Comparison of the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter in term nulliparous women with borderline oligohydramnios / 中华医学杂志(英文版)

BACKGROUNDS@#At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios.@*METHODS@#We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups.@*RESULTS@#The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8%, [11/141] P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50).@*CONCLUSIONS@#Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.

Intravaginal progesterone device (1. 9g) and estradiol benzoate for follicular control in the mare during spring and summer / [Implante intravaginal de progesterona (1, 9g) e benzoato de estradiol no controle folicular de éguas durante a primavera e o verão]

The objective of this study was to evaluate follicular growth and ovulatory rates in mares treated with an intravaginal progesterone device (P4) during the 10-day period, associated with the use of estradiol benzoate (EB). The results were compared during the transition period (ET) in the spring and the breeding season in the summer (ER). The variables were submitted to ANOVA (Tukey's test), considering P<0.05. No ovulation occurred during the permanence of the P4 implant in both experimental periods. The ovulatory rate in the ER was 100% (n = 8) and in the ET 62.5% (n = 5; P = 0.0547). Significant differences were observed (<0.001), in both periods, comparing follicular growth rates during the permanence of P4 device (ER: 1.33 ± 0.89mm/d; ET: 1.00 ± 0.81mm/d) to the period without P4 (ER: 3.63 ± 1.33 mm/d; ET: 3.31 ± 1.66 mm/d). The present study demonstrated applicability and efficiency of a hormonal protocol using P4 intravaginal device and EB for follicular control in mares, both during ET and ER.

O objetivo deste trabalho foi avaliar a taxa de crescimento folicular e a taxa ovulatória em éguas tratadas com dispositivo intravaginal de progesterona (P4) durante o período de 10 dias, associado à utilização de benzoato de estradiol (BE). Os resultados foram comparados durante o período de transição (ET) da primavera com a época de reprodução no verão (ER). As variáveis foram submetidas à ANOVA (teste de Tukey), considerando-se P<0,05. Nenhuma ovulação ocorreu durante a permanência do dispositivo de P4 em ambos os períodos experimentais. A taxa ovulatória na ER foi de 100% (n = 8) e na ET, de 62,5% (n=5; P=0,0547). Diferença significativas (<0,001) foram observadas, em ambos os períodos experimentais, comparando as taxas de crescimento folicular durante a permanência da P4 (ER: 1,33 ± 0,89mm/d; ET: 1,00 ± 0,81mm/d) com o período sem P4 (ER: 3,63 ± 1,33mm/d; ET: 3,31 ± 1,66mm/d). O presente estudo demonstrou aplicabilidade e eficiência do protocolo hormonal utilizando dispositivo intravaginal de P4 e BE para controle folicular de éguas, tanto na ET quanto na ER.

Cervical pessary plus progesterone for twin pregnancy with short cervix compared to unselected and non-treated twin pregnancy: a historical equivalence cohort study (EPM twin pessary study) / Pessário cervical associado a progesterona em gestações gemelares com colo curto comparado a gestações gemelares não selecionadas e não tratadas: estudo de coorte histórica de equivalência (Estudo de Pessário em Gêmeos EPM)

Abstract Objective The present study aims to determine if the use of cervical pessary plus progesterone in short-cervix (≤ 25 mm) dichorionic-diamniotic (DC-DA) twin pregnancies is equivalent to the rate of preterm births (PBs) with no intervention in unselected DC-DA twin pregnancies. Methods A historical cohort study was performed between 2010 and 2018, including a total of 57 pregnant women with DC-DA twin pregnancies. The women admitted from 2010 to 2012 (n = 32) received no treatment, and were not selected by cervical length (Non-Treated group, NTG), whereas those admitted from 2013 to 2018 (n = 25), were routinely submitted to cervical pessary plus progesterone after the diagnosis of short cervix from the 18th to the 27th weeks of gestation (Pessary-Progesterone group, PPG). The primary outcome analyzed was the rate of PBs before 34 weeks. Results There were no statistical differences between the NTG and the PPG regarding PB < 34 weeks (18.8%; versus 40.0%; respectively; p = 0.07) and the mean birthweight of the smallest twin (2,037 ± 425 g versus 2,195 ± 665 g; p = 0.327). The Kaplan-Meyer Survival analysis was performed, and there were no differences between the groups before 31.5 weeks. Logistic regression showed that a previous PB (< 37 weeks) presented an odds ratio (OR) of 15.951 (95%; confidence interval [95%;CI]: 1.294-196.557; p = 0.031*) for PB < 34 weeks in the PPG. Conclusion In DC-DA twin pregnancies with a short cervix, (which means a higher risk of PB), the treatment with cervical pessary plus progesterone could be considered equivalent in several aspects related to PB in the NTG, despite the big difference between these groups.

Resumo Objetivo Este estudo tem como objetivo determinar se o uso de pessário cervical associado a progesterona em gestações de gêmeos dicoriônicos-diamnióticos (DC-DAs) com colo do útero curto (≤ 25 mm) apresenta taxa de parto prematuro (PP) equivalente à de gestações gemelares DC-DA sem nenhuma intervenção/não selecionadas. Métodos Um estudo de coorte histórica foi realizado entre 2010 e 2018, incluindo um total de 57 mulheres grávidas com gestações gemelares DC-DA. As mulheres admitidas de 2010 a 2012 (n = 32) não receberam tratamento, e não foram selecionadas pelo comprimento cervical (grupo Não Tratado, GNT), enquanto as admitidas de 2013 a 2018 (n = 25) receberam pessário cervical rotineiramente associado a progesterona após o diagnóstico de colo curto entre a 18a e a 27ª semanas de gestação (grupo Pessário-Progesterona, GPP). O desfecho primário analisado foi a taxa de PP antes de 34 semanas. Resultados Não houve diferenças estatísticas entre o GNT e o GPP em relação ao PP < 34 semanas (respectivamente, 18,8%; versus 40,0%;; p = 0,07) e ao peso médio ao nascer do gêmeo menor (2.037 ± 425 g versus 2.195 ± 665 g; p = 0,327). A análise de Kaplan-Meyer foi realizada, e não houve diferenças entre os grupos antes de 31,5 semanas. A regressão logística demonstrou que o nascimento prematuro anterior (< 37 semanas) apresentou razão de probabilidades (odds ratio, OR) de 15,951 (intervalo de confiança de 95%; [IC95%;]: 1,294-196,557; p = 0,031*) para o nascimento prematuro < 34 semanas no GPP. Conclusão Em gêmeos DC-DA com colo uterino curto (o que significa maior risco de nascimento prematuro), o tratamento com pessário cervical associado a progesterona pode ser considerado equivalente em diversos aspectos relacionados à prematuridade no GNT, apesar da grande diferença entre os grupos.

Avaliação metabólica de um dispositivo intravaginal polimérico para a administração de cálcio e magnésio em ruminantes / Metabolic evaluation of a polymer intravaginal device for the administration of calcium and magnesium in ruminants

O objetivo do estudo foi avaliar a disponibilidade de cálcio (Ca2+) a partir de duas formas farmacêuticas (oral e intravaginal) e o seu efeito sobre o metabolismo de ruminantes. O estudo foi realizado na fazenda experimental da Universidade Federal de Pelotas, foram estudadas 24 ovelhas lactantes, divididas de forma randomizada em 4 grupos: dispositivo tratamento (DT); dispositivo controle (DC); oral tratamento (OT); e oral controle (OC). Os animais tratados receberam formiato de cálcio e cloreto de magnésio, as avaliações foram realizadas após a administração dos tratamentos. Foi feita avaliação de cálcio total (CaT), magnésio (Mg), proteínas plasmáticas totais (PPT), aspartato aminotransferase (AST), gama glutamil transpeptidase (GGT), ureia, albumina e pH urinário, e realizado exame clínico em todos os animais. As concentrações séricas de CaT, CaI e Mg diferiram entre os grupos (P≤ 0,05), os animais dos grupos DT e DC, diferiram nas três avaliações, o grupo DT apresentou as maiores médias, sendo significativamente igual ao grupo OT. Não houve diferença nas concentrações séricas de PPT, AST, GGT, Albumina, Ureia e pH urinário. Conclui-se que a disponibilidade sanguínea de CaT, CaI e Mg é igual quando a administração de formiato de cálcio e magnésio é por via intravaginal ou por via oral, sem alterar outros parâmetros metabólicos avaliados.(AU)

The aim of the study was to evaluate the availability of calcium (Ca2+) from two pharmaceutical forms (oral and intravaginal) and its effect on the metabolism of ruminants. The study was carried out at the experimental farm of the Federal University of Pelotas. Twenty-four lactating ewes were randomly divided into 4 groups: treatment device (TD); control device (DC); oral treatment (OT); and oral control (OC). Treated animals received calcium formate and magnesium chloride, evaluations were performed after administration of the treatments. Total calcium (CaT), magnesium (Mg), total plasma proteins (PPT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), urea, albumin and urinary pH, and clinical examination were performed on all animals. Serum CaT, CaI and Mg levels differed between the groups (P≤ 0.05), the animals in the DT and DC groups differed in the three evaluations, the DT group had the highest mean values, being significantly equal to the OT group. There was no difference in the serum concentrations of PPT, AST, GGT, Albumin, Urea and urinary pH. In conclusion, the blood availability of CaT, CaI and Mg is the same when administration of calcium and magnesium formate is intravaginal or orally, without altering other metabolic parameters evaluated.(AU)

Revisión de la utilidad del uso de progesterona en aborto recurrente de causa no precisada / Review of the usefulness of the use of progesterone in recurrent abortion of unknown cause

Resumen Introducción El AR de causa no precisada es un problema de salud reproductiva que impacta importantemente a las parejas. En casi el 50% de los casos de AR no se encuentra una etiología clara, por lo que es necesario lograr encontrar estrategias de tratamiento que puedan ayudar a mejorar las probabilidades de lograr un embarazo de término. Objetivo analizar la bibliografía existente en cuanto a la utilidad de la progesterona para reducir tasa de aborto en las parejas con AR de causa no precisada en ciclos naturales Métodos: Revisión sistemática cualitativa respecto al uso de progesterona en casos de aborto recurrente de causa no precisada. Resultados Se encontraron 3 artículos. Todos usaron progesterona vaginal, 2 desde el inicio de la fase lútea con disminución de los abortos, uno no demostró este efecto con inicio más tardío de la intervención. Conclusiones Los estudios encontrados orientan a que el uso de progesterona vaginal podría ser de utilidad para disminuir abortos en pacientes con AR iniciando la suplementación al comienzo de la fase lútea.

Efecto de la frecuencia de aplicación de estrógenos locales sobre el grosor endometrial en mujeres posmenopáusicas / Effect of local estrogen application frequency on endometrial thickness in postmenopausal women

Resumen Introducción: Los estrógenos conjugados vía vaginal para aliviar la atrofia y sequedad vaginales pueden producir cambios endometriales. Objetivo: Conocer el efecto de la frecuencia de aplicación de estrógenos conjugados vía vaginal en el grosor endometrial en mujeres posmenopáusicas. Método: Se estudiaron 70 mujeres posmenopáusicas con sequedad vaginal que recibieron estrógenos conjugados en crema (0.625 mg/1 g) durante 12 semanas divididas de la siguiente manera según la frecuencia de aplicación: grupo 1, dos veces por semana (n = 35) y grupo 2, tres veces por semana (n = 35). Al inicio y final del tratamiento se determinó el valor estrogénico en la citología vaginal y se realizó ultrasonido endovaginal para medir el grosor endometrial. La comparación entre los grupos se realizó con U de Mann-Whitney y entre los valores pre y postratamiento con prueba de Wilcoxon. Resultados: De 70 mujeres reclutadas solo se estudiaron 38 mujeres, 19 en cada grupo, pareadas por valor estrogénico inicial. No se encontró diferencia entre los grupos, ni antes ni después del tratamiento, en el índice de maduración, valor estrogénico ni grosor endometrial. Conclusión: No hubo diferencias en el grosor endometrial entre las distintas frecuencias de aplicación de estrógenos conjugados en crema.

Abstract Introduction: Conjugated estrogens, when used by the vaginal route for the relief of vaginal dryness and atrophy, can produce endometrial changes. Objective: To know the effect of vaginal conjugated estrogens application frequency on endometrial thickness in postmenopausal women. Method: Seventy postmenopausal women with vaginal dryness who received conjugated estrogen cream (0.625 mg/1 g) for 12 weeks were studied. The women were divided according to application frequency as follows: group 1, twice-weekly (n = 35), and group 2, thrice-weekly (n = 35). At baseline and at end-of-treatment, vaginal cytology was examined to determine the estrogenic value, and an endovaginal ultrasound was performed to measure endometrial thickness. The comparison between groups was carried out with Mann Whitney's U-test, and the comparison between baseline and post-treatment values, with Wilcoxon's test. Results: Of 70 recruited women, only 38 were studied, 19 in each group, paired by baseline estrogenic value. No difference was found between groups, neither at baseline nor after treatment, in the maturation index, estrogenic value or endometrial thickness. Conclusion: There were no differences in endometrial thickness between the conjugate estrogen cream different application frequencies.

Use of human intravaginal tampon embedded with natural progesterone induces synchronous estrus in Santa Inês ewes / Uso de tampão intravaginal humano embebido com progesterona humana para indução e sincronização de estro em ovelhas Santa Inês

Este estudo avaliou a eficiência de três protocolos de indução de estro síncronizado em ovelhas da raça Santa Inês. Vinte e quatro ovelhas adultas foram equitativamente distribuídas em três grupos, de acordo com ordem de parto, peso corporal (kg) e escore da condição corporal. As ovelhas receberam implante vaginal de progesterona natural por seis dias mais 37,5µg de d-cloprostenol laterovulvar e 300UI de eCG i.m., 24 horas antes da remoção do dispositivo. Ovelhas controle receberam CIDR330mg de progesterona, e as demais receberam dispositivo absorvente intravaginal humano, tamanho mini, embebido com 200 (OB200) ou 400mg (OB400) de progesterona. Coletas de sangue foram feitas nos momentos D0 (antes da inserção dos dispositivos), D0+6h e diariamente, até um dia após retirada do dispositivo (D7). A progesterona (ng/mL) foi semelhante (P>0,05) em todos os tratamentos ao longo do período experimental, exceto no dia da remoção do dispositivo, quando as ovelhas controle (2,5±0,3) tiveram progesterona superior (P<0,05) às ovelhas OB200 (0,6±0,1) e OB400 (1,2±0,4). O percentual de animais em estro (100,0, 62,5 e 100,0%) foi semelhante (P>0,05) e o intervalo para o estro (46,3±3,9a, 26,4±4,5b e 31,2±5,8a,b) foi diferente (P<0,05) entre os animais dos grupos controle, OB200 e OB400, respectivamente. A taxa de concepção das ovelhas foi de 50,0% (4/8) para cada grupo (P>0,05). Dispositivos humanos e fonte de progesterona podem ser usados para induzir o estro sincronizado em ovelhas Santa Inês.(AU)

No es hora de abandonar el uso de terapias locales de hormonas vaginales / It is not time to abandon the use of local therapies of vaginal hormones

Los médicos que atienden a mujeres menopáusicas están familiarizados con el sín- drome genitourinario de la menopausia (SGM), anteriormente conocido como atrofia vulvova- ginal, una afección progresiva que afecta la función sexual y la calidad de vida. Aunque la SGM afecta hasta al 45% de las mujeres de mediana edad y mayores, la mayoría de las personas con esta afección no se diagnostican ni se tratan.1

Acute and chronic toxicity of 0.5% podophyllotoxin-loaded nanostructured lipid carriers to vaginal mucosa in rabbits and rats / 南方医科大学学报

OBJECTIVE@#To test the acute and chronic toxicity of topical application of 0.5% podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) to the vaginal mucosa.@*METHODS@#Twelve New Zealand rabbits were randomized into 3 groups and subjected to daily topical applications of normal saline (control group), 0.5% podophyllotoxin tincture (POD-T) or 0.5% POD-NLC on the vaginal mucosa for 10 consecutive days, and the pathological changes in the mucosa were graded using the Eckstein scoring system.The acute toxicity of POD-NLC was tested in 20 SD female rats, which received intravaginal administration of POD-NLC or vehicle for 3 times within 24 h; After 14 days of continuous observation, the rats were dissected for calculating the viscera coefficient.For testing the chronic toxicity of POD-NLC, 80 SD female rats were randomized into 4 groups and subjected to daily intravaginal administration of the vehicle or POD-NLC at low, moderate or high doses for 13 consecutive weeks.The rats were weighed once a week and at the end of the experiment, 2/3 of the rats from each group were sacrificed to collect blood samples, calculate the viscera coefficient, and examine the pathological changes in the liver.The remaining 1/3 rats were observed for another 2 weeks without further drug treatment and the same examinations were performed.@*RESULTS@#In the rabbits, 0.5% POD-NLC elicited only mild irritation while POD-T caused moderate irritation of the vaginal mucosa.In the acute toxicity test, the organ coefficients were comparable between the rats treated with the vehicle and POD-NLC (>0.05).Long-term intravaginal administration of POD-NLC did not produce significant changes in the behavior, activity, body weight, blood biochemical profiles or organ coefficient as compared with the vehicle control group (>0.05).@*CONCLUSIONS@#Intravaginal administration of 0.5% POD-NLC causes very mild irritation without obvious acute or chronic toxicity to the vaginal mucosa in rabbits and rats.

Medical Termination of Delayed Miscarriage: Four-Year Experience with an Outpatient Protocol / Terminação médica de gravidez inviável do 1° trimestre: quatro anos de experiência com um protocolo de tratamento em ambulatório

Abstract Purpose To evaluate the efficacy of an outpatient protocol with vaginal misoprostol to treat delayed miscarriage. Methods Retrospective analysis of prospectively collected data on women medically treated for missed abortion with an outpatient protocol. The inclusion criteria were: ultrasound-based diagnosis of missed abortion with less than 10 weeks; no heavy bleeding, infection, inflammatory bowel disease ormisoprostol allergy; nomore than 2 previous spontaneous abortions; the preference of the patient regarding the medical management. The protocol consisted of: 1) a single dose of 800 μg of misoprostol administered intravaginally at the emergency department, after which the patients were discharged home; 2) clinical and ultrasonographic evaluation 48 hours later - if the intrauterine gestational sac was still present, the application of 800 μg of vaginal misoprostol was repeated, and the patients were discharged home; 3) clinical and ultrasonography evaluation 7 days after the initiation of the protocol - if the intrauterine gestational sac was still present, surgical management was proposed. The protocol was introduced in January 2012. Every woman received oral analgesia and written general recommendations. We also gave them a paper form to be presented and filled out at each evaluation. Results Complete miscarriage with misoprostol occurred in 340 women (90.2%). Surgery was performed in 37 (9.8%) patients, representing the global failure rate of the protocol. Miscarriage was completed after the first misoprostol administration in 208 (55.2%) women, with a success rate after the second administration of 78.1% (132/169). The average age of the women with complete resolution using misoprostol was superior to the average age of those who required surgery (33.99 years versus 31.74 years; p = 0.031). Based on the ultrasonographic findings in the first evaluation, the women diagnosed with fetal loss achieved greater success rates compared with those diagnosed with empty sac (p = 0.049). Conclusions We conclude this is an effective and safe option in the majority of delayed miscarriage cases during the first trimester, reducing surgical procedures and their consequences.

Resumo Objetivo Avaliar a eficácia de um protocolo de tratamento médico da gravidez inviável do primeiro trimestre (GI1°T) com misoprostol vaginal em regime de ambulatório. Métodos Análise retrospectiva de dados colhidos prospectivamente de grávidas tratadas com misoprostol vaginal em ambulatório. Os critérios de inclusão foram: diagnóstico de GI1°T com < 10 semanas de gestação; ausência de hemorragia abundante, infeção, doença inflamatória intestinal ou alergia ao misoprostol; 2 abortamentos anteriores; e preferência da paciente por tratamento médico. O protocolo consiste em: dia 0-aplicação demisoprostol intravaginal (800μg) no Serviço de Urgência e alta para o domicílio; dia 2-se persistência de saco gestacional intrauterino, aplicação de segunda dose de misoprostol (800μg) e alta; Dia 7-se persistência de saco gestacional intrauterino, proposto esvaziamento uterino instrumentado. O protocolo foi implementado em janeiro de 2012. Todas as grávidas receberam analgesia oral e informação por escrito com recomendações gerais. Receberam ainda um formulário a ser preenchido em cada vinda à urgência. Resultados Das 377 mulheres incluídas, observou-se abortamento completo em 340 (90,2%). As restantes 37 (9,8%) necessitaram de tratamento cirúrgico - taxa de falência global do protocolo. Em 208 (55,2%), o sucesso foi observado ao fim da 1ª dose, com uma taxa de eficácia da 2ª dose de 78,1% (132/169). A idade média das mulheres com sucesso do tratamento médico foi superior à das mulheres sem sucesso do mesmo (33,99 versus 31,74 anos; p = 0,031). O sucesso do tratamento foi maior quando o diagnóstico ecográfico inicial era de um embrião sem vitalidade comparado com os casos de ovo anembrionado (p = 0.049). Conclusões Conclui-se que esta é uma opção de tratamento eficaz e segura na maioria das situações de GI1°T, evitando a necessidade de internamento e de intervenção cirúrgica.

Induction of Labor using Misoprostol in a Tertiary Hospital in the Southeast of Brazil / Indução de parto utilizando misoprostol em um hospital terciário no sudeste do Brasil

Abstract Purpose To assess cases of labor induction with vaginal 25-μg tablets of misoprostol and maternal outcomes in a tertiary hospital in southeastern Brazil. Methods This was a retrospective cohort study of 412 pregnant women with indication for labor induction. Labor induction was performed with vaginal 25-μg tablets ofmisoprostol in pregnant women with Bishop scores < 6. Stepwise regression analysis was used to identify the factors present at the beginning of induction that could be used as predictors of successful labor induction. Results A total of 69% of the pregnant women who underwent labor induction progressed to vaginal delivery, and 31% of the women progressed to cesarean section. One or two misoprostol tablets were used in 244 patients (59.2%). Of the 412 patients, 197 (47.8%) required oxytocin later on in the labor process, after induction with misoprostol. The stepwise regression analysis showed that only Bishop scores of 4 and 5 and previous vaginal delivery were independent factors with statistical significance in the prediction of successful vaginal labor induction (β = 0.23, p < 0.001, for a Bishop score of 4 and 5, and β = 0.22, p < 0.001, for previous vaginal delivery). Conclusion Higher Bishop scores and previous vaginal delivery were the best predictors of successful labor induction with vaginal 25-μg tablets of misoprostol.

Resumo Objetivo Avaliar os casos de indução do trabalho de parto com misoprostol 25 mcg por via vaginal e seus desfechos maternos em um hospital terciário do Sudeste do Brasil. Métodos Realizou-se um estudo retrospectivo de coorte com 412 gestantes com indicações para indução de trabalho de parto. A indução do trabalho de parto foi realizada com misoprostol 25 mcg vaginal em gestantes com índice de Bishop < 6. Realizou-se análise de regressão stepwise para identificar os fatores presentes ao início da indução que poderiam ser usados como prognosticadores do sucesso da indução do trabalho de parto. Resultados A indução de trabalho de parto determinou 69% de partos normais, sendo que 31% evoluíram para cesárea. Em relação ao número de comprimidos de misoprostol, 1 ou 2 comprimidos foram utilizados em 244 pacientes (59,2%). Das 412 pacientes, 197 (47,8%) necessitaramde ocitocina após a indução commisoprostol para dar continuidade ao trabalho de parto. Na análise de regressão stepwise, apenas a presença de índice de Bishop 4 e 5 e parto vaginal prévio foram fatores independentes com significância estatística na predição do sucesso da indução emobter parto vaginal (β = 0,23, p < 0,001, para índice de Bishop 4 e 5, e β = 0,22, p < 0,001, para parto vaginal prévio). Conclusão Maiores índices de Bishop e parto vaginal prévio são os maiores prognosticadores do sucesso de indução de trabalho de parto com misoprostol 25 mcg vaginal.

Ospemifene: A Novel Option for the Treatment of Vulvovaginal Atrophy

Ospemifene—a third-generation selective estrogen receptor modulator approved by the Food and Drug Administration in 2013—is an oral medication for the treatment of dyspareunia. In postmenopausal women with vulvovaginal atrophy, ospemifene significantly improves the structure and pH levels of the vagina, reducing dyspareunia. It is available as a 60-mg tablet; hence, women who may have had prior difficulty with vaginal administration or on-demand use of nonprescription lubricants and moisturizers would likely prefer this form of treatment. Preclinical studies demonstrated that ospemifene has an estrogen agonist action on the bone, reducing the cell proliferation of ductal carcinoma in an in situ model. Studies evaluating the safety of treatment for up to 52 weeks have shown that ospemifene is a safe medication with minimal impact on the endometrium. Further studies with larger number of subjects are necessary to better conclude its effects and long-term safety.

Serum β-hCG concentration is a predictive factor for successful early medical abortion with vaginal misoprostol within 24 hours

OBJECTIVE: To evaluate the predictive factors associated with the success of medical abortion by misoprostol monotherapy within 24 hours in the first trimester of pregnancy. METHODS: The records of 228 women with miscarriage up to 11 weeks of gestational age who underwent medical abortion by intravaginal misoprostol monotherapy were reviewed. Success of abortion was defined as complete expulsion of the conceptus without the need for surgical intervention. Outcomes of interest were success of abortion within 24 hours following administration of misoprostol. RESULTS: Among 222 women who continued the process of medical abortion for 24 hours, 209 (94.1%) had a successfully completed abortion. Multivariate logistic regression showed that serum β-human chorionic gonadotropin (β-hCG) above 40,000 mIU/mL is significantly associated with failed medical abortion within 24 hours (odds ratio [OR], 7.13; 95% confidence interval [CI], 1.60–37.32; P=0.011). The area under the receiver operating characteristic curve of β-hCG level associated with successful abortion within 24 hours was 0.705 (95% CI, 0.63–0.77; P=0.007). Previous vaginal delivery seems to be significantly associated with successful abortion within 24 hours on univariate analysis (P=0.037), but the association was lost in multivariate analysis. CONCLUSION: Misoprostol monotherapy has a high success rate for first trimester abortion. Women with serum β-hCG less than 40,000 mIU/mL are likely to achieve a successful abortion within 24 hours after intravaginal administration of misoprostol.

Comportamento de éguas após a inserção de dispositivo intravaginal impregnado com progesterona / Behavior of mares after insertion of intravaginal progesterone device / Comportamiento en yeguas después de la inserción del dispositivo intravaginal impregnado con progesterona

Considerando a escassez de estudos sobre o temperamento ou reatividade de equinos, objetivou-se com esse estudo avaliar o comportamento de éguas após a inserção do implante intravaginal de progesterona, para utilização em bovinos, por meio da observação de comportamentos individuais e coletivos. Para tanto, utilizou-se sete éguas que receberam dispositivo intravaginal impregnado com progesterona e agente luteolítico. Após a colocação dos implantes e soltura das éguas, se iniciou a observação (cinco observadores sem contato entre eles) de seus comportamentos até o tempo de 120 minutos, seguindo o modelo proposto por Heleski et al. (2002). Os resultados indicaram que durante os 120 minutos de observação todas as éguas demonstraram estar alertas, pelo menos em uma observação; que o ato de comer foi observado em todos os animais durante o período estudado e que o ato de urinar e defecar foram observados, em aproximadamente, 70 e 60%, respectivamente, dos comportamentos avaliados. Comportamentos prováveis da indicação de dor e/ou desconforto, como bater da cauda, mímica de urinar, eversão do clitóris e urinando foram observados até 65 minutos, sendo que os três primeiros cessaram aos 55 minutos. De todos os comportamentos analisados, nenhum deles foi visualizado após 65 minutos de observação. Concluiu-se que a inserção do dispositivo intravaginal impregnado com progesterona não afeta negativamente o comportamento de éguas, podendo ser utilizado sem comprometer o bem-estar desses animais.

Considering the scarcity of studies on the behavior or reactivity of horses, this study aimed to assess the behavior of mares after insertion of intravaginal progesterone implant for use in cattle, through the observation of individual and collective behavior. In order to do so, seven mares received intravaginal devices impregnated with progesterone and luteolitic agent. After the implant was placed, the mares were released, and their behavior was observed (five observers with no contact between them) for a period of 120 minutes, following the model proposed by Heleski et al. (2002). The results indicated that during the 120-minute period, all mares were alert, in at least one observation; that all animals ate during the study period, and urination and defecation were observed in approximately 70 and 60%, respectively, of the assessed behavior. Behaviors that were likely an indication of pain and/or discomfort, like hitting the tail, miming to urinate, eversion of the clitoris and urinating were observed in up to 65 minutes, with the first three symptoms ceasing after 55 minutes. None of the analyzed behaviors were viewed after 65 minutes of observation. It can be concluded that the insertion of the intravaginal device impregnated with progesterone does not adversely affect the behavior of mares, and therefore, it can be used without compromising the well-being of the animals.

Teniendo en cuenta la escasez de estudios sobre el temperamento o la reactividad de equinos, este estudio buscó evaluar el comportamiento de yeguas después de la inserción del implante de progesterona intravaginal, para su uso en ganado, a través de observación de conductas individuales y colectivas. Para ello, se utilizó siete yeguas que recibieron dispositivo intravaginal impregnado con progesterona y agente luteolítico. Después de los implantes y la liberación de las yeguas, comenzó la observación (cinco observadores sin contacto entre ellos) de sus comportamientos hasta el tiempo de 120 minutos, siguiendo el modelo propuesto por Heleski et al. (2002). Los resultados indicaron que durante los 120 minutos de observación todas las yeguas demostraron estar alertas, por lo menos en una observación; el acto de comer se observó en todos los animales durante el periodo de estudio y que el acto de la micción y la defecación, en aproximadamente, 70 y 60%, respectivamente, de los comportamientos evaluados. Comportamientos probables de indicación de dolor y/o malestar, como golpear la cola, la mímica de orinar, eversión del clítoris y orinando, observados hasta 65 minutos, siendo que los tres primeros cesaron después de 55 minutos. De todos los comportamientos analizados, ninguno de ellos se visualizó después de la observación de 65 minutos. Se concluyó que la inserción del dispositivo intravaginal impregnado con progesterona no afecta negativamente el comportamiento de yeguas, que puede ser utilizado sin comprometer el bienestar de esos animales.

Vaginal progesterone on the prevention of preterm birth and neonatal complications in high risk women: a randomized placebo-controlled double-blind study

Background: Preterm birth is the major cause of neonatal mortality and morbidity

Objective: The aim of this study was to evaluate the effect of prophylactic vaginal progesterone on decreasing preterm birth rate and neonatal complications in a high-risk population

Materials and Methods: A randomized, double-blind, placebo-controlled study was performed on 100 high-risk singleton pregnancies. Vaginal suppository progesterone [400 mg] or placebo was administered daily between 16-22 wks to 36 wks of gestation. Progesterone [n=50] and placebo [n=50] groups were compared for incidence of preterm delivery and neonatal complications

Results: The preterm birth rate was 52%. Preterm birth rate before the 37 wks of gestation [68% vs. 36%: RR=1.89, 95% CI: 1.25-2.86] and also before the 34 wks of gestation [42% vs. 18%: RR=2.33, 95% CI: 1.19-4.58] in placebo group was significantly higher than progesterone group. Our study also showed that the administration of vaginal progesterone was associated with a significant reduction in the risk of birth weight

Conclusion: Prophylactic vaginal progesterone reduced the rate of preterm delivery, the risk of a birth weight

The efficacy of evening primrose oil as a cervical ripening agent for gynecologic procedures: A single-blinded, randomized controlled trial / Philippine Journal of Obstetrics and Gynecology

BACKGROUND: Evening Primrose Oil (EPO) is one of the most commonly prescribed cervical ripening agents. Cervical ripening is the softening, effacement, and dilation of the cervix that occur prior to active labor, and is an intervention that is used for certain indications, such as postdates pregnancy. There are gynecologic cases wherein the cervix is closed and dilatation has not occurred making the procedure difficult. In studies, EPO works by softening and ripening the cervix in the pregnant woman. More likely it has the same effects in a non-pregnant patient with regards to softening and dilating the cervix during gynecologic procedures.METHODS: The study was conducted in a tertiary hospital. Patients scheduled for gynecologic procedures were randomly grouped under the control and study group. Both groups had an internal examination during admission. The study group, in addition, were given EPO 4 capsules intra-vaginally, 6 hours prior to the contemplated procedure. Cervical characteristics were assessed initially on admission and pre-proedure.Consistency were assessed using the Consistency Index (CI) and graded as firm=1, medium=2 and soft=3. Dilatation were assessed using the Dilatation Index (DI) and graded as closed=1, admits tip =2 , >1cm= 3. Pre-procedure, cervical characteristics and the CDI of both groups were assessed. Hegars dilators were used to assess the degree of dilatation, noting the diameter of dilator that can be introduced freely, and to what diameter the cervix can be maximally dilated.RESULTS: 80 patients were enrolled in the study; 39 patients were assigned in the control group and 38 patients were assigned in the study group (3 were excluded). In the study group, their DI improved by 36.2% (pre = 1.53+/-0.51 to post = 2.08+/-0.49) (pCONCLUSION: EPO 4 capsules punctured and administered intra-vaginally 6 hours prior to contemplated gynecologic procedure can promote cervical ripening as exhibited by the improvement of the CDI from initial assessment to pre-procedure assessment.

Intravaginal Misoprostol for Cervical Ripening and Labor Induction in Nulliparous Women: A Double-blinded, Prospective Randomized Controlled Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In China, no multicenter double-blinded prospective randomized controlled study on labor induction has been conducted till now. This study is to evaluate the efficacy and safety of intravaginal accurate 25-μg misoprostol tablets for cervical ripening and labor induction in term pregnancy in nulliparous women.</p><p><b>METHODS</b>This was a double-blinded, prospective randomized controlled study including nulliparous women from 6 university hospitals across China. Subjects were randomized into misoprostol or placebo group with the sample size ratio set to 7:2. Intravaginal 25-μg misoprostol or placebo was applied at an interval of 4 h (repeated up to 3 times) for labor induction. Primary outcome measures were the incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h. Safety assessments included the incidences of maternal morbidity and adverse fetal/neonatal outcomes.</p><p><b>RESULTS</b>A total of 173 women for misoprostol group and 49 women for placebo were analyzed. The incidence of cumulative Bishop score increases ≥3 within 12 h or vaginal delivery within 24 h was higher in the misoprostol group than in the placebo (64.2% vs. 22.5%, relative risk [RR]: 2.9, 95% confidence interval [CI]: 1.4-6.0). The incidence of onset of labor within 24 h was significantly higher in the misoprostol group than in the placebo group (48.0% vs. 18.4%, RR: 2.6, 95% CI: 1.2-5.7); and the induction-onset of labor interval was significantly shorter in the misoprostol group (P = 0.0003). However, there were no significant differences in the median process time of vaginal labor (6.4 vs. 6.8 h; P = 0.695), incidence (39.3% vs. 49.0%, RR: 0.8, 95% CI: 0.4-1.5) and indications (P = 0.683) of cesarean section deliveries, and frequencies of maternal, fetal/neonatal adverse events between the groups.</p><p><b>CONCLUSION</b>Intravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.</p>

Efectividad del tratamiento médico con misoprostol según dosis administrada en aborto retenido menor de 12 semanas / Effectiveness of medical treatment with misoprostol as abortion retained dose administered in less than 12 weeks

Antecedentes: El manejo terapéutico del aborto retenido consiste en evacuar la cavidad uterina espontáneamente o utilizando misoprostol previo al legrado quirúrgico. Objetivo: Evaluar la necesidad de dilatación mecánica post maduración cervical con misoprostol y la tasa de perforación uterina post legrado, utilizando diferentes dosis de misoprostol en pacientes con diagnóstico de aborto retenido menor a 12 semanas. Métodos: Se registraron datos demográficos y ginecológicos de una cohorte retrospectiva de pacientes con diagnóstico de aborto retenido menor a 12 semanas, entre enero de 2008 y diciembre de 2010. Se establecieron 3 grupos de trabajo según la dosis de misoprostol administrada vía vaginal, siendo de 100 (n=131), 200 (n=231) y 400 micrones (n=230), y se observaron las complicaciones asociadas al procedimiento. Resultados: La necesidad de dilatación mecánica fue significativamente mayor en el grupo que recibió 100 micrones de misoprostol al compararlo con el de 200 micrones y 400 micrones (p<0,01). No hubo diferencias estadísticamente significativas entre las que recibieron 200 versus 400 micrones de misoprostol. No hubo diferencias significativas respecto a perforación uterina. Conclusión: En el aborto retenido menor a 12 semanas, la necesidad de dilatación mecánica post maduración cervical, es menor si se utiliza 200 o 400 micrones de misoprostol, sin diferencias en la tasa de perforación uterina.

Background: The therapeutic management of missed abortion consists on evacuating the uterine cavity, spontaneously or by administration of misoprostol previous to curettage. Objectives: Evaluate the need of mechanical dilatation after cervical maturation with misoprostol and the rate of uterine perforation before curettage, using different doses of misoprostol in patients with diagnosis of missed abortion before 12 weeks. Methods: Demographic and gynecologic data were registered of a retrospective cohort of patients with the diagnosis of missed abortion before 12 weeks, between January 2008 and December 2010. Three groups were established according to the dose of misoprostol: 100 (n=131), 200 (n=231) and 400 microns (n=230). Complications associated to the procedure were observed. Results: The need of mechanical dilatation was significant higher for the group with 100 microns of misoprostol in comparison with 200 and 400 microns (p<0.001). There was no statistical significance among who received 200 versus 400 microns of misoprostol. No statistical significance was found for uterine perforation. Conclusion: In the missed abortion before 12 week, the need of mechanical dilatation is lower with 200 or 400 microns of misoprostol, without difference in uterine perforation rate.

Preparation and release mechanism of gestodene reservoir-type intravaginal rings / 药学学报

This study taking gestodene (GEST) as a model, investigated the factors affecting reservoir-type intravaginal ring (IVR)'s drug release. This paper reported a gestodene intravaginal ring of reservoir design, comprising a gestodene silicone elastomer core encased in a non-medicated silicone sheath, separately manufactured by reaction injection moulding at 80 degrees C and heating vulcanization at 130 degrees C is reported. The test investigated the factors affecting drug release through a single variable method, taking the drug release rates of 21 days as standards. When changing the thickness of the controlling sheath outside, the ratio of the first day of drug release and mean daily release (MDR), named the relatively burst effect, is closing to 1 with the thickness of controlling sheath increasing, while the 1.25 mm sheath corresponding to 1.04 controlled the burst release effectively; a positive correlation (r = 0.992 2) existed between the average drug release (Q/t) and drug loading (A) within a certain range. The C6-165 controlling sheath with high solubility of GEST is easier to achieve controlled release of the drug; GEST crystalline power is more effective to implement controlled release of drugs among difficent states of the drug. A 1/4 fractional segment core gives a relatively burst effect of 1.76, while the 1/1 and 1/2 are 1.93 and 1.87 separately, at the same drug loading, concluding that use of a fractional segment core would allow development of a suitable GEST reservoir IVR. In summary, GEST reservoir-type IVR could be adjusted by the thickness of controlling sheath, the loading of drug, the material properties of controlling sheath, the dispersion state of drug, the additive composition and structure of intravaginal ring, to control the drug release behavior and achieve the desired drug release rate.

Development of a liquid chromatography-tandem mass spectrometry method for determination of butoconazole nitrate in human plasma and its application to a pharmacokinetic study / 华中科技大学学报（医学）（英德文版）

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of butoconazole in human plasma. Human plasma samples of 0.2 μL were pretreated by a single step protein precipitation procedure and analyzed using a high performance liquid chromatography (HPLC) electrospray tandem mass spectrometer system. The compounds were eluted isocratically on an Inertsil ODS-SP column (100 mm×2.1 mm, 3 μm), ionized using a positive ion atmospheric pressure electrospray ionization source and analyzed using multiple reaction monitoring (MRM) mode. The ion transitions monitored were m/z 412.8→165.1 for butoconazole and m/z 453.4→230.3 for the internal standard. The chromatographic run time was 3.5 min per injection, with retention time of 2.47 min and 2.15 min for butoconazole and repaglinide, respectively. The method was validated to be linear over the range of 20 to 8000 pg/mL (r>0.999) by using a weighted (1/x(2)) quadratic regression. The mean recovery rate was more than 86.7%, and the intra- and inter-day precision of the quality control samples (QCs) was less than 8.3% and the accuracy ranged from 96.0% to 110.2%, which indicated that the quantitative method was reliable and accurate. The method is simple, rapid, and has been applied successfully to a pharmacokinetics study of butoconazole nitrate suppositories in healthy Chinese females.