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Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

BACKGROUND: A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). METHOD: All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). RESULTS: Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. CONCLUSION: Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

Administration, Intravaginal↗

Randomized study of pre-induction cervical ripening with sequential use of intravaginal prostaglandin E2 gel.

OBJECTIVE: To evaluate the safety and efficacy of serial frequent intravaginal prostaglandin (PG) E2 gel applications in shortening the time required to achieve an inducible cervix. METHODS: From May 1, 1993, through April 30, 1994, 101 pregnant women with medical indications for induction of labor and Bishop scores less than 7 were randomized to receive intravaginal 2.5 mg of PGE2 gel every 6 hours or as often as every hour until the Bishop score was at least 7 or intervention was required. RESULTS: The mean total number of PGE2 gel applications was significantly different between the 1- and 6-hour groups, 6.5 and 4.4 PGE2 applications, respectively. The mean time from PGE2 application to delivery was similar, 42 and 45 hours, for the 1- and 6-hour groups, respectively. The intervention rate, occurrence of labor during ripening, and neonatal outcomes were also similar. CONCLUSION: Intravaginal application of 2.5 mg PGE2 gel as frequently as every hour appears to be safe, but it does not decrease the time interval to induction or delivery, nor does it decrease the cesarean rate.

Administration, Intravaginal↗

Neither sildenafil nor vaginal estradiol improves endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages.

PURPOSE: To determine if sildenafil improves endometrial thickness better than vaginal estradiol (E2) in women with a history of thin endometria. METHODS: Women failing to attain an 8 mm endometrial thickness on either the oocyte retrieval cycle or their first frozen embryo transfer (ET) despite an oral graduated E2 regimen were treated again with graduated oral E2 and were also randomly assigned to vaginal sildenafil or vaginal E2 therapy. Endometrial thickness was compared between the groups. RESULTS: Neither vaginal E2 nor sildenafil significantly improved endometrial thickness or blood flow in the subsequent frozen ET-cycle. CONCLUSIONS: These data fail to corroborate previous claims that 25 mg sildenafil four times daily intravaginally can improve endometrial thickness.

Administration, Intravaginal↗

Termination of second trimester, complicated gestation.

To assess the effectiveness of intravaginal misoprostol for second trimester uterine evacuation, we studied 70 women with singleton pregnancies complicated by fetal malformation or dead fetuses. Participants received 200 microg misoprostol administered at 4-hour intervals. Gestations with dead fetuses had a shorter induction-abortion interval [14.2 hours, standard deviation (SD) 4.3] than those with live, malformed fetuses (20.2 hours, SD 7.3) (P< 0.001). The abortion rate was significantly higher for gestations with dead fetuses (92.1%) than those with live, malformed fetuses (68.8%) (P< 0.05). There were no major complications and no significant difference in the incidence of side-effects. All women aborted within 38 hours. Administration of misoprostol is an effective clinical method to terminate second trimester, complicated pregnancy.

Abdominal Pain↗

A comparison between 25 micrograms and 50 micrograms of intravaginal misoprostol for labor induction.

Our purpose was to compare the efficacy 25 micrograms and 50 micrograms dosage of intravaginal misoprostol for labor induction in patients with an unfavorable cervix. Fifty pregnant women were randomly assigned to receive either 25 micrograms (24 cases) or 50 micrograms (26 cases) of intravaginal misoprostol every 6 hours. The mean interval from induction to vaginal delivery was significantly shorter in the 50 micrograms group (13.8 +/- 6.6 hours) when compared with the 25 micrograms group (20.9 +/- 9.5 hours) (P = 004). The average number of misoprostol doses needed per patient was significantly fewer in the 50 micrograms group (1.6 +/- 0.7 versus 2.3 +/- 1.2, P = 0.018). The frequencies of uterine tachysystole were 4.2 per cent and 7.7 per cent in the 25 micrograms and 50 micrograms groups respectively which did not significantly differ. Requirement for oxytocin infusion in the 25 micrograms group was significantly more than in the 50 micrograms group (66.6% versus 23.1% respectively, P = 0.004). Analgesia requirement, delivery method, and perinatal outcomes were comparable in both groups. In summary, intravaginal application of 50 micrograms misoprostol at 6-hour interval is comparable in safety but more effective for labor induction than the 25 micrograms dosage.

Administration, Intravaginal↗

Outpatient management of the uncomplicated postdate pregnancy with intravaginal prostaglandin E2 gel and membrane stripping.

The purpose of the study was to determine the safety and efficacy of outpatient intravaginal prostaglandin E2 (PGE2) and membrane stripping in promoting labor in the uncomplicated postdate pregnancy. In a double-blind placebo-controlled study, 150 enrollees were randomized to one of four treatment groups; group I, no membrane stripping and placebo gel; group II, no membrane stripping and PGE2 gel; group III, membrane stripping and placebo gel; and group IV, membrane stripping and PGE2 gel. The treatments were administered at 287 days (41 weeks) and 294 days (42 weeks) of gestation, then every 3-4 days until 307 days (43 completed weeks) of gestation. The patients in group IV had the shortest interval to delivery with a median of 1 day, P = .001, and the fewest antenatal surveillance visits with only 21% requiring more than one visit, P = .02. Group I patients in comparison, had a 7-day median to delivery, and 61% required more than one visit. The time spent in labor and delivery and the need for oxytocin augmentation was not significantly reduced in groups II, III, and IV. No adverse side effects to either mother or neonate could be directly attributed to this outpatient treatment combination. We conclude that intravaginal PGE2 gel combined with membrane stripping reduces postterm pregnancies and antenatal visits in our patients.

Administration, Intravaginal↗

Potential patient preference for 3-day treatment of bacterial vaginosis: responses to new suppository form of clindamycin.

Treatment options for bacterial vaginosis (BV) include oral and topical formulations of metronidazole or topical formulations of clindamycin. Opinions of a new vaginal suppository form of clindamycin, administered for 3 days, were obtained in a survey of 96 women who had been generally satisfied with their previous treatment. Following manipulation of the clindamycin ovule and metronidazole vaginal gel, more respondents expressed a preference for the ovule (52% vs 47%), and 54% preferred the ovule to the gel (44%) for possible future use. The gel was rated easier to use, but the ovule was found to be less messy. After manipulating both products, respondents read a profile of the ovule and identified the 3-day course as its most beneficial feature, citing this reason as increasing their likelihood of completing therapy with the ovule than with the gel. Approximately three fourths of the respondents who initially preferred the gel switched their preference to the ovule after reading the product profile. At that point, 86.5% of all respondents preferred the ovule. These results suggest the potential for improved compliance with therapy for BV with the clindamycin ovule.

Administration, Intravaginal↗

A comparison of two methods of labor induction with vaginal misoprostol.

OBJECTIVES: To evaluate if labor induction with 50 microg of vaginal misoprostol twice per day is as effective as and safer than 100 microg used once per day. METHODS: Misoprostol was used to induce labor in 204 consecutive pregnant women assessed as needing labor induction, 104 at the University Hospital of the West Indies in Kingston, Jamaica, and 100 at the Victoria Jubilee Hospital, also in Kingston. At the former institution the women were administered 100 microg of misoprostol once per 24 h and at the latter 50 microg every 12 h. The doses were repeated if there was no cervical change or if the woman was not in labor. Bishop scores were determined before initiation of induction and again 12 h later. Women's records were reviewed after 24 h to determine delivery outcome. RESULTS: The indications for labor induction were similar in each group. There was no significant difference in the group demographics. In the group given 50 microg of misoprostol twice per day the mean time+/-S.D. from insertion of misoprostol to delivery was significantly shorter than in the other group (560.14+/-269.20 min vs. 729.90+/-471.65 min; P<0.01), and the percentage of women who were delivered within 12 h was higher (75% vs. 56.8%; P<0.002). There was no significant difference between the two groups in the rate of cesarean births, the need for oxytocin, or blood loss. Only two patients experienced uterine hyperstimulation, both in the group that had received 100 microg of misoprostol per day. There was no significant difference between the two groups in the birthweight of the neonates and in the number of neonates with Apgar scores less than 7 at 1 min and 5 min. There were, however, significantly fewer neonates who needed resuscitation (6% vs. 14.7%; P=0.04) and admission to the special care nursery (7% vs. 17%; P=0.03) in the group that had received 50 microg of misoprostol twice per day. CONCLUSIONS: A dose of 50 microg of misoprostol twice per day appears to be more efficient and safer than a dose of 100 microg once per day, but this may partially be due to weaknesses in the study design.

Administration, Intravaginal↗

The effect of tablet moistening on labor induction with intravaginal misoprostol: a randomized trial.

OBJECTIVE: To estimate whether a dosage of 50 microg of misoprostol tablets moistened with 3% acetic acid and administered intravaginally is more efficacious for labor induction than a similar dosage regimen using dry tablets. METHODS: A total of 177 women who presented with an indication for cervical ripening and labor induction were randomly assigned to one of two treatment groups: 1) intravaginal misoprostol in dry tablet form, or 2) intravaginal misoprostol moistened with 1 mL of 3% acetic acid solution. The primary outcome assessed was the interval from start of induction to vaginal delivery. To detect at least a 3.5-hour difference in the primary outcome with 80% power, 87 subjects were required in each group. RESULTS: Among 162 patients evaluated, 80 were allocated to the misoprostol dry group and 82 to the misoprostol moistened group. No significant difference was noted for the mean +/- standard deviation interval to vaginal delivery: 1130 +/- 636 minutes for the group who received dry tablets and 1004 +/- 636 minutes for those who received moistened misoprostol tablets (P =.25). Additionally, no statistically significant differences were noted between the groups with respect to need for oxytocin, proportion of patients delivered after a single dose, intrapartum complications (including tachysystole and uterine hyperstimulation), mode of delivery, or perinatal outcomes. CONCLUSION: Tablet moistening with 3% acetic acid solution does not seem to improve the efficacy of intravaginally administered misoprostol for labor induction.

Acetic Acid↗

Levonorgestrel. Clinical pharmacokinetics.

Published values for the serum concentrations and pharmacokinetic parameters of levonorgestrel after administration of various doses of levonorgestrel alone or with ethinylestradiol are reviewed. Most data apply to oral administration of the gestagen, with the smaller amount of data for other modes of administration, e.g. subcutaneous, intravaginal and intra-uterine administration, also included. There is a large variability among the different studies for both serum concentration and pharmacokinetic parameters and not all of this is due to the large interindividual variability demonstrated in all of the studies. The factors responsible for the inter- and intraindividual variability have not been discovered. Sex hormone binding globulin (SHBG) plays an important role in levonorgestrel pharmacokinetics since: (i) levonorgestrel binds strongly to this protein; and (ii) serum SHBG levels are influenced by a large number of different factors including the administration of levonorgestrel and ethinylestradiol. However, not all of the anomalies in the metabolism of levonorgestrel can be ascribed to its interaction with SHBG.

Contraception↗

Successful treatment of a prolactin-producing pituitary macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy.

A 37-year-old woman with a symptomatic 18-mm prolactin-secreting pituitary adenoma could not be managed with oral bromocriptine mesylate because of unacceptable gastrointestinal side effects. However, when given the medication intravaginally, the patient was successfully treated as assessed by evident tumor shrinkage and diminished secretory activity. Serum bromocriptine levels were approximately six to eight times higher than those reported after oral administration. The vaginal route may help reduce some of the adverse effects of bromocriptine mesylate experienced during oral administration and may possibly allow lowering of the overall effective dose by avoiding first liver passage.

Administration, Intravaginal↗

Randomized comparison between intravaginal misoprostol and dinoprostone for cervical ripening and induction of labor.

OBJECTIVE: We sought to evaluate the efficacy and safety of intravaginal misoprostol and dinoprostone for labor induction. STUDY DESIGN: One hundred eighty-nine women with singleton term pregnancies and unfavorable cervices were randomly assigned to receive intravaginal misoprostol or dinoprostone. The outcome variables were change in Bishop score, time from application to active phase of labor and delivery, fetal and maternal morbidity, and the incidence of cesarean deliveries. RESULTS: The interval from application of the initial dose to the beginning of the active phase of labor was 9.8 +/- 5.8 and 14.2 +/- 10.2 hours (P <.01), and the interval from initial dose to delivery was 15.3 +/- 9.8 and 19.1 +/- 13.2 hours (P =.027) for the misoprostol and dinoprostone groups, respectively. There were no significant differences in Bishop score change, cesarean delivery rate, and the incidence of tachysystole, hypersystole, and hyperstimulation. No maternal and neonatal adverse effects were noted. CONCLUSION: Intravaginal misoprostol is more effective than intravaginal dinoprostone for labor induction in low-risk patients at term with unfavorable cervices.

Administration, Intravaginal↗

Patient acceptability of and tolerance to a placebo intravaginal ring in hysterectomized women: a pilot study.

OBJECTIVE: To assess the tolerance to and patient acceptability of a placebo intravaginal ring in hysterectomized, postmenopausal women over a 28-day period. DESIGN: Open, single-center. SETTING: University hospital specialist menopause clinic. PARTICIPANTS: A total of 24 healthy postmenopausal women attending menopause clinics at King's College Hospital and the Amarant Centre, London. MAIN OUTCOME MEASURES: Discomfort, ring expulsions, bowel, urinary and sexual difficulties associated with the ring and women's overall views on this method. RESULTS: The major problems with use of the intravaginal ring were patient discomfort, involuntary ring expulsion and sexual partner discomfort. These were experienced by 13, 11 and seven women and their partners, respectively, and resulted in premature discontinuation by three women who suffered discomfort and two women who experienced recurrent involuntary ring expulsion. CONCLUSIONS: Two-thirds of the patients found the intravaginal ring acceptable, one-third did not.

Administration, Intravaginal↗

Misoprostol for second-trimester pregnancy termination in women with a prior cesarean delivery.

OBJECTIVE: To evaluate the use of misoprostol in second-trimester abortion in women with prior cesarean deliveries. METHODS: A review of women with prior cesarean deliveries undergoing abortion at 14-28 weeks of gestation for a fetal anomaly over a 7.5-year period. Outcome data were compared with a contemporaneous cohort of women with unscarred uteri undergoing the same procedure. Misoprostol was used to induce abortion in all cases, and a variety of dosage regimens were used, the most frequent being 400 mug vaginally every 6 hours (71.3%). RESULTS: During the study period, 720 consecutive women underwent a second-trimester abortion for a fetal anomaly using misoprostol. One hundred one women (14%) had at least 1 prior cesarean delivery: 78 women had 1, 19 women had 2, and 4 women had 3 prior cesarean deliveries. Women with a prior cesarean birth were significantly older (30 years [interquartile range 26-35] versus 33 years [29-37], no cesarean delivery versus cesarean delivery, P = < .001) and of increased parity. The median gestational age at delivery was 19.4 weeks (interquartile range 18-20.7) versus 19.3 weeks (17.7-21), no cesarean delivery versus cesarean delivery, P = .48. The presence of a prior uterine scar did not impact upon abortion duration (16.6 hours [12.1-23.8] versus 14.5 hours [11.4-21.4], no cesarean delivery versus cesarean delivery, P = .07). No differences in blood loss, major hemorrhage, or blood transfusion occurred. There was no case of uterine rupture or hysterectomy. CONCLUSION: In second-trimester abortion, the use of misoprostol in women with prior cesarean delivery was not associated with an excess of complications compared with women with unscarred uteri. LEVEL OF EVIDENCE: II-2.

Abortion, Therapeutic↗

Comparison of three-day butoconazole treatment with seven-day miconazole treatment for vulvovaginal candidiasis.

In this multicenter, parallel, randomized, investigator-blind trial, we compared the safety and efficacy of a three-day regimen of 2% butoconazole vaginal cream with those of a seven-day regimen of 2% miconazole vaginal cream. Enrolled were 271 nonpregnant women with vulvovaginal candidiasis. Each patient administered her assigned study medication to the posterior vaginal fornix for three or seven consecutive nights. All 271 patients were included in the safety evaluation, and 225 (111 receiving butoconazole and 114 receiving miconazole) were included in the efficacy evaluation. Eight to ten days after treatment completion, 88% of the butoconazole-treated patients and 91% of the miconazole-treated patients were Candida negative; 80% of the butoconazole-treated patients and 82% of the miconazole-treated patients were considered clinically cured. Thirty days after treatment completion, 73% of the butoconazole-treated patients and 69% of the miconazole-treated patients remained Candida negative; 78% of the butoconazole-treated patients and 80% of the miconazole-treated patients remained free of clinical symptoms of vulvovaginitis. None of the differences between the two treatment groups was statistically significant. Six patients (four receiving butoconazole and two receiving miconazole) reported increased symptoms of vulvovaginal irritation, and three of them (two receiving butoconazole and one receiving miconazole) withdrew from the trial. Thus, the efficacy and safety of the three-day butoconazole treatment regimen were equivalent to those of the seven-day miconazole treatment regimen. The advantage of the shorter butoconazole treatment is increased patient compliance with maintenance of high efficacy.

Administration, Intravaginal↗

Methamphetamine toxicity secondary to intravaginal body stuffing.

BACKGROUND: People who ingest packets of illicit drugs or insert them into body cavities in an attempt to smuggle them are termed body packers. People who do this in an attempt to hide the drugs when encountered by law enforcement are called body stuffers. Severe toxicity and death occurs in body packers and body stuffers, and this is usually secondary to leaking of drug from packets in the gastrointestinal tract. This is well reported with cocaine and heroin and occurs less commonly with methamphetamine. We report an unusual case of intravaginal body stuffing that lead to severe methamphetamine toxicity in a young woman. CASE REPORT: A 20-year old female, who was in police custody, developed multiple seizures, altered mental status, tachycardia and hypertension shortly after admitting to having drugs enclosed in plastic bags in her vagina. She was hospitalized for 4 days with gradual improvement in her symptoms with the exception of a resting tachycardia. Gas chromatography and mass spectrometry of the urine at this time confirmed the presence of methamphetamine and the amphetamine metabolite, co-intoxicants were excluded based on comprehensive urine drug screening using GCMS. Quantitative serum levels of methamphetamine and amphetamine were 3100 ng/ml and 110 ng/ml, repectively. CONCLUSION: We report an unusual case of intravaginal body stuffing that lead to severe methamphetamine toxicity in a young woman. This case highlights the potential for severe methamphetamine poisoning secondary to intravaginal stuffing. If either body packing or stuffing is suspected, a vaginal exam may be warranted.

Administration, Intravaginal↗

Short-Term (13-week) toxicity study of 5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate (WHI-07), a novel anti-HIV and contraceptive agent, in B6C3F1 mice.

The zidovudine derivative, WHI-07 (5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl) methoxyalaninyl phosphate), is a dual-function spermicidal agent with potent anti-HIV activity. In this study, groups of 20 female B6C3F1 mice were exposed intravaginally to a gel microemulsion containing 0, 0.5, 1.0, or 2.0% WHI-07, 5 days per week for 13 consecutive weeks. On a molar basis, these concentrations of WHI-07 are 1400- to 5700-times higher than its spermicidal EC(50) and 1.4 x 10(6) to 5.7 x 10(6) times higher than its in vitro anti-HIV IC(50). After 13 weeks of intravaginal treatment, mice were evaluated for toxicity. The endpoints that were used for evaluation included survival, body weight, hematologic and clinical chemistry profiles, absolute and relative organ weights, and histopathology. No effects related to WHI-07 treatments were observed on survival, mean body weight, and mean body-weight gain. Repeated intravaginal exposure of mice to WHI-07 for 13 weeks had no toxicologically significant effect on organ weights, and did not cause any adverse changes in hematology parameters or blood chemistry profiles. Extensive histopathologic examination of tissues showed no lesions of pathologic significance. Thus, intravaginal application of WHI-07, for up to 13 weeks, does not cause systemic toxicity.

Administration, Intravaginal↗

Use of different prostaglandin analogues for terminating pregnancy at different terms.

The abortifacient effect has been compared of 15 me-PGF2 alpha, ONO 802 and 16 phenoxy-w-17,18,19,20-tetranor PGE2 given intra-muscularly, intravaginally and with or without laminaria dilatation of the cervix. Locally administered, 15 me-PGF2 alpha, proved to be more efficient than ONO 802. Laminaria had a beneficial effect on dilatation. Intramuscular administration involved the necessity of frequent injections and gastrointestinal side effects. A total of 143 patients participated in the study.

Abortifacient Agents↗