Familial Mediterranean fever during pregnancy: an independent risk factor for preterm delivery

Objective

To investigate pregnancy outcome of patients with Familial Mediterranean fever (FMF).

Study design

A population-based study comparing all pregnancies of women with and without FMF between the years 1988 and 2006 was conducted. Stratified analyses, using the Mantel–Haenszel procedure and multiple logistic regression models, were performed to control for confounders.

Results

During the study period there were 175,572 deliveries, of which 239 occurred in patients with FMF. Using a multivariable analysis, the following conditions were significantly associated with FMF: preterm delivery (PTD, <37 weeks) (odds ratio (OR) = 1.5; 95% confidence interval (CI) 1.1–2.2), fertility treatments (OR = 2.5; 95% CI 1.4–4.4), recurrent abortions (OR = 2.2; 95% CI 1.5–3.2), labor induction (OR = 1.9; 95% CI 1.5–2.5) and malpresentations (OR = 1.8; 95% CI 1.2–2.8). Patients with FMF were more likely to deliver by cesarean delivery (CD) as compared to the comparison group (18.0% vs. 12.8%; P = 0.017). However, while controlling for possible confounders such as malpresentations, labor dystocia and failed induction, using multivariable analysis with CD as the outcome variable, FMF was not found as an independent risk factor for CD (adjusted OR = 1.2; 95% CI 0.8–1.8, P = 0.388). No significant differences were noted between the groups regarding perinatal outcomes such as low Apgar scores (<7) at 1 and 5 min (2.4% vs. 4.3%, P = 0.153 and 0.4% vs. 0.6%, P = 0.692; respectively), congenital malformations (5.2% vs. 4.9%, P = 0.838), or perinatal mortality (0.8% vs. 1.4%, P = 0.445). Stratified analysis, using the Mantel–Haenszel technique, was used to assess the association between FMF and PTD while controlling for possible confounders such as iatrogenic labor induction, fertility treatments, recurrent abortions and placental abruption. None of those variables explained the higher incidence of PTD in the group of patients with FMF.

Conclusion

Familial Mediterranean fever is an independent risk factor for preterm delivery. Nevertheless, perinatal outcome is comparable to the general population.     

Urbanization and the likelihood of a cesarean section

Objective

This study examines the association between the likelihood of cesarean section (CS) and the degree of urbanization in Taiwan, exploring possible explanations for the difference.

Study design

The database used in this study was the Taiwan 2004 National Health Insurance Research Database. A total of 200,207 singleton deliveries fulfilled our criteria and were included in our study. The urbanization level of cities/towns where parturients resided at the time of delivery was stratified into seven categories. A multilevel logistic regression model was applied to examine the relative likelihood of CS by urbanization level after adjusting for parturient, physician and hospital characteristics.

Results

There was an upward trend in the CS rate with advancing urbanization level; the CS rates for urbanization level 1 (most urbanized) through 7 (least urbanized) were 33.7, 32.3, 30.4, 30.2 29.7, 29.5, and 28.6%, respectively. Compared with participants living at the highest urbanization level, the adjusted odds of a CS were 0.91 (95% CI = 0.85–0.98, p = 0.014), 0.84 (95% CI = 0.78–0.91, p < 0.001), 0.83 (95% CI = 0.68–0.88, p < 0.001), 0.79 (95% CI = 0.72–0.86, p < 0.001), and 0.70 (95% CI = 0.62–0.80, p < 0.001) times, respectively, for those living in cities/towns ranked from the third highest to the lowest levels of urbanization.

Conclusions

We conclude that higher urbanization levels were associated with higher odds of CS. Highly urbanized communities could therefore be targeted for policy intervention aimed at reducing the unnecessary CS rate.     

Combination of uterine artery Doppler velocimetry and maternal serum placental growth factor estimation in predicting occurrence of pre-eclampsia in early second trimester pregnancy: a prospective cohort study

Objective

To determine the effectiveness of the combined use of uterine artery Doppler velocimetry (UADV) and estimation of maternal serum placental growth factor (PlGF) levels in early second trimester (20–22 weeks of gestation) in identifying pregnant women at risk of developing pre-eclampsia.

Study design

Prospective cohort study on 1104 pregnant women with singleton pregnancies between May 2009 and December 2010. UADV and maternal serum PlGF estimation were done at 20–22 weeks’ gestation. Association between the two variables and the occurrence of pre-eclampsia was analyzed by logistic regression analysis and odds ratio was computed. The results were considered significant when p was <0.05.

Results

Logistic regression analysis showed that both abnormal UADV (odds ratio (OR) 4.1; 95% CI 2.3–7.2; p = 0.000) and serum PlGF < 188 pg/ml (OR 3.6; 95% CI 1.95–6.5; p = 0.000) are independent variables in the occurrence of pre-eclampsia, and the difference between the association of these two variables with pre-eclampsia was statistically insignificant as 95% CI values overlap. Multivariate logistic regression analysis showed that a combination of abnormal UADV and serum PlGF < 188 pg/ml at 20–22 weeks had a very poor association (OR 1.1; 95% CI 0.3–3.8; p = 0.938) with the occurrence of pre-eclampsia, as the 95% CI values encompass 1 and p is >0.05.

Conclusion

UADV and maternal serum PlGF estimation at 20–22 weeks of gestation are strong predictors of the occurrence of pre-eclampsia when used individually but in combination their association with pre-eclampsia is not significant.     

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11-13 weeks' gestation in pregnancies delivering small for gestational age neonates

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11–13 weeks’ gestation in the prediction of small-for-gestational age (SGA) neonates.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls.

Results

In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4–93.4 ng/mL vs 94.9, IQR 56.7–131.2 ng/mL, p = 0.002) and IGFBP-1 (58.2, IGR 39.8–84.9 ng/mL vs 81.4, IGR 57.3–105.5 ng/mL, p = 0.002) but not IGFBP-3 (54.5, IGR 45.6–61.5 ng/mL vs 55.4, IGR 47.4–64.9 ng/mL, p = 0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA.

Conclusion

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11–13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.     

First-trimester maternal serum metastin, placental growth factor and chitotriosidase levels in pre-eclampsia

Objective

To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive.

Study design

A retrospective case–control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11–14 weeks and stored at −70 °C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls.

Results

Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p < 0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 13.5 pg/mL, p < 0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p < 0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p < 0.001, p < 0.001 and p < 0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia.

Conclusions

Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia.     

Effectiveness of local anaesthetics with and without vasoconstrictors for perineal repair during spontaneous delivery: double-blind randomised controlled trial

Objective

to investigate the use of local anaesthetics, in the presence or absence of vasoconstrictors, for perineal repair during spontaneous delivery.

Design

double-blind, randomised-controlled trial.

Setting

a birth centre, in the city of Sao Paulo, Brazil.

Participants

from June to December 2004, a total of 96 women were allocated into three groups (first-degree perineal lacerations, second-degree perineal lacerations or episiotomy), and treated with local anaesthesia (1% lidocaine or 1% lidocaine with epinephrine) (n=16 per treatment per group).

Interventions

an initial local infiltration of the anaesthetic solution was given so that episiotomy could be carried out (5 ml) and to suture spontaneous lacerations (1 ml), followed by repeated doses (1 ml) until pain was completely inhibited.

Measurements and findings

the main outcome measurement was the volume of anaesthetic used during episiotomy and perineal suture. Our data suggest that the concomitant use of the vasoconstrictor resulted in a significantly lower average volume used in the treatment of first-degree (1 ml, 95% confidence interval (CI) 0.4–1.6) and second-degree (3.7 ml, 95% CI 1.6–5.8) lacerations (p=0.002 and 0.001, respectively). A 0.3 ml (95% CI 1.5–2.1) average decrease in anaesthetic volume was observed with episiotomy (p=0.724). The maximum volume of anaesthetic used with and without vasoconstrictor was 1–2 ml in 95% and 3–4 ml in 50% of first-degree lacerations, respectively, and 1–6 ml in 88% and 7–15 ml in 81% of second-degree lacerations, respectively. For episiotomy, the maximum dose was 15 ml, regardless of anaesthetic solution used.

Key conclusions

our data confirm the hypothesis that the use of anaesthetics in conjunction with vasoconstrictors is more effective than anaesthetics alone in the repair of perineal lacerations, but not for episiotomy.     

Use of oxytocin to prevent haemorrhage at caesarean section--a survey of practice in the United Kingdom

Objective

Preterm birth remains one of the most challenging areas in obstetrics. The pathogenesis of preterm labor is multifactorial and research on preterm birth has focused principally on infection and inflammatory markers. Recently the focus has turned to potential genetic factors influencing preterm birth. Uteroplacental insufficiency and thrombotic vasculopathy are considered part of the pathogenesis of preterm labor. Investigating the gene expression in the maternal/fetal interface seems of importance to expand our knowledge of the pathophysiology of preterm birth. The renin–angiotensin system (RAS) appears to play an important role in fetal/placental development and uteroplacental circulation. Hence, the aim of this study was to investigate angiotensin converting enzyme (ACE) activity and I/D polymorphisms in the ACE gene in mothers and infants with appropriately grown infants in relation to preterm birth and infant birth weight.

Study design

We conducted a cross-sectional study of 113 term pregnancies (≥37 weeks) and 18 preterm pregnancies (<37 weeks). Umbilical cord bloods (venous and arterial) were obtained from the placenta immediately after delivery for serum ACE activity, ACE genotype analysis of the I/D polymorphism and the acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype.

Results

The distribution of the maternal ACE genotypes was similar for preterm and term births as was maternal ACE activity. Preterm infants were more likely to be of the DD genotype than term infants (7/18 (39%) vs. 11/83 (13%), p = 0.02) (adjusted p = 0.04). There was no correlation between ACE activity and birth weight (r² 0.00, p = 0.82).

Conclusions

These findings suggest that the ACE genotype of the infant may influence the risk of preterm birth among appropriately grown fetuses.     

Inhibitory effects of electrical stimulation on delivery in pregnant rats

Objective

To study the efficacy of uterine electrical stimulation (ES) with various parameters in delaying delivery in term- and preterm-laboring animals.

Study design

Catheters and electrodes, as well as ES electrodes, were sutured onto the uterine horn in day-15 pregnant rats. ES with various durations/frequencies (five sets of parameters) was tested from gestation day 21 to determine its effects on uterine contractility. The best set of ES parameters was applied in term (day 21) and preterm (day 18—labor induced) animals to determine the effects of ES on delivery.

Results

(1) Significant reduction in uterine contractions (0.54 ± 0.11 vs. 0.86 ± 0.08 contractions per minute, P < 0.001) was noted with ES of only one of the five sets of parameters (set #5 with pulse train of 10 s on and 10 s off, 28 ms pulse width, frequency of 30 Hz and amplitude of 4 mA); (2) ES with parameter set 5 delayed delivery by 12.5 h (P = 0.01) and reduced area under the curve of intrauterine pressure in mmHg s (311 ± 147.21 vs. 848.75 ± 350.38, P < 0.05) and AUC-electromyographic activity is area under rectified (i.e. absolute value) uterine EMG trace in mV s (145.25 ± 93.1 vs. 410 ± 182.46, P < 0.05) in the term rats; and (3) similar effects were noted with ES in preterm rats with a delay in delivery by 28 h (P < 0.001), and a decrease in IUP–AUC (intrauterine pressure–area under curve) (101.5 ± 55.45 vs. 551 ± 269.06, P = 0.017) and EMG–AUC (64.25 ± 43.63 vs. 172.5 ± 62.91, P = 0.03).

Conclusion

ES of the uterus with appropriate parameters inhibits uterine contractions and delays delivery in both term and preterm rats.     

Does 45,X/46,XX mosaicism with 6–28% of aneuploidy affect the outcomes of IVF or ICSI?

Objective

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI.

Study design

Forty-six women with a 45,X/46,XX karyotype with 6–28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype.

Results

No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p = 0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p = 0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p = 0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p = 0.51).

Conclusion

45,X/46,XX mosaicism with 6–28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies.     

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer

Objective

To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET).

Study design

Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts. Outcome measures were gestational age at delivery, birth weight, birth length, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA) infants, perinatal mortality and minor/major birth defects (evaluated by parent questionnaire).

Results

Gestational age (38.6 ± 2 versus 38.7 ± 1.9 weeks) and preterm delivery rate (6.9% versus 6.9%, aOR: 0.96 95%CI: 0.76–1.22) in singletons born after the transfer of vitrified embryos were comparable to those born after the transfer of fresh embryos. Children born after the transfer of vitrified embryos had a higher birth weight (3028 ± 465 versus 2943 ± 470 g, p < 0.0001) and lower LBW (8.5% versus 11.9%, aOR: 0.65 95%CI: 0.53–0.79) and SGA (3.6% versus 7.6% aOR: 0.43 95%CI: 0.33–0.56) rates. Total birth defect rates (including minor anomalies) (2.4% versus 1.9%, aOR: 1.41 95%CI: 0.96–2.10) and perinatal mortality rates (0.6% versus 0.5%, aOR: 1.02 95%CI: 0.21–4.85) were comparable between the vitrified and fresh groups.

Conclusions

Vitrification of embryos/blastocysts did not increase the incidence of adverse neonatal outcomes or birth defects following single embryo transfer.     

Follow-up after LLETZ: a study of 682 cases of CIN 2–CIN 3 in a single institution

Objective

To evaluate the importance of resection margins in the risk of persistent/recurrent lesions and to investigate other factors such as detection of high-risk HPV, which could potentially predict persistent/recurrent disease before patients engage in follow-up.

Study design

682 women with a histologically confirmed diagnosis of CIN 2–3 treated by loop electrosurgical excision procedure (LEEP) were included, between January 2000 and December 2006. Age, high-risk HPV detection determined by Hybrid Capture II and cone margins were evaluated as possible predictors of persistent/recurrent disease.

Results

The mean age at diagnosis was 37.8 years (range 18–73). The mean follow-up period was 39.9 months (SD 25.8). 6.6% of patients (45/682) were lost to follow-up. 64.7% of patients (441/682) had clear margins in the specimen and 20.1% of patients had positive surgical margins (137/682). In 8.6% of patients (59/682) the resection margins were uncertain. Positive endocervical sweep was found in 10.8% of cases (73/682). Residual/recurrent disease was demonstrated by colposcopy-guided biopsy in 13.9% of patients (88/637); 77.3% (68/88) of them developed CIN 1 while only 22.7% (20/88) developed high-grade premalignant lesions or carcinomas during the follow-up. We found significant differences in the frequency of persistent/recurrent disease depending on the status of margins: 24.8% of cases with positive margins vs 11.1% of cases with negative margins (p < 0.0001). Multivariate analysis showed that only post-treatment high-risk HPV detection and status of the cone margins were significantly predictive of persistent/recurrent disease (OR 4.1, 95%CI 2.4–7.3, p < 0.0001 and OR 2.7, 95%CI 1.5–4.7, p = 0.001; respectively).

Conclusion

The combination of histological examination of resection margins plus post-treatment tests for HPV detection would help to classify LEEP-treated patients into categories at different risk of recurrence.     

A randomised controlled trial evaluating the effect of immersion bath on labour pain

Objective

to evaluate the effect of an immersion bath on pain magnitude during the first stage of labour.

Design

a randomised controlled trial comparing the pain scores of bathing and non-bathing nulliparous women during birth was employed.

Setting

the study was conducted at the Normal Birth Center of Amparo Maternal, São Paulo, Brazil.

Participants

108 birthing women, with 54 women randomly assigned to each group.

Interventions

when the birthing women presented at 6–7 cm of cervical dilation, they were placed in an immersion bath for 60 mins.

Outcome measures

pain scores, using a behavioural pain scale and a numeric scale, were recorded at two evaluation time points: at 6–7 cm of cervical dilation and 1 h after the first pain score evaluation.

Findings

at the first evaluation, on the behavioural scale, the means were 2.1 for both groups (p=0.914; 95% confidence intervals (CI) 1.9–2.3 for the control group and 2.0–2.2 for the experimental group). On the numeric scale, the means were 8.7 and 8.5 for the control and experimental groups, respectively (p=0.235; 95% CI 8.2–9.2 for the control group and 8.1–8.9 for the experimental group). At the second evaluation, the pain score means for both scales were statistically higher in the control group than in the experimental group. On the behavioural scale, the scores were 2.4 vs. 1.9, respectively, for the control and experimental groups (p<0.001; 95% CI 2.2–2.6 for the control group and 1.7–2.1 for the experimental group). On the numeric scale, the scores were 9.3 vs. 8.5, respectively, for the control and experimental groups (p<0.05; 95% CI 8.9–9.7 for the control group and 8.1–8.9 for the experimental group).

Conclusions

mean labour pain scores in the control group were significantly higher than those in the experimental group. The present findings suggest that use of an immersion bath is a suitable alternative form of pain relief for women during labour.     

Serum C-reactive protein in the differential diagnosis of ovarian masses

Objective

A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer.

Study design

In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n = 44, epithelial ovarian cancer [EOC]: n = 198) ovarian masses. Results were correlated to clinical data.

Results

Median (25th, 75th percentiles) serum CRP in patients with benign ovarian tumors, with ovarian tumors of LMP, and with EOC were 0.5 (0.5, 0.6) mg/dL, 0.5 (0.5, 0.9) mg/dL, and 1.36 (0.5, 4.9) mg/dL, respectively (p < 0.001). In the subgroup of patients with EOC, serum CRP significantly correlated with FIGO stage (p < 0.001), residual tumor mass (p < 0.001), and patients’ age (p = 0.04), but not with tumor grade (p = 0.2) and histologic type (p = 0.4). In univariable and multivariable models including serum CRP, serum CA 125, and patients’ age, serum CRP independently predicted the presence of malignant ovarian masses (p < 0.0001; Odds Ratio [OR] 5.3, 95% Confidence Interval [CI] 3.8–7.4). Serum CRP had a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying malignant ovarian masses of 49.8%, 84.1%, 57.1%, and 79.8%, respectively.

Conclusion

Serum CRP is associated with the presence of malignant ovarian tumors independent of serum CA 125 and patients’ age and can therefore be used as additional diagnostic marker in the differential diagnosis of ovarian masses.     

Systematic review and meta-analysis of "inside-out" versus "outside-in" transobturator tapes in management of stress urinary incontinence in women

Objectives

To directly compare the current evidence for the efficacy, complications, quality of life and cost to health services of both transobturator tension free vaginal tape procedures – “inside-out” versus “outside-in” – in the surgical treatment of female stress urinary incontinence.

Study design

A prospective peer-reviewed protocol was prepared a priori, and a systematic search of relevant databases from 1966 to January 2011 was performed. Meta-analyses of five randomised trials and three cohort studies were performed separately in accordance with PRISMA and MOOSE, respectively.

Results

There was no significant difference in patient-reported cure/improvement (OR 1.25, 95%CI 0.78, 1.99; p = 0.35) nor in objective cure/improvement (OR 1.66, 95%CI 0.8, 3.43, p = 0.17) between the two groups at 12-month follow-up. Vaginal angle injuries were significantly higher with the outside-in route (OR 0.14, 95%CI 0.05, 0.41, p = 0.0003). Groin/thigh pain and de-novo urgency were non-significantly higher with the inside-out route (OR 1.42, 95%CI 0.94, 2.13, p = 0.10 and OR 1.46, 95%CI 0.63, 3.36, p = 0.38, respectively). There was no significant difference in postoperative quality of life scores between the two groups (WMD -1.65; 95% CI -5.76, 2.46, p = 0.43). None of the trials reported a “health-cost” analysis. Meta-analysis of cohort studies confirmed similar results.

Conclusions

This is the first reported direct meta-analysis comparing both routes of transobturator tapes. It showed no evidence of significant differences in the efficacy and impact on women's quality of life between “inside-out” and “outside-in” transobturator tapes up to one-year follow-up. The “inside-out” route was associated with significantly fewer vaginal angle injuries but with trends towards higher risk of postoperative groin pain. Long-term follow-up of adequately powered RCTs is required to assess if these results pertain.     

The impact of plasma fibrinogen levels on patients with vulvar cancer

Objective

To investigate the association between plasma fibrinogen levels and clinico-pathological parameters of patients with vulvar cancer and to determine their value as prognostic parameters.

Study design

In this retrospective study, we evaluated pretreatment plasma fibrinogen levels in 120 patients with invasive squamous cell vulvar cancer and correlated them with clinico-pathological parameters and patients’ survival.

Results

Pretreatment plasma fibrinogen levels were directly associated with tumor stage (pT1a vs. pT1b vs. pT2 vs. pT3-4, p = 0.001), lymph node involvement (pN0 vs. pN1, p = 0.04), and histological grade (G1 vs. G2 vs. G3, p = 0.03), but not with patients’ age (≤70 years vs. >70 years, p = 0.6). In a multivariate survival analysis, tumor stage (p = 0.006/p = 0.02) and lymph node involvement (p < 0.001/p < 0.001), but neither histological grade (p = 0.2/p = 0.9) nor plasma fibrinogen levels (p = 0.6/p = 0.6) were associated with disease-free and overall survival, respectively. In a multivariate analysis, patient's age (≤70 years vs. >70 years) was associated with overall survival (p = 0.03) but not with disease-free survival (p = 0.1).

Conclusion

Pretreatment plasma fibrinogen levels were directly associated with tumor stage, lymph node involvement and histological grade. Although we could demonstrate a prognostic value of pretreatment plasma fibrinogen levels on survival, we were unable to establish fibrinogen as an independent prognostic parameter in patients with vulvar cancer.     

Ultra-high dose of intra-amniotic or direct fetal intramuscular betamethasone for lung maturation in the preterm goat model

Objective

To evaluate the effects of intra-amniotic (IA) and fetal injections of a single ultra-high dose of betamethasone (BM) 48 h before preterm delivery on neonatal pulmonary function, using an experimental goat model.

Study design

Eighteen date-mated singleton pregnant Hair goats were randomized into four groups. At gestational day 118 (alveolar phase, term 150–155 days) after obtaining a sample of amniotic fluid, fetuses in group 1 (n = 5) received 8 mg/kg IA BM, and in group 2 (n = 5) 4 mg/kg fetal IM BM. In group 3 (n = 4) (0.3 mg/kg/day) maternal BM was administered at day 118 and 119 with a 24 h interval; control fetuses (n = 4) received 1 mL/kg of IA saline at day 118. At gestational day 120, after obtaining second sample of amniotic fluids 18 kids were delivered by preterm cesarean section, entubated, weighed, and mechanically ventilated for 15 min. Arterial blood gas samples and deflation/inflation lung pressure–volume measurements were obtained. After sacrifice, lungs were removed, weighed, gross examined and processed for further histological and immunohistochemical (IHC) evaluations. On hematoxylin and eosin (HE) stained slides, presence and severity of lung emphysema was evaluated; slides stained for surfactant proteins, and caspases were used for semi-quantitative evaluation of lung maturation. Kruskal–Wallis, Mann–Whitney, Wilcoxon signed rank, and chi-square tests were used for comparisons.

Results

IA BM was associated with increased number of stillbirths (60% vs. 0% in control) (p = 0.06) and emphysematous changes. Bodyweight-adjusted pressure–volume measurements were improved after maternal, but not IA or fetal, BM (p = 0.06). Following mechanical ventilation, arterial blood gas parameters did not significantly alter across maternal and fetal administrations. However, pH was significantly lower (p < 0.05) and carbon dioxide partial pressure was higher (p < 0.05) in the control group, indicating hypercapnic acidemia in non-treated pregnancies. None of the treatments induced measurable alterations in amniotic fluid lecithin/sphingomyelin (L/S) values. IA and fetal routes were associated with decreased surfactant protein expressions and increased apoptotic activity in alveolar and bronchio-alveolar epithelial cells.

Conclusion

Ultra-high dose IA and fetal IM BM is not superior to the standard dose and maternal way of administration in our experimental design.     

The role of radiotherapy in the management of resected uterine papillary serous and clear cell carcinoma

Objective

Primary uterine papillary serous (PS) and clear cell (CC) carcinoma are aggressive histologies characterized by elevated risk of loco-regional recurrence and disease-specific mortality following hysterectomy. The impact of adjuvant radiotherapy remains to be elucidated. The present study is a single institution, retrospective cohort comparison to determine whether post-hysterectomy radiotherapy improves loco-regional control and/or disease-specific survival outcomes in a population of women with PS and/or CC.

Study design

Between June 1992 and November 2006, 50 women underwent hysterectomy alone (H) or hysterectomy with adjuvant radiotherapy (H + RT) for primary uterine PS and/or CC. RT involved either high dose-rate (HDR) brachytherapy, external beam RT, or both.

Results

At a median survivor follow-up of 27 months (range 2.7–137.3) for the H + RT group and 61 months (range 11.9–114.6) for the H group (range 3–137), patients in the H + RT group demonstrated a trend toward superior disease-free survival (not yet attained at 26 months versus 25 months; p = 0.0625). For patients with ≥24 months of follow-up, disease recurrence was significantly higher in H patients over H + RT patients (45% versus 12.5%; p < 0.05). Additionally, the H + RT group demonstrated significant improvement in loco-regional control (0% versus 37.5%; p < 0.001), most pronounced within FIGO stages I–II H + RT patients (0% versus 70%; p < 0.001). Overall survival was not significantly different between the two cohorts (H = 32 months, H + RT = not yet attained at 26 months; p = non-significant).

Conclusions

Hysterectomy with adjuvant radiotherapy significantly improves disease-free survival within 2 years post-hysterectomy and significantly reduces loco-regional failures over hysterectomy alone.     

Learning curve analysis of laparoscopic radical hysterectomy and lymph node dissection in early cervical cancer

Objective

Locally advanced bulky cervical cancer (LABCC) is characterized by poor local control. The objective of this study was to identify the clinicopathologic variables associated with one-year central-only recurrence, which will serve as criteria for adjuvant hysterectomy after radiation (AHR) in patients with LABCC.

Study design

Between January 2000 and August 2007, we retrospectively evaluated outcomes in 225 patients with LABCC who were initially treated with radiation or chemoradiation.

Results

Among the 225 patients with LABCC, there were 41 recurrences within one year after treatment (8 central-only and 33 pelvis and/or distant site recurrences). Age, stage, and treatment type were not associated with the one-year central-only recurrences, but tumor size ≥8 cm had a statistically significant association based on multivariate analysis (OR, 5.39; 95% CI, 1.15–25.31; p = 0.03). The combination of non-squamous cell (non-SCC) type and tumor size ≥8 cm had a significantly higher rate of recurrence within one year (OR, 43.0; 95% CI, 4.78–386.68; p < 0.01).

Conclusions

Of patients with LABCC, those with non-SCC tumors ≥8 cm in size were at high risk for early central-only recurrence after cisplatin-based chemoradiation, and represent the subset of patients for whom AHR is beneficial.     

Predictors of spontaneous reduction in multiple pregnancies conceived following assisted reproductive technology

Objective

To identify patient and cycle parameters that relate to spontaneous reduction in multiple pregnancies following in vitro fertilization (IVF) and embryo transfer (ET).

Study design

A retrospective cohort study was conducted in an academic infertility center. All IVF cycles between January 2007 and June 2008 were evaluated and 69 infertile women were diagnosed with multiple gestation following IVF. Multiple pregnancy was diagnosed by transvaginal sonography at 6–7 weeks gestation following embryo transfer (ET). Repeat ultrasonography undertaken in late first trimester assessed ongoing multiple pregnancy versus occurrence of spontaneous reduction. Patient and IVF cycle parameters were compared between patients experiencing spontaneous reduction (n = 26, cases) compared to those where the multiple pregnancy proceeded uneventfully (n = 43, controls).

Results

Spontaneous reduction (SR) was observed in almost 38% of the studied multiple gestations (n = 69). Women experiencing SR were significantly older (p = .047), of a leaner body mass (p = .049), and exhibited significantly higher serum estradiol (E₂) levels in the early follicular phase (p = .016) compared to the controls. Endometrial thickness (EMT) on the day of hCG administration related inversely (p = .017), whereas the number of embryos transferred (ET) related positively with the likelihood of SR (p = .027). On multivariate analyses, EMT and the number of ET were identified as independent predictors of SR following IVF–ET; EMT of less than 10 mm was associated with a fourfold increased likelihood of SR (OR 4.18; 95% CI 1.02–17.01) whereas each additional embryo transferred doubled the risk of SR in multiple pregnancies resulting from IVF (OR 2.39; CI 1.02–5.58).

Conclusions

In multiple pregnancies conceived following IVF, occurrence of SR is relatively common. Increasing number of ET and EMT measuring <10 mm are identified as independent predictors of likelihood of SR. While advancing age, body mass and baseline E₂ levels were associated with likelihood of SR, these associations disappeared on adjusted analyses. The observed relationship between EMT and SR is novel: the underlying mechanisms are unclear and merit further investigation.