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.
Administration, Intravaginal ; Catheters ; Dinoprostone/therapeutic use* ; Female ; Fetal Weight ; Humans ; Infant, Newborn ; Labor, Induced/methods* ; Nuchal Cord ; Oligohydramnios ; Oxytocics ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies

To evaluate the traits and rheological properties of thermosensitive in situ gel of Yihuang Decoction and its common gel for vaginal use, and predict the release behavior of Yihuang Decoction in situ gel in vitro. Poloxamer was used as thermosensitive material to prepare Yihuang Decoction vaginal in situ gel, and Yihuang Decoction common gel was prepared with carbopol. Then the differences of the two gels before and after diluting with vaginal fluid were compared. The rheological parameters of Yihuang Decoction in situ gel and its common gel were determined with Anton Paar MCR102 rheometer. In addition, berberine hydrochloride was selected as an index component to evaluate the in vitro release properties of Yihuang Decoction vaginal thermosensitive in situ gel. Yihuang Decoction vaginal thermosensitive in situ gel was Newtonian fluid under low-temperature conditions, which was yellow and transparent. After reaching the gelling temperature of 24.5 ℃, it became semi-solid, pseudoplastic fluid. The gelling temperature was predicted to be 37 ℃, and the phase transition time was 30 s after diluting with simulated vaginal fluid. However, the rheological properties of Yihuang Decoction common gel had no significant changes with temperature. Compared with in situ gel, the color of common gel was darker and more translucent. Besides, its mobility was stronger after diluting with simulated vaginal fluid. The in vitro release study showed that the kinetic behavior of berberine hydrochloride in Yihuang Decoction vaginal thermosensitive in situ gel was matched with the Higuchi equation. Through simulation of vaginal administration, physical properties and dynamic rheological parameters were used to intuitively and scientifically evaluate the two gels. Compared with the common gel, the thermosensitive in situ gel could quickly attached to the vaginal mucosa and release drug, and thus was more suitable for developing vaginal administration of Yihuang Decoction, which also provides references for studying new vaginal preparation of Yihuang Decoction.
Administration, Intravaginal ; Drugs, Chinese Herbal/chemistry* ; Female ; Gels/chemistry* ; Humans ; Poloxamer ; Rheology ; Temperature ; Viscosity

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.
Administration, Intravaginal ; Animals ; Female ; Liposomes ; Mucous Membrane ; drug effects ; Nanostructures ; toxicity ; Podophyllotoxin ; administration & dosage ; toxicity ; Rabbits ; Random Allocation ; Rats ; Vagina ; drug effects

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.
Administration, Intravaginal ; Atrophy* ; Carcinoma, Ductal ; Cell Proliferation ; Dyspareunia ; Endometrium ; Estrogens ; Female ; Humans ; Hydrogen-Ion Concentration ; Lubricants ; Menopause ; Selective Estrogen Receptor Modulators ; Tamoxifen ; United States Food and Drug Administration ; Vagina ; Vulva

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.
Abortion, Spontaneous ; Administration, Intravaginal ; Chorionic Gonadotropin ; Female ; Gestational Age ; Humans ; Logistic Models ; Misoprostol* ; Multivariate Analysis ; Pregnancy ; Pregnancy Trimester, First ; ROC Curve

BACKGROUNDIn 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.

METHODSThis 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.

RESULTSA 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.

CONCLUSIONIntravaginal misoprostol 25 μg every 4 h is efficacious and safe in labor induction and cervical ripening.

Administration, Intravaginal ; Adult ; Cervical Ripening ; drug effects ; Double-Blind Method ; Female ; Humans ; Labor, Induced ; methods ; Misoprostol ; administration & dosage ; therapeutic use ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Third ; Young Adult

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) (p<0.001), CI increased by 115.9% (pre=1.16+/-0.37 to post = 2.50+/-0.65) (p<0.001), and their CDI changed by 70.6% (pre=2.68+/-0.74 to post = 4.58+/-0.95) (p<0.001). The changes of scores in all the cervical parameters in the study group were statistically significant.
CONCLUSION: 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.

Human ; Female ; Pregnancy ; Cervical Ripening ; Cervix Uteri ; Efamol ; Dilatation ; Capsules ; Gamma-linolenic Acid ; Linoleic Acids ; Plant Oils ; Administration, Intravaginal

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.
Administration, Intravaginal ; Contraceptive Agents, Female ; administration & dosage ; Contraceptive Devices, Female ; Delayed-Action Preparations ; Drug Delivery Systems ; methods ; Norpregnenes ; administration & dosage ; chemistry ; Silicone Elastomers ; chemistry ; Solubility

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.
Administration, Intravaginal ; Adult ; Antifungal Agents ; blood ; chemistry ; pharmacokinetics ; Calibration ; Chromatography, Liquid ; methods ; Female ; Humans ; Imidazoles ; administration & dosage ; blood ; pharmacokinetics ; Middle Aged ; Molecular Structure ; Reproducibility of Results ; Tandem Mass Spectrometry ; methods ; Time Factors ; Young Adult

To compare an injectable progesterone (MAD-4) with an intravaginal device (IPD), and natural O17 with synthetic oestradiol (OB) in a synchronisation protocol, 51 cows were divided into four groups. Each group was treated with one of the two sources of progesterone and one of the two oestradiol formulations. Oestrus behaviour, follicle diameter, and pregnancy rates were evaluated. Oestrus behaviour (p = 0.902), numbers of cows in oestrus (p = 0.917), follicle diameter (p = 0.416), and pregnancy rates (p = 0.873) were similar among the four groups. More cows in the group treated with the IPD and OB scored > 200 oestrus behaviour points compared to the other groups (p = 0.038). A longer interval between the end of treatment and oestrus was observed among cows treated with MAD-4 than cows given the IPD (p = 0.030), but no differences were found between animals receiving the two oestradiol formulations (OB and O17). While the use of MAD-4 requires further testing, similar responses to natural oestradiol observed in the present study could allow the use of this formulation in reproductive protocols because it is not associated with the potential human health risks of OB.
Administration, Intravaginal ; Animals ; Cattle ; Estradiol/administration & dosage/*analogs & derivatives/*pharmacology ; Estrus/drug effects ; Estrus Synchronization/*methods ; Female ; Injections, Subcutaneous/veterinary ; Ovarian Follicle/drug effects ; Postpartum Period/drug effects ; Pregnancy ; Pregnancy Rate ; Progesterone/administration & dosage/*pharmacology ; Reproduction/drug effects