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A randomized trial comparing misoprostol three and seven days after methotrexate for early abortion.

OBJECTIVE: Our purpose was to determine whether vaginal misoprostol 7 days rather than 3 days after methotrexate injection increases the percent of successful abortions on the day of misoprostol administration. STUDY DESIGN: A randomized controlled trial was performed in women requesting an abortion at < or = 56 days' gestation. Eighty-six women were treated with methotrexate 50 mg/m2 intramuscularly followed 3 days (group 1) or 7 days (group 2) later by vaginal misoprostol 800 micrograms. The misoprostol dose was repeated if the abortion did not occur. RESULTS: Complete abortion occurred in 38 of 46 (83%) patients in group 1 and 39 of 40 (98%) in group 2 (p = 0.033). Of the women with complete abortions, 30 of 46 (65%) in group 1 and 27 of 40 (68%) in group 2 aborted the same day as the first or second dose of misoprostol (p = 0.823). Vaginal bleeding lasted 14 +/- 5 (mean +/- SD) days in group 1 and 17 +/- 9 days in group 2. The remaining women aborted after a delay of 24 +/- 6 days in group 1 and 28 +/- 13 days in group 2. For these women vaginal bleeding lasted 18 +/- 17 and 14 +/- 7 days, respectively, and the human chorionic gonadotropin-beta level was < or = 25 IU/L by 22 +/- 7 days after the abortion in group 1 and 19 +/- 9 days in group 2. Treatment failures in group 1 were four continuing pregnancies (9%), two incomplete abortions (4%), and two women who requested surgical termination after receiving both medications (4%). The treatment failure in group 2 was an incomplete abortion. Methotrexate and misoprostol side effects were infrequent. CONCLUSIONS: Methotrexate and vaginal misoprostol are more effective abortifacients when the misoprostol is given 7 days rather than 3 days after methotrexate. This treatment regimen may offer an alternative to surgical abortion or the use of antiprogestins and prostaglandin for medical abortion.

Abortifacient Agents, Nonsteroidal↗

Vaginal misoprostol in the management of first-trimester missed abortions.

OBJECTIVE: To evaluate the efficacy of a regimen of vaginal misoprostol in causing the complete expulsion of first-trimester missed abortions, or alternatively dilating the cervix for surgical evacuation. METHOD: Seventy-four women with a transvaginal ultrasound diagnosis of a first-trimester missed abortion and no more than slight vaginal bleeding were consecutively enrolled. Misoprostol (600 microg) was administered vaginally and repeated 4 h later if necessary. Surgical evacuation was performed when complete expulsion was not documented on the ultrasound 10-12 h after treatment. RESULTS: Complete medical evacuation occurred in 42 women (56.8%), 11 (14.9%) of which required only one dose. Seventy women (94.6%) experienced abdominal pain, 73 (98.6%) vaginal bleeding, 10 (13.5%) nausea, 4 (5.4%) vomiting, 5 (6.8%) diarrhea, and 4 (5.4%) transient hyperthermia. There was one case of heavy vaginal bleeding requiring emergency surgical evacuation, and one re-admission for incomplete abortion at 30 days. All but 4 (5.4%) women had permeable cervices at the time of surgery. CONCLUSION: The described regimen of vaginal misoprostol is safe and reasonably effective in inducing complete evacuation in missed abortions. When this does not occur, it almost always provides adequate cervical dilatation for surgery.

Abdominal Pain↗

Successful pregnancy and delivery after delaying the initiation of progesterone supplementation in a postmenopausal donor oocyte recipient.

Progesterone luteal support has become a standard procedure during IVF cycles. Donor egg cycle women without inherent ovarian function require complete hormone replacement, in contrast with women undergoing IVF in which luteal support is used to supplement endogenous progesterone production. Progesterone support is clearly beneficial, although the timing of its initiation can affect overall outcomes. This paper describes a case in which a postmenopausal woman attending for oocyte donation did not receive her first progesterone injection at the correct time. Treatment with progesterone began when she arrived for the transfer of the donor embryos. The two embryos were maintained in culture and one was transferred on day 6 when the delayed progesterone administration had induced a secretory transformation in her endometrium. A single gestation sac was recorded 8 weeks later, and a healthy baby was subsequently born. On the morning of day 6, delayed progesterone supplementation had induced the secretory endometrial transformation typical of the second phase of the menstrual cycle.

Administration, Intravaginal↗

Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial.

OBJECTIVE: To evaluate whether the frequency of overactive bladder (OAB) symptoms increases in menopause patients after a tension-free vaginal tape (TVT) procedure, and to determine if topical estrogen therapy can help prevent these symptoms. DESIGN: After undergoing a preoperative assessment, enrolled patients were randomly allocated to receive TVT plus postoperative vaginal estrogen therapy (ET group) or TVT without adjunctive medical treatment (No ET group). The pre- and postoperative assessments included: acquisition of a urogynecologic history with standardized questions regarding urinary function (including a 10-grade visual analogue scale score), urogynecologic clinical examination, and urodynamic assessment. Follow-up assessments were performed at 1, 3, and 6 months after surgery. RESULTS: Fifty-six of 59 patients were evaluable; 28 received topic vaginal estrogen after surgery (ET group) and 28 did not receive adjunctive medical treatment (No ET group). The overall OAB syndrome rate in menopause patients (No ET group) was 7% (2 of 28 patients) at baseline and 32% (9 of 28 patients) 6 months after surgery (P = 0.04). At the 6-month follow-up assessment, the incidence of urinary urgency was 4% (1 of 28 patients) and 29% (8 of 28 patients) in the ET and No ET groups, respectively (P = 0.01). Differences in frequency and nocturia were not statistically significant. Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment, urgency significantly improved in the ET group compared with the No ET group (0.23 +/- 1.0 vs 2.30 +/- 3.7, respectively; P = 0.02). CONCLUSIONS: The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients. Vaginal estriol therapy significantly reduces symptoms of urinary urgency, has a high rate of patient satisfaction, and can be used to treat postmenopausal women for at least 6 months after a TVT procedure.

Administration, Intravaginal↗

Vaginal progesterone administration before ovulation induction with exogenous gonadotropins in polycystic ovarian syndrome.

We studied the value of vaginal progesterone (P4) in suppressing serum LH concentrations and restoring normal luteal phase serum LH concentrations before administration of exogenous gonadotropins in anovulatory women with the polycystic ovarian syndrome (PCOS). P4 (50 mg every 12 h) was administered by vaginal suppository to 9 women (18 cycles) for 14 days before ovulation induction with human menopausal gonadotropin (hMG) and hCG. Serum LH, FSH, estradiol, P4, and PRL levels were measured daily. A biphasic effect on LH secretion occurred during P4 administration. Peak serum LH levels occurred on day 5 (125% of basal levels; P less than 0.05) of vaginal P4 suppository use, followed by a progressive fall (P less than 0.05) to 79% of basal levels, but serum LH levels were still higher than those in normal women despite achieving physiological luteal phase P4 concentrations. Ovulation occurred in 56% of cycles after P4 and hMG/hCG treatment and in 65% of control cycles after hMG/hCG alone. In 7 women, serum LH was measured at 10-min intervals for 6 h before and after vaginal P4 administration for 10 days. LH pulse frequency decreased from 7.4 +/- 1.1 to 4.4 +/- 1.2 pulses/6 h (P less than 0.01), and LH pulse amplitude increased from 3.8 +/- 1.8 to 6.1 +/- 2.9 IU/L (P less than 0.01) after P4 administration. We conclude that vaginal P4 (50 mg every 12 h) 1) produces serum P4 concentrations within the normal range for the luteal phase of the menstrual cycle; 2) elevates serum LH, but not FSH, within 5 days; 3) decreases LH pulse frequency and increases LH pulse amplitude after 10 days, but does not normalize serum LH values; and 5) fails to improve the results of subsequent ovulation induction with exogenous gonadotropins in patients with PCOS.

Administration, Intravaginal↗

Comparison between vaginal misoprostol and cervical dinoprostone for cervical ripening and labor induction.

OBJECTIVE: To compare the efficacy of intravaginal misoprostol (Cytotec) to intracervical dinoprostone (Prepidil) for pre-induction cervical ripening. METHODS: Sixty-one patients admitted for induction of labor, whose cervices were unfavorable (Bishop score: 4), were randomly assigned to either intravaginal placement of a 50 micrograms misoprostol tablet or intracervical administration of dinoprostone gel. RESULTS: Eighteen women (56%) in the misoprostol group and five (17%) in the dinoprostone group achieved cervical ripening within 12 hours (P = 0.007). Fewer doses of misoprostol were required to achieve cervical ripening, and the interval from induction of labor to delivery was shorter in the misoprostol group. Sixteen patients (50%) in the misoprostol group required oxytocin, whereas 26 (90%) in the dinoprostone group required oxytocin augmentation (P = 0.008). There was no significant difference in mode of delivery or neonatal outcome between the two groups. CONCLUSION: Vaginal misoprostol appears to be a more effective cervical ripening agent than cervical dinoprostone.

Administration, Intravaginal↗

[Gameprost, sulproston and dinoproston for induced abortion in the 15th-24th week of pregnancy].

In a randomized, prospective study at the Dept. of Obstetrics and Gynecology of the University Hospital of Giessen 4 different ways of inducing abortions with prostaglandins were tested between the 15th and 24th week of gestation. The aim of the study was to determine the best approach to inducing abortion in order to minimize the psychological and physical stress to the patient. Subjects randomized to the first two groups got a single cervical installation of either 0.5 mg Dinoprostongel (Prepidil, N = 22) or 0.5 mg Sulprostongel (Nalador, N = 21). Six hours later, i.v. infusion with Sulproston (8.3 micrograms/min) was started and continued until the abortion was complete. Patients randomized to the third and fourth group received either 0.5 mg Dinoprostongel intracervically (N = 15) or 1 mg Gemeprost vaginal suppositories (Cergem, N = 21) every 6 hours until the cervix was 1-2 cm dilated. Subsequently the patients received an i.v. infusion with Sulproston until the abortion was complete. In the first group with intracervical application of Sulproston the total time until abortion was 17.8 h +/- 7.8 h. This was shorter than following a single application of Dinoprostongel (22.5 h +/- 14.7 h). Although there was a five hours difference, the between-group differences were not statistically different because of a wide range in values following Dinoproston treatment. This range could not be explained by the age of the mother, week of gestation or parity. In the group receiving multiple intracervical applications of Dinoproston the time till expulsion was twice as long as that after multiple vaginal suppositories of Gemeprost (33.8 h +/- 13.9 h vs. 15.6 +/- 6.0 h, p < 0.01). The time span until a cervical dilatation of 1-2 cm was 27.0 h +/- 13.7 h in the group with repeated Dinoproston application. This period of time was more than twice the time span seen in the group with repeated Gemeprost application (12.5 h +/- 4.2 h, p < 0.01). On the average four treatments with intracervical Dinoprostongel were required while the average with Gemeprost vaginal suppositories was two to achieve a cervical dilatation of 1-2 cm. Furthermore in 7 of 21 cases treatment with Gemeprost achieved the expulsion of the fetus without Sulproston infusion (11.4 h +/- 5.2 h). Comparing single versus repetitive prostaglandin application we could demonstrate that the duration of Sulproston infusion was cut in half after repeated therapy with Gemeprost. We conclude that repetitive application of Gemeprost vaginal suppositories decreases the time to abortion and subject discomfort tremendously. The application of Gemeprost suppositories provides the easiest and most efficient therapeutic approach for both patients and staff. Furthermore the regiment that provided the best results was also the most cost-effective (range 180,-DM to 317,- DM per case).

Abortifacient Agents, Nonsteroidal↗

Intravaginal morphine: an alternative route of administration.

The availability of various dosage forms allows morphine to be administered in a number of ways. However, if the oral and rectal routes are not feasible, the parenteral one may appear to be the only viable option. Morphine was administered by the intravaginal route in a 44-year-old woman as an alternative to intravenous patient-controlled analgesia. The dosage forms included sustained- and immediate-release tablets as well as regular suppositories. The initial dosage was calculated according to guidelines for switching to oral administration and titrated to response. Adequate pain control was achieved, but due to unpredictable bioavailability, close monitoring was essential.

Administration, Intravaginal↗

Systemic absorption of clindamycin following intravaginal application of clindamycin phosphate 1% cream.

The extent to which clindamycin is absorbed systemically following intravaginal application of clindamycin phosphate 1% cream was assessed in 12 healthy female volunteers. Each subject received a single intravenous dose of clindamycin phosphate sterile solution (48 mg). A week later, each subject received 50 mg (5 mL) doses of intravaginal cream according to one of two dosage regimens: once daily (qd) for seven consecutive doses or twice daily (q12hr) for 13 consecutive doses. Steady state was achieved on or before day 4 for both regimens. The absolute bioavailabilities of the two intravaginal treatments were 6% for qd dosing and 13% for q12hr dosing, indicating that only a small fraction of the intravaginal dose is absorbed systemically.

Administration, Intravaginal↗

Treatment of suckling beef cattle with a progestagen sponge and oestradiol benzoate or equine chorionic gonadotrophin.

The ovarian responses of anoestrus beef cows to a combined treatment with medroxy-progesterone acetate (MAP) sponges and oestradiol benzoate or equine chorionic gonadotrophin (eCG) were evaluated. Forty-five suckling Hereford cows were allocated to three equal groups. Group 1 received a MAP sponge for seven days plus an injection of 2 mg oestradiol benzoate when the sponge was inserted (day 0) and 1 mg when the sponge was withdrawn; group 2 received identical treatment until day 7, when a dose of 400 iu of eCG was administered, and group 3 were left untreated as control animals. From day 0 to day 11 the cows' ovaries were examined daily by transrectal ultrasonography, and their oestrous behaviour was observed from 24 hours to 96 hours after the sponge was removed. Data from cows that had a corpus luteum present before the sponge was withdrawn were not used in subsequent analyses; there were four in group 1, five in group 2 and four in group 3. In 19 of the 21 cows in groups 1 and 2 a new follicular wave was observed to emerge at a mean (sd) interval of 3.9 (0.3) days after the insertion of the sponge, whereas in group 3 it occurred in all 11 cows after 3.4 (0.6) days. Only the six cows that had a follicle of 9 mm or larger in diameter ovulated (P < or = 0.001). Nine of the 11 cows in group 1 came into oestrus, compared with two of the 10 in group 2 and none of the control cows (P < or = 0.001). Ovulation was observed in four, two and none of the cows in groups 1, 2 and 3, respectively.

Administration, Intravaginal↗