A randomized, controlled, double-blind trial comparing two loading doses of aminophylline.

OBJECTIVE: To compare 8 mg/kg and 6 mg/kg loading doses of aminophylline. STUDY DESIGN: Sixty-one preterm infants weighing <1500 g were enrolled once a decision to administer intravenous aminophylline was made. A standard maintenance dose was used. Serum levels of theophylline were drawn 8 hours after the loading dose and before the fifth maintenance dose. RESULTS: After the initial loading dose, the 8 mg/kg group achieved recommended serum theophylline levels (7-12 microg/ml) more frequently than the 6 mg/kg group (39% vs 3%, p=0.002). Subsequent levels were similar between the groups. There were no increases in side effects with the higher loading dose. CONCLUSION: If a clinical decision to start intravenous aminophylline therapy in preterm infants has been made, the use of an 8 mg/kg loading dose appears to be a better and safe way to quickly achieve serum theophylline levels within the recommended range.     

A prospective randomized double-blind trial of ceftriaxone versus no treatment for abdominal hysterectomy.

The value of preoperative prophylactic parenteral treatment with ceftriaxone at elective abdominal hysterectomy was investigated in a prospective, randomized, double-blind study, in which 157 women participated, 77 in the antibiotic group and 80 in the control group. Increased febrile morbidity and a significant preponderance of women with urinary tract infections were observed in the untreated group, whereas there was no significant difference between the two groups regarding wound infections or infiltration at the top of the vagina. We find no indication for routine prophylactic use of antibiotics at elective abdominal hysterectomy.     

A randomized double-blind trial of two low dose combined oral contraceptives.

Fifty-five women using Loestrin-20 (20 microgram ethinyl oestradiol and 1 mg norethisterone acetate) as an oral contraceptive have been compared with a like number using Microgynon-30 (30 microgram ethinyl oestradiol and 150 microgram levonorgestrel) in a randomized, double-blind trial. Despite the small sample size, the main finding in the trial is clear-cut; Loestrin-20 provides poor cycle control and is thus less acceptable as an oral contraceptive than Microgynon-30. Although there is also a suggestion that Loestrin-20 may be less effective than Microgynon-30, the difference in the accidental pregnancy rates is not statistically significant.     

Gonadotropin-releasing hormone agonist plus "add-back" hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial

OBJECTIVE: To assess the effect of add-back therapy with continuous combined estrogen-progestin on the GnRH agonist-induced hypoestrogenic state and its effectiveness in healing of endometriotic lesions. DESIGN: A prospective, randomized, placebo-controlled, double-blind trial. SETTING: Multiple centers in The Netherlands. PATIENT(S): 41 premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Society scores >/=2). INTERVENTION(S): Patients were randomly assigned to receive a subcutaneous depot formulation of goserelin, 3. 6 mg, every 4 weeks, plus oral placebo or oral continuous combined estradiol-norethisterone acetate add-back therapy daily for 24 weeks. MAIN OUTCOME MEASURE(S): Endometriosis response, bone mineral density, transvaginal ultrasonographic changes, endocrinologic effects, and subjective side effects. RESULT(S): The number of endometriotic implants was significantly reduced in both groups. In the group that received GnRH agonist plus placebo, bone mineral density of the lumbar spine decreased by 5.02%. CONCLUSION(S): The effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy. Bone mineral density of the lumbar spine was maintained and subjective side effects were diminished.     

A prospective randomized clinical trial comparing two oxytocin induction protocols.

OBJECTIVE: Our objective was to compare the safety and efficacy of two accepted oxytocin induction protocols that differ in oxytocin dose increments. STUDY DESIGN: At the Carolinas Medical Center in Charlotte, North Carolina, 151 women with indications for induction of labor were prospectively randomized into one of two oxytocin induction protocols. Safety and efficacy of the two protocols were analyzed with two-tailed t tests and chi 2. RESULTS: Time from induction to establishment of a regular labor pattern was significantly shorter in the experimental group compared with the traditional group (p = 0.03). However, no significant difference was seen from onset of induction to time of delivery. Incidences of hyperstimulation were not significantly different between the two protocols, but there was a trend toward a higher incidence of fetal heart rate changes in the experimental group (p = 0.08). CONCLUSION: These data suggest that induction with larger dose increments will shorten time to adequate labor without an associated increase in uterine hyperstimulation or poor neonatal outcome. The differences in heart rate changes are concerning and merit further investigation. If confirmed by further studies, an increased risk of cord compression could outweigh the benefit of a faster onset of contractions.     

A prospective randomized safety trial of celecoxib for treatment of preterm labor

OBJECTIVE: We compared the safety of celecoxib, a selective cyclo-oxygenase-2 inhibitor, with the safety of the nonselective cyclo-oxygenase inhibitor indomethacin, when it was administered for treatment of preterm labor. STUDY DESIGN: In a randomized, double-blind, placebo-controlled trial, 24 pregnant women in preterm labor at 24 to 34 weeks of gestation received either indomethacin or celecoxib for 48 hours. Clinical assessment, fetal sonography, and Doppler blood flow studies of the fetal ductus arteriosus were performed daily. RESULTS: Mean maximum ductal flow velocity was significantly elevated over baseline (82.9 +/- 4.6 cm/s vs 111.14 +/- 14.3 cm/s; P =.02) after 24 hours of indomethacin, but not celecoxib. Both medications were associated with a transient decrease in amniotic fluid volume, with a greater effect by indomethacin. The medications were equally effective in the maintenance of tocolysis. There were no significant maternal or neonatal adverse events. CONCLUSION: In this initial evaluation, the safety of short-term celecoxib in women with preterm labor was superior to that of indomethacin.     

A randomized trial of ovulation induction with two different doses of Letrozole in women with PCOS

Objective  

To compare the effects of either a 5 or 7.5 mg daily dose of Letrozole in PCOS women undergoing ovulation induction and timed intercourse.     

Efficacy of danazol treatment for minimal endometriosis in infertile women. A prospective, randomized study

We compared pregnancy rates between a danazol-treated and an untreated group of infertile women with minimal endometriosis. After completion of a basic infertility workup and laparoscopy, women with minimal endometriosis were entered into the study and randomly selected to receive either a six-month course of danazol or no treatment at all. Those patients with other infertility factors were included in the study only if the factors were correctable and ultimately determined to be noncontributory. Life-table analysis was used to compare pregnancy rates between the two groups over a 12-month period that started immediately after laparoscopy in the untreated group and after completion of danazol therapy in the treated group. The cumulative pregnancy rate (+/- SEM) was 37.2 +/- 8.4% in the danazol group (n = 37) and 57.4 +/- 10.4% in the untreated group (n = 36) (NS, P greater than .10). This prospective, randomized study showed danazol to be ineffective in improving pregnancy rates over doing nothing at all in patients with minimal endometriosis.     

Effect of gestrinone in endometriosis tissue and endometrium

The effects of gestrinone (R 2323) on endometrial and endometriosis tissue concentrations of cytosol estrogen and progestin receptors and the activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were investigated in 11 patients operated on because of suspected external endometriosis. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol (E2), progesterone, testosterone (T), and sex-hormone-binding globulin (SHBG) were also investigated. After one control cycle, the patients received 2.5 mg of oral gestrinone twice weekly from the fifth day of the first treatment cycle until the eighth day of the second treatment cycle, the day of operation being day 10. Treatment with gestrinone decreased serum concentrations of T during the second treatment cycle and effected a major decrease in SHBG during both treatment cycles, resulting in highly increased free T and free E2 indices. The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions. These parameters remained unchanged in endometriosis tissue. Our data indicate that gestrinone has effects that are typical of androgens and progestins in patients with endometriosis.     

A double-blind randomized trial of two dose regimens of misoprostol for cervical ripening and labor induction

Objectives: The objective of this study was to compare the efficacy and safety of two dosing regimens of misoprostol for cervical ripening and labor induction.

Methods: Patients who fulfilled the study criteria were randomized to received misoprostol 25 μg or 50 μg intravaginally every 3 h for a total of eight doses for cervical ripening or until labor was established. Endpoints for successful cervical ripening was achievement of Bishop score of nine or greater, and for labor induction reaching the active phase of labor in the first 24 h. The rates of success, duration of first and second stages of labor, type of delivery, significant side effects, and neonatal outcome were measured and compared between the two study groups. Two hundred and fifty-one patients were randomized in two groups—126 received 50 μg and 125 received 25 μg misoprostol. Demographics of the two study groups were similar.

Results: Patients in the 50 μg group had a shorter first stage (848 min vs. 1,122 min, P < 0.007), shorter induction-to-vaginal delivery interval (933 min vs. 1,194 min, P < 0.013), decreased incidence of oxytocin augmentation (53.9% vs. 68%, P < 0.015), and decreased total units of oxytocin (2,763 mU vs. 5,236 mU, P < 0.023), but there was a higher hyperstimulation rate (19% vs. 7.2%, P < 0.005).

Conclusions: Successful induction rate, delivery types, and fetal outcome were similar in both groups. Although the rate of vaginal delivery and neonatal outcome were similar in both groups, the 50 μg regimen had shorter first and second stages of labor, and a higher hyperstimulation rate that was easily manageable, allowing for flexibility in using the higher dose in low-risk pregnancies.     

Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial

The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group.     

A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia

OBJECTIVE: To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia. DESIGN: Placebo-controlled double-blind randomized trial. SETTING: University tertiary referral center. PATIENT(S): Sixty infertile patients (aged 20-40 years) with the following baseline sperm selection criteria: concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study. INTERVENTION(S): Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up. MAIN OUTCOME MEASURE(S): Variation in the semen parameters that were used for patient selection. RESULT(S): Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate). CONCLUSION(S): Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.     

A randomized double-blind placebo-controlled phase II trial of the cyclooxygenase-2 inhibitor Celecoxib in the treatment of cervical dysplasia

OBJECTIVES: The objective of the study was to evaluate the efficacy of daily Celecoxib in the regression of moderate and severe cervical dysplasia, when compared to placebo. MATERIALS AND METHODS: Women, over the age of 18, with the histologic diagnosis of moderate or severe cervical dysplasia were enrolled in this IRB approved study. Women were randomized to receive either Celecoxib 200 mg twice a day or placebo. Both examining physician and patients were blinded to treatment option. Follow-up colposcopy with cervical cytology was obtained at 2-month intervals for 6 months, with cytologic and histologic specimens. RESULTS: From June 2002 until October 2003, a total of 25 patients were enrolled in this randomized phase II study. There was no statistical difference in screening entry criteria, clinical histologic and cytologic variables between the two groups. 60% of patients enrolled had an overall response in the trial. The mean time to response was 72 days. 75% of patients who received Celecoxib had a clinical response. This was significantly higher than the 31%, of the placebo patients that had a clinical response, P<0.03. 33% of patients in the Celecoxib group had complete pathologic response to therapy, which was higher than the placebo group 15%. CONCLUSION: We have observed that Celecoxib could have activity in the treatment of high-grade cervical dysplasia. As a result, medical treatment of cervical dysplasia with Celecoxib could offer a minimally invasive treatment with minor morbidity and time constraints. Further trials with larger numbers are needed to confirm these results.     

Treatment of endometriosis by vaginal administration of gestrinone

The effectiveness and acceptability of gestrinone administered by vaginal route was evaluated in a group of 110 patients with endometriosis. Patients were divided into four groups. The first three groups were treated by vaginal route. Group I (n = 17) received two 2.5-mg tablets weekly; group II (n = 31) received three 2.5-mg tablets weekly; group III (n = 35) received two 5.0-mg tablets weekly. Group IV consisted of 27 patients who received 2.5 mg of gestrinone orally twice weekly. Ninety-eight women completed the 6- to 8-month treatment period. Amenorrhea developed in all treatment groups, including group I (34%). The disappearance of both dyspareunia and dysmenorrhea occurred in most patients in all treatment groups soon after the second month of therapy. Patients treated by vaginal route had significantly less seborrhea and acne than those treated by oral route. Weight gain was also significantly less in vaginally treated women than in those treated orally. Pregnancy rate following discontinuation was not significantly different for the various groups.