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Anti-nidatory effect of vaginally administered fumagillin in the rhesus monkey.

In the present study, fumagillin, which is an antibiotic with potent angiostatic activity secreted from Aspergillus fumigatus was administered intravaginally during peri-implantation stage in the rhesus monkey and its effects on ovarian function, blastocyst implantation and pregnancy outcome in the rhesus monkey were investigated. Female monkeys (n = 18) showing normal menstrual cycles were vaginally inserted with tampons containing fumagillin (0 mg/animal in group 1; 1 mg/animal in group 2; 2 mg/animal in group 3; 4 mg/animal in group 4) on cycle day 20 of the mated treatment cycle, and these were removed on day 26 of the treatment cycle. Pregnancy was found to occur in animals treated with 1 mg and 2 mg fumagillin. However, animals treated with 4 mg fumagillin remained non-pregnant along with decreased (p <0.001) concentration of progesterone in circulation during the luteal period compared with that in normal, non-mated, ovulatory cycle.

Administration, Intravaginal↗

A comparison of the effects of progesterone sponges and ear implants, PGF2alpha, and their combination on efficacy of estrus synchronization and fertility of Mashona goat does.

Efficacy of estrus synchronization and fertility after synchronization of 60 multiparous Mashona goat does using intravaginal progesterone (P4) sponges (Group 1), norgestomet ear implants (Group 2), cloprostenol (Group 3), or a combination of P4 sponges and cloprostenol (Group 4) was compared with untreated does (Group 5). At the end of treatments, all does were mated to intact fertile bucks for 21 d. The number of does bred within 11 to 96 h was significantly higher (P < 0.05) in the treated groups than the untreated control, with rates of 80, 80, 64, 67 and 30% for Groups 1 to 5, respectively. There were no differences (P > 0.05) among treated does. Kidding rates ranged from 64 to 83% but were not different (P > 0.05) between groups. Prolificacy and overall fecundity were similar (P > 0.05) among the groups. The results indicate that all 4 treatment methods were effective in synchronizing estrus and that none of the methods affected overall fertility of the does.

Administration, Intravaginal↗

Immunization for protection of the reproductive tract: a review.

PROBLEM: Local application of non-replicating antigens to the female reproductive tract is ineffective in stimulating the common mucosal immune system, and induces only weak genital antibody responses. Studies of immune responses to genital infections such as gonorrhea also support the concept that, lacking mucosal immune inductive sites, the reproductive tract is ill-equipped to mount effective immune responses. METHOD OF STUDY: Intranasal (i.n.) and intravaginal (i.vag.) routes of immunization of mice with a protein antigen coupled to cholera toxin (CT) B subunit, or genetically engineered as chimeric proteins with the A2/B sunbunits of CT or type II heat-labile enterotoxin, were compared for their ability to induce specific antibody responses in vaginal fluids, saliva, and serum. RESULTS: Mice immunized i.n. developed substantially stronger vaginal immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum IgG and IgA antibodies, than those immunized i.vag. which also failed to develop salivary antibodies. Vaginal antibody responses induced i.n. persisted for at least 1 year, and were recallable by booster immunization after a prolonged period. CONCLUSIONS: Such alternative strategies for inducing potent genital antibody responses offer the prospect of prophylactic immunization against genital infections. Further studies are required to evaluate their applicability to humans, and to comprehend the cellular and molecular mechanisms involved in delivering effective immune responses to the reproductive tracts.

Administration, Intranasal↗

Evaluation of two self-care treatments for prevention of vaginal candidiasis in women with HIV.

Vaginal candidiasis (VC) is a common concern for women living with HIV infection. The authors evaluated the effectiveness of two self-care approaches to prophylaxis of VC among HIV-infected women, weekly intravaginal application of Lactobacillus acidophilus or weekly intravaginal application of clotrimazole tablets, in a randomized, double-blind, placebo-controlled trial. VC was defined as a vaginal swab positive for Candida species in the presence of signs/symptoms of vaginitis and the absence of a diagnosis of Trichomonas vaginalis or bacterial vaginosis. Thirty-four episodes of VC occurred among 164 women followed for a median of 21 months. The relative risk of experiencing an episode of VC was 0.4 (95% CI = 0.2, 0.9) in the clotrimazole arm and 0.5 (95% CI = 0.2, 1.1) in the Lactobacillus acidophilus arm. The estimated median time to first episode VC was longer for clotrimazole (p = .03, log rank test) and Lactobacillus acidophilus (p = .09, log rank test) compared with placebo. Vaginal yeast infections can be prevented with local therapy. Education about self-care for prophylaxis of VC should be offered to HIV-infected women.

Administration, Intravaginal↗

Randomized trial in multiparous patients: investigating a single vs. two-dose regimen of intravaginal misoprostol for induction of labor.

BACKGROUND: Multiparous patients have a higher risk of hyperstimulation and uterine rupture than nulliparous patients. The minimum possible dose of uterotonic drug should be used in induction of labor for multiparous patients to avoid excessive uterine activity, which could increase both maternal and fetal risks. METHODS: One hundred and four women were randomized to either a single dose of 50 micro g of intravaginal misoprostol in 24 h, or two consecutive doses of intravaginal 50 micro g misoprostol 6 h apart. RESULTS: The mean induction to delivery interval (789 min [95% CI: 637-941] vs. 576 min [95% CI: 484-667], p = 0.018) and delivery rate within 12 h (63% vs. 83%, p = 0.035) were higher in the two-dose group. The oxytocin augmentation rate (14% vs. 2%, p = 0.03) was higher in the single-dose group. There was a higher rate of clinician input related to suspicious cardiotocographic readings in the single-dose arm (p = 0.04). There was no statistical difference (p > 0.05) between the one- and two-dose regimens with respect to the rates of tachysystole (21% vs. 15%), hyperstimulation (3.9% vs. 0%), and meconium staining at delivery (9.8% vs. 13.2%). CONCLUSIONS: The two-dose regimen was most efficient, but both regimens were well tolerated by the fetuses.

Administration, Intravaginal↗

A randomized trial that compared intravaginal misoprostol and dinoprostone vaginal insert in pregnancies at high risk of fetal distress.

OBJECTIVE: The purpose of this study was to compare the safety and efficacy of misoprostol and dinoprostone in pregnancies at high risk of fetal distress. STUDY DESIGN: Medical indications for the induction of labor with postdate pregnancy or intrauterine growth restriction were randomized. A sequential design that was based on the triangular test was used. RESULTS: At the fourth interim analysis, which included 140 patients, the trial was stopped because no significant difference was found in neonatal safety between misoprostol and dinoprostone, which was assessed on arterial cord pH <7.20 (14.3% vs 10.0%, respectively; P=.60). Neonatal tolerance was similar in the 2 groups, with no difference in the cesarean delivery rate for fetal distress or in the incidence of meconium-stained amniotic fluid. Time to vaginal delivery was shortened by misoprostol (P=.03). CONCLUSION: Misoprostol and dinoprostone are equally safe for the induction of labor in pregnancies that are at high risk of fetal distress; however, misoprostol allowed the earlier induction of labor than did dinoprostone.

Administration, Intravaginal↗

Reproductive performance in anestrous dairy cows following treatment with two protocols and two doses of progesterone.

The objectives of this study were to evaluate the effect using two doses of progesterone (P4) releasing devices in two different programs on reproductive performance of anestrous dairy cows. Cows (n = 1555) not detected in estrus by 10 d before the planned start of the seasonal breeding program and in which no CL was palpable were treated with an intravaginal P4-releasing device ('Single'; approximately 1.56 g of P4) or a modified device with triple the normal P4 dose ('Triple'; approximately 4.7 g of P4). The devices were in place for either 6 d ('Short') or 8 d ('Long'), with 1mg estradiol benzoate (EB) given 24 h after device removal. The 'Long' program also included treatment with 2 mg EB at device insertion. The Long program resulted in a higher first service conception rate (RR = 1.18 (95% CI = 1.03-1.33); P = 0.02), but had no effect on the 28-d, 56-d or final pregnancy rate compared to the Short program. There were no effects of dose of P4 on any outcome. In conclusion, the Long compared to the Short program, but not the dose of P4, improved first service conception rates in anestrous cows.

Administration, Intravaginal↗

Generation of female genital tract antibody responses by local or central (common) mucosal immunization.

Genital antibody responses were compared in female mice immunized intravaginally (i.vag.) or intranasally (i.n.) with a bacterial protein antigen (AgI/II of Streptococcus mutans) coupled to the B subunit of cholera toxin. Serum and salivary antibodies were also evaluated as measures of disseminated mucosal and systemic responses. Although i.vag. immunization induced local vaginal immunoglobulin A (IgA) and IgG antibody responses, these were not disseminated to a remote secretion, the saliva, and only modest levels of serum antibodies were generated. In contrast, i.n. immunization was substantially more effective at inducing IgA and IgG antibody responses in the genital tract and in the circulation, as well as at inducing IgA antibodies in the saliva. Moreover, mucosal and systemic antibodies induced by i.n. immunization persisted for at least 12 months. Analysis of the molecular form of genital IgA indicated that the majority of both total IgA and specific IgA antibody was polymeric, and likely derived from the common mucosal immune system.

Administration, Intranasal↗

Misoprostol for cervical ripening and labor induction in pregnancies with oligohydramnios.

The efficacy and safety of misoprostol for cervical ripening and labor induction in patients with oligohydramnios was investigated. 57 pregnancies with oligohydramnios and 58 cases with a normal amniotic fluid volume (controls) were enrolled in this prospective trial. All patients received 50 microg of intravaginal misoprostol every 5 h. Primary outcomes were: cesarean section rate; induction to delivery time; oxytocin augmentation; uterine hyperstimulation; meconium passage; fetal heart rate (FHR) changes; fetal distress requiring delivery, and Apgar scores. There were no differences in the mean time to delivery, cesarean section rate, oxytocin augmentation or Apgar scores. The mean induction to delivery time in oligohydramnios and control groups were, 11 h 43 min and 11 h 18 min, respectively (p > 0.05). FHR changes were observed in 26.3% of oligohydramnios group and 32.7% of control group (p > 0.05). There was no statistically significant difference in the cesarean section rate and the uterine hyperstimulation between the 2 groups. These data suggest that misoprostol can be used as an effective agent for cervical ripening and labor induction in pregnancies with oligohydramnios without increasing the risk for perinatal outcome, compared to those with normal amniotic fluid volumes.

Administration, Intravaginal↗

Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex virus type-2.

We compared nasal and vaginal immunizations using attenuated herpes simplex virus type-2 (HSV-2) for protection against vaginal infection with wild-type HSV-2. Mice were immunized once intranasally, intravaginally after progestin (DP) treatment, or intravaginally with scarification after oestradiol treatment. Compared with vaginal immunizations, nasal immunization did not increase immunoglobulin A (IgA) plasma cell numbers in the vagina or elicit a higher antiviral IgA titre in vaginal secretions. Both types of vaginal immunizations increased the number of immunoglobulin G (IgG) plasma cells in the vagina and the secretion/serum titre ratio of IgG antiviral antibody, indicating local production of virus-specific IgG in these groups. Cell-mediated immunity in the vagina, as indicated by memory T-cell secretion of interferon-gamma (IFN-gamma) in situ 20 hr after HSV-2 challenge, was essentially equivalent in the vaginally immunized groups but significantly lower in the nasal group, while lymphocyte recruitment to the vagina was similar in all three groups. All three immunizations protected all mice from neurological disease after challenge, but vaginal DP immunization induced the greatest immunity against reinfection of the vaginal epithelium.

Administration, Intranasal↗

Misoprostol moistened with acetic acid or saline for second trimester pregnancy termination: a randomized prospective double-blind trial.

BACKGROUND: This study was conducted to evaluate the efficacy and side effects of a new regimen of 800 microg misoprostol administered intravaginally every 6 h up to a maximum of three doses in 24 h for second trimester pregnancy termination. METHODS: A total of 66 women seeking termination of second trimester pregnancy (30 fetal structural anomaly, six chromosomal abnormality and 30 fetal death) were randomly assigned to one of two treatment groups: (i) intravaginal misoprostol moistened with 3 ml of 5% acetic acid in group A (n = 33); or (ii) intravaginal misoprostol moistened with 3 ml of saline in group B (n = 33). RESULTS: The overall median (range) induction-abortion interval was 10 h (2-46) [10 h (4-35) in 36 live fetuses and 9 h (2-46) in 30 dead fetuses, P = 0.515]. All of the patients in both groups aborted within 48 h (100% success rate). The median (range) induction-abortion interval revealed a significantly faster delivery time (P < 0.001) in group A [8 h (2-24)] than in group B [14 h (3-46)]. CONCLUSIONS: This new regimen of 800 microg of vaginal misoprostol every 6 h for a maximum of three doses in 24 h was an effective alternative method for second trimester abortion. In addition, misoprostol moistened with acetic acid was significantly more effective than misoprostol moistened with saline.

Abortifacient Agents, Nonsteroidal↗

Effect of the deletion of US2 and US3 from herpes simplex virus type 2 on immune responses in the murine vagina following intravaginal infection.

We investigated the effects of US2 and US3 deficiencies of herpes simplex virus type 2 (HSV-2) on host immunity in a murine model of genital herpes infection. Viral clearance from the vaginal mucosa was more rapid in mice infected with a US3-deficient mutant L1BR1 as compared with a wild-type 186 or YY2 (US2-deficient mutant) infection, although there was no significant difference among them in initial growth in the early stage of infection. Flow cytometric studies revealed that the number of vaginal mononuclear cells in L1BR1-infected mice was significantly greater than that in 186- or YY2-infected mice. Dendritic cells, macrophages and T cells were induced more rapidly and in greater numbers within the vaginas of L1BR1-infected mice. Moreover, the levels of IL-12 and IFN-gamma increased in L1BR1-infected mice over levels in 186-infected mice. These results indicate that a US3 deficiency alters the induction of the host immune response; therefore, the inactivation of US3 may be a promising strategy in the development of novel vaccines for genital herpes.

Administration, Intravaginal↗

Comparison of methods for the synchronization of estrous cycles in dairy cows. 2. Effects of progesterone and parity on conception.

Three experiments with 571 dairy cows indicated that significantly more primiparous cows given two prostaglandin F2 alpha injections 14 d apart conceived within 30 d of first AI than did cows given two injections 11 d apart (84 vs. 62%). Fewer multiparous cows given two injections 14 d apart and inseminated after estrus conceived than did cows given two injections and a progesterone intravaginal coil inserted 8 d after the first injection (42 vs. 66%). Fewer cows given one injection of prostaglandin and inseminated at estrus conceived than did cows given two injections 14 d apart and a progesterone coil (39 vs. 66%). Conception rates of cows given two prostaglandin injections were positively related to plasma progesterone concentrations 2 and 4 d before the second injection (r = .81 and .86). Cows with progesterone concentrations below 5 ng/ml, 2 d before the second prostaglandin injection, and synchronized by two prostaglandin injections or by two injections and a progesterone coil had conception rates of 36 and 63%, respectively. Cows with progesterone concentrations above 5 ng/ml had a conception rate of 75 and 46% in the two treatments, respectively. Conception after estrus synchronization depends on the method and on the plasma concentrations of progesterone. Progesterone coils may be used before AI to enhance fertility in cows with low progesterone concentrations.

Administration, Intravaginal↗

Modification of immunological responses and clinical disease during topical R-837 treatment of genital HSV-2 infection.

R-837, a compound with no in vitro anti-HSV activity, was administered intravaginally to guinea pigs (5 mg/kg every 12 h) for five days beginning 12 h after genital HSV-2 inoculation. Drug treatment reduced vaginal viral replication (P less than 0.0001), completely protected against primary disease and reduced recurrent genital HSV disease (P less than 0.0001). Drug treatment also induced mild fever, weight loss, and decreased water intake. R-837 was a potent interferon inducer, which also induced variable enhancement of cell-mediated cytolytic activity against HSV-2 targets. Less than 36 h of vaginal HSV shedding was observed in animals with R-837 induced early enhancement of HSV-target cytolysis. Compared to placebo, R-837 decreased ELISA and ADCC antibody to HSV-2, but accelerated HSV-2 specific in vitro IL-2 production and peripheral blood mononuclear cell (PBMC) proliferation. R-837 exhibited potent anti-HSV activity in vivo apparently due to cytokine induction and enhancement of cell-mediated responses.

Administration, Intravaginal↗

The effects of intravaginal clindamycin and metronidazole therapy on vaginal lactobacilli in patients with bacterial vaginosis.

OBJECTIVE: The purpose of this study was to determine the effects of 3 intravaginal antibacterial treatments on vaginal lactobacilli in patients with bacterial vaginosis (BV). STUDY DESIGN: Retrospective analyses were performed on Lactobacillus scores from 3 similar studies evaluating 2 2% clindamycin vaginal creams and 0.75% metronidazole gel at baseline and at 21 to 30 days in 408 patients with BV. Scores were compared using a 1-way global F test and McNemar's test. RESULTS: All groups had similar mean Lactobacillus scores at baseline (P = 0.37) and at 21 to 30 days (P = .71). The 3 groups were also comparable at both visits with respect to the distributions of scores within each group. In all groups, there was significant improvement in the percentages of patients with no lactobacilli present at 21 to 30 days compared with baseline (P < .0001 for all comparisons). CONCLUSION: Clindamycin and metronidazole promoted similar levels of restoration of vaginal lactobacilli at 21 to 30 days.

Administration, Intravaginal↗

Distribution of a spermicide containing Nonoxynol-9 in the vaginal canal and the upper female reproductive tract.

Topical, intravaginal microbicides and spermicides are greatly needed to prevent transmission of sexually transmitted diseases and/or unwanted pregnancies. The development of such compounds is a high research priority. The presumed method of action of existing, or novel, microbicides/spermicides is to provide a chemical barrier to the vaginal epithelium preventing exposure to micro-organisms. Other intravaginal products are used to treat vaginal bacteria of fungal infections. Little is known, however, about the actual or optimal initial distribution and subsequent spread of medications placed in the vagina. We describe a sensitive new technique to quantify the spread of a gel placed in the vagina using magnetic resonance imaging (MRI). Five millilitres of an over-the-counter spermicide containing Nonoxynol-9 was mixed with Gadolinium. MRI was used to quantify spread of the mixture 10 min after insertion with a standard applicator. We demonstrated contiguous spread of gel throughout the vagina. The coverage of material was thicker in the upper vagina than in the lower vagina. We also demonstrated, for the first time, that spermicidal compounds may migrate from the vaginal canal into the endocervix within 10 min of insertion. This finding suggests that topical microbicides/spermicides may act both in the vaginal canal and in the upper female genital tract.

Administration, Intravaginal↗

Pregnancy and delivery after cryopreservation of zygotes produced by in-vitro matured oocytes retrieved from a woman with polycystic ovarian syndrome.

This case report describes the birth of a healthy infant after cryopreservation of zygotes produced by in-vitro matured oocytes retrieved from an anovulatory woman with polycystic ovarian syndrome (PCOS). To initiate the treatment cycle, the patient received intravaginal progesterone at night for 10 days to induce a withdrawal bleed. Oocyte retrieval was performed on day 11 following a withdrawal bleed. The patient was administered 10,000 IU of HCG subcutaneously 36 h prior to oocyte collection. A total of 63 immature oocytes were obtained; 10 were morphologically abnormal. Following incubation for 24--48 h in the maturation medium, TC-199 supplemented with 20% patient's own serum, 75 mIU/ml FSH and LH, 77.4% (41/53) of the oocytes were at the metaphase-II stage. Thirty-one (31/41, 75.6%) were fertilized using ICSI with her husband's spermatozoa, 15 fertilized oocytes were cultured for embryo transfer and 16 were frozen at the pronuclear stage. Pregnancy ensued following fresh embryo transfer. Unfortunately, the pregnancy was miscarried eight weeks later. However, the second frozen-thawed embryo transfer attempt resulted in a full-term pregnancy with delivery of a healthy male infant.

Administration, Intravaginal↗

Clinical response of ovarian cysts in dairy cows after PRID treatment.

We investigated the therapeutic effects of a progesterone releasing intravaginal device (PRID) on cystic ovarian disease (COD) and reproduction performance of cows. The possible influence of PRID on metabolic and/or health status was also examined. A total of 40 Holstein-Friesian cattle, with ovarian cystic structures, > or =2.5 cm in diameter, persisting for more than 7-14 days, without a corpus luteum (CL) were used for the study. PRID or placebos were inserted into the vagina for 12 days. Five animals lost the intravaginal device before removal and one was culled. Based on plasma progesterone concentration on the day of treatment, 20 (17 PRID and 3 placebos) of the remaining 34 cows had follicular cysts (progesterone < or =1 ng/ml) and 14 (10 PRID and 4 placebos) had luteal cysts (progesterone >1 ng/m l). Fourteen (82%) of the PRID-treated follicular cystic cows responded with formation of a CL within 14 days after treatment, and an overall conception rate of 53.8%. Likewise, 70% of the treated luteal cystic cows responded with CL formation and 71.4% conception rate. No significant differences were observed in hematocrit (Ht), white blood cell count and serum levels of glucose, blood urea nitrogen, aspartate aminotransferase, and alanine aminotransferase, between the day of PRID insertion and removal, in animals with follicular and luteal cysts. PRID treatment resulted in ovulation 2-4 days later and formation of a CL in cows that recovered.

Administration, Intravaginal↗