Delivery Progress, Labor Interventions and Perinatal Outcome in Spontaneous Vaginal Delivery of Singleton Pregnancies between Nulliparous and Primiparous Women with One Previous Elective Cesarean Section: A Retrospective Comparative Study.

Trial of labor after cesarean (TOLAC) is an alternative to repeated cesarean for women with singleton pregnancy and one previous transverse lower segment cesarean section (LSCS), resulting in most cases being a successful vaginal birth after cesarean section (VBAC). The primary objective of this study was to examine if the progress and the duration of the active first stage and the second stage of labor in nulliparous women with singleton pregnancy, spontaneous start of labor and vaginal birth differ from primiparous women succeeding VBAC after one previous elective LSCS in a country with a low cesarean section and high VBAC rate. Secondary objectives were to compare labor interventions and maternal-neonatal outcomes between the two groups. METHODS: This is a retrospective comparative study. Data were collected in a four-year period at the departments of Obstetrics and Gynecology at Kristianstad and Ystad hospitals in Sweden. Out of 14,925 deliveries, 106 primipara women with one previous elective LSCS and a spontaneous labor onset in the subsequent singleton pregnancy were identified. Of these women, 94 (88.7%) delivered vaginally and were included in the study (VBAC group). The comparison group included 212 randomly selected nulliparous women that had a normal singleton pregnancy, spontaneous labor onset and delivered vaginally. RESULTS: The rate of cervical dilation during the active first stage of labor as well as the duration of the second stage did not differ between the two groups. When adjusting for cervical dilation at admission, there was no significant difference between the two groups regarding the duration of the active phase of the first stage of labor. No significant differences were found in maternal-neonatal outcomes between the two groups except for higher birth weight in the VBAC group. The use of epidural analgesia was associated with slower dilation rhythm over the duration of the active phase and second stage of labor, need for labor augmentation, postpartum bleeding and need for transfusion at higher rates, irrespective of parity when epidural was used. CONCLUSIONS: Our study provides evidence that in women with one previous elective LSCS undergoing TOLAC in the subsequent pregnancy resulting in vaginal birth, the progress and duration of labor are not different from those in nulliparous women when labor is spontaneous and the it is a singleton pregnancy. The use of epidural was associated with prolonged labor, need for labor augmentation and higher postpartum bleeding, irrespective of parity. This information may be useful in patient counseling and labor management in TOLAC.

Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine.

BACKGROUND: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. METHODS: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. RESULTS: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. DISCUSSION: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.

Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18.

Human papillomavirus (HPV) infection causes cervical cancer and genital warts. Young women (1106) were randomized to receive one of three formulations of a quadrivalent HPV (Types 6/11/16/18) L1 virus-like particle (VLP) vaccine or one of two placebo formulations. The goal was to assess vaccine safety and immunogenicity in baseline HPV 6/11/16 or 18-naïve and previously infected subjects. All three formulations were highly immunogenic. At Month 2 (postdose 1), among women with vaccine-type antibodies at baseline, vaccine-induced anti-HPV responses were approximately 12- to 26-fold higher than those observed in baseline-naïve women, suggesting an anamnestic response. Following an initial, similar sized decline, anti-HPV responses plateaued and remained stable through end-of-study (3.0 years). No vaccine-related serious adverse experiences were reported.

Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial.

BACKGROUND: A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). METHODS: 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. FINDINGS: Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. INTERPRETATION: A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.

The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor.

Relcovaptan (SR 49059) is a non-peptide, orally active vasopressin V1a receptor inhibitor. The effect on uterine contractions in 18 women with preterm labor in pregnancy weeks 32-36 was assessed in a double-blind investigation. The inclusion criterion was at least four regular uterine contractions over 30 min as measured by external tocodynamometry. Twelve patients received at random a single oral dose of 400 mg relcovaptan and six received placebo, and contractions were monitored up to 6 h thereafter. Rescue medication (beta-adrenoceptor-stimulating drug) was allowed after 2 h. Before drug administration a mean (+/- SE) of 8.2 +/- 1.4 and 9.7 +/- 1.6 contractions/30 min were recorded in the relcovaptan- and placebo-treated groups, respectively. In the former group, the frequency of uterine contractions started to decrease within the first half hour, and 1.5-2 h after dosing it was steady at 3.2 +/- 0.9 contractions/30 min. Correspondingly, after placebo, 7.8 +/- 2.2 contractions/30 min were recorded, a statistically significant difference (p = 0.017). The activity in the relcovaptan-treated women remained low, whereas in the placebo group inhibited uterine contractions were observed only in women receiving 'rescue' tocolytic treatment. It is concluded that relcovaptan inhibits preterm labor.

Oxytocin mRNA content in the endometrium of non-pregnant women.

OBJECTIVE: To study oxytocin mRNA in the human endometrium at different phases of the menstrual cycle. DESIGN: An exploratory study in non-pregnant women. SETTING: The Department of Obstetrics and Gynecology, Lund University Hospital, Sweden. PARTICIPANTS: Thirty-three women of fertile age undergoing hysterectomy or endometrial curettage on routine benign gynaecologic indications. METHODS: Endometrial tissue was obtained throughout the menstrual cycle. The presence of oxytocin mRNA was investigated by in situ hybridisation and by real time PCR. MAIN OUTCOME MEASURES: Oxytocin mRNA signalling intensity found by in situ hybridisation of tissue obtained at different times of the menstrual cycle. Relative amounts of oxytocin mRNA measured by real time PCR. RESULTS: The signal for oxytocin mRNA obtained by in situ hybridisation was more pronounced in glandular epithelial cells than in stromal cells. Furthermore, it was most marked around mid-cycle. The expression of oxytocin mRNA was confirmed by real time PCR. CONCLUSIONS: The results indicate that oxytocin may be synthesised in the endometrium of non-pregnant women, particularly in the glandular epithelial cells. Hormone released from these sources may have a paracrine action on the uterus. Oxytocin mRNA expression seems to be ovarian hormone dependent with the highest concentration around mid-cycle.

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women.

BACKGROUND: Compounds that block uterine oxytocin and vasopressin V1a receptors have a therapeutic potential in preterm labor and primary dysmenorrhoea. The orally active vasopressin V1a receptor antagonist, SR49059, inhibits the effect of vasopressin on human uterine activity in vivo, but the influence on the response to oxytocin is unknown. METHODS: In a placebo-controlled, double-blind, parallel-group, four-dose comparison, the inhibitory effect of SR 49059 on oxytocin- and vasopressin-induced uterine contractions in humans was investigated. Sixteen healthy female subjects, who had previously undergone sterilization with tubal ligation, participated in intrauterine pressure recordings at one of the first 3 days of bleeding of two menstrual cycles. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin (Period 1) and of 50 pmol/kg body weight of oxytocin (Period 2) were given 1 h before and 1, 2 and 4 h after oral administration of 0 (placebo), 25, 75 or 200 mg of SR 49059. The area between the recording curve and zero level of intrauterine pressure (AUC) was calculated. Vital signs as well as urine and plasma safety parameters were measured. The plasma concentrations of oxytocin, vasopressin and the study drug were also estimated. RESULTS: The plasma concentrations of SR 49059 appeared to be dose related, with mean maximal values of 62.0, 163.7 and 468.0 ng/ml in the 25, 75 and 200 mg dose groups, respectively, in Period 1 with vasopressin and 34.4, 116.7 and 418.0 ng/mL, respectively, in Period 2 with oxytocin. Tmax was observed at about 1 h. The cumulative AUC over 50 min after vasopressin injection per se was significantly higher than that after oxytocin in spite of a five times lower dose and lower plasma concentrations. Pretreatment by SR 49059 caused a dose-related reduction in AUCs for vasopressin, whereas no such effect was seen for oxytocin. With vasopressin as an agonist, a lower diastolic blood pressure was observed in all SR 49059 treatment groups, but not with oxytocin. CONCLUSIONS: The much higher potency of vasopressin compared with oxytocin on uterine activity in non-pregnant women at menstruation was confirmed. SR 49059 dose-dependently inhibits vasopressin-induced contractions, whereas such an effect was not seen with the present doses of SR 49059 and oxytocin. A marked reduction by SR 49059 of diastolic blood pressure after vasopressin injection was observed, indicating an inhibition by this compound of vascular vasopressin receptors.

FE 200 440: a selective oxytocin antagonist on the term-pregnant human uterus.

OBJECTIVE: To compare a newly developed oxytocin antagonist, FE 200 440, with atosiban and ANTAG III, as to potency and selectivity of inhibitory effects on oxytocin- and vasopressin-induced myometrial responses. FE 200 440 has high affinity for the human cloned oxytocin receptor, approximately 300-fold that for the vasopressin V(1a) receptor, whereas atosiban binds well to both receptors. DESIGN: In vitro study of human myometrial contractility. The Research Laboratory of the Department of Obstetrics and Gynecology, Lund University Hospital, Sweden. PARTICIPANTS: Forty-seven term-pregnant women not in labour who were delivered by caesarean section. INTERVENTIONS: Concentration-response curves with oxytocin and arginine vasopressin on isolated myometrial strips were recorded in control experiments, in the presence of atosiban in concentrations of 25, 250 and 750 nmol/L, and after pretreatment with ANTAG III and FE 200 440, both in concentrations of 2.5, 25 and 250 nmol/L.pA(2) values (i.e. an index of inhibitory action). RESULTS: With oxytocin as the agonist, the median pA(2) values for atosiban, ANTAG III and FE 200 440 were 10.6, 9.5 and 8.3, respectively. With vasopressin as the agonist, the pA(2) values for atosiban and ANTAG III were 8.8 and 8.7, whereas no inhibitory effect of FE 200 440 was seen in five out of six experiments. CONCLUSION: The new analogue FE 200 440 is a selective oxytocin antagonist and, in contrast to atosiban and ANTAG III, has practically no effect on vasopressin-induced contractions of isolated term-pregnant human myometrium.