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Objective The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. Study Design Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. Results We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval (CI): 0.19–0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20–1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. Conclusion While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. Key Points Dual therapy did not decrease preterm birth risk compared with monotherapy. Dual therapy prolonged pregnancy compared with monotherapy. Dual therapy can be considered but further studies are needed. [ABSTRACT FROM AUTHOR]

There is controversial evidence that acidification of vaginal pH may increase the efficacy of vaginal prostaglandins in labor induction, with research being mainly focused on misoprostol. This study aims to evaluate the impact of this intervention on the progress of labor induction with dinoprostone (PGE2) vaginal tablet. This double-blind, parallel-group, randomized study was conducted between October 2021 and December 2022 at Alexandra General Hospital, Athens, Greece. A total of 230 women with singleton, full term pregnancy that were scheduled for labor induction were randomly divided into two groups: Group A, who received acidic vaginal wash (5 % acetic acid) and Group B, who received a normal saline vaginal wash. Afterwards, participants received a vaginal tablet of 3 mg dinoprostone every 6 h (maximum two doses). There were no statistically significant differences in mode of delivery, duration of different labor stages, Bishop score changes and possible complications. Participants in the acidification group needed less often labor augmentation with oxytocin and epidural anesthesia (p=0.03). Vaginal acidification seems to have no effect on the efficacy of the dinoprostone vaginal tablet. Even though it may reduce the need for oxytocin augmentation, there is no apparent benefit on clinical outcomes, such as reduction in cesarean section rates or shorter labor duration. Future research is necessary in order to validate these findings. [ABSTRACT FROM AUTHOR]

We evaluated correlates of adherence to PrEP, including daily oral tenofovir disoproxil fumarate in combination emtricitabine (oral FTC/TDF) and the monthly dapivirine ring (ring)among adolescent girls and young women (AGYW) in the MTN-034/REACH study. We enrolled 247 AGYW aged 16–21 years in South Africa, Uganda and Zimbabwe (ClinicalTrials.gov: NCT03074786). Participants were randomized to the order of oral FTC/TDF or ring use for 6 months each in a crossover period, followed by a 6-month choice period. We assessed potential adherence correlates—individual, interpersonal, community, study, and product-related factors—quarterly via self-report. We measured biomarkers of adherence monthly; high adherence was defined as > 4 mg dapivirine released from returned rings or intracellular tenofovir diphosphate levels ≥ 700 fmol/punch from dried blood spots (DBS). We tested associations between correlates and objective measures of high adherence using generalized estimating equations. High adherence to oral FTC/TDF was significantly associated with having an older primary partner (p = 0.04), not having exchanged sex in the past 3 months (p = 0.02), and rating oral FTC/TDF as highly acceptable (p = 0.003). High ring adherence was significantly associated with unstable housing (p = 0.01), disclosing ring use to a male family member (p = 0.01), and noting a social benefit from study participation (p = 0.03). All associations were moderate, corresponding to about 6%–10% difference in the proportion with high adherence. In our multinational study, correlates of adherence among African AGYW differed for oral FTC/TDF and the ring, highlighting the benefit of offering multiple PrEP options. [ABSTRACT FROM AUTHOR]

• The 30 days administration of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) was effective in postmenopausal women, as previously published in perimenopausal women-. • The effect of treatment was more pronounced in post- than peri- mmenopausal women. • Treatment prolongation up to 210 days was safe and further improved vaginal atrophy and its symptoms in both peri- and postmenopausal women. This TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women. Sexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days. Women in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of −24.4 ± 3.6, and −52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of −18.6 ± 4.4 and −47.8 ± 3.2, VAS of pain decreased (p < 0.001) of −26.2 ± 4.3 and −55.6 ± 3.1 and the GSS decreased (p < 0.001) of −3.9 ± 0.3, and −4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of –53.6 ± 1.9 (p < 0.001) VAS of irritation of −42.6 ± 1.4 (p < 0.001) VAS of pain of −46.7 ± 2.3 (p < 0.001) and the GSS of −6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported. In peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy. [ABSTRACT FROM AUTHOR]

Background: The serum P concentrations are suggested to have an impact on pregnancy outcome. However there is no consensus about the optimal progesterone cut-off during the luteal phase. Few studies evaluated the effectiveness of a "rescue protocol" for low serum P concentrations and most of these studies used vaginal progesterone administration. There is paucity of data on the effectiveness of rescue protocol using intramuscular progesterone (IM-P) in frozen-thawed embryo transfer (FET). Methods: This study is a retrospective cohort study included 637 single or double blastocyst FETs with artificially prepared endometrium receiving 100 mg IM progesterone (P) after incremental estrogen treatment. Serum P concentrations were evaluated using blood samples obtained 117-119 hours after the first IM-P administration and 21 ± 2 hours after the last IM-P administration. Patients with serum P concentrations <20.6 ng/ml on the ET day were administrated 400 mg vaginal progesterone for rescue. Results: Demographic and cycle characteristics were similar between patients receiving rescue vaginal P (embryo transfer (ET)-day P concentration < 20.6 ng/ml) and patients who did not need rescue vaginal P (ET-day P concentration = 20.6 ng/ml). Clinical pregnancy, miscarriage, and live birth rates were similar between two groups: 52.9%(45/85) vs 59.6%(326/552), p=0.287; 11.1%(5/45) vs 14.1%(46/326), p=0.583; and 47.1%(40/85) vs 50.7%(280/552), p=0.526, respectively. Logistic regression analysis revealed that the female age (p = 0.008, OR=0.942, 95% CI = 0.902-0.984) and embryo quality (ref: good quality for moderate: p=0.02, OR=0.469, 95% CI =0.269-0.760; for poor: p=0.013, OR= 0.269, 95% CI = 0.092-0.757) were independent variables for live birth. Following rescue protocol implementation, ET-day P concentration was not a significant predictor of live birth. Conclusions: Rescue vaginal P administration for low ET day serum P concentrations following IM-P yields comparable live birth rates. [ABSTRACT FROM AUTHOR]

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT. [Display omitted] [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the impact of oral progesterone (altrenogest) administered after mating on fertility in goats synchronized during the breeding season. A total of 47 Hair goats were included in the study. A progesterone-impregnated intravaginal sponges were administered for 12 days. On day 10 of intravaginal sponge administration, 480 IU pregnant mare's serum gonadotropin (PMSG) and 0.075 mg cloprostenol were injected intramuscularly to the goats. Animals were exposed to bucks for 12 hours after detection of estrus by the foraging buck. The goats were randomly assigned to two distinct groups: Group 1 (G1, n=23) and Group 2 (G2, n=24). G1 goats were orally administrated 4.4 mg of altrenogest per day for 30 days after mating. G2 goats served as controls. Pregnancy examinations were performed by transrectal ultrasonography on the 30th and 42nd days after mating. Blood samples were taken from one day after mating to 30 days (3-day intervals). Statistical analysis comparing G1 and G2 revealed no significant differences between the groups regarding progesterone concentrations, conception rate, pregnancy rate, lambing rate, multiple birth rate, fecundity, and litter size (p>0.05). In conclusion, this study revealed that oral progesterone use had no impact on fertility parameters. Moreover, further research is warranted to explore the efficacy of various oral progesterone analogs. [ABSTRACT FROM AUTHOR]

Objective Combining pharmacologic agents with mechanical ripening achieves the shortest labor duration, yet there is no clear evidence on route of drug administration in obese individuals. The use of buccal misoprostol has shown greater patient acceptance but remains understudied. Our objective was to evaluate the difference in time to delivery of buccal compared with vaginal misoprostol in combination with a Foley catheter (FC) for induction of labor (IOL) in the obese population. Study Design This was a secondary analysis of a randomized controlled trial comparing identical dosages (25 μg) of buccal and vaginal misoprostol in combination with a FC. The parent trial was an institutional review board-approved, randomized clinical trial conducted from June 2019 through January 2020. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2 cm were included. Body mass index (BMI, kg/m 2) was stratified. The primary outcome was time to delivery. Results A total of 215 participants were included. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a body mass index greater than or equal to 30 kg/m 2 (vaginal misoprostol–FC: 21.3 hours vs. buccal misoprostol–FC: 25.2 hours, p = 0.006). There was no difference in the cesarean delivery rate between the two groups. Furthermore, patients with a BMI greater than or equal to 30 kg/m 2 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for cesarean delivery and adjusting for parity (hazard ratio: 1.2, 95% confidence interval: 1.1–1.7). There were no significant differences in maternal and neonatal outcomes. Conclusion We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI greater than or equal to 30 kg/m 2. Vaginal misoprostol should be the preferred route of drug administration for term IOL in this population. Key Points Vaginal misoprostol was superior to buccal route among patients with obesity. There was no difference in the cesarean delivery rate between the two groups. Vaginal misoprostol should be the preferred route of administration among patients with obesity. [ABSTRACT FROM AUTHOR]

Background Widespread antibiotic resistance has sparked interest in the identification of nonantibiotic strategies, particularly probiotics for the prevention of recurrent urinary tract infections (UTIs). We evaluated the effectiveness of prophylactic probiotic supplementation through oral and intravaginal routes in the prevention of recurrent UTIs. Methods This double-blind, placebo-controlled study enrolled 174 premenopausal women with a history of recurrent UTIs and randomized them to 1 of the 4 treatment groups: placebo (G1, oral placebo + vaginal placebo), oral probiotic (G2, oral lactic acid bacteria and bifidobacteria + vaginal placebo), vaginal probiotic (G3, oral placebo + vaginal lactobacilli), and probiotic combination (oral lactic acid bacteria and bifidobacteria + vaginal lactobacilli), for 4 months. Participants were followed up for symptomatic UTIs for 1 year. The primary end points were the number of symptomatic UTIs at 4 months, the proportion of participants with at least 1 symptomatic UTI, and the time to the first symptomatic UTI. Results The incidence of UTI at 4 months in G1, G2, G3, and G4 was 70.4%, 61.3%, 40.9%, and 31.8%, respectively. The mean number of symptomatic UTI recurrences at 4 months was significantly lower (P <.05) in G3 (1.06) and G4 (1.07) compared with G1 (2.1) and G2 (1.63). Further, the time to first symptomatic UTI (days) was significantly longer (P <.05) in G3 (123.8) and G4 (141.8) compared with G1 (69.3) and G2 (71.9). Probiotic supplementations were well tolerated with no serious adverse events. Conclusions Prophylactic supplementation with either vaginal probiotics or in combination with oral probiotics demonstrated effectiveness in preventing recurrent symptomatic UTI episodes. Clinical Trials Registration Registered at Clinical Trials Registry India (CTRI): CTRI/2014/02/004425 (https://ctri.nic.in). [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the current status of progestogen treatment for pregnant women at a high risk for preterm birth (PTB) in childbirth healthcare facilities in Japan. Methods: A web‐based nationwide questionnaire survey regarding progestogen use for prevention of PTB was conducted among childbirth healthcare facilities from 2019 to 2021. Results: Valid responses were obtained from 528 facilities (25.2% of those surveyed), including 155 tertiary perinatal facilities (making up 92.3% of all tertiary perinatal care facilities). In the survey period, progestogen treatment was implemented in 207 facilities (39.2%) for PTB prevention. Regarding types of progestogens, 17α‐hydroxyprogesterone caproate was used in 170 facilities (82.1%), with a low dose (125 mg/week) administered in 62.9% of the facilities to comply with the regulations of the national health insurance system, although 250 mg/week is considered the best dose. Vaginal progesterone was used in 36 facilities (17.4%), although the cost of vaginal progesterone was not covered by health insurance. Of the facilities not administering progestogen treatment, approximately 40% expressed that vaginal progesterone would be their first choice for PTB prevention in daily practice if it would be covered by health insurance in the future. Conclusions: Due to the current regulations of the Japanese health insurance system, 17α‐hydroxyprogesterone caproate, rather than vaginal progesterone, was mainly used for PTB prevention. Despite global evidence supporting vaginal progesterone as the approach with the highest efficacy, only a limited number of facilities have utilized it due to the current drug use regulations in Japan. [ABSTRACT FROM AUTHOR]

Background: Considering the considerable influence of the vaginal microbiome on endometrial receptivity and embryo implantation, we hypothesized that cases of recurrent implantation failure (RIF) might benefit from the intravaginal probiotic administration. Objective: Evaluation of the effects of intravaginal probiotic administration before frozen embryo transfer (FET) on the rates of pregnancy and the status of vaginal lactobacillary flora in cases of RIF. Materials and Methods: This was a randomized, parallel-group, clinical trial conducted at an infertility clinic in Tehran, Iran between January 2021 and September 2022. A total of 166 reproductive-aged women with a history of unexplained RIF were randomly assigned to either the probiotic group or the control group (n = 83/each group). The probiotic group received intravaginal probiotics (LactoVag®) daily for 2 wk from the second day of the menstrual cycle along with the routine treatment of FET. The control group received only the routine treatment of FET. The primary outcome was the chemical pregnancy rate, and the secondary outcomes were the clinical pregnancy rate and the status of vaginal lactobacillary flora. Results: A total of 163 participants were included in the final analysis. The probiotic group had a slightly higher chemical pregnancy rate than the control group (39.02% vs. 33.33%), but the difference was not statistically significant (risk ratio: 1.71, 95% CI: 0.77-1.76; p = 0.449). The clinical pregnancy rate was also non-significantly higher in the probiotic group than the control group (37.80% vs. 33.33%; RR: 1.14, 95% CI: 0.76-1.74; p = 0.623). Conclusion: Intravaginal probiotic administration did not significantly improve the pregnancy rates in RIF cases undergoing FET. Further studies are needed to explore the optimal dose, duration, and timing of probiotic administration, as well as the mechanisms of action and the potential adverse effects of probiotics on the vaginal microbiome and the implantation process. [ABSTRACT FROM AUTHOR]

Vaginal inflammation is a prevalent gynecological condition. If left untreated, it can potentially spread to the urinary and reproductive systems. In this study, we propose a resveratrol-loaded microemulsion-based thermosensitive hydrogel (Res-Me-Tsgel) and compare it with a chitosan hydrogel-based Res-Me-Cogel. We characterized the different characters of Res-Me-Tsgel. The safety of Res-Me-Tsgel was also evaluated in vitro and in vivo. Finally, we measured the retention of Res in the vagina after drug administration. The Res-Me-Tsgel we prepared is a transparent liquid solution at room temperature that rapidly forms a gel at 37oC. Compared to Res solution and Res-Me, both Res-Me-Cogel and Res-Me-Tsgel demonstrate superior sustained release properties. Both in vitro and in vivo studies confirm the excellent biosafety profile of Res-Me-Cogel and Res-Me-Tsgel. Vaginal administration of these formulations in rats results in prolonged retention of resveratrol within the vagina. Notably, due to its improved flow into vaginal folds after administration, the retention of Resveratrol was approximately three times higher for the Res-Me-Tsgel group compared to the Res-Me-Cogel group at 24 h post-administration. Overall, these findings highlight the potential application of Res-Me-Tsgel as an effective means for vaginal inflammation. We developed a novel micromulsion based thermosensitive hydrogel for the delivery of Res. The sustained release of Res and favorable vaginal retention from Res-Me-Tsgel make them promise as a potential candidate for local intravaginal therapy. [ABSTRACT FROM AUTHOR]

Aim: Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora. Methods: This study included patients diagnosed with repeated implantation failure—defined as failure to achieve pregnancy after two or more transfers of viable embryos—who were classified as non‐Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1‐week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1‐week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%. Results: Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242). Conclusions: This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies. [ABSTRACT FROM AUTHOR]

This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings. [ABSTRACT FROM AUTHOR]

Background & Objective: The purpose of this study was to compare the effectiveness of Buccal, Vaginal, and Sublingual misoprostol for induction of labor in term pregnancy. Materials & Methods: The research was done as an RCT from 2017 to 2018. About 300 participants were randomly allocated to obtain 50 µg Buccal, 25 µg Vaginal, and 50 µg Sublingual misoprostol in Kosar Hospital, Qazvin, Iran. The maternal and fetal complications, Bishop score hour 1, and hour 6 were observed. Results: There were no differences between fetal complications (P>0.05) and maternal complications (P>0.05) among the three groups. Bishop score hour 1 (P = 0.146), Bishop Score hour 6 (P = 0.704), and total dose (P = 0.15) also were no differences among these groups. Our study found a difference between the three groups (P = 0.015) in achieving standard vaginal delivery within 24 hours, as Buccal, Sublingual and Vaginal groups were performed respectively. The use of Oxytocin in the Buccal group was higher than that of other groups (P = 0.022). Conclusion: This study found that there is no difference in terms of fetal complications and maternal complications in the three groups, but there was a significant difference in Oxytocin use and vaginal delivery within 24 h from the start of induction. [ABSTRACT FROM AUTHOR]

Infertility is a disease with a complex pathophysiology and concurrent presence of gynaecological and reproductive disorders associated with it. A significant hurdle that infertility faces is the limitation of the success rate per couple per cycle in one assisted reproductive technology treatment. A central role is played by the complex embryo endometrial crosstalk that has been a subject of study since the very beginning of natural conception failures. The endometrium is a key player in the attempt for a healthy live birth. Thought to be previously sterile, the uterus is now known as home to a unique community of microorganisms. The microbiota and their genomic content: the endometrial microbiome is a complex and heterogeneous endocrine system that plays a pivotal role in the master orchestration of successful embryo implantation in a receptive uterine cavity. The microbial community inside the uterus is now known to influence reproductive pathologies and complex aetiologies that influence infertile outcomes. This review is aimed to understand the correlations of the endometrial microbiome and more specifically, bacterial communities and their pathophysiology in reproductive pathologies leading to infertility. The role of personalised regimens and therapies for treatment through nutritional, microbiotic or pharmaceutical interventions is discussed. The use of selected strains that are part of this bacterial community as probiotics could be a successful therapy for uterine diseases and concomitant infertility alongside nutritional and pharmaceutical interventions. Further longitudinal studies in infertile patients with specific pathologies with stratified selection are necessary to progress microbiome evaluation and eventually, modulation for infertility. [ABSTRACT FROM AUTHOR]

Sodium alginate and poloxamer 407 were both studied in order to design a hydrogel-based delivery system as a platform for the formulation of vaginal medecines. Sodium alginate is a natural anionic mucoadhesive polymer while poloxamer 407 is a temperature-sensitive polymer. A commercial alginate was characterized. Then, its solutions (0.5-2 % w/w), poloxamer 407 solutions (16-21.5 % w/w) and their mixtures were prepared. Their rheological properties and the influence of vaginal simulated fluid were assessed. This commercial alginate had a mannuronate-to-guluronate ratio of 1.24, a weight-average molecular weight of 300 000 ± 2% g.mol-1, a polydispersity index of 1.8 ± 3%. Alginate solutions displayed a viscous behavior not suitable for a vaginal administration. Poloxamer solutions and their mixtures with alginate were temperature-sensitive, shear-thinning, non-thixotropic and had an elastic behavior suitable for a vaginal administration. Their resistance to dilution with vaginal fluid could prolonge vaginal residence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictive value of obstetric findings when using dinoprostone (prostaglandin E2 [PGE2]) vaginal inserts for cervical ripening, and to assess the optimal cervical‐ripening method between PGE2 vaginal insert and/or cervical dilators. Methods: This prospective observational study enrolled pregnant women who underwent cervical ripening for labor induction in 37–41 week' gestation in 2020. In evaluation 1, optimal obstetric findings predictive of rapid cervical ripening using PGE2 were assessed. In evaluation 2, the duration from PGE2 administration to labor onset and perinatal outcomes were compared between cases in which only PGE2 was used and cases that were treated with PGE2 after mechanical cervical dilators (Dilapan®) for extremely immature cervical ripening (uterine cervical os <2 cm). Results: In evaluation 1, uterine dilatation before the use of a PGE2 vaginal insert was mostly correlated with the time from PGE2 administration to labor onset (r = −0.428, p < 0.001). When the uterine cervical os dilatation was ≥2 cm, a shorter time‐to‐labor onset was found. In addition, os dilatation, effacement, and station at the time of PGE2 vaginal insert removal also significantly progressed. In evaluation 2, the median duration from PGE2 administration to labor onset was 1740 min in cases where only PGE2 was used, and 610 min in those where PGE2 was used after mechanical cervical dilators (p = 0.011). Conclusion: PGE2 vaginal inserts are relatively effective when the uterine cervical os is ≥2 cm in diameter. However, in cases of extremely immature cervical‐ripening, it was feasible to use PGE2 vaginal inserts before mechanical cervical dilatation. [ABSTRACT FROM AUTHOR]

This study aimed to assess vaginal progesterone's effect on different populations and performed comparation between women with varied risk factors. Embase, PubMed, Cochrane library (CENTRAL) were searched without restriction to language up to February 25, 2021. Randomized controlled trials (RCTs) assessing vaginal progesterone administered to women at risk of preterm birth at <37 weeks. Two reviewers independently extracted data, and pooled relative risk (RR) with 95% confidence intervals (CIs) was calculated as well. Women with short cervix have a significantly lower risk of preterm birth at <34 weeks (pooled RR = 0.65; 95% CI: 0.55–0.77; I2 = 0; p < 0.001; nine studies) and some neonatal morbidities; interaction tests showed that effect of vaginal progesterone differs significantly between women with short cervix and those with other risk factors (history of preterm birth, exclusive twin gestation, and vaginal bleeding). Evidences of this study showed that singleton gestations, as well as women with short cervix, benefit from vaginal progesterone in preventing preterm birth at <34 weeks and some neonatal morbidities. Women with short cervix are populations who benefit the most among other risk populations. Key Points Vaginal progesterone reduces preterm birth and neonatal morbidities. Vaginal progesterone effects on some specific populations. Women with short cervix benefit the most. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is the most common fungal infection in the vaginal mucosa caused by an overgrowth of Candida albicans. The pathogenesis of C. albicans is determined by the presence of virulence secretory factors. Secreted Aspartyl Protease 5 (SAP5) is the dominant virulence factor that plays a critical role in the morphology switching of yeast cells into hyphae which causes tissue invasion and induces an immunopathological response. Levels of SAP5 are often associated with the severity various types of infection. As a potential supportive therapy to treat VVC, identification of the probiotic's administration route determines the level of efficacy of probiotics. This study aims to compare the decrease in SAP5 levels between oral and intravaginal administration of L. plantarum. The study was true experimental using a completely randomized pretest-posttest group design. There were 32 female rats were divided into 8 groups i.e negative control, positive control, 3 groups of oral and 3 of intravaginal administration. Positive control and 6 treatment group were injected with estradiol valerate 0.5 mg and then inoculated with suspension of C. albicans 2×107 CFU to create VVC model. L. plantarum was administered orally and intravaginally with 3 concentration variants i.e. 2.25×1010, 4.5×1010 and 9×1010 CFU. Both of oral and intravaginal group were given with probiotics for 14 days. SAP5 levels were measured by ELISA from vaginal lavage sample. The statistical analysis used was the Paired T-Test to measure SAP5 levels pre-post oral and intravaginal administration of L. plantarum. The results showed a significant decrease in SAP5 levels in oral administration (p = 0.001 < 0.05) and intravaginal administration (p = 0.000 < 0.05). From the results of the statistical analysis, it can be concluded that both oral and intravaginal administration of the probiotic L. plantarum has the same efficacy in reducing the virulence factor of C. albicans in cases of VVC. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare twice-daily versus once-daily administration of intravaginal PGE2 for induction of labor at term. Efficacy, safety, and patient satisfaction were evaluated. For this single-center, randomized, comparative, open-label, two-arm, and parallel study, pregnant women with term singleton live pregnancies ≥ 37 weeks of gestation, medical indications for induction of labor, and Bishop score ≤ 6 were randomized to either the control group (induction of labor with PGE2 gel with repeat dose after 24 h) or the experimental group (repeat dose after 12 h). The primary outcome was induction-to-delivery interval time. Secondary outcomes were maternal and neonatal outcomes and patient satisfaction. In total, 246 women were randomized to the control (n = 121) or experimental groups (n = 125). The mean time for initiation of induction to delivery was 9.4 h shorter in the experimental group compared to controls (p = 0.007). For control vs experimental, there were no differences in tachysystole (19/121, 15.7 % vs 21/124, 16.9 %, respectively; p = 0.79), cesarean section rate (18/121, 14.9 % vs 28/124, 22.6 % respectively; p = 0.12), or other main obstetrical or neonatal outcomes. Patients in the experimental group reported higher satisfaction with their induction (48/96, 50 % with once-daily vs 60/86, 69.8 % with twice-daily; p = 0.010). Among women admitted for induction of labor at term, closer interval of vaginal PGE2 administration was associated with a significantly shorter induction-to-delivery time without increasing maternal or neonatal morbidity. Furthermore, the reduction in induction time was associated with improved patient experience of delivery. [ABSTRACT FROM AUTHOR]

Background & Objective: Inducing labor is a common practice in obstetrics to prevent maternal and fetal complications. There are several methods of labor induction, including pharmacological and mechanical approaches. The objective of this study was to determine the most effective approach for labor induction. Materials & Methods: A cross-sectional study at Al-Kadhimiya Teaching Hospital compared labor induction in pregnant females at their third trimester using Misoprostol & Foley Catheter (group A) and Misoprostol alone (group B). The study collected data on maternal age, gestational age, BMI, time frames, mode of delivery, and neonatal outcomes such as Apgar scores and ICU admissions. Results: In a cross-sectional study comparing labor induction with Misoprostol & Foley Catheter (group A) vs. Misoprostol alone (group B), most females in both groups had no cesarean section inductions, normal vaginal deliveries, and no complications. The study found significant differences in BMI, time frame, and time for ripening between the two groups, with group A having lower values for these variables. Conclusion: Foley's with vaginal misoprostol results in a shortened time between induction and delivery than misoprostol alone. [ABSTRACT FROM AUTHOR]

Sodium alginate and poloxamer 407 were both studied in order to design a hydrogel-based delivery system as a platform for the formulation of vaginal medecines. Sodium alginate is a natural anionic mucoadhesive polymer while poloxamer 407 is a temperature-sensitive polymer. A commercial alginate was characterized. Then, its solutions (0.5-2 % w/w), poloxamer 407 solutions (16-21.5 % w/w) and their mixtures were prepared. Their rheological properties and the influence of vaginal simulated fluid were assessed. This commercial alginate had a mannuronate-to-guluronate ratio of 1.24, a weight-average molecular weight of 300 000 ± 2% g.mol-1, a polydispersity index of 1.8 ± 3%. Alginate solutions displayed a viscous behavior not suitable for a vaginal administration. Poloxamer solutions and their mixtures with alginate were temperature-sensitive, shear-thinning, non-thixotropic and had an elastic behavior suitable for a vaginal administration. Their resistance to dilution with vaginal fluid could prolonge vaginal residence. [ABSTRACT FROM AUTHOR]

Aim: To develop a model that predicts low progesterone (P) levels on the day of embryo transfer (ET) based on patient and cycle characteristics, including serum estradiol (E2) concentration after vaginal administration of micronized E2 for endometrial preparation. Methods: A prospective cohort of 193 patients scheduled for cryopreserved blastocyst transfer during an artificial endometrial preparation cycle, using micronized E2 vaginally for first 4 days (4 mg/day), followed by oral administration (6 mg/day). Blood sampling for E2 was performed prospectively on day‐5 of vaginal administration and analysis was performed retrospectively. On sixth day of P treatment (daily 300 mg of vaginal micronized P tablets), P levels were measured on ET day. Primary outcome measure was serum P levels after vaginal E2 administration. Results: Patients with low P levels on the day of ET (<7.8 ng/mL, 25th percentile) were heavier (p < 0.001) and exhibited lower day 5 serum E2 levels (p < 0.001) compared with patients with adequate P levels. Multivariate linear regression analysis revealed that weight (p = 0.003) and day 5 E2 levels (p < 0.001) were independently associated with the P levels. The sensitivity, specificity, and positive and negative predictive values (%) were 71.4, 55.6, 35.4, and 85.1 for weight ≥ 65 kg; 71.4, 61.8, 38.9, and 86.4 for day 5 E2 ≤ 1615 pg/mL; 59.2, 83.3, 54.7, and 85.7 for the combination of these two variables; and 82.9, 62.5, 54.7, and 87.0 for the sequential inclusion of these variables, respectively. Conclusions: Low day 5 E2 levels following vaginal administration and high weight are independently associated with low P levels on the day of ET. Predictive performance is enhanced when these variables are considered sequentially or in combination. [ABSTRACT FROM AUTHOR]

Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept in situ for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite N-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were Cmax 5.4 ± 2.7 ng/mL, AUCinf 34.9 ± 17.4 h ng/mL, t1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were Cmax 3.9 ± 2.5 ng/mL, AUCinf 51.1 ± 43.1 h ng/mL, t1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated. [ABSTRACT FROM AUTHOR]

Twins represent 3.2% of all live births. However, they account for 20% of all preterm deliveries, 60% delivering <37 weeks, 10.7% <32 weeks, and 5 times higher risk of infant death. Risk factors for preterm birth (PTB) include the history of preterm delivery, monochorionic twins, short cervical length, and cervical surgery. Transvaginal cervical length <24 weeks is the best tool to predict PTB. Only vaginal progesterone in women with transvaginal cervical length <25 mm and physical exam indicated cerclage in women with cervical dilation >1 cm have shown a significant decrease in PTB and improvement in neonatal outcomes. INSET: 0. [ABSTRACT FROM AUTHOR]

Pharmaceutical films are polymeric formulations used as a delivery platform for administration of small and macromolecular drugs for local or systemic action. They can be produced by using synthetic, semi-synthetic, or natural polymers through solvent casting, electrospinning, hot-melt extrusion, and 3D printing methods, and depending on the components and the manufacturing methods used, the films allow the modulation of drug release. Moreover, they have advantages that have drawn interest in the development and evaluation of film application on the buccal, nasal, vaginal, and ocular mucosa. This review aims to provide an overview of and critically discuss the use of films as transmucosal drug delivery systems. For this, aspects such as the composition of these formulations, the theories of mucoadhesion, and the methods of production were deeply considered, and an analysis of the main transmucosal pathways for which there are examples of developed films was conducted. All of this allowed us to point out the most relevant characteristics and opportunities that deserve to be taken into account in the use of films as transmucosal drug delivery systems. [ABSTRACT FROM AUTHOR]

We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11 • REBACIN is safe and effective for eliminating persistent high-risk HPV infection in a real-world clinical setting. • HPV16/18 is cleared more easily than HPV52/58. • Single-type infections are cleared more easily than multiple-type infections. • Young patients have a higher clearance rate than older patients. • Providing valuable guidance for clinical use of REBACIN while also suggesting potential areas for future basic research. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare duration of labor induction between diabetic and nondiabetic women receiving dinoprostone vaginal insert (10 mg). Study Design This is a secondary analysis of two large randomized controlled trials using dinoprostone vaginal inserts for labor induction. We compare time to active labor, overall delivery, and vaginal delivery between diabetic and nondiabetic women undergoing induction of labor with a 10-mg dinoprostone vaginal insert. Results Diabetic women receiving dinoprostone vaginal insert had a longer time to onset of active labor, overall delivery, and vaginal delivery than their nondiabetic counterparts. There was no difference in abnormal labor affecting fetal heart rate pattern in diabetic women compared with nondiabetic women. The rates of neonatal hyperbilirubinemia were higher in diabetic women. Conclusion Diabetes may represent an independent factor associated with prolonged induction among women undergoing induction of labor with dinoprostone. Dinoprostone is well tolerated in both diabetic and nondiabetic women. Key Points Diabetic women receiving DVI have slower labor curves than nondiabetic women. Nulliparous diabetic women took longer to achieve active labor, overall delivery, and vaginal delivery than nondiabetic women. Parous diabetic women took longer to achieve vaginal delivery than nondiabetic women. [ABSTRACT FROM AUTHOR]

Objective This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). Study Design This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. Results Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: −3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. Conclusion We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. Key Points Vaginal progesterone is not noninferior to 17OHP-C. PTB risk may be 10% higher with vaginal progesterone. Associations did not differ based on obesity status. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11–12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): −2.6%; 95% CI: −9.0% to 3.8%, P- value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: −6.4%; 95% CI: −12.6% to −0.1%, P -value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE May 2018. DATE OF FIRST PATIENT'S ENROLMENT November 2018. [ABSTRACT FROM AUTHOR]

Introduction: Vulvovaginal candidiasis (VVC) is a common cause of vaginal discharge in women of reproductive age-group. It affects 75% of women at least once during their lifetime and 10% of them have recurrent episodes. Most common offending organism is Candida albicans, and Candida glabrata being the most common non albicans species. Based on clinical presentation, microbiology, host factor like immunosuppression and recurrence, VVC is classified into complicated and uncomplicated VVC. The treatment of VVC is reasonably effective with a range of oral and intravaginal agents with Azoles being the predominant antifungals used. Aim And Objective: To compare the safety and efficacy of oral tablet fluconazole 150 mg single dose with intravaginal sertaconazole 500mg in the treatment of vulvovaginal candidiasis. MATERIALS AND METHODS: After obtaining informed consent, 100 patients who were clinically and mycologically confirmed to have vulvovaginal candidiasis were included in the study. They were randomly assigned into 2 groups, containing 50 patients each. Group A was treated with single dose of oral tablet fluconazole 150mg and group B was treated with sertaconazole 500mg vaginal pessary. The patients were reviewed at day 7 and 14 after the treatment. At each visit, symptomatic and mycological improvements were assessed and recorded. Results: A total of 97 patients completed the study. The symptomatic cure rate in both the groups at day 7 was 64.58% and 81.63% and in day 14 was 95.8% and 91.8% respectively in each group. The mycological cure rate in both groups at day 7 was 54.1%and 65.3% and day 14 was 75.1% and 85.7% respectively. Conclusion: Treatment of VVC with single dose Sertaconazole 500mg vaginal pessary results in rapid symptom clearance and lesser recurrence rate than oral Fluconazole 150mg tablet in the treatment of uncomplicated VVC, in women with personal preference of vaginal route of drug administration without significant drug interactions and adverse effects. This can also be beneficial in the era of emerging fluconazole resistance. [ABSTRACT FROM AUTHOR]

To determine if 17α-hydroxyprogesterone caproate (17OHPC) or vaginal progesterone use for patients at risk for preterm birth has changed since the publication of the 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG) trial, and to assess which organizations' (Food and Drug Administration's [FDA], American College of Obstetrics and Gynecology's [ACOG] or Society of Maternal Fetal Medicine's [SMFM]) statements most influenced change. Through a vignette-based physician survey, we sought to measure (by Likert scale) how counseling tendencies regarding 17OHPC and vaginal progesterone have changed since the PROLONG trial publication. Participants were also asked which organizations' statements most influenced change. With response rate of 97 % (141/145), a pre-to-post PROLONG trial comparison revealed significant changes in counseling for progesterone. Respondents were less likely to recommend 17OHPC (p<0.001) and more likely to recommend vaginal (p<0.001). The FDA statement most influenced the decision not to recommend 17OHPC for the prevention of preterm birth (r=−0.23, p=0.005). Providers have made significant changes in their counseling regarding progesterone use for patients at risk for preterm birth after the publication of the PRLONG trial. [ABSTRACT FROM AUTHOR]

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments. [ABSTRACT FROM AUTHOR]

Secretion of pulsatile gonadotropin-releasing hormone (GnRH) is essential for reproduction. Kisspeptin neurons in the arcuate nucleus (ARC), which coexpress neurokinin B (NKB) and its receptor (NK3R), are believed to be components of the GnRH pulse generator that regulates pulsatile GnRH secretion. We examined the effects of peripheral infusion of senktide, an NK3R selective agonist, on GnRH pulse generator activity by monitoring multiple unit activity (MUA) in the goat ARC. Previous studies have shown that characteristic increases in MUA (MUA volleys) reflect GnRH pulse generator activity. Senktide was infused intravenously or intravaginally for 2 h while recording MUA. Both infusions significantly increased the MUA volley frequency compared with the control. These results demonstrate that peripherally administered senktide acts centrally to sustainably accelerate the neural activity of the GnRH pulse generator throughout the infusion period. This suggests the possibility of practical applications of NK3R agonists for improving reproductive activity in farm animals.

Objective: To determine whether addition of evening primrose to a misoprostol-based abortion regimen can increase the success of abortion. Materials and Methods: In this randomized clinical trial., 148 women referring to Niknafas Hospital in Rafsanajn with diagnosis of missed abortion were randomly allocated into two 74-subject groups. The intervention group used 2000 mg vaginal evening primrose capsules the night before the hospitalization, while the control group did not receive any medication. Both groups received an initial dose of 800 μg of vaginal misoprostol after admission and the next dose was given three hours later if necessary. Results: The two groups had significant differences in terms of full abortion, consistency and dilatation of cervix, duration between the first dose of misoprostol until the ejection of fetus, the misoprostol dose administered, and the level of vaginal bleeding during the hospitalization. They had no significant differences regarding curettage, duration of hospitalization, or side effects. The mean pain score had no significant difference between the two groups, though the score was lower in the intervention group (p>0.05). Conclusion: Administration of vaginal evening primrose before vaginal misoprostol was found to be more effective compared to misoprostol alone in missed abortion. [ABSTRACT FROM AUTHOR]

Backgrounds: Outpatient induction of labor (IOL) is an alternative choice offered to pregnant women requiring cervical ripening. Outpatient IOL can provide solutions in terms of women empowerment, but most importantly promotes as normal labor as possible, within the medical context of the IOL. The objectives of this systematic review were to assess safety and effectiveness of cervical ripening performed with a slow‐release dinoprostone vaginal insert in term pregnancies in two settings: the outpatient (home) versus the inpatient (hospital). Methods: The electronic databases Cinahl, Embase, Medline and Maternity and Infant Care were searched to detect studies that met the inclusion criteria. Both reviewers collected the data and assessed the quality of the studies and assessed the pooled odds ratio using a 95% confidence interval and a random‐effects model. Primary outcomes were linked to maternal and neonatal morbidity. Secondary outcomes were related to birth outcomes. Results: No statistical difference was seen between the outpatient and inpatient setting in terms of maternal complications, neonatal morbidity, cesarean section, and labor onset <24 h. Women in the outpatient setting were significantly less likely to experience uterine hyperstimulation, and they were also significantly more likely to require oxytocin to augment or induce their labor than the women in the inpatient setting. Women in the outpatient setting were more satisfied with the cervical ripening experience. Conclusions: Cervical ripening with a slow‐release dinoprostone vaginal insert in term pregnancies in the outpatient setting appears as safe as the inpatient setting in terms of maternal, neonatal, and birth outcomes. [ABSTRACT FROM AUTHOR]

Background: Recurrent vulvovaginal candidiasis management primarily entails azole therapy used as required or as an extended daily or weekly maintenance therapy for 6 months or more. Unfortunately, relapse within 3–6 months of ceasing maintenance therapy is experienced for more than half the patients, for whom indefinite treatment is required. Objectives: To explore the feasibility of trial design examining a prophylaxis treatment to prevent recurrent vulvovaginal candidiasis symptomatic episodes and reduce adverse effects. Study Design: A double-blinded randomized controlled feasibility trial was conducted in Australia. Women with recurrent vulvovaginal candidiasis were enrolled. Methods: An intravaginal prophylaxis application of lactic acid and acetic acid (Intravaginal Combination Therapy of Acetic and Lactic Acid) was compared with placebo. Primary outcomes comprised recruitment and retention, compliance to study medications and study assessments. Secondary outcomes included the reduction of symptomatic recurrence over the trial period and the acceptability, satisfaction, safety and tolerability of the intervention. The feasibility of quality-of-life measures was also explored. Results: Fifteen participants were enrolled and randomized (active = 9, placebo = 6). Consent rate was 23.4%. Eight participants were lost to follow-up (active = 5, placebo = 3). Forty-seven per cent of participants (n = 7) were 100% compliant with the intervention, six of which completed the trial with good assessment compliance. The blinding process was effective. The study demonstrated a reduction in relapse in both active and placebo groups with only four participants across both groups reporting symptomatic episodes while enrolled. The intervention demonstrated good tolerability. Quality-of-life data showed minimal variance with a high quality-of-life measure. Conclusion: This trial assesses the feasibility of conducting a large-scale study exploring the efficacy of the Intravaginal Combination Therapy of Acetic and Lactic Acid intravaginal intervention and hints on the importance of psychological support through appropriate disease-specific communication and clinical attention. Consideration of the reported recruitment challenges, the inclusion of suitable quality-of-life measures and digital data collection is warranted for adaptation to a fully powered trial. [ABSTRACT FROM AUTHOR]

Background: Fetal inflammatory response mediated by the influx of immune cells and activation of pro-inflammatory transcription factor NF-κB in feto-maternal uterine tissues is the major determinant of infection-associated preterm birth (PTB, live births < 37 weeks of gestation). Objective: To reduce the incidence of PTB by minimizing inflammation, extracellular vesicles (EVs) were electroporetically engineered to contain anti-inflammatory cytokine interleukin (IL)-10 (eIL-10), and their efficacy was tested in an ascending model of infection (vaginal administration of E. coli) induced PTB in mouse models. Study design: EVs (size: 30-170 nm) derived from HEK293T cells were electroporated with recombinant IL-10 at 500 volts and 125 Ω, and 6 pulses to generate eIL-10. eIL-10 structural characters (electron microscopy, nanoparticle tracking analysis, ExoView [size and cargo content] and functional properties (co-treatment of macrophage cells with LPS and eIL-10) were assessed. To test efficacy, CD1 mice were vaginally inoculated with E. coli (1010CFU) and subsequently treated with either PBS, eIL-10 (500ng) or Gentamicin (10mg/kg) or a combination of eIL-10+gentamicin. Fetal inflammatory response in maternal and fetal tissues after the infection or treatment were conducted by suspension Cytometer Time of Flight (CyTOF) using a transgenic mouse model that express red fluorescent TdTomato (mT+) in fetal cells. Results: Engineered EVs were structurally and functionally stable and showed reduced proinflammatory cytokine production from LPS challenged macrophage cells in vitro. Maternal administration of eIL-10 (10 µg/kg body weight) crossed feto-maternal barriers to delay E. coli-induced PTB to deliver live pups at term. Delay in PTB was associated with reduced feto-maternal uterine inflammation (immune cell infiltration and histologic chorioamnionitis, NF-κB activation, and proinflammatory cytokine production). Conclusions: eIL-10 administration was safe, stable, specific, delayed PTB by over 72 hrs and delivered live pups. The delivery of drugs using EVs overcomes the limitations of in-utero fetal interventions. Protecting IL-10 in EVs eliminates the need for the amniotic administration of recombinant IL-10 for its efficacy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. Methods: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). Results: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. Conclusion: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. Trial registration: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139). [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the efficacy and safety of evening primrose oil (EPO) for cervical ripening before gynecologic procedures and compare it to misoprostol. In this study, 40 hysteroscopy and dilation and curettage candidates were enrolled. Patients were randomly assigned to receive either 2000 mg of vaginal EPO (n = 20) or 200 μg of vaginal misoprostol (n = 20) 2 hours before the expected procedure. The measured outcomes were the size of the Hegar dilator that passed through the cervix effortlessly, uterine cervicovaginal complications, and drug‐related side effects. The two groups were not significantly different in age, number of gravity, parity, type of delivery, and menopausal status (P >.05). The mean ± SD size of the first dilator was 5.25 ± 1.55 in the misoprostol group and 7.30 ± 1.08 in the EPO group (P <.001). The pain complaint in the EPO group was significantly lower (P =.027), but the two groups were not significantly different in terms of other complications. No cases of uterine or cervical rupture were seen in either group. The present study showed that 2000 mg of vaginal EPO was significantly more effective for cervical ripening than 200 μg of vaginal misoprostol before gynecological surgery. Therefore, it is recommended to use EPO as an alternative to misoprostol. [ABSTRACT FROM AUTHOR]

Background: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). Methods: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. Results: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. Conclusions: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration. [ABSTRACT FROM AUTHOR]

Simple Summary: Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. Although in the case of low-grade lesions the conventional approach is watchful waiting, some infections may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. In this context, Papilocare® is a vaginal gel that combines components with moisturizing, tissue regeneration, and microbiota-balancing properties with ingredients that have positive effects on HPV-dependent cervical lesions and HPV clearance. According to the results obtained in this observational study with real-world data, most participants repaired their cervical lesions and cleared HPV through Papilocare® treatment, with a good treatment tolerability, adherence, and satisfaction rates, regardless of being infected with high-risk HPV, age over 40 years or both of them. Data reported in this study strengthen the role of the vaginal gel Papilocare® as a complementary action to the simple watchful waiting approach in HPV-related low-grade cervical lesions management. Human papillomavirus (HPV) is responsible for virtually all cervical cancers in women. HPV infection and persistency may lead to different-grade squamous intraepithelial lesions that can result in high-grade lesions and cancer. The objective was to prospectively evaluate the results of using a Coriolus-versicolor-based vaginal gel (Papilocare®) on HPV-dependent low-grade cervical lesion repair in a real-life scenario. HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). A 6-month second treatment cycle was prescribed when needed. Repair of the cervical low-grade lesions through cytology and colposcopy, HPV clearance, and level of satisfaction, and tolerability were evaluated. In total, 192 and 201 patients accounted for the total and safety analyses, respectively, and 77.1% repaired cervical lesions at 6 or 12 months (76.0% for high-risk HPV). Additionally, 71.6% achieved HPV clearance throughout the study's duration (70.6% for high-risk HPV). Satisfaction level was rated 7.9 and 7.5 out of 10 at 6 and 12 months, respectively. Only three mild–moderate product-related adverse events were reported, and all of them were resolved by the end of the study. In our study, we observed higher regression rates of low-grade cervical lesions in women treated with Papilocare® vaginal gel than spontaneous regression rates reported in the literature. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is the most common fungal infection in the vaginal mucosa and vulva caused by Candida albicans. C. albicans cell walls recognized as PAMPs by PRR then activate the innate and adaptive immune responses. The components of the innate immune response which has an important role against C. albicans during the acute phase are neutrophils and macrophages which produce proinflammatory cytokines such as TNF-α and IL-6. Probiotic Lactobacillus plantarum is an alternative strategy to treat VVC. Identification of the efficacy of the probiotic administration route determines the level of effectiveness of probiotics used as a supportive therapy in cases of VVC. This study aims to assess the decrease in TNF-α and IL-6 serum levels after administration of L. plantarum in vivo model study with a posttest randomized experimental group design. Group intervention was divided into 8 groups i.e. Negative Control (NC), Positive Control (PC), P1, P2, P3, P4, P5, P6. L. plantarum was administered orally and intravaginally with three concentration variants 2.25x1010, 4.5x1010, and 9x1010 CFU/ml. The statistical analysis used was ANOVA to measure the significant difference between TNF-α and IL-6 serum levels after the administration of L. plantarum. The results showed a significant decrease in both TNF-α (p=0.000<0.05) and IL-6 (p=0.000<0.05). Based on Post Hoc Tukey HSD there are P2, P3 and P6 groups that have significantly decreased levels of TNF-α. In addition, P2, P3, P5 and P6 groups also have significantly decreased levels of IL-6. Following to identification the association decrease of TNF-α and IL-6 due to L. plantarum using Correlation Pearson, the result was -0.836 and -0.685. From the results of the statistical analysis, it can be concluded that both oral and intravaginal administration of the probiotic L. plantarum has the same rate of effectivity to decrease proinflammatory cytokines in cases of VVC. [ABSTRACT FROM AUTHOR]

Objective The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth. Study Design We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group). Results The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23–4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58–2.16) Conclusion Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP. Key Points Previous studies have been underpowered to detect potential association between progesterone and ICP. Vaginal progesterone was significantly associated with ICP. Intramuscular 17α-hydroxyprogesterone was not associated with ICP. [ABSTRACT FROM AUTHOR]

• Inclusion of women from two clinics enhance the transferability of the results. • The majority of women are positive towards the subcutaneous administration. • The subcutaneous administration does not meet all expectations. • Some women prefer the vaginal administration of progesterone. • Several women are interested in being included in the decision-making. The hormones used in fertility treatment come in various forms. Progesterone used for luteal phase support is often administered vaginally as either suppositories, tablets or gel. However, in Denmark the administration of progesterone as a subcutaneous injection has newly been introduced. The aim of the study was to explore patient attitudes towards and satisfaction with subcutaneous injection of progesterone versus vaginal administration of progesterone in Assisted Reproductive Technology (ART) treatments. A qualitative study with online and face to face interviews with a total of 19 women undergoing an ART treatment. Only women with at least one previous blastocyst transfer using vaginal progesterone or subcutaneous progesterone could be recruited. All participants were included from either the Fertility Clinic at Copenhagen University Hospital – Herlev and Gentofte or from the Fertility Unit at Aalborg University Hospital. The analysis resulted in four themes: (1) medication, (2) everyday life, (3) bodily experiences and (4) infertility or hope. Most informants highlighted the administration of subcutaneous progesterone only once a day and avoidance of the vaginal discharge as clear advantages. Reasons for preferring the vaginal administration were inconvenience of bringing the subcutaneous medication along and resistance to inject oneself. The findings of this study suggest that the satisfaction with the subcutaneous progesterone is generally positive. However, valuable thoughts have given insights into possible areas, which could be improved. Further, that some women prefer vaginal progesterone. The results show that the women are interested in being included in the decision-making when choosing the administration form of progesterone. [ABSTRACT FROM AUTHOR]

Background: Misoprostol is the choice drug for inducing an abortion with intrauterine fetal death, but it has several side effects that increase with accumulating the dose received. Induction abortion with cheap and non-invasive methods with minimal complications is essential. This study aimed to compare the effect vaginal misoprostol plus vaginal evening primrose oil capsule with vaginal misoprostol alone on the consequences of abortion in pregnant women with intrauterine fetal death at 12–20 weeks of pregnancy. Methods: This study is a randomized, triple-blind clinical trial with two parallel groups at a ratio of 1:1. We randomized 82 women with indications of termination of pregnancy due to intrauterine fetal death into two groups. The experimental group (n = 42) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil capsule intravaginal. The control group (n = 40) received 200 mcg of misoprostol tablet with 1000 mg evening primrose oil placebo capsule intravaginal. Both groups received the drugs every 4 h for up to five doses. The primary outcome was the mean induction-to-fetal expulsion interval. Secondary outcomes were the mean dose of misoprostol, the highest pain intensity in the induction-to-fetal expulsion interval, the frequency of participants requiring blood transfusion, curettage, and the frequency of side effects of misoprostol or evening primrose oil. Pain intensity was measured through the Visual Analog Scale. Results: The mean age of the experimental group was 32.30 ± 6.19 years, and the control group was 30.27 ± 7.68 years. The mean gestational age of the experimental group was 15.29 ± 2.26 weeks, and the control group was 15.10 ± 1.89 weeks. The mean induction-to-fetal expulsion interval in the experimental group (3.12 ± 2.17 h) was significantly lower than that in the control group (8.40 ± 4.1 h) (p < 0.001). The mean dose of misoprostol received in the experimental group (271.42 ± 115.39 mcg) was significantly lower than that in the control group (520 ± 201.53 mcg) (p < 0.001). Also, the mean pain intensity in the experimental group (5.02 ± 0.60) was significantly lower than that in the control group (8.65 ± 1.001) (p < 0.001). The two groups were not significantly different in the frequency of blood transfusion requirements, analgesia and drug side effects. The need for curettage in the experimental group (4.8%) was significantly lower than that in the control group (47.5%) (p < 0.001). Conclusions: Vaginal administration of evening primrose oil with misoprostol reduced duration of time of fetal expulsion, pain intensity, mean dose of misoprostol received, and the need for curettage in participants. Therefore, we suggest this method for induced abortion in women with intrauterine fetal death. Trial registration: IRCT20181207041873N3. Dated 16/2/2021 prospectively registered https://en.irct.ir/user/trial/53681/view. [ABSTRACT FROM AUTHOR]

Research question: Does a frozen-embryo transfer in an artificially-prepared endometrium (FET-HRT) cycle yield similar clinical pregnancy rate with 7 days of oestrogen priming compared to 14 days? Design: This is a single-centre, randomized, controlled, open-label pilot study. All FET-HRT cycles were performed in a tertiary centre between October 2018 and January 2021. Overall, 160 patients were randomized, with a 1:1 allocation, into two groups of 80 patients each: group A (7 days of E2 prior to P4 supplementation) and group B (14 days of E2 prior to P4 supplementation). Both groups received single blastocyst stage embryos on the 6th day of vaginal P4 administration. The primary outcome was the feasibility of such strategy assessed as clinical pregnancy rate, secondary outcomes were biochemical pregnancy rate, miscarriage rate, live birth rate and serum hormone levels on the day of FET. Chemical pregnancy was assessed by an hCG blood test 12 days after FET and clinical pregnancy was confirmed by transvaginal ultrasound at 7 weeks. Results: The analysis included 160 patients who were randomly assigned to either group A or group B on the seventh day of their FET-HRT cycle if the measured endometrial thickness was above 6.5 mm. Following screening failures and of drop-outs, 144 patients were finally included both in group A (75 patients) or group B (69 patients). Demographic characteristics for both groups were comparable. The biochemical pregnancy rate was 42.5% and 48.8% for group A and group B, respectively (p 0.526). Regarding the clinical pregnancy rate at 7 weeks, no statistical difference was observed (36.3% vs 46.3% for group A and group B, respectively, p = 0.261). The secondary outcomes of the study (biochemical pregnancy, miscarriage, and live birth rate) were comparable between the two groups for IIT analysis, as well as the P4 values on the day of FET. Conclusions: In a frozen embryo transfer cycle, performed with artificial preparation of the endometrium, 7 versus 14 days of oestrogen priming are comparable, in terms of clinical pregnancy rate; the advantages of a seven-day protocol include the shorter time to pregnancy, reduced exposure to oestrogens, and more flexibility of scheduling and programming, and less probability to recruit a follicle and have a spontaneous LH surge. It is important to keep in mind that this study was designed as a pilot trial with a limited study population as such it was underpowered to determine the superiority of an intervention over another; larger-scale RCTs are warranted to confirm our preliminary results. Trial registration: Clinical trial number: NCT03930706. [ABSTRACT FROM AUTHOR]