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The article discusses a case of a 76-year-old woman who developed iatrogenic Cushing syndrome and secondary adrenal insufficiency from using a compounded mouthwash containing clobetasol propionate, a potent corticosteroid. The patient experienced symptoms such as fatigue, weight loss, and bruising, leading to a diagnosis of secondary adrenal insufficiency. Treatment involved transitioning from the magic mouthwash to a steroid-sparing agent and oral hydrocortisone therapy, resulting in symptom improvement and recovery of the hypothalamic-pituitary-adrenal axis. The article highlights the importance of recognizing the potential systemic effects of topical corticosteroids, especially in dental treatments, and recommends vigilance and endocrine evaluation for patients experiencing cushingoid features or adrenal insufficiency symptoms. [Extracted from the article]

Depot medroxyprogesterone acetate causes a hypo‐estrogenic state in over half of users although clinical vaginal atrophy causing superficial dyspareunia is thought rarely to occur. This is a case series of ten women using depot medroxyprogesterone acetate who presented with superficial dyspareunia and clinical vaginal atrophy. The women were treated with vaginal estriol cream and their contraception was discontinued or changed. All patients had either a complete resolution of symptoms or a substantial improvement at follow‐up, and the clinical and laboratory findings of vaginal atrophy had resolved. This case series demonstrates that vaginal atrophy may occur more frequently than previously thought. [ABSTRACT FROM AUTHOR]

Introduction: The use of oral azithromycin (AZI) as a preventive measure against postpartum infections of planned vaginal births has garnered a lot of interest in recent years and has been the subject of many randomized controlled trials (RCTs). However, the results from these trials have not been consistent. Therefore, we aim to perform a systematic review and meta‐analysis to determine whether the use of a single‐dose of oral AZI is clinically significant. Methods: We systematically searched PubMed, Embase, and Cochrane Central for RCTs from May to June 2023, comparing a single dose of oral AZI with placebo in patients undergoing planned vaginal delivery at a minimum of 28 weeks of gestational age. The main outcomes were puerperal and neonatal sepsis. Statistical analyses were performed using Review Manager 5.4.1 (Cochrane Collaboration). Heterogeneity was assessed with I2 statistics. Results: Four RCTs were included (mothers, n = 42 235; newborns n = 42 492). Approximately 49.8% of mothers received a single dose of oral AZI for sepsis prophylaxis. Compared with placebo, AZI significantly reduced the incidence of puerperal sepsis (risk ratio [RR], 0.65 [95% confidence interval (CI), 0.55–0.77]; P < 0.001), mastitis or breast abscess (RR, 0.58 [95% CI, 0.42–0.79]; P < 0.001), endometritis (RR, 0.65 [95% CI, 0.54–0.77]; P < 0.001), wound infection (RR, 0.81 [95% CI, 0.69–0.96]; P = 0.013), infection rate (RR, 0.62 [95% CI, 0.51–0.76]; P < 0.001), and fever (RR, 0.50 [95% CI, 0.28–0.89]; P = 0.018) in mothers. No statistically significant differences were identified between groups regarding maternal all‐cause mortality and the use of prescribed postpartum antibiotics. Similarly, no statistical differences were noted in the neonatal group regarding sepsis, infection rate, and all‐cause mortality. Conclusion: AZI appears to be an effective preventive measure against many postpartum infections in mothers but a substantial impact on neonatal outcomes has not yet been conclusively observed. Synopsis: Administration of azithromycin has been shown to prevent postpartum infections and sepsis in mothers undergoing vaginal delivery. [ABSTRACT FROM AUTHOR]

Introduction: When scanning for deep endometriosis a 20 mL syringe is used to insert gel into the vagina for a gel sonovaginography (SVG) examination. This is invasive and can cause discomfort. The aim of this study is to compare participant experience with the self‐administration of 20 mL of gel total using a 10 mL syringe versus 20 mL syringe for participants undergoing a gel SVG ultrasound to assess for any participant discomfort. Methodology: This study was a quantitative pilot study with 31 participants. Consenting participants were instructed to insert a total of 20 mL of gel divided equally into one 20 mL and one 10 mL syringe, into their own vagina prior to SVG. After the SVG, a questionnaire was provided to determine the level of discomfort experienced. Results: Overall participants found the instructions clear and the insertion of either syringe tolerable. The results demonstrated that 22/31 (71%) of participants had no discomfort inserting the 10 mL syringe. In comparison, 17/31 (55%) reported slight or mild discomfort inserting the 20 mL syringe. The majority of participants preferred inserting one 20 mL syringe rather than two 10 mL syringes. Conclusion: Participants found the gel insertion using either syringe tolerable with most participants finding the 10 mL syringe more comfortable but would overall prefer inserting one 20 mL syringe instead of two 10 mL syringes. Future studies on larger numbers of multicultural participants using variable syringe sizes with varying amounts of gel should be considered. [ABSTRACT FROM AUTHOR]

Aim: In modern obstetrics, need of labor induction is increasing along with increased caesarean deliveries. Major contributions for these operative deliveries are due to induction failure. This demands a potent labor‐inducing agent. Dinoprostone gel is an established method but having some drawbacks. Misoprostol could be an effective alternative to Dinoprostone, but its fetal safety is not yet well established. This study aimed to evaluate the fetal safety of vaginal Misoprostol tablet by measuring fetal heart rate changes during induction of labor. Methods: This was a single‐center randomized controlled trial incorporating 140 term women, equally randomized to get either tablet Misoprostol or Dinoprostone gel. Fetal heart rate patterns were compared in both the groups by continuous cardiotocographic tracing. All the data were analyzed on an intention‐to‐treat basis. Results: There were no statistically significant changes in fetal heart rate pattern in both Misoprostol and Dinoprostone groups. Vaginal deliveries were statistically higher in Misoprostol group. Neonatal parameters like 1 min Appearance, Pulse, Grimace, Activity, and Respiration score and neonatal intensive care unit admission were comparable, and there was no significant difference in terms of major adverse events and side effects. Conclusions: Misoprostol is a safe alternative to Dinoprostone gel for induction of labor and found to be more effective labor‐inducing agent. In the background of higher caesarean rate, vaginal Misoprostol can be a potential labor‐inducing agent especially in a resource poor setting. [ABSTRACT FROM AUTHOR]

Aim: To compare the success rate of vaginal misoprostol versus intravenous (IV) oxytocin in termination of pregnancy in the second trimester intrauterine fetal death (IUFD). Methods: This was an open‐label randomized controlled study for 106 women with second trimester IUFD. Patients were randomly divided into two groups: women given vaginal misoprostol (400 mcg every 6 h up to 48 h) versus those given IV oxytocin (starting with 50 units up to a maximum of 300 units). When the first‐line treatment (as mentioned above) failed, treatment methods were replaced with each other. When the second‐line treatment failed, the patients underwent dilation and evacuation. Results: The first‐line treatment yielded the successful rate of 88.7% versus 73.7% for misoprostol versus oxytocin, respectively (p = 0.047). Among those with first‐line treatment failure, the second‐line treatment yielded success rate of 85.7% versus 83.3% for misoprostol versus oxytocin (p = 0.891). The mean duration of induction to delivery in women with successful response to first‐line treatment was 28.72 and 20.55 h after initially receiving misoprostol versus oxytocin, respectively (p < 0.001). While during second‐line treatment, this mean interval was not significantly different among those with misoprostol versus oxytocin (p = 0.128). No severe adverse events were observed. Conclusion: Vaginal misoprostol was associated with higher termination rate than oxytocin without adverse events when used as the first‐line treatment. Both methods yielded the same success rate when used as the second‐line treatment. [ABSTRACT FROM AUTHOR]

Objectives: To present a flexible protocol of vaginal pessaries for older women with significant pelvic organ prolapse (POP). Design A prospective cohort study of 140 consecutive older women (aged ≥65 years) with significant POP treated with individually fitted vaginal pessaries. After initial insertion, each patient was invited for a first evaluation after 1 month and subsequent follow‐ups at increasing intervals of 1 month. During each examination, the pessary was removed and the vagina was inspected for infection, bleeding, or erosions. All patients were advised to use a vaginal estrogen cream twice a week. Setting: The study was conducted during 2020 in the urogynecology clinic of a tertiary medical center. Participants: The study cohort included 140 consecutive older women with significant and symptomatic POP treated with vaginal pessaries. Main outcome: Primary outcomes included time intervals between follow‐up visits, pessary‐associated complications, need to change the pessary, need to remove the pessary temporarily, and whether the patients eventually underwent POP surgery. Results: The mean age of the patients at the time of pessary fitting was 76.7 ± 9.2 years (range 65–100 years). Mean interval between follow‐up examinations was 3.3 ± 1.1 months (range 1–6 months). Most patients (83.6%) used a ring pessary with support, but only a small number of patients were able to maintain the pessary by themselves. Of the 140 patients, five (3.6%) patients only eventually underwent POP surgery, and in 11 (7.9%) patients, the vaginal pessary had to be removed for 2–4 weeks because of significant vaginal discharge or superficial erosions. Additionally, 12 (8.6%) patients developed stress urinary incontinence following pessary insertion. Conclusions: Customized management with vaginal pessary for symptomatic POP in older women is effective and safe, and is a suitable therapeutic alternative for older women who are unable or unwilling to undergo reconstructive pelvic surgery. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of dinoprostone vaginal insert (DVI) alone versus DVI with adjunctive sweeping of membranes (ASM) for induction of labor (IOL). Methods: Single‐center, prospective, randomized controlled trial; women with singleton term pregnancies, cervical dilation ≥1 and <3 cm, intact membranes allocated to either DVI or DVI with ASM. The primary outcome was vaginal delivery within 24 h of insertion. Secondary outcomes included mean time from insertion to delivery, tachysystole, operative delivery for non‐reassuring fetal status (NRFS), tocolytics, fetal outcomes, pain information, and subject satisfaction. Results: One hundred and four received DVI (Group 1) alone and 104 DVI with ASM (Group 2). The rate of vaginal delivery within 24 h was 53% versus 56%, cesarean rate 8.7% versus 10.6% in Groups 1 and 2 respectively. Although the duration of labor was similar in both groups, about 6% of women required additional ripening with dinoprostone vaginal tablets in Group 2 compared to 11.5% in Group 1 (p‐value = 0.2). The frequency of hyperstimulation syndrome, failed induction, analgesic requirements, and fetal outcomes were comparable. The majority (83%–86%) in either cohort were satisfied with their labor experience. Multivariate logistic regression demonstrated a slightly better chance for vaginal delivery within 24 h (odds ratio [OR] 1.22 [95% confidence interval, CI 0.65–2.29]; p‐value 0.53] for DVI with ASM, although statistically insignificant. Younger maternal age and multiparity (OR 10.36 [95% CI 4.88–23.67]; p‐value <0.0001) contributed to successful IOL. Conclusion: DVI with ASM is at least as efficacious as DVI for cervical ripening with no increase in morbidity. Although DVI with ASM group less often needed additional dinoprostone tablets to complete the process of IOL (p‐value = 0.2), adjunctive sweeping has not been shown to have a significant impact on the duration of labor or mode of delivery. [ABSTRACT FROM AUTHOR]

Cervical status has a great impact on the duration and success of its dilatation especially during hysteroscopy, so cervical ripening employed before the procedure can increase the success rate and minimize the complications. Aim To compare the efficacy of vaginal misoprostol and intracervical normal saline infiltration as cervical ripening agents. Methods: A randomized comparative clinical trial had been conducted in AL Yarmouk Teaching Hospital involving two methods for cervical ripening before the hysteroscopic procedure. One Hundred women were enrolled in the study, fifty of them were those who used preoperative vaginal misoprostol and the other fifty patients were those who had been submitted to intracervical normal saline infiltration during surgery. Basal cervical dilatation, time to achieve 8 mm cervical dilatation, difficulties, and complications encountered during the procedure were evaluated and compared for both groups. Results: The participants had been admitted for hysteroscopy for the following indications: Abnormal uterine bleeding, missed loop, infertility, polypectomy, endometrial resection, and myomectomy. Regarding operative findings, the basal cervical dilatation was not significantly different between them, the time required to achieve the required dilatation was significantly shorter for the normal saline infiltration group, 66.95 sec. ± 10.85 than for the misoprostol group which was 87.9 sec. ± 13.11. There was more difficulty in dilatation with more complications in the misoprostol group than in the normal saline infiltration group. Conclusions: Normal saline infiltration is a simple, readily available at the time of surgery and with fewer complications and shorter time of dilatation in comparison to vaginal misoprostol for a comparable efficacy. [ABSTRACT FROM AUTHOR]

The article focuses on the U.S. Food and Drug Administration (FDA) is to address the high cost of medicines by promoting market competition. Topics include the FDA has announced the Drug Competition Action Plan which aims to remove barriers to generic drug development and encourage timely entry of generic competition, and the FDA has focused its efforts under this plan to improve the efficiency and transparency to the regulatory review process for generic drug applications.

This systematic review evaluates the efficacy of intravaginal diazepam in treating chronic pelvic pain and sexual dysfunction associated with high‐tone pelvic floor dysfunction. A literature search was conducted in Medline and Web of Science, including articles from the database's inception to July 2019. The search identified 126 articles, and 5 articles met study inclusion criteria: 2 observational reviews and 3 small randomized, controlled trials (RCTs) evaluating intravaginal diazepam for high‐tone pelvic floor dysfunction. The 2 observational studies identified subjective reports of improvement in sexual function for a majority of women, 96% and 71%, in each study. However, there were no statistical differences between Female Sexual Function Index (FSFI) and Visual Analog Scale (VAS) scores for pain identified. One RCT found no significant changes between groups in median FSFI or VAS scores, and a second RCT found no significant changes between groups in 100‐mm VAS scores. The third RCT demonstrated that compared with placebo, treatment with transcutaneous electrical nerve stimulation and intravaginal diazepam for women with vestibulodynia and high‐tone pelvic floor dysfunction yielded significant differences in reduction of dyspareunia (P ≤.05), ability to relax pelvic floor muscles after contraction (P ≤.05), and current perception threshold values at a 5‐Hz stimulation related to C fibers (P <.05), but no significant changes in 10‐cm VAS scores. Intravaginal diazepam may be helpful in women with a specific diagnosis of high‐tone pelvic floor dysfunction, but more and larger studies are needed to confirm these potential effects. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to explore the outcome of low-risk singleton pregnancies with very short cervical length (CL ≤15 mm) according to method of treatment and CL at diagnosis.Material and Methods: Retrospective study on singleton pregnancies devoid of risk factors for spontaneous preterm delivery identified in the course of universal screening programs by vaginal sonography at 20-24 weeks of gestation to have very short CL ≤ 15 mm.Results: The study group consisted of 233 pregnancies with CL ≤ 15 mm of which 88 had cervical cerclage inserted and the remaining 145 were treated with vaginal progesterone. Mean CL at diagnosis was significantly shorter in the cerclage group (5 mm) compared with the progesterone group (12 mm). Regardless of treatment there was no difference in the rate of spontaneous preterm delivery at <32 weeks of gestation in women with CL ≥ 9 mm at screening (11% and 12% in the cerclage and progesterone groups, respectively). In contrast, in the subgroup with CL ≤ 8 mm cervical cerclage resulted in significantly lower rates of spontaneous preterm delivery at <32 weeks of gestation compared with progesterone treatment (20% and 45%, respectively, P = .009) and the median gestational age at birth was significantly greater (37 weeks vs 36 weeks, respectively, P = .013).Conclusions: The majority of asymptomatic singleton pregnancies with short CL will remain undelivered until 32 weeks of gestation whether treated with progesterone or cerclage. Women with extreme cervical shortening appear to benefit more from cervical cerclage. [ABSTRACT FROM AUTHOR]

Menopause is the condition when a woman no longer manifests menstrual periods. Genitourinary syndrome (GSM) is the acronym to describe possible symptoms of this condition. Vaginal dryness can be a particular problem for women entering menopause, it can make the intercourse painful and may cause the increase in the need to urinate. Aim of this study is to evaluate the efficacy of combined fractional CO2 (10 500 nm) ablative and 1540 nm nonablative lasers on these symptoms. About 40 postmenopausal nonestrogenized women with moderate to severe vaginal atrophy referring symptoms related to GSM were recruited. A treatment cycle included three laser applications (every 4 weeks), was performed. Time points of the study were baseline (T1), week 4 (T2), week 8 (T3), and week 12 (T4).. Results evaluation was done with a modified female sexual function index (FSFI) and a modified stress urinary incontinence (SUI) scale. A significant improvement both of FSFI total score and each individual FSFI domain score was observed. No undesired side effects or short‐term or long‐term complications were shown. This study shows that the "two wavelengths endovaginal laser treatment" is a safe and effective technique to treat signs and symptoms related to GSM syndrome. For the treatment of women with severe urogenital symptoms who do not benefit from lifestyle changes, vaginal moisturizers, or local estrogen therapy, clinicians should consider the use of vaginal fractional laser treatment. [ABSTRACT FROM AUTHOR]

Introduction: Recto-vaginal endometriosis surgical management needing partial colpectomy is a surgically challenging condition and has been associated with a notable risk of major postoperative complications. In the present study we sought to compare feasibility and safety of total laparoscopic (TL) and vaginal-assisted (VA) routes in women affected by symptomatic recto-vaginal endometriosis with vaginal mucosa infiltration scheduled for minimally invasive surgery.Material and Methods: Multi-centric, retrospective cohort study on medical records of consecutive reproductive age women submitted to complete macroscopic eradication of symptomatic recto-vaginal endometriosis with vaginal mucosa infiltration between March 2013 and November 2017. The two groups were compared in terms of preoperative data and surgical outcomes.Results: 84 women were included in the study (TL = 57 and VA = 27). The two groups were comparable in terms of preoperative, surgical and postoperative data. The major postoperative complications rate was 5.3% (3 of 57) in the TL group and 7.4% (2 of 27) in the VA group, without a significant difference. In the TL group we reported one case of bowel anastomosis dehiscence and two cases of pelvic abscess. In the VA group, one case of small bowel perforation after extensive adhesiolysis treated with ileal resection and one case of rectal sub-occlusion after segmental resection and mechanical anastomosis were noticed.Conclusions: In women affected by recto-vaginal endometriosis with vaginal mucosal infiltration, perioperative outcomes do not seem to be influenced by the surgical route adopted. [ABSTRACT FROM AUTHOR]

Objective: To compare cervical pessaries plus vaginal progesterone versus long-term tocolysis for preventing preterm birth for women with a short cervix.Methods: Retrospective evaluation of women with singleton pregnancy who received cervical pessaries plus vaginal progesterone (combined group) or ritodrine hydrochloride (tocolysis group) for short cervix (≤25 mm at 20-24 weeks, or ≤20 mm at 25-34 weeks) at a general hospital in Kagoshima, Japan, 2015-2019. The primary outcome was rate of preterm birth (<36 weeks); secondary outcomes were maternal hospital admittance and treatment complications.Results: Data were evaluated from 95 women (combined group, n=43; tocolysis group, n=52). There was no significant difference in cervical length or gestational age at intervention between the groups. Overall, 3/43 (7.0%) women delivered before 36 weeks in the combined group versus 16/52 (30.8%) in the tocolysis group (relative risk, 0.56; 95% confidence interval, 0.41-0.76; P=0.004). Median maternal admittance was shorter in the combined group (6.6 vs 41.0 days, P<0.001). Although 36/43 (83.7%) women in the combined group reported increased vaginal discharge, no major complications occurred.Conclusion: A combination of pessaries and vaginal progesterone reduced the rate of preterm birth (<36 weeks) for women with short cervix as compared with long-term tocolysis. [ABSTRACT FROM AUTHOR]

Background: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent.Objective: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage.Search Strategy: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019.Selection Criteria: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage.Data Collection and Analysis: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes.Main Results: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone.Conclusion: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone.Tweetable Abstract: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of 25 μg of estradiol gel on postmenopausal vaginal tissue. Methods: This randomized double‐blind controlled trial included postmenopausal women with vaginal atrophy who attended our menopause clinic during July 2017–January 2018. Women were randomly assigned to the estradiol gel group or control group (K‐Y® Jelly). Treatment consisted of 2 mL of product applied intravaginally daily for 2 weeks, and two doses per week for the next 6 weeks. The most bothersome symptom (MBS), vaginal health index (VHI), vaginal pH, vaginal maturation index, vaginal maturation value (VMV), female sexual function index (FSFI), serum estradiol level and endometrial thickness were evaluated at baseline, 4 and 8 weeks. Results: Seventy‐five of 80 women completed the trial. After 8 weeks of treatment, VMV, VHI, vaginal pH and FSFI improved significantly in the estradiol group, with no observed change in the control group. The MBS was decreased in both groups with no significant difference between groups. Serum estradiol level and endometrial thickness were not significantly different between groups at baseline or at week 8. Conclusion: Estradiol vaginal gel demonstrated an ability to reverse vaginal atrophy with a high safety profile and low systemic absorption of estradiol. [ABSTRACT FROM AUTHOR]

Progestogens (vaginal progesterone and intramuscular 17-hydroxyprogesterone acetate) are widely recommended for women at high risk of preterm birth. Typical regimens include 17-hydroxyprogesterone caproate (250 mg intramuscularly weekly), starting at 16-20 gestational weeks until 36 weeks or delivery for women with a singleton gestation and a history of spontaneous preterm birth, or vaginal progesterone (90-mg vaginal gel or 200-mg micronized vaginal soft capsules) for women with a short cervix (typically ≤25 mm). Although some randomized trials support this approach, neither of the largest trials (PROLONG for 17-hydroxyprogesterone acetate or OPPTIMUM for vaginal progesterone) demonstrated efficacy. There are almost no data on long-term effects, and none that shows benefit beyond the neonatal period. Although some analyses suggest the cost-effectiveness of the approach, a cervical length screening program followed by progesterone for those with a short cervix will reduce preterm birth rates by less than 0.5%. The present review assesses evidence on the efficacy, likely impact, and long-term effects of implementing the recommendations for progestogens in full. Clinicians and pregnant women can look forward to resolution of the conflicting views on efficacy once the Patient-Centered Outcomes Research Initiative (PCORI)-funded individual patient data meta-analysis is published. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of adjunctive use of vaginal progesterone after McDonald cerclage on the rate of second-trimester abortion in singleton pregnancy.Methods: A randomized controlled trial at Woman's Health Hospital, Assiut University, Egypt, between April 2017 and March 2019 enrolled women eligible for McDonald cerclage. After cerclage, participants were randomly assigned to receive progesterone (400 mg pessary) once daily until 37 weeks or no progesterone. The primary outcome was rate of abortion before 28 weeks. Secondary outcomes included gestational age at delivery, preterm delivery, mean birthweight, Apgar score, and admission to the neonatal intensive care unit (NICU).Results: The rate of spontaneous abortion was higher in the no-progesterone group (P=0.016). Mean gestational age and mean birthweight was higher in the progesterone group (P<0.001 and P=0.002, respectively). The frequency of preterm neonates, neonates with Apgar score less than 7, and admission to NICU was higher in the progesterone group than in the no-progesterone group (P=0.005, P=0.008, and P=0.044, respectively).Conclusion: Adjunctive use of vaginal progesterone after McDonald cerclage was found to decrease the frequency of second-trimester abortion and to improve perinatal outcomes in singleton pregnancy. Clinicaltrials.gov: NCT02846909. [ABSTRACT FROM AUTHOR]

Aim: The misoprostol vaginal insert (MVI) was reported to be more effective than dinoprostone but discussed critically because of high rates of fetal heart rate changes due to uterine tachysystole. The aim of this study was to investigate the outcome of induced labor using the MVI compared to off‐label orally‐administered misoprostol (OM). Methods: Retrospective study including a total of 401 patients with singleton pregnancies in whom labor was induced at ≥36 0/7 gestational weeks with MVI (203) or OM (198). Primary outcomes were the time from induction to delivery, vaginal delivery in 24 h and the mode of delivery and the neonatal outcome. Results: Median time until any delivery was 833 min (645–1278) for MVI and 1076.5 min (698–1686.3) for OM group; 83.7% of the patients in the MVI group gave birth within 24 h versus 63.6% in the OM group. The MVI group needed significantly less pre‐delivery oxytocin (29%). Tachysystole (6.4%) and pathological CTG (30.5%) occurred at a significantly higher frequency in the MVI group. The cesarean section rate was significantly higher in the MVI group amounting to 21.7% versus 14.6% in the OM group (P < 0.05). Neonatal outcome did not differ between the groups. Conclusion: The MVI might be an option if you are in need for an approved and faster method to induce labor. Although we observed a significantly higher rate of fetal heart rate changes and cesarean sections in the MVI group this did not affect the neonatal outcome. [ABSTRACT FROM AUTHOR]

Objective: To compare the cost-effectiveness of cervical pessary vs vaginal progesterone to prevent preterm birth and neonatal morbidity in women with twin pregnancy and a short cervix.Methods: Between 4 March 2016 and 3 June 2017, we performed this economic analysis following a randomized controlled trial (RCT), performed at My Duc Hospital, Ho Chi Minh City, Vietnam, that compared cervical pessary to vaginal progesterone in women with twin pregnancy and cervical length < 38 mm between 16 and 22 weeks of gestation. We used morbidity-free neonatal survival as a measure of effectiveness. Data on pregnancy outcome, maternal morbidity and neonatal complications were collected prospectively from medical files; additional information was obtained via telephone interviews with the patients. The incremental cost-effectiveness ratio was calculated as the incremental cost required to achieve one extra surviving morbidity-free neonate in the pessary group compared with in the progesterone group. Probabilistic and one-way sensitivity analyses were also performed.Results: During the study period, we screened 1113 women with twin pregnancy, of whom 300 fulfilled the inclusion criteria of the RCT and gave informed consent to participate. These women were assigned randomly to receive cervical pessary (n = 150) or vaginal progesterone (n = 150), with two women and one woman, respectively, being lost to follow-up. The rate of morbidity-free neonatal survival was significantly higher in the pessary group compared with the progesterone group (n = 241/296 (81.4%) vs 219/298 (73.5%); relative risk, 1.11 (95% CI, 1.02-1.21), P = 0.02). The mean total cost per woman was 3146 € in the pessary group vs 3570 € in the progesterone group (absolute difference, -424 € (95% CI, -842 to -3 €), P = 0.048). The cost per morbidity-free neonate was significantly lower in the pessary group compared with that in the progesterone group (2492 vs 2639 €; absolute difference, -147 € (95% CI, -284 to 10 €), P = 0.035).Conclusion: In women with twin pregnancy and a short cervix, cervical pessary improves significantly the rate of morbidity-free neonatal survival while reducing costs, as compared with vaginal progesterone. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Aim: Gestational hypertension is a common disorder of pregnancy. This study aims to evaluate the effect of labor induction with dinoprostone vaginal suppositories (Propess) on pregnancy outcomes in pregnant women with gestational hypertension. Methods: The retrospective study included 375 patients with gestational hypertension. All patients were included into three groups according to the characteristics at admission. Women who had initiated labor spontaneously at admission were enrolled in Spontaneous labor group. According to Bishop score, other patients underwent labor induction with Propess or oxytocin were enrolled in Propess group or Oxytocin group. Demographic information and perinatal outcome data were collected. Results: The vaginal delivery rate of the women with gestational hypertension was respectively 93.5% (Spontaneous labor group), 77.0% (Propess group), and 52.5% (Oxytocin group) in three groups with significant difference (P < 0.001). The duration of labor was 8.29 ± 3.70 h (Spontaneous labor group), 8.45 ± 5.21 h (Propess group) and 12.37 ± 11.47 h (Oxytocin group) in three groups, respectively. No differences were found in the intrapartum fever (P = 0.588), intrapartum hemorrhage (P = 0.953), intrapartum maximum blood pressure (P = 0.301 and P = 0.535) and post‐partum hemorrhage (P = 0.075) among three groups. Neonatal outcomes were similar among three groups (Neonatal hospitalization rate, P = 0.437; 1‐min Apgar score, P = 0.304; 5‐min Apgar score, P = 0.340; Birth weight, P = 0.089). No poor maternal and neonatal outcomes occurred. Conclusion: Pregnant women with gestational hypertension could have favorable pregnancy outcomes. Using Propess as a mode of labor induction in gestational hypertension is safe and effective, without increasing intrapartum blood pressure and inducing poor pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Controversy exists regarding the benefits of treating bacterial vaginosis (BV) during pregnancy to reduce the incidence of preterm labor (PTL).Objectives: To evaluate whether treatment of BV with vaginal clindamycin or oral metronidazole before 28 weeks of pregnancy reduces PTL incidence.Search Strategy: PubMed, Scopus, Web of Science, Science Direct, CENTRAL, and SciELO databases were searched until December 30, 2017. Search terms included "bacterial vaginosis" and "preterm labor." No language restrictions were applied.Selection Criteria: Randomized clinical trials that evaluated treatment of BV with clindamycin or metronidazole to reduce PTL incidence.Data Collection and Analysis: The risk of PTL was evaluated by the odds ratio (OR) and 95% confidence interval (CI). Dichotomous data from each study were combined for meta-analysis using the Mantel-Haenszel model.Main Results: Nine reports were included in the systematic review, with eight reports included in the meta-analysis. No reduction in the incidence of PTL was found for either metronidazole (OR 0.94, 95% CI 0.71-1.25) or clindamycin (OR 1.01, 95% CI 0.75-1.36).Conclusions: Use of oral metronidazole or vaginal clindamycin to treat BV before 28 weeks of pregnancy did not reduce the incidence of PTL. PROSPERO registration: CRD42018086173. [ABSTRACT FROM AUTHOR]

Background: There is no consensus about the ideal cervical ripening method to use for induction of labour.Objective: To compare in current practice the effectiveness and safety of four cervical ripening methods.Methods: We performed a matched comparative study using data from the MEDIP prospective population-based cohort conducted during one month in 2015 in all maternity units of seven French perinatal networks (3042 consecutive women with a live fetus and induction of labour). We analysed 1671 women with singleton cephalic fetus, unscarred uterus, and bishop score <7. Dinoprostone vaginal pessary (reference) was compared to dinoprostone vaginal gel, misoprostol vaginal tablet, and balloon catheter. Effectiveness outcomes were the need for more than one induction agent, oxytocin use, failure to achieve vaginal delivery within 24 hours (VD < 24 hours), and caesarean delivery. Safety outcomes were meconium-stained amniotic fluid, uterine hyperstimulation, NICU admission, and post-partum haemorrhage. Coarsened exact matching was used to balance confounders among the groups. Outcomes were compared using multivariable logistic regression models.Results: Compared to the dinoprostone pessary (N = 1142, 68.3%), dinoprostone gel (N = 335, 20.1%) was associated with less failure to achieve VD < 24 hours (adjusted OR 0.66, 95% CI 0.47, 0.91). Misoprostol (N = 103, 6.2%) was associated with less need of more than one induction agent (aOR 0.56, 95% CI 0.34, 0.92) and less oxytocin use (aOR 0.60, 95% CI 0.37, 0.99). The balloon catheter (N = 91, 5.4%) was associated with more failure to achieve VD < 24 hours (aOR 2.62, 95% CI 1.37, 5.01), more caesarean delivery (aOR 1.84, 95% CI 1.09, 3.08), and less meconium-stained amniotic fluid (aOR 0.12, 95% CI 0.02, 0.70). Uterine hyperstimulation rates seemed lower with the balloon catheter (1.2% vs 4.2% for the pessary).Conclusions: In current practice, no cervical ripening method appears clearly superior to the others considering all effectiveness and safety outcomes. [ABSTRACT FROM AUTHOR]

Background. Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG) was the first step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and less painful alternative. Objectives and Rationale. The aim of this narrative review is to provide an overview of the currently available HyFoSy literature and related clinical aspects. Search Methods. A literature search was conducted using PubMed and Embase from the introduction of HyFoSy to March 2019. Unfortunately, a meta-analysis was not possible due to a too small number of studies, being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes. Nine small studies concluded that the accuracy and effectiveness as a test for tubal patency of 2D- and 3D-HyFoSy are comparable or even better than HSG or HyCoSy. With or without using Doppler techniques, 3D-HyFoSy does not seem to offer benefits above real-time 2D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less painful procedure compared to HSG, without a need for the use of analgesics. There are suggestions about an increased pregnancy rate in the first three cycles after the procedure but in no studies pregnancy outcome after HyFoSy was compared with other or no intervention. Wider Implications. HyFoSy is a promising and safe alternative for HSG with regard to accuracy and effectiveness. HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for analgesics. However more research is needed to make clear statements regarding a therapeutic effect of HyFoSy. [ABSTRACT FROM AUTHOR]

Intravaginal rings (IVRs) are an established option for continuous administration of drugs in women. The combination of anastrozole (ATZ) and levonorgestrel (LNG) in an IVR with an intended 4‐week wearing period has been considered for long‐term treatment of endometriosis‐associated pelvic pain. A randomized, parallel‐group, multicenter phase 2b study to assess the efficacy and safety of different dose combinations in women with symptomatic endometriosis has recently been performed. This paper will focus on the investigation of pharmacokinetic (PK) effects of ATZ on LNG using data collected from this study. Two hundred sixteen patients were randomized to the treatment group with IVRs releasing LNG 40 μg/day alone or in combination with ATZ 300 μg/day, 600 μg/day, or 1050 μg/day for 12 weeks. PK blood samples were taken before dosing and before IVR replacement or removal (days 28, 56, and 84). The primary PK parameter was the plasma concentration in apparent steady state of ATZ and LNG at the end of each IVR wearing period. Results of PK analysis demonstrate that ATZ concentrations increased proportionally with increasing dose (geometric mean values of 7.85, 15.48, and 22.61 μg/L at 300, 600, and 1050 μg/day nominal release, respectively). All point estimates for LNG concentration in apparent steady state ratios between the mono and combination IVR groups were close to 1, and the 90% confidence interval limits were in the 0.80 to 1.25 range (1.01 [0.85‐1.19], 1.03 [0.88‐1.20], 0.94 [0.80‐1.10]). In conclusion, our data indicate there is no evidence of drug‐drug interaction of ATZ on LNG. [ABSTRACT FROM AUTHOR]

Background: Recent progesterone trials call for an update of previous syntheses of interventions to prevent preterm birth.Objectives: To compare the relative effects of different types and routes of administration of progesterone, cerclage, and pessary at preventing preterm birth in at-risk women overall and in specific populations.Search Strategy: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science up to 1 January 2018.Selection Criteria: We included randomised trials of progesterone, cerclage or pessary for preventing preterm birth in at-risk singleton pregnancies.Data Collection and Analysis: We used a piloted data extraction form and performed Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI), as well as pairwise meta-analyses, rating the quality of the evidence using GRADE.Main Results: We included 40 trials (11 311 women). In at-risk women overall, vaginal progesterone reduced preterm birth <34 (OR 0.43, 95% CrI 0.20-0.81) and <37 weeks (OR 0.51, 95% CrI 0.34-0.74), and neonatal death (OR 0.41, 95% CrI 0.20-0.83). In women with a previous preterm birth, vaginal progesterone reduced preterm birth <34 (OR 0.29, 95% CI 0.12-0.68) and <37 weeks (OR 0.43, 95% CrI 0.23-0.74), and 17α-hydroxyprogesterone caproate reduced preterm birth <37 weeks (OR 0.53, 95% CrI 0.27-0.95) and neonatal death (OR 0.39, 95% CI 0.16-0.95). In women with a short cervix (≤25 mm), vaginal progesterone reduced preterm birth <34 weeks (OR 0.45, 95% CI 0.24-0.84).Conclusions: Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth.Tweetable Abstract: In updated NMA, vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound.Methods: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery.Results: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth.Conclusions: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Aim: To assess the preventive effect on preterm birth of intravaginal ulinastatin (urinary trypsin inhibitor; UTI) administration during the mid‐trimester in women with singleton pregnancy and both cervical shortening and lower genital infections. Methods: Pregnant women with a short cervical length < 25 mm between 16 and 26 weeks of gestation and who had been diagnosed with a lower genital infection were randomly assigned for intravaginal UTI administration or placebo. All of the women were screened for infection or inflammation of the lower genital tract, and women with negative results were excluded. Results: Of the 92 patients with a short cervical length who were assessed for eligibility for this study, 86 singleton patients were enrolled. All patients were randomized to one of two treatment groups: patients administered UTI (n = 35) and placebo (n = 35). There were no differences between the two groups in the incidence of preterm delivery before 28, 30, 32, 34 and 37 weeks of gestation and in perinatal outcomes. Conclusion: For women diagnosed with a short cervical length < 25 mm) between 16 and 26 weeks of gestation and lower genital infection, who were at risk of preterm birth, administration of transvaginal UTI with vaginal irrigation showed no apparent benefit. Future research on the efficacy of UTI should evaluate modified modes of UTI application. [ABSTRACT FROM AUTHOR]

Aim: Prostaglandins have a dual action of cervical ripening and induction of uterine contraction. This study was designed to compare the effectiveness of vaginal washing just before insertion of intravaginal dinoprostone. Methods: A randomized controlled trial was conducted at the Zeynep Kamil Women and Children's Health Training and Research Hospital. One hundred and ninety‐one women with singleton, term pregnancy who underwent labor induction were randomly assigned to two groups: Group 1 consisted of 95 pregnant women with vaginal washing before intravaginal dinoprostone (Propess system for slow release system of 10 mg of dinoprostone) insertion (study group), and 96 pregnant women constituted the control group who did not undergo vaginal washing before intravaginal dinoprostone insertion. A parallel randomized controlled trial was conducted with an allocation ratio of 1:1 to compare the effectiveness of vaginal washing before intravaginal dinoprostone insertion. Results: The groups had similar mean age, body mass index, gestational age, gravidity, parity and Bishop score before agent insertion (P > 0.05). Duration of dinoprostone kept intravaginally, duration from the beginning of dinoprostone insert vaginally to the active phase of labor and duration from the time of intravaginal dinoprostone insertion to delivery were significantly longer in the control group (P < 0.05). Uterine hyperstimulation rate was significantly higher in study group compared to control group (P < 0.05). Meconium passage, fetal infection and neonatal intensive care unit admission were significantly higher in the control group (P < 0.05). Conclusion: Vaginal washing before intravaginal dinoprostone insertion may increase Prostaglandin E2 bioavailability as we found shorter duration and better outcome of labor induction in the present study. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2018 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2018 article‐contains‐esm Yes article‐numbering‐style Unnumbered article‐registration‐date‐year 2018 article‐registration‐date‐month 10 article‐registration‐date‐day 24 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2018_Article_213.pdf pdf‐type Typeset target‐type OnlinePDF issue‐type Regular article‐type OriginalPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine open‐access true --> Background: Adherence is critical for successful topical, vaginally delivered anti‐retroviral (ARV)‐based HIV pre‐exposure prophylaxis (PrEP). Quantitating systemic or tissue ARV levels through LC–MS/MS is currently viewed as the most reliable measure of adherence. However, for placebo‐controlled trials, this is a high cost analysis that measures adherence only in the drug treatment group. A desirable marker of adherence is one that is measured in both placebo and drug treatment groups using a simple on‐site clinical laboratory test, which allows necessary interventions for supporting participant adherence. Our objective was to develop adherence markers for four vaginal placebo products currently used as microbicide delivery systems: gel, film, insert, and intravaginal ring. Excipient and spectroscopy‐based approaches were used for preclinical development of the placebo markers and subsequently validated by the CONRAD 135 study. The study collected vaginal swabs collected each day for 1 week post vaginal application of gel, film, or insert in the clinic with or without sex. Intravaginal rings were collected after 1 day, 7, and 30 days of use. Results: Placebo gel, film, and insert in vaginal swabs were successfully detected by specific excipient colorimetric or probe‐based assays for hydroxyethylcellulose, glycerin, and sorbitol respectively, as well as spectroscopy‐based prediction models. The range of detection for gel, film, and insert in swabs collected up to 16 h post vaginal application was 70‐100% of the total swabs per time point, with some markers showing potential for longer duration. Decreasing residual glycerin levels and increasing bioanalyte penetration of vaginally used intravaginal rings showed significant changes between 1 and 30 days of use. Conclusions: We demonstrated clinical proof‐of‐concept that adherence markers for placebo product can be measured using simple, lower cost approaches. Measuring adherence in both placebo and drug arms of a HIV PrEP study would better inform future trial designs. [ABSTRACT FROM AUTHOR]

Medical management of miscarriage is an acceptable option available to women, and has advantages of providing timely treatment, while avoiding exposure to surgery and anaesthesia. This retrospective cohort study aimed to determine factors predictive of successful medical management, utilising a single dose protocol of 800 µg vaginal misoprostol. In this cohort, the success rate was 67% (199/296), and smaller mean gestational sac diameter independent of gestational age predicted success (P = 0.046). Success is not significantly related to parity, miscarriage type, pelvic pain or vaginal bleeding at the outset of treatment. [ABSTRACT FROM AUTHOR]

Aims: A physiologically‐based pharmacokinetic (PBPK) model of the vaginal space was developed with the aim of predicting concentrations in the vaginal and cervical space. These predictions can be used to optimize the probability of success of vaginally administered dapivirine (DPV) for HIV prevention. We focus on vaginal delivery using either a ring or film. Methods: A PBPK model describing the physiological structure of the vaginal tissue and fluid was defined mathematically and implemented in MATLAB. Literature reviews provided estimates for relevant physiological and physiochemical parameters. Drug concentration–time profiles were simulated in luminal fluids, vaginal tissue and plasma after administration of ring or film. Patient data were extracted from published clinical trials and used to test model predictions. Results: The DPV ring simulations tested the two dosing regimens and predicted PK profiles and area under the curve of luminal fluids (29 079 and 33 067 mg h l–1 in groups A and B, respectively) and plasma (0.177 and 0.211 mg h l–1) closely matched those reported (within one standard deviation). While the DPV film study reported drug concentration at only one time point per patient, our simulated profiles pass through reported concentration range. Conclusions: HIV is a major public health issue and vaginal microbicides have the potential to provide a crucial, female‐controlled option for protection. The PBPK model successfully simulated realistic representations of drug PK. It provides a reliable, inexpensive and accessible platform where potential effectiveness of new compounds and the robustness of treatment modalities for pre‐exposure prophylaxis can be evaluated. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To evaluate factors predictive of the success of dinoprostone slow release vaginal insert for cervical ripening. Methods: A total of 169 women who underwent cervical ripening with dinoprostone slow release vaginal insert were included in the study cohort. The correlation between parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes were analyzed. Results: Dinoprostone slow release vaginal insert was successful in achieving vaginal delivery in 148 of 169 (87.6%), while sufficient ripening was achieved in 140 (83%) cases. Factors associated with successful vaginal delivery were multiparity and younger gestational age at delivery. Factors predictive of the success of cervical ripening with dinoprostone slow release vaginal insert were lower body mass index (BMI), higher parity and perceived contractions prior to insertion. Intrauterine growth restriction was associated with a significant risk for dinoprostone insert removal. Neonatal outcomes were similar in cases of successful or failed ripening. Conclusion: The success of cervical ripening with dinoprostone slow release vaginal insert can be predicted by factors that can be recognized at admission. [ABSTRACT FROM AUTHOR]

Problem: Susceptibility to HIV is associated with the menstrual cycle and vaginal microbiome, but their collective impact on vaginal inflammation remains unclear. Here, we characterized the cervicovaginal proteome, inflammation, and microbiome community structure and function during the menstrual cycle. Method of study: Cervicovaginal secretions were collected from regularly cycling women (n = 16) at median day 10, 16, and 24 of each menstrual cycle and analyzed by mass spectrometry, 16S rRNA gene sequencing, and a multiplex bead array immunoassay. Follicular, ovulatory, and luteal phases were defined by serum sex hormone levels. Results: Ovulation showed the largest mucosal proteome changes, where 30% and 19% of the 406 human proteins identified differed compared to the luteal and follicular phases, respectively. Neutrophil/leukocyte migration pathways were lowest during ovulation and peaked in the luteal phase, while antimicrobial and epithelial barrier promoting proteins were highest during ovulation. Vaginal microbial community structure and function did not vary significantly during the menstrual cycle, with the majority consistently Lactobacillus‐dominant (63%) or non‐Lactobacillus‐dominant (25%). Fluctuations in the epithelial barrier protein RPTN between the ovulatory and luteal phase were amplified in women with Gardnerella vaginalis and anaerobic bacteria and reduced when Lactobacillus was dominant. Conclusion: This small study demonstrates that sex hormones modulate neutrophil/leukocyte inflammation, barrier function, and antimicrobial pathways in the female genital tract with the strongest changes occurring during ovulation. The data further suggest a microbiome context for hormone‐driven changes in vaginal immunity which may have implications for HIV susceptibility. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the potential of microparticles based on biocompatible phytolipids [Softisan® 154 (SF) (hydrogenated palm oil) and super-refined sunseed oil (SO)] and polyethylene glycol- (PEG-) 4000 to improve intravaginal delivery of miconazole nitrate (MN) for effective treatment of vulvovaginal candidiasis (VVC). Lipid matrices (LMs) consisting of rational blends of SF and SO with or without PEG-4000 were prepared by fusion and characterized and employed to formulate MN-loaded solid lipid microparticles (SLMs) by melt-homogenization. The SLMs were characterized for physicochemical properties, anticandidal activity, and stability. Spherical discrete microparticles with good physicochemical properties and mean diameters suitable for vaginal drug delivery were obtained. Formulations based on SO:SF (1:9) and containing highest concentrations of PEG-4000 (4 %w/w) and MN (3.0 %w/w) were stable and gave highest encapsulation efficiency (83.05–87.75%) and inhibition zone diameter (25.87±0.94–26.33±0.94 mm) and significantly (p<0.05) faster and more powerful fungicidal activity regarding killing rate constant values (7.10 x 10−3–1.09 x 10−2 min−1) than commercial topical solution of MN (Fungusol®) (8.00 x 10−3 min−1) and pure MN sample (5.160 x 10−3 min−1). This study has shown that MN-loaded SLMs based on molecularly PEGylated lipid matrices could provide a better option to deal with VVC. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the role of adjuvant endovaginal brachytherapy HDR (High Dose Rate) or observation, as well as identification of risk factors of tumor recurrence. The study included 178 women after radical hysterectomy. All patients belonged to the group of low- and medium-risk stage I FIGO. Analysis consisted of 3-, 5-, and 10-year OS, DFS, and LRFS in both groups. Follow-up was more than 6.5 years. The 5-OS, 5-DFS, and 5-LRFS were 93%, 96%, and 98% in the treated group and 95%, 94%, and 96% in the observed group, respectively. These differences were not statistically significant. There was a statistically significant difference in 5-OS in the treated group, between low- and medium-risk subgroups (100% versus 87.55%, p=0.018). There was a better prognosis among the patients with FIGO IA compared to FIGO IB (5-DFS, 97 versus 86%, p=0.047). Among the risk factors, there were only statistically significant differences in the 5-OS, between the ages of ≤ 70 years and >70 years. Use of brachytherapy may affect the reduction in the number of local recurrences at the vaginal stump (6% versus 2%). This is particularly noticeable in the low-risk subgroup (9% versus 0%). [ABSTRACT FROM AUTHOR]

A study was performed to investigate the effect of an intravaginally administered antimycotic, an antibiotic, and a spermicide plus the co-usage of tampons on the pharmacokinetics (PK) of levonorgestrel (LNG) and anastrozole (ATZ) administered as an intravaginal ring (IVR) releasing 1050 μg ATZ per day and 40 μg LNG per day. In this parallel-group, randomized, open-label study, healthy premenopausal women received an IVR as the main treatment. Comedications were administered on 3 consecutive evenings during treatment with IVR on days 9-11 (group A, 400 mg miconazole; group B, 100 mg clindamycin; group C, 75 mg nonoxynol-9); tampon co-usage (group D) was performed on days 20-23. The primary PK parameter was the average plasma concentration (Cav,ss) of ATZ and LNG at defined intervals, mainly prior to, during, and up to 7 days after the start of comedication. Fifty-two subjects were included, and at least 11 subjects per group completed the treatments. Overall, the medications and comedications were safe and well tolerated. Very similar ATZ and LNG plasma levels were observed across all groups. The calculated ratios of Cav,ss confirmed the absence of PK interactions because all relevant point estimates and 90% confidence intervals were within the range of 0.800-1.250, which is typically used in bioequivalence studies. These results demonstrate the absence of PK interactions between ATZ/LNG released from IVR and the tested antibiotic, antimycotic, spermicide, and tampons. Therefore, no restrictions for the use of the IVR are needed to continue the clinical program intended to treat endometriosis symptoms. [ABSTRACT FROM AUTHOR]

Oxytocin is a neuropeptide hormone used clinically for more than 50 years due to its ability to induce uterine contractions and milk ejection. Vagitocin is a vaginal oxytocin gel developed as a potential treatment of vaginal atrophy in postmenopausal women. The aim of this study was to characterize the oxytocin pharmacokinetics following vaginal and intravenous administration in postmenopausal women. Data from 33 participants enrolled in 2 clinical studies were used in the analysis, with a total of 651 observed oxytocin plasma concentrations, of which 78 were baseline observations, 178 observations following intravenous administration (10 IU), and 395 observations following vaginal administration (100 or 400 IU). The population pharmacokinetics of oxytocin was described using a 2-compartment disposition model with a flexible parallel absorption model accounting for doublepeak profiles following vaginal administration. The clearance, volume of distribution at steady state, distribution half-life, and terminal half-life were estimated to be 27 L/h, 15 L, 5.5 minutes, and 1.2 hours, respectively. The bioavailability following vaginal administration was estimated to be 2.5% for the typical patient, but with considerable variability both between individuals (interindividual variability of 374%) and between occasions (interoccasion variability of 79%). The data and the developed model add new and important information as to the clinical pharmacokinetics of oxytocin. [ABSTRACT FROM AUTHOR]

Thermosensitive hydrogels have increasingly received considerable attention for local drug delivery based on many advantages. However, burst release of drugs is becoming a critical challenge when the hydrogels are employed. Microspheres- (MS-) loaded thermosensitive hydrogels were thus fabricated to address this limitation. Employing an orthogonal design, the spray-dried operations of tenofovir (TFV)/Bletilla striata polysaccharide (BSP)/chitosan (CTS) MS were optimized according to the drug loading (DL). The physicochemical properties of the optimal MS (MS F) were characterized. Depending on the gelation temperature and gelating time, the optimal CTS-sodium alginate- (SA-) α,β-glycerophosphate (GP) (CTS-SA-GP) hydrogel was obtained. Observed by scanning electron microscope (SEM), TFV/BSP/CTS MS were successfully encapsulated in CTS-SA-GP. In vitro releasing demonstrated that MS F-CTS-SA-GP retained desirable in vitro sustained-release characteristics as a vaginal delivery system. Bioadhesion measurement showed that MS-CTS-SA-GP exhibited the highest mucoadhesive strength. Collectively, MS-CTS-SA-GP holds great promise for topical applications as a sustained-release vaginal drug delivery system. [ABSTRACT FROM AUTHOR]

Background: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk.Objectives: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies.Search Strategy: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016.Selection Criteria: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour.Data Collection and Analysis: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses.Main Results: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%).Conclusion: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes.Tweetable Abstract: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it.Objectives: To compare progesterone, cerclage and pessary, determine their relative effects and rank them.Search Strategy: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews.Selection Criteria: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study.Data Collection and Analysis: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT).Main Results: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks.Conclusions: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae.Tweetable Abstract: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis. [ABSTRACT FROM AUTHOR]

Background: Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed.Objectives: To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD.Search Strategy: Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery.Selection Criteria: Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included.Data Collection and Analysis: Study data were extracted and meta-analyses were performed when outcomes were comparable.Main Results: The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone.Conclusions: Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. [ABSTRACT FROM AUTHOR]

Objective: To establish the safety and efficacy of misoprostol for second-trimester termination of pregnancy among women with one or more previous cesarean deliveries.Methods: In a retrospective study, data were reviewed from women attending a reproductive health clinic in Bloemfontein, South Africa, for second-trimester termination between 2010 and 2013. The study group, comprising women with one or more previous cesareans, was compared with a control group, comprising women with no previous cesarean or uterine scarring. Procedure-specific information was compared, including misoprostol use, termination duration, need for other methods (e.g. oxytocin), placenta delivery, termination outcome, and bleeding.Results: The study group comprised 268 women: 231 (86.2%) with one and 37 (13.8%) with two previous cesareans. The control group comprised 266 women. Incomplete abortion was recorded in 223 (85.4%) of 261 women in the study group and 213 (80.4%) of 265 in the control group. The number of women with retained placenta was higher in the study than in the control group (158/261 [60.5%] vs 146/265 [55.1%]; P<0.001). Severe bleeding was observed only in the control group (7/266 [2.6%]). No uterine rupture was observed.Conclusion: Misoprostol was safe for second-trimester termination among women with previous cesareans; however, the efficacy of the local regimen was reduced owing to high placental retention. [ABSTRACT FROM AUTHOR]

Objective To evaluate the percentage change in total βeta-unit human chorionic gonadotropin (βhCG) levels (%Δβh CG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13 weeks. Methods A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total βh CG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound ( TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %Δβh CG ((baseline βh CG - follow-up βh CG)/baseline βh CG × 100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. Results %Δβh CG was calculated for cases with βh CG levels within two days of misoprostol and TVUS; calculation interval determined case number. The median %Δβh CG for 24 cases with a persistent sac (6-9 day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% ( IQR: 95.44-98.43); P < 0.0001). The median %Δβh CG for eight cases needing surgery on clinical criteria (5-9 day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% ( IQR: 64.63-91.15; maximum 94.06) vs 97.68% ( IQR: 95.61-98.50); P < 0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %Δβh CG > 87% predicted no sac at TVUS. %Δβh CG > 94.5% predicted no surgery on clinical criteria. Conclusion %Δβh CG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage. [ABSTRACT FROM AUTHOR]

Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. [ABSTRACT FROM AUTHOR]

Background. Our previous Gräfenberg spot findings confirmed that the distal-third areas of the anterior vaginal wall bore a significantly greater number of nerves and sexual hormone may have certain degree of influence on these significant differences. However, the role of estrogen in vaginal innervations remains controversial. Methods. To investigate whether hormonal-neural interactions occur in the vagina, sixty rats were randomly divided into six groups: Sham-operated, ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry. Results. The density of small nerve fibers was significantly higher in the distal-half areas of intact vaginal walls than the proximal-half areas (P=0.001). In contrast, the overall PGP 9.5-ir fiber innervation density was significantly decreased in the OVX rats subjected to surgical menopause. Sustained estrogen administration for 2 weeks resulted in nerve fiber proliferation, with values reaching normal levels in the low-dose estradiol valerate group. Conclusion. Our findings indicate that systemic hormonal therapy with low-dose estradiol valerate is effective and safe for treating deficient vaginal innervation caused by low level of estrogen activity in menopausal women and may aid studies to identify an optimal estradiol dose to provide relief from vaginal discomfort. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid-trimester.Methods: This was an updated systematic review and meta-analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a mid-trimester sonographic cervical length ≤ 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks' gestation. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated.Results: IPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD meta-analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks' gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51-0.93); moderate-quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks' gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35-0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56-0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34-0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36-0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35-0.80)) (all moderate-quality evidence). There were no significant differences in neurodevelopmental outcomes at 4-5 years of age between the vaginal progesterone and placebo groups.Conclusion: Administration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix in the mid-trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Objective: Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB.Methods: Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed.Results: Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53-0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40-0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0.53 (95% CI, 0.31-0.91); very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared with 17-OHPC (18.7% vs 23.5%; RR, 0.63 (95% CI, 0.47-0.83); low quality of evidence). For the comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was not reached) and by at least one degree due to indirectness (different interventions).Conclusions: Daily vaginal progesterone (either suppository or gel) started at about 16 weeks' gestation is a reasonable, if not better, alternative to weekly 17-OHPC injection for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low or very low as assessed by GRADE, indicating that the true effect may be, or is likely to be, substantially different from the estimate of the effect. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. COMPARACIÓN ENTRE LA PROGESTERONA VAGINAL Y EL 17Α-HIDROXIPROGESTERONA CAPROATO INTRAMUSCULAR PARA LA PREVENCIÓN DEL PARTO PRETÉRMINO ESPONTÁNEO RECURRENTE EN EMBARAZOS CON FETO ÚNICO: REVISIÓN SISTEMÁTICA Y METAANÁLISIS DE ENSAYOS CONTROLADOS ALEATORIOS: RESUMEN OBJETIVO: Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en inglés) por vía intramuscular con la progesterona por vía vaginal para la reducción del riesgo de parto pretérmino espontáneo (PPTE) en embarazos con feto único de gestantes con historial de PPTE. El objetivo de esta revisión sistemática y metaanálisis fue evaluar la eficacia de la progesterona vaginal en comparación con la 17-OHPC en la prevención de embarazos con feto único de gestantes con historial de PPTE. MÉTODOS: Se realizaron búsquedas en bases de datos electrónicas para identificar todos los ECA con embarazos de feto único asintomáticos con historial de PPTE antes de ser asignados al azar a un tratamiento profiláctico, ya fuera con progesterona vaginal (grupo de intervención) o con 17-OHPC intramuscular (grupo de control). No se aplicaron restricciones respecto al idioma o la ubicación geográfica. El resultado primario fue PPTE < 34 semanas. Los resultados secundarios fueron PPTE <37 semanas, < 32 semanas, < 28 semanas y < 24 semanas, la reacción materna adversa al fármaco y los resultados neonatales. Las medidas del resumen se reportaron como riesgo relativo (RR) con IC del 95%. Para cada estudio incluido se evaluó el riesgo de sesgo.Resultados: Se incluyeron tres ECA (680 mujeres). La media de la edad gestacional en el momento de la aleatorización fue de 16 semanas. A las mujeres se les administró progesterona hasta la semana 36 o hasta el parto. Con respecto a la progesterona vaginal, un estudio utilizó gel de 90 mg diariamente, otro utilizó un supositorio diario de 100 mg y el otro utilizó un supositorio diario de 200 mg. Todos los ECA incluidos en el grupo de comparación utilizaron 250 mg semanales de 17-OHPC por vía intramuscular. Las mujeres que recibieron progesterona vaginal tuvieron tasas significativamente más bajas de PPTE < 34 semanas (17,5% vs. 25,0%; RR 0,71 (IC 95%, 0,53-0,95); calidad de la evidencia baja) y < 32 semanas (8,9% vs. 14,5%; RR 0,62 (IC 95%, 0,40-0,94); calidad de evidencia baja), en comparación con las mujeres que recibieron 17-OHPC. No hubo diferencias significativas en las tasas de PPTE < 37 semanas, < 28 semanas y < 24 semanas. La tasa de mujeres que reportaron reacciones adversas a los medicamentos fue significativamente menor en el grupo de progesterona vaginal en comparación con el grupo de 17-OHPC (7,1% vs. 13,2%; RR 0,53 (IC 95%, 0,31-0,91); calidad de la evidencia muy baja). En cuanto a los resultados neonatales, la progesterona vaginal se asoció a una menor tasa de admisiones en la unidad neonatal de cuidados intensivos en comparación con la 17-OHPC (18,7% vs. 23,5%; RR 0,63 (IC 95%, 0,47-0,83); calidad de evidencia baja). Para la comparación del 17-OHPC con la progesterona vaginal se rebajó la calidad de las pruebas para todos los resultados en al menos un grado debido a imprecisiones (no se alcanzó el tamaño óptimo de la información) y en al menos un grado debido al carácter indirecto de los estudios (diferentes intervenciones).Conclusiones: La progesterona vaginal administrada diariamente (ya fuera como supositorio o como gel) desde la semana 16 de gestación es una alternativa razonable, si no mejor, a una inyección semanal de 17-OHPC para la prevención de PPTE en mujeres con embarazos de feto único e historial de PPTE. Sin embargo, el nivel de calidad de las estimaciones del resumen fue bajo o muy bajo según lo evaluado por GRADE, lo que indica que el verdadero efecto puede ser, o es probable que sea, sustancialmente diferente de la estimación del efecto. 17Α-:META: : (randomized controlled trials,RCTs)(spontaneous preterm birth,SPTB)17α-(intramuscular 17α-hydroxyprogesterone caproate,17-OHPC)SPTB。metaSPTB17-OHPCSPTB。 : ,SPTBRCTs,RCTs()17-OHPC()。。34SPTB。37、32、2824SPTB,。(relative risk,RR)95%CI。。 : 3RCTs(680)。16。,36。,90 mg,100 mg,200 mg。,RCTs250 mg 17-OHPC。17-OHPC,34 [17.5%25.0%;RR,0.71(95% CI,0.53 ~ 0.95);]32[8.9%14.5%;RR,0.62(95% CI,0.40 ~ 0.94);]SPTB。37、2824SPTB。17-OHPC,[7.1%13.2%;RR,0.53(95% CI,0.31 ~ 0.91);]。,17-OHPC,[18.7%23.5%;RR,0.63(95% CI,0.47 ~ 0.83);]。17-OHPC,(),()。 : SPTBSPTB,16()17-OHPC,。,GRADE,,。. [ABSTRACT FROM AUTHOR]

Background The process of induction of labour ( IOL) commonly involves cervical ripening, using mechanical or pharmacological methods. However, the optimum protocol of IOL remains undetermined. Aims To report the maternal, neonatal and process outcomes for women being induced with a balloon catheter or prostaglandin E2 gel ( PGE2). Materials and methods Matched retrospective cohort study of women requiring IOL at term with a modified Bishop's score ( MBS) <7. Those who underwent cervical ripening with a double balloon catheter were matched 1:1 for parity, indication and MBS score to those using PGE2 gel. The primary outcome measure was mode of birth. Results After exclusions, data from 427 women induced with a balloon catheter were able to be matched to 427 women induced with PGE2 gel. Compared to women receiving PGE2 gel, those induced using a balloon catheter were more likely to have an unassisted vaginal birth (50.4% vs 42.9%; P = 0.028), a lower mean estimated blood loss (420 vs 481 mL; P = 0.028), a reduction in fetal acidaemia (2.4% vs 8.8%; P = 0.003) and a greater likelihood experiencing vaginal delivery within 24 h (33.7% vs 25.8%; P = 0.011). Conclusion Similar to findings in randomised controlled trials and meta-analyses of IOL methods, we observed more unassisted vaginal births, less blood loss, decreased fetal acidaemia, and a greater likelihood of vaginal delivery within 24 h, with use of balloon catheter as compared to PGE2 vaginal gel. [ABSTRACT FROM AUTHOR]