical length less than 20 mm. At the time of diagnosis, all patients were prescribed vaginal progesterone. Starting in 2013, they were also offered pessary placement in addition to vaginal progesterone. We compared outcomes between patients who received a pessary and matched women in a control group in a one-to-three ratio. Women in the control group were matched to women in the case group according to cervical length and gestational age (within 5 mm and 1 week, respectively, of the case patient at the time of pessary placement). We excluded patients with cerclage, monochorionic-monoamniotic placentation, major fetal congenital anomalies discovered before or after birth, patients with twin-twin transfusion syndrome, and patients for whom there were no appropriate controls. Chi-square, Fisher exact, and Student's t tests were used, as appropriate. Regression analysis was performed to control for significant differences at baseline., Results: Twenty-one patients received a cervical pessary, and they were compared with 63 matched women in the control group. As expected (as a result of matching), baseline gestational age (25.7±2.1 compared with 25.9±2.1 weeks of gestation, P=.671) and cervical length (10.9±3.6 mm compared with 11.9±4.5 mm, P=.327) were similar between the groups. Patients with a pessary had a significantly lower incidence of delivery at less than 32 weeks of gestation (1/21 [4.8%] compared with 18/63 [28.6%], adjusted P=.05), longer interval to delivery (65.2±16.8 compared with 52.1±24.3 days, adjusted P=.025), and a lower incidence of severe neonatal morbidity (2/21 [9.5%] compared with 22/63 [34.9%], adjusted P=.04)., Conclusion: For twin pregnancies with a short cervix, the addition of a cervical pessary to vaginal progesterone is associated with prolonged pregnancy and reduced risk of adverse neonatal outcomes. A large randomized trial should be performed to verify these retrospective findings.

Cancer treatment should address female-specific survivorship issues, including the hypoestrogenic- related adverse effects of cancer therapies or of natural menopause in survivors. Systemic and vaginal estrogen are widely used for symptomatic relief of vasomotor symptoms, sexual dysfunction, and lower urinary tract infections in the general population. However, given that some types of cancer are hormone sensitive, there are safety concerns about the use of local hormone therapy in women who currently have breast cancer or have a history of breast cancer. Nonhormonal approaches are the first-line choices for managing urogenital symptoms or atrophy-related urinary symptoms experienced by women during or after treatment for breast cancer. Among women with a history of estrogen-dependent breast cancer who are experiencing urogenital symptoms, vaginal estrogen should be reserved for those patients who are unresponsive to nonhormonal remedies. The decision to use vaginal estrogen may be made in coordination with a woman's oncologist. Additionally, it should be preceded by an informed decision-making and consent process in which the woman has the information and resources to consider the benefits and potential risks of low-dose vaginal estrogen. Data do not show an increased risk of cancer recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen to relieve urogenital symptoms.

Cancer treatment should address female-specific survivorship issues, including the hypoestrogenic- related adverse effects of cancer therapies or of natural menopause in survivors. Systemic and vaginal estrogen are widely used for symptomatic relief of vasomotor symptoms, sexual dysfunction, and lower urinary tract infections in the general population. However, given that some types of cancer are hormone sensitive, there are safety concerns about the use of local hormone therapy in women who currently have breast cancer or have a history of breast cancer. Nonhormonal approaches are the first-line choices for managing urogenital symptoms or atrophy-related urinary symptoms experienced by women during or after treatment for breast cancer. Among women with a history of estrogen-dependent breast cancer who are experiencing urogenital symptoms, vaginal estrogen should be reserved for those patients who are unresponsive to nonhormonal remedies. The decision to use vaginal estrogen may be made in coordination with a woman's oncologist. Additionally, it should be preceded by an informed decision-making and consent process in which the woman has the information and resources to consider the benefits and potential risks of low-dose vaginal estrogen. Data do not show an increased risk of cancer recurrence among women currently undergoing treatment for breast cancer or those with a personal history of breast cancer who use vaginal estrogen to relieve urogenital symptoms.

Objective: To compare the efficacy of vaginal misoprostol with buccal misoprostol for second-trimester termination of pregnancies., Methods: In a randomized trial, we compared 400 micrograms vaginal and buccal misoprostol every 3 hours for up to six doses for induction of labor at 13-24 weeks of gestation with a live fetus and intact membranes. Women who had a uterine scar were excluded from the study. The primary outcome of the study was induction-to-abortion interval. Based on a two-tailed α of 0.05, we planned to include 65 patients per group to detect a 50% difference in the primary outcome with a power of 80%., Results: From January 2014 to December 2014, 172 women were screened and 130 were randomized: 65 vaginal and 65 buccal misoprostol. Characteristics of patients were similar between groups. Patients administered vaginal misoprostol compared with buccal misoprostol had a shorter induction-to-abortion interval (25±17 hours compared with 40±29 hours, P=.001) and a higher abortion rate within both 24 hours (41 [63%] compared with 27 [42%] P=.014) and 48 hours (59 [91%] compared with 44 [68%], P=.001). Complete abortion rates were similar in both groups (vaginal 51 [78%] compared with buccal 54 [83%]). The incidence of side effects was similar for both groups. The perceived pain was higher in the buccal group, but the small difference did not appear to be clinically meaningful., Conclusion: Vaginal compared with buccal misoprostol administration has a shorter induction-to-abortion interval for second-trimester termination of viable pregnancies. However, both administration routes are equally effective for induction of termination., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT02048098., Level of Evidence: I.

Vulvovaginal atrophy is a common condition associated with decreased estrogenization of the vaginal tissue. Symptoms include vaginal dryness, irritation, itching, soreness, burning, dyspareunia, discharge, urinary frequency, and urgency. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is approximately 50%. Despite the high prevalence and the substantial effect on quality of life, vulvovaginal atrophy often remains underreported and undertreated. This article aims to review the physiology, clinical presentation, assessment, and current recommendations for treatment, including aspects of effectiveness and safety of local vaginal estrogen therapies.

Objective: To examine the prevalence, predictors, and effects of nocturia in women and evaluate overlaps with established urinary tract disorders., Methods: This was a cross-sectional analysis of 2,016 women, aged 40 years and older, recruited from Kaiser Permanente Northern California from 2008 to 2012. Nocturia and other urinary symptoms were assessed using structured interviewer-administered questionnaires. Nocturia was defined as patient-reported nocturnal voiding of two or more times per night over a typical week., Results: Thirty-four percent (n=692) reported nocturia, and 40% of women with nocturia reported no other urinary tract symptom. Women with nocturia were older (mean age 58 compared with 55 years) (odds ratio [OR] per 5-year increase 1.21, 95% confidence interval [CI] 1.12-1.31), more likely black (45%) (OR 1.75, 95% CI 1.30-2.35) or Latina (37%) (OR 1.36, 95% CI 1.02-1.83) compared with non-Latina white (30%), have worse depression (mean Hospital Anxiety and Depression Scale score 3.8 compared with 2.8) (OR per 1-point increase in Hospital Anxiety and Depression Scale score 1.08, 95% CI 1.04-1.12), and worse mobility (mean Timed Up-and-Go 11.3 compared with 10 seconds) (OR per 5-second increase in Timed Up-and-Go 1.29, 95% CI 1.05-1.58). Nocturia occurred more among women with hysterectomy (53% compared with 33%) (OR 1.78, 95% CI 1.08-2.94), hot flushes (38% compared with 32%) (OR 1.49, 95% CI 1.19-1.87), and vaginal estrogen use (42% compared with 34%) (OR 1.50, 95% CI 1.04-2.18)., Conclusion: Nocturia is common in women and not necessarily attributable to other urinary tract disorders. Factors not linked to bladder function may contribute to nocturia risk, underlining the need for multiorgan prevention and treatment strategies., Level of Evidence: II.

Objective: To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines., Data Sources: MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators., Methods of Study Selection: We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence., Tabulation, Integration, and Results: Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer., Conclusion: All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia., Clinical Trial Registration: PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42013006656.

Progestogens are a promising treatment in the prevention of spontaneous preterm birth in high-risk women. In women with a prior history of spontaneous preterm delivery and in women with a sonographic shortened cervix, there is considerable evidence supporting a benefit of progestogen therapy in the reduction of preterm delivery. In women with multifetal gestations, progestogen therapy has not been shown to be beneficial. Data are inconclusive in women with arrested preterm labor. Questions remain about the mechanism of progestogen action, the optimal type of progestogen, the best mode of administration, and the ideal dosing regimen.

Assessing the feasibility, acceptability and safety of outpatient labour induction. MEDLINE database was searched for "outpatient labor induction" from January 1, 1986 to February 28, 2013. Main outcomes of interest included hyperstimulation, cesarean births, Apgar scores <7 at 5 minutes, arterial-cord pH of <7.10, and neonatal morbidity/mortality. Overall cesarean rates vary significantly (2.6% to 42%). Hyperstimulation with CTG changes is rare. Neonatal admissions for diverse reasons are often not associated with outpatient induction agent. Overall, maternal satisfaction is high. Outpatient labor induction is feasible and important adverse events are rare. However, paucity of available data and heterogeneity of different studies make it difficult to quantify adverse events or identify a preferred induction method.

Purpose of Review: Vaginal lubricants are commonly utilized to facilitate more comfortable and enjoyable intercourse. The impact of these lubricants on fertility is unclear. The aim of this review is to summarize the current in-vitro and clinical data pertaining to lubricants' effect on natural conception., Recent Findings: In-vitro studies suggest lubricants can be toxic to sperm in the artificial laboratory environment. Lubricants formulated to be nontoxic to sperm have no effect on sperm motility or viability in vitro compared to controls. However, a recent longitudinal cohort study suggests lubricant use and choice has no effect of fecundity., Summary: As a result of the conflicting in-vitro and clinical data, the effect of vaginal lubricants on fertility is still unresolved. A randomized controlled trial is needed to determine the effects of vaginal lubricants on fertility.

Objective: To compare the efficacy of the vaginal and sublingual administration of the synthetic prostaglandin misoprostol with the currently used oral administration route in second-trimester medical abortion., Methods: This was a prospective randomized trial of medical abortion with misoprostol after mifepristone priming at 14-24 weeks of gestation. From 2009 to 2013, recruited women received 200 mg mifepristone orally followed 24-48 hours later by an 800-microgram vaginal loading dose of misoprostol. Women were then randomized to receive additional 400-microgram misoprostol doses orally every 3 hours, vaginally every 4 hours, or sublingually every 3 hours. The main outcome was the duration of abortion with emphasis on the proportion of women undelivered 12 hours after the misoprostol loading dose in the three groups., Results: A total of 302 women were randomized: 100 to oral, 100 to vaginal, and 102 to sublingual misoprostol. The median gestation at recruitment was oral 19.1 weeks (interquartile range 17.2-20.8), vaginal 19.4 weeks (interquartile range 17.3-20.4), and sublingual 19.7 weeks (interquartile range 17.6-21.0). The overall abortion duration was longer in women receiving oral misoprostol: oral 9.5 hours (95% confidence interval [CI] 8.5-11.4), vaginal 7.4 hours (95% CI 6.5-8.2), and sublingual 7.8 hours (95% CI 7.0-9.2). Overall, 84 of 302 (27.8%) women were undelivered at 12 hours, comprising 37.0% (95% CI 28.7-47.8) oral, 20.5% (95% CI 14.0-30.1) vaginal, and 21.0% (95% CI 14.3-30.7) sublingual groups., Conclusion: Vaginal or sublingual misoprostol administered after a vaginal loading dose in second-trimester medical abortion with mifepristone priming is associated with a shorter time to pregnancy termination compared with an oral regimen., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00864799., Level of Evidence: I.

Objective: To assess efficacy of the Foley catheter compared with the dinoprostone vaginal insert for beginning labor inductions at or near term., Methods: We performed a multicenter randomized controlled trial. We enrolled women at 36 weeks of gestation or greater with a singleton live fetus in cephalic presentation, intact membranes, an unfavorable cervix (dilation less than 3 cm; if 2 cm, less than 80% effaced), and no contraindication to labor or either study agent. Women were allocated to either a cervical Foley catheter inflated to 30 mL or dinoprostone for up to 12 hours. Oxytocin was allowed only after study agent removal. The primary outcome was time from agent placement to delivery. Secondary outcomes included delivery by 24 hours, vaginal delivery by 24 hours, time to vaginal delivery, cesarean delivery rate, and rate of tachysystole. Analysis was by intent-to-treat., Results: We enrolled 376 patients, 185 allocated to Foley catheter and 191 to dinoprostone. In the Foley catheter group, time to delivery was shorter (median 21.6 compared with 26.6 hours; P=.003), more patients delivered within 24 hours (56% compared with 40%; P=.003), more delivered vaginally within 24 hours (44% compared with 30%; P=.004), and time to vaginal delivery was shorter (median 20.1 compared with 24.3 hours; P=.005). The cesarean delivery rates were 29% compared with 39% (P=.07). Uterine tachysystole occurred in 0% compared with 3% (P=.06)., Conclusion: Starting labor inductions with a Foley catheter, compared with the dinoprostone vaginal insert, results in a shorter time to delivery and a higher proportion of women delivered and delivered vaginally within 24 hours. Cesarean delivery rates were not statistically significantly different., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01402050. LEVEL OF EVIEDENCE: I.

Objective: To determine the outcomes of women treated for vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) with intravaginal estrogen., Material and Methods: A retrospective chart review was performed of 106 patients with VaIN 2/3 evaluated at a single institution between 2000 and 2008. Medical records were reviewed for demographic information, risk factors, HPV status, treatment type, pathologic diagnosis, and outcome information. Patients with VaIN 1 and invasive disease at the time of initial presentation were excluded. In addition, patients who were lost to follow-up or who developed other genital tract malignancies during the study period were excluded from the final analysis., Results: After exclusions, 83 patient records were included in the statistical analysis. The mean age at diagnosis was 54.3 years. Of these patients, 88.0% were postmenopausal and 88.0% had undergone previous hysterectomy. Moreover, 63.9% of the patients reported previous treatment for preinvasive disease (cervical, vaginal, or vulvar dysplasia). Of all the patients, 44.6% reported prior and/or current tobacco use and 48.2% tested positive for high-risk HPV types. Treatment modalities included intravaginal estrogen, CO(2) laser ablation, topical 5-fluorouracil, wide local excision, loop electrosurgical excision procedure, and vaginectomy. Some patients underwent more than 1 treatment modality. Of those patients treated with intravaginal estrogen alone (n = 40), 90.0% had regression or cure of high grade disease. Of those patients treated with intravaginal estrogen and 1 or more other treatment modalities (n = 32), 81.3% experienced regression or cure. In contrast, 71.4% of patients undergoing treatment without intravaginal estrogen experienced regression or cure of high-grade disease. Conditions of 2 patients progressed to invasive vaginal carcinoma during the study period. The mean length of follow-up for all patients was 47.6 months., Conclusions: This cohort of women with VaIN 2/3 further delineates the demographic and clinical risk factors associated with VaIN 2/3. High rates of regression and cure were found in patients treated with intravaginal estrogen, whether alone or in combination with other treatment modalities. Treatment of VaIN 2/3 with intravaginal estrogen therapy offers an alternative to standard therapies with a success rate that is comparable to that previously reported with other more potentially morbid therapies.

Over the past three decades, medical methods of abortion have been developed throughout the world and are now a standard method of providing abortion care in the United States. Medical abortion, which involves the use of medications rather than a surgical procedure to induce an abortion, is an option for women who wish to terminate a first-trimester pregnancy. Although the method is most commonly used up to 63 days of gestation (calculated from the first day of the last menstrual period), the treatment also is effective after 63 days of gestation. The Centers for Disease Control and Prevention estimates that 64% of abortions are performed before 63 days of gestation (1). Medical abortions currently comprise 16.5% of all abortions in the United States and 25.2% of all abortions at or before 9 weeks of gestation (1). Mifepristone, combined with misoprostol, is the most commonly used medical abortion regimen in the United States and Western Europe; however, in parts of the world, mifepristone remains unavailable. This document presents evidence of the effectiveness, benefits, and risks of first-trimester medical abortion and provides a framework for counseling women who are considering medical abortion.