Ultrasound and pulsed electromagnetic energy treatment for perineal trauma. A randomized placebo-controlled trial

Ultrasound and pulsed electromagnetic energy therapies are increasingly used for perineal trauma sustained during childbirth. The study included 414 women with moderate or severe perineal trauma randomly allocated to receive active ultrasound, or active pulsed electromagnetic energy, or corresponding placebo therapies; the allocation was double-blind for each machine. Overall, more than 90% thought that treatment made their problem better. There were no clear differences between the groups in outcome either immediately after treatment, or 10 days or 3 months postpartum, other than more pain associated with pulsed electromagnetic energy treatment at 10 days. Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly. Neither therapy had an effect on perineal oedema or haemorrhoids. The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care.     

The Southmead perineal suture study. A randomized comparison of suture materials and suturing techniques for repair of perineal trauma

Commonly used suture materials and techniques for perineal repair following vaginal delivery were compared in a randomized controlled trial involving 1574 women. Three comparisons were made using a modified factorial design. In the comparison of teflon-coated polyglycolic acid (Dexon plus) with chromic catgut for repair of the vagina and deep perineal tissues there was no clear difference other than less short-term analgesia being required in association with polyglycolic acid. Outcome was also similar after skin repair with either polyglycolic acid or chromic catgut or silk, although silk repair required more packets of material and was associated with delay in resuming sexual intercourse; polyglycolic acid was more likely to need removal than chromic catgut but it appeared to reduce the need for resuturing. There was no clear difference between continuous subcuticular and interrupted transcutaneous sutures for repair of perineal skin.     

A randomized, double-blind, placebo-controlled trial of 5-fluorouracil for the treatment of cervicovaginal human papillomavirus.

OBJECTIVE: To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV). METHODS: A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap) test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression of HPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4-6-month and 12-month follow-up evaluations. Data were analyzed using the Chi square test with significance established at P < 0.05. RESULTS: A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P < 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months. CONCLUSION: Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo.     

A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy

OBJECTIVE: Hyperemesis gravidarum, a severe form of nausea and vomiting due to pregnancy for which there is no proven pharmacological treatment, is the third leading cause for hospitalization during pregnancy. Corticosteroids are commonly used for the treatment of nausea and vomiting due to cancer chemotherapy-induced emesis and might prove useful in hyperemesis gravidarum. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 126 women who previously had not responded to outpatient therapy for hyperemesis gravidarum during the first half of pregnancy. Intravenous methylprednisolone (125 mg) was followed by an oral prednisone taper (40 mg for 1 day, 20 mg for 3 days, 10 mg for 3 days, 5 mg for 7 days) versus an identical-appearing placebo regimen. All women also received promethazine 25 mg and metoclopramide 10 mg intravenously every 6 hours for 24 hours, followed by the same regimen administered orally as needed until discharge. The primary study outcome was the number of women requiring rehospitalization for hyperemesis gravidarum. RESULTS: A total of 110 women delivered at our hospital and had pregnancy outcomes available for analysis; 56 were randomized to corticosteroids and 54 were administered placebo. Nineteen women in each study group required rehospitalization (34% versus 35%, P =.89, for corticosteroids versus placebo, respectively). CONCLUSION: The addition of parenteral and oral corticosteroids to the treatment of women with hyperemesis gravidarum did not reduce the need for rehospitalization later in pregnancy.     

A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients

OBJECTIVE: Phytoestrogens are popular in treatment of menopause, although scientific evidence is insufficient as to their efficacy. We studied the effects of daily use of isoflavonoids on climacteric symptoms and quality of life in patients with a history of breast cancer. METHODS: Sixty-two postmenopausal symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for 3 months; the treatment regimens were reversed after a 2-month washout period. Fifty-six women completed the study. Menopausal symptoms were recorded on the Kupperman index and the visual analogue scale, and working capacity and mood changes were assessed via validated questionnaires. In addition, we followed the levels of phytoestrogens, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and sex hormone-binding globulin. Liver enzymes and creatinine were also assessed at each visit. RESULTS: The phytoestrogen regimen raised the circulating levels of phytoestrogens (daidzein, genistein, equol) 19- to 106-fold. The Kupperman index was reduced by 4.2 +/- 9.6 (mean +/- standard deviation) (15.5%) during phytoestrogen use and similarly by 4.0 +/- 8.1 (14.7%) during placebo use (P nonsignificant). The quality of life parameters (working capacity, mood changes) were unaffected by phytoestrogen. In addition, the phytoestrogen regimen caused no changes in FSH, LH, estradiol, or sex hormone-binding globulin. Phytoestrogen treatment was well tolerated and caused no changes in liver enzymes, creatinine, body mass index, or blood pressure. Of the 56 women, 25 (44.6%) preferred the phytoestrogen regimen, 15 preferred the placebo (26.8%), and 16 (28.6%) reported no preference (nonsignificant). CONCLUSION: Pure isoflavonoids did not alleviate subjective menopausal symptoms in breast cancer patients.     

Oral misoprostol for third stage of labor: a randomized placebo-controlled trial.

OBJECTIVE: To investigate whether orally administered misoprostol during the third stage of labor is efficient in reducing postpartum blood loss. METHODS: In a double-masked trial, during vaginal delivery women were randomly assigned to receive a single oral dose of misoprostol (600 microg) or placebo in third stage of labor, immediately after cord clamping. The third stage of labor was managed routinely by early cord clamping and controlled cord traction; oxytocin was administered only if blood loss seemed more than usual. Blood loss was estimated by the delivering physician and differences in hematocrit were measured before and after delivery. RESULTS: Mean (+/- standard error of the mean) estimated blood loss (345 +/- 19.5 mL versus 417 +/- 25.9 mL, P = .031) and hematocrit difference (4.5 +/- 0.9% versus 7.9 +/- 1.2%, P = .014) were significantly lower in women who received misoprostol than those who received placebo. Fewer women in the misoprostol group had postpartum hemorrhage (blood loss of at least 500 mL), but that difference was not statistically significant (7% versus 15%, P = .43). Additional oxytocin before or after placental separation was used less often in the misoprostol group (16% versus 38%, P = .047). There were no differences in the length of third stage of labor (8 +/- 0.9 minutes versus 9 +/- 1 minutes, P = .947). There were no differences in pain during third stage of labor, postpartum fever, or diarrhea, but shivering was more frequent in the misoprostol group. CONCLUSION: Oral misoprostol administered in the third stage of labor reduced postpartum blood loss and might be effective in reducing incidence of postpartum hemorrhage.     

A randomized comparison of glycerol-impregnated chromic catgut with untreated chromic catgut for the repair of perineal trauma

Summary. Glycerol-impregnated chromic catgut and untreated chromic catgut were compared in a randomized controlled trial involving 737 consecutive women who required repair of perineal trauma following spontaneous vaginal delivery. Medical staff preference was equally divided between the two materials. More untreated chromic catgut sutures required removal both by 10 days and by 3 months postpartum. Women whose perineal trauma was repaired with glycerol-impregnated chromic catgut were 10% more likely to have perineal pain at 10 days and 33% more likely to suffer from dyspareunia in the 3 months following delivery. The high rates of maternal morbidity associated with glycerol-impregnated chromic catgut appear to preclude its use for perineal repair.     

A randomized comparison of glycerol-impregnated chromic catgut with untreated chromic catgut for the repair of perineal trauma

Summary. Glycerol-impregnated chromic catgut and untreated chromic catgut were compared in a randomized controlled trial involving 737 consecutive women who required repair of perineal trauma following spontaneous vaginal delivery. Medical staff preference was equally divided between the two materials. More untreated chromic catgut sutures required removal both by 10 days and by 3 months postpartum. Women whose perineal trauma was repaired with glycerol-impregnated chromic catgut were 10% more likely to have perineal pain at 10 days and 33% more likely to suffer from dyspareunia in the 3 months following delivery. The high rates of maternal morbidity associated with glycerol-impregnated chromic catgut appear to preclude its use for perineal repair.     

A randomized comparison of glycerol-impregnated chromic catgut with untreated chromic catgut for the repair of perineal trauma

Glycerol-impregnated chromic catgut and untreated chromic catgut were compared in a randomized controlled trial involving 737 consecutive women who required repair of perineal trauma following spontaneous vaginal delivery. Medical staff preference was equally divided between the two materials. More untreated chromic catgut sutures required removal both by 10 days and by 3 months postpartum. Women whose perineal trauma was repaired with glycerol-impregnated chromic catgut were 10% more likely to have perineal pain at 10 days and 33% more likely to suffer from dyspareunia in the 3 months following delivery. The high rates of maternal morbidity associated with glycerol-impregnated chromic catgut appear to preclude its use for perineal repair.     

Bupivacaine plus epinephrine for laparoscopic myomectomy: a randomized placebo-controlled trial

OBJECTIVE: To evaluate the effectiveness of the injection of bupivacaine plus epinephrine before laparoscopic myomectomy. METHODS: Sixty premenopausal women with uterine leiomyomata were enrolled in a randomized controlled design and intraoperatively treated with injection of bupivacaine plus epinephrine (group A) or saline solution (group B) during laparoscopic myomectomy. Uterine size and volume, number of leiomyomata, hematological parameters, total operative time, enucleation time of each myoma, suturing time of the myomectomy, blood loss, degree of surgical difficulty, and postoperative pain were evaluated. Just before and after the injection of vasoconstrictive or saline solution, systolic and diastolic blood pressure and heart rate were recorded in each subject. RESULTS: Blood loss, total operative and enucleation time, and degree of surgical difficulty was significantly (P <.05) lower in group A than in group B. No difference was observed between groups in suturing time of the myomectomy. The number of vials of pain medication used postoperatively was significantly (P <.05) lower in group A than in group B. No differences in systolic and diastolic blood pressure or heart rate was recorded between the 2 groups. CONCLUSION: The injection of bupivacaine plus epinephrine during laparoscopic myomectomy is effective in reducing blood loss, total operative and enucleation time, degree of surgical difficulty, and postoperative pain.     

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 placebo-controlled trial of erythromycin for the treatment of Ureaplasma urealyticum to prevent premature delivery. The Vaginal Infections and Prematurity Study Group

Ureaplasma urealyticum has been associated with low birth weight and histologic chorioamnionitis and it is a frequent isolate from the chorioamnion of patients who are delivered prematurely. In prior clinical trials using antibiotics active against U. urealyticum, antibiotic treatment was associated with reduced prematurity and increased mean birth weight. In this multicenter, randomized, double-blind clinical trial, pregnant women with U. urealyticum were treated with 333 mg of erythromycin base or placebo three times daily, starting between 26 and 30 weeks' gestation and continuing through 35 completed weeks of pregnancy. Women with urinary tract infection or Neisseria gonorrhoeae infection were excluded from the trial, and women with Chlamydia trachomatis or group B streptococci were excluded from these analyses. Erythromycin did not eliminate U. urealyticum from the lower genital tract. There were no significant differences between erythromycin- and placebo-treated women in infant birth weight or gestational age at delivery, in frequency of premature rupture of membranes, or in neonatal outcome.     

Episiotomy and perineal tears presumed to be imminent: randomized controlled trial

BACKGROUND: The indication of the restricted use of episiotomy at tears presumed to be imminent is not clear. METHODS: Randomized controlled trial with two perineal management policies. Use of episiotomy: (a). only for fetal indications and (b). in addition at a tear presumed to be imminent. Participants: 146 primiparous women with an uncomplicated singleton pregnancy at >34 weeks of gestation. For the intention-to-treat analysis those 109 women were included who vaginally delivered a live full-term baby between January 1999 and September 2000: 49 women in group a, 60 in group b. OUTCOME MEASURES: Reduction of episiotomies, increase of intact perinea or only minor perineal trauma (intact perineum and first-degree tears), third-degree tears, anterior perineal trauma, perineal pain in the postpartum period, pH of the umbilical artery, Apgar scores, maternal blood loss. RESULTS: Episiotomy rates were 41% in group a and 77% in group b (p < 0.001). Women in the restrictive policy group had a greater chance of an intact perineum (29% vs. 10%; p = 0.023) or only minor perineal trauma (39% vs. 13%; p = 0.003) and had significant lower pain scores postpartum at different activities. There were no statistically significant differences with regard to third-degree tears, anterior trauma, pre- and postpartum hemoglobin concentrations, Apgar scores and pH of the umbilical artery. CONCLUSIONS: Avoiding episiotomy at tears presumed to be imminent increases the rate of intact perinea and the rate of only minor perineal trauma, reduces postpartum perineal pain and does not have any adverse effects on maternal or fetal morbidity.     

Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial

Pathogenesis and optimal treatment and prevention of preterm labor remain incompletely understood. Entry of cervical/vaginal microorganisms into lower uterine tissues has been implicated in preterm labor and may be amenable to specific therapy. Fifty-eight women with less than 34 completed weeks of gestation and without other obstetric complications, who were receiving intravenous tocolytics because of uterine contractions and who had cervical alteration (less than 5 cm dilated), were enrolled in a prospective randomized, double-blinded evaluation of 7 days of adjunctive therapy with enteric-coated erythromycin base (333 mg three times daily by mouth) versus placebo. Microbiologic examination included cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and group B streptococcus. Fifty-eight women with singleton pregnancies (29 erythromycin; 29 placebo) completed the protocol. Among women with cervical dilatation greater than or equal to 1 cm at the beginning of treatment, mean time until delivery was 32.5 days with erythromycin and 22.4 days with placebo treatment (p = 0.027). Of the erythromycin-treated women, seven of eight were delivered at greater than or equal to 37 weeks and only three of nine placebo-treated women were delivered at greater than or equal to 37 weeks (p = 0.035). Orally administered enteric-coated erythromycin as adjunctive treatment of pregnant women in labor less than or equal to 34 weeks is well tolerated. Adjunctive erythromycin given to women treated for preterm labor less than or equal to 34 weeks is associated with prolongation of pregnancy and delivery at 37 weeks only in women with cervical dilatation at the beginning of treatment.     

Antibiotic prophylaxis for prevention of postpartum perineal wound complications: a randomized controlled trial

OBJECTIVE: To estimate whether prophylactic antibiotics at the time of repair of third- or fourth-degree perineal tears after vaginal delivery prevent wound infection and breakdown. METHODS: This was a prospective, randomized, placebo-controlled study. Patients who sustained third- or fourth-degree perineal tears after a vaginal delivery were recruited for the study. Each patient was given a single intravenous dose of a second-generation cephalosporin (cefotetan or cefoxitin) or placebo before repair of third- or fourth-degree perineal tears. Obstetricians and patients were blinded to study drug. The perineum was inspected for evidence of infection or breakdown at discharge from the hospital and at 2 weeks postpartum. Primary end points were gross disruption or purulent discharge at site of perineal repair by 2 weeks postpartum. RESULTS: One hundred forty-seven patients were recruited for the study. Of these, 83 patients received placebo and 64 patients received antibiotics. Forty patients (27.2%) did not return for their 2-week appointment. Of the patients seen at 2 weeks postpartum, 4 of 49 (8.2%) patients who received antibiotics and 14 of 58 (24.1%) patients who received placebo developed a perineal wound complication (P=.037). There were no differences between groups in parity, incidence of diabetes, operative delivery, or third-degree compared with fourth-degree lacerations. CONCLUSION: By 2 weeks postpartum, patients who received prophylactic antibiotics at the time of third- or fourth-degree laceration repair had a lower rate of perineal wound complications than patients who received placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clincaltrials.gov, NCT00186082. LEVEL OF EVIDENCE: I.     

Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation

OBJECTIVE: To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum. METHOD: A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4 cm dilation) and ending with delivery. RESULTS: A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26 min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use. CONCLUSION: Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters.