Gabriele Saccone | Università degli Studi di Napoli "Federico II" (original) (raw)

Papers by Gabriele Saccone

BACKGROUND: Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interven... more BACKGROUND:
Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality. Interventions aimed at preventing PTB can be classified as primary, secondary, or tertiary prevention.

OBJECTIVE:
To conduct a review of systematic reviews on the effectiveness and safety of primary and secondary preterm birth prevention interventions.

SEARCH STRATEGY:
A systematic literature search of the Cochrane, PubMed/Medline, EMBASE and CINAHL databases was conducted on 2 September 2015, and updated on 21 November 2016.

SELECTION CRITERIA:
We included any published systematic review of randomized controlled trials (RCTs) or individual patient data (IPD) of RCTs related to primary or secondary prevention of PTB, published between 2005-2016 where gestational age at birth (of any interval) was a pre-specified outcome. Individual trials and non-systematic reviews were not eligible.

DATA COLLECTION AND ANALYSIS:
The population of interest was all pregnant women, regardless of PTB risk. The primary outcome was PTB < 37 weeks.

MAIN RESULTS:
In total, 112 reviews were included in this study. Overall there were 49 Cochrane and 63 non-Cochrane reviews. Eight were individual participant data (IPD) reviews. Sixty reviews assessed the effect of primary prevention interventions on risk of PTB. Positive effects were reported for lifestyle and behavioural changes (including diet and exercise); nutritional supplements (including calcium and zinc supplementation); nutritional education; screening for lower genital tract infections. Eighty-three systematic reviews were identified relating to secondary PTB prevention interventions. Positive effects were found for low dose aspirin among women at risk of preeclampsia; clindamycin for treatment of bacterial vaginosis; treatment of vaginal candidiasis; progesterone in women with prior spontaneous PTB and in those with short midtrimester cervical length; L-arginine in women at risk for preeclampsia; levothyroxine among women with tyroid disease; calcium supplementation in women at risk of hypertensive disorders; smoking cessation; cervical length screening in women with history of PTB with placement of cerclage in those with short cervix; cervical pessary in singleton gestations with short cervix; and treatment of periodontal disease.

CONCLUSION:
The overview serves as a guide to current evidence relevant to PTB prevention. Only a few interventions have been demononstrated to be effective, including cerclage, progesterone, low dose aspirin, and lifestyle and behavioural changes. For several of the interventions evaluated, there was insufficient evidence to assess whether they were effective or not.

OBJECTIVE: To evaluate whether postpartum nonsteroidal antiinflammatory drug (NSAID) administrati... more OBJECTIVE:
To evaluate whether postpartum nonsteroidal antiinflammatory drug (NSAID) administration is associated with increased blood pressure in women with hypertensive disorders of pregnancy and to estimate the association between NSAID administration and use of opioid medication.

METHODS:
We conducted a retrospective cohort study of women with hypertensive disorders of pregnancy. Patients were analyzed in two groups according to whether they received NSAIDs postpartum. Study participants were women delivered at a tertiary care center from 2008 to 2015. The primary outcome was change in mean arterial pressure during the postpartum period. Secondary outcomes were postpartum pain scores, cumulative postpartum opioid requirement, initiation or dose escalation of antihypertensive agents, and adverse postpartum outcomes including acute renal failure, change in hematocrit, and maternal readmission for hypertensive disorder.

RESULTS:
Two hundred seventy-six women with hypertensive disorders of pregnancy were included (129 NSAID-unexposed and 147 NSAID-exposed). Postpartum NSAID administration was not associated with a statistically significant change in mean arterial pressure compared with no NSAID administration (-0.7 vs -1.8; mean difference 1.10, 95% CI -1.44 to 3.64). Similarly, no difference was observed between the cohorts in terms of need for initiation or escalation in dose of antihypertensive agents or maternal readmission for hypertensive disorder. The study was underpowered to determine whether NSAID administration was associated with any difference in less frequent secondary outcomes (eg, incidence of acute renal insufficiency, need for postpartum transfusion) or cumulative opioid use.

CONCLUSION:
Nonsteroidal antiinflammatory drug administration to postpartum patients with hypertensive disorders of pregnancy is not associated with a change in blood pressure or requirement for antihypertensive medication.

Prenatal carrier screening has expanded to include a large number of genes offered to all couples... more Prenatal carrier screening has expanded to include a large number of genes offered to all couples considering pregnancy or with an ongoing pregnancy. Expanded carrier screening refers to identification of carriers of single-gene disorders outside of traditional screening guidelines. Expanded carrier screening panels include numerous autosomal recessive and X-linked genetic conditions, including those with a very low carrier frequency, as well as those with mild or incompletely penetrant phenotype. Therefore, the clinical utility of these panels is still subject of debate. Priority should be given to carrier screening panels that include a comprehensive set of severe childhood-onset disorders. Psychosocial support and genetic couseling should be available prior to screening and for the return of positive results. Systems are needed to reduce the risk of misinterpreting results. Finally, attention should be paid on the impact of expanded carrier screening on health care organizations and burden of cost.

OBJECTIVE: Several markers have been studied to predict the responsiveness of endometrial hyperpl... more OBJECTIVE:
Several markers have been studied to predict the responsiveness of endometrial hyperplasia (EH) and early endometrial cancer (EEC) to progestin therapy. PTEN has played a major role in this field, although its predictive significance is still undefined. We aimed to assess if loss of PTEN expression on pre-treatment endometrial specimen may be a predictive markers of response to progestins in EH and EEC.

STUDY DESIGN:
MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched for relevant articles from the inception to May 2018. All studies assessing PTEN expression as predictive marker in EH and EEC treated with progestin were included. Relative risk (RR) for therapy failure was calculated with 95% confidence interval (CI) and a significant p-value<0.05, with a subgroup analysis based on the histologic category (EEC or EH) and the administration route of progestin (oral or intrauterine).

RESULTS:
Seven cohort studies assessing 376 patients were included. PTEN loss was not significantly associated with the outcome of therapy in the overall analysis (RR = 1.24, 95% CI, 0.88-1.76, p = 0.21), in + the subgroups of EEC (RR = 0.89, 0.32-2.49, p = 0.83), EH (RR = 1.30, 0.90-1.87 p = 0.16), oral progestin (RR = 1.25 0.88-1.79, p = 0.22) and intrauterine device (RR = 1.02, 0.36-2.87, p = 0.97).

CONCLUSION:
PTEN seems not to be useful as predictive marker of response to the conservative treatment of EH and EC, regardless of the administration route (oral or intrauterine) of progestins. We advise future researcher not to further assess PTEN as a stand-alone predictive marker.

BACKGROUND: Endometrial hyperplasia (EH) is classified into benign and precancerous according to ... more BACKGROUND:
Endometrial hyperplasia (EH) is classified into benign and precancerous according to two different histomorphologic systems: WHO (based on the subjective evaluation of cytologic atypia) and EIN (based on a combination of several parameters, assessable subjectively, or objectively through computerized analysis). ACOG recommends the use of EIN system. Nonetheless, higher prognostic value for EIN criteria was demonstrated only with the objective assessment, which is not routinely applicable.

OBJECTIVE:
To evaluate which subjective classifications of EH (WHO or EIN) has a better prognostic value, by assessing the risk of coexistent cancer.

METHODS:
Electronic databases were searched for relevant articles from the inception to July 2018. All studies assessing the presence of cancer on hysterectomy specimen after a preoperative histologic diagnosis of EH were included. Odds Ratio (OR), sensitivity and specificity were calculated with 95% confidence interval (CI). Sixteen cohort studies and three case-control studies, assessing 2582 EH, were included.

RESULTS:
WHO criteria showed an OR of 11.15 (95% CI, 7.65-16.24), a sensitivity of 0.86 (0.82-0.90) and a specificity of 0.67 (0.64-0.70) for coexistent cancer. Subjective EIN system had similar OR (11.85, 4.91-28.62; p=0.90), higher sensitivity (0.98, 0.94-0.99) and lower specificity (0.29, 0.24-0.34).

CONCLUSION:
WHO and subjective EIN system have similar prognostic value. However, EIN criteria appears more sensitive and thus more suitable for selecting women who need to be treated, while WHO criteria, based on cytologic atypia, seem more specific for lesion at higher risk of cancer. Therefore, an integration of EIN system with cytologic atypia should be considered. This article is protected by copyright. All rights reserved.

BACKGROUND: Morcellation of undiagnosed uterine sarcoma is cause of abdominal/pelvic disseminatio... more BACKGROUND:
Morcellation of undiagnosed uterine sarcoma is cause of abdominal/pelvic dissemination, residual tumor and recurrence. In the preoperative evaluation of suspect uterine masses, magnetic resonance imaging (MRI) and serum lactate dehydrogenase (LDH) total activity are referred to as the most effective tools, while computed tomography scan (CT) and LDH isoenzymes are less considered in literature.

CASE PRESENTATION:
A 46 year old woman was admitted to our department with a large uterine mass. Ultrasonography, MRI and LDH total activity did not allow a diagnosis of malignancy, and the woman expressed the wish to avoid hysterectomy. In spite of this, we opted for a total abdominal hysterectomy instead of a laparoscopic myomectomy, due to an elevation of LDH5/LDH1 ratio and CT findings indicative of sarcoma. Histological examination revealed a high grade leiomyosarcoma, confirming our suspicion. Thus, we had avoided the risks linked to morcellation.

CONCLUSIONS:
Our experience suggests that LDH isoenzymes assessment may be relevant in preoperative diagnosis of uterine sarcoma. Further studies are necessary to determine its role in a diagnostic algorithm. We think it may be useful especially for patients with clinical or ultrasonographic suspicion of uterine sarcoma not confirmed by imaging techniques. Furthermore, the role of less considered imaging techniques, such as CT, should not be underestimated in challenging cases.

OBJECTIVE: To determine if oral methylergometrine administration during the first 10 days followi... more OBJECTIVE:
To determine if oral methylergometrine administration during the first 10 days following spontaneous vaginal delivery has any beneficial effect on the increase of hemoglobin levels.

METHODS:
This was a parallel group double-blind placebo-controlled clinical trial conducted at single center university hospital in Italy. Participants were puerperal women, who delivered singleton gestation with spontaneous vaginal delivery at term. Participants were randomized into a 1:1 ratio to receive either 0.125 mg methylergometrine per os twice a day or placebo for 10 days. Hemoglobin levels was recorded on the day of delivery and after 10 days. The primary outcome was the variation in hemoglobin levels between the first and the 10th day of treatment.

RESULTS:
From December 2012 to October 2015, 220 agreed to take part in the study, underwent randomization, and were enrolled and followed-up. Of the randomized women, 110 (50%) were randomized to the methylergometrine group and 110 (50%) to the placebo group. No women were excluded after randomization or lost to follow-up (100%). We found no significant difference in the median variation of hemoglobin levels between the intervention and the placebo group Conclusions: Use of 10 days oral methylergometrine in puerperal women was not associated with any benefit in the variation of hemoglobin levels from delivery to 10 days after delivery.

TRIAL REGISTRATION:
EudraCT N. 2010-019809-42 on 23.03.2010 ( https://eudract.ema.europa.eu ).

Objective: To evaluate effects of exercise during pregnancy in asymptomatic singleton pregnancies... more Objective: To evaluate effects of exercise during pregnancy in asymptomatic singleton pregnancies without prior spontaneous preterm birth (SPTB) but with short transvaginal ultrasound cervical length (TVU CL). Study design: This is a secondary analysis of the Italian Pessary Trial for the Italian Preterm Birth Prevention (IPP) Working Group. In the original prospective randomized controlled trial asymptomatic singleton pregnancies without prior SPTB but with TVU CL 25 mm at 18 0/6–23 6/7 weeks were randomized into 1:1 ratio to either cervical pessary or no pessary. During their follow-up visits, women were asked about their activity. For the purpose of this secondary analysis, women were classified in the following groups, using the information obtained in the follow-up visit one month after randomization: 1) Exercise group, defined as women performing exercise !2 days a week for !20 min each day. 2) No exercise group, defined as women performing exercise <2 days a week for !20 min each day. The primary outcome of this secondary analysis was PTB < 37 weeks. Results: 300 women were included in this analysis. 99 (33.0%) were included in the exercise group. 201 (67.0%) were included in the no exercise group. Of the 201 women in the no exercise group, 90 (44.8%) affirmed that they had reduced their activity after the diagnosis of short cervix despite the research staff recommendations, while the other 111 (55.2%) women performed a sedentary life style even before the diagnosis of short cervix. PTB < 37 weeks occurred in 22 women (22.2%) in the exercise group, and 66 women (32.8%) in the no exercise group (aOR 0.65, 95% CI 0.33–1.03). Conclusion: In asymptomatic singleton pregnancies with short cervix, performing exercise !2 days a week for !20 min each day does not increase the risk of PTB but is indeed associated with a non-significant reduction in PTB < 37 weeks by 32%.

BACKGROUND: Monoamniotic twins are at increased risk of perinatal complications. Perinatal mortal... more BACKGROUND:
Monoamniotic twins are at increased risk of perinatal complications. Perinatal mortality has been reported to be high, primarily related to cord entanglement. International guidelines made no recommendation regarding whether these women should be managed in the hospital or can be safely managed in outpatient settings. Moreover, timing of planned delivery in these women is also a subject of debate.

OBJECTIVE:
To compare the perinatal outcomes of inpatient versus outpatient fetal surveillance approaches employed among 22 participating study centers; and to calculate the fetal and neonatal death rate according to gestational age in non-anomalous monoamniotic twins from 26 weeks' gestation.

STUDY DESIGN:
The MONOMONO study was a multinational cohort study. Clinical records of all consecutive women with monochorionic monoamniotic twin pregnancies, who were referred to 22 university hospitals in Italy, the United States, the United Kingdom, and Spain, from January 2010 to January 2017, were included in the study. Only non-anomalous uncomplicated monoamniotic twins with both fetuses alive at 26 0/7 weeks were included in the study. Management of monoamniotic twins was different in the different included centers. In 10 centers all monoamniotic twins were routinely managed inpatient. In 12 centers all monoamniotic twins were routinely managed as outpatients. The primary outcome was intrauterine fetal death in the inpatient versus outpatient group. We also planned to assess the fetal death rate and the neonatal death rate according to gestational age per 1-week interval. Outcomes were presented as odds ratio (OR) with the 95% of confidence interval (CI). In addition to the standard logistic regression analysis, we used a generalized mixed model approach, with twin pair as the cluster unit. This model was used because the outcomes of each twin were not independent of the co-twin.

RESULTS:
195 consecutive pregnant women with non-anomalous uncomplicated monoamniotic twin gestations (390 fetuses) were included. Of them, 75 (38.5%) were managed as inpatients and 120 (61.5%) were managed as outpatients. The overall perinatal loss rate was 10.8% (42/390) with the peak fetal death rate occurring at 29 weeks gestation (15/348, 4.3%). There was no significant difference in mean gestation age at delivery (31 weeks), birth weight (~1.6 kg), or emergency delivery rate between the inpatient and outpatient surveillance groups. There was no statistically significant difference in fetal death rates between inpatient surveillance protocols commencing from around 26 weeks compared with outpatient surveillance protocols from 30 weeks (3.3% vs 10.8%; adjusted OR 0.21, 95% CI 0.04 to 1.17). Maternal LOS in the hospital was 42.1 days in the inpatient group, and 7.4 days in the outpatient group (MD 34.70 days, 95% CI 31.31 to 38.09). From 32 0/7 to 36 6/7 weeks, no fetal or neonatal death in either group was recorded. 46 fetuses delivered after 34 0/7 weeks, and none of them died in utero or within the first 28 days of life.

CONCLUSION:
In uncomplicated monoamniotic twins, when compared with outpatient management, inpatient surveillance is associated with similar fetal mortality. After 31 6/7 weeks there were no intrauterine fetal deaths or neonatal deaths even up to 36 6/7 weeks

OBJECTIVE: To evaluate the impact of antibiotic therapy for chronic endometritis (CE) on IVF outc... more OBJECTIVE:
To evaluate the impact of antibiotic therapy for chronic endometritis (CE) on IVF outcome.

DESIGN:
Systematic review and meta-analysis.

SETTING:
Not applicable.

PATIENT(S):
Infertile women with history of recurrent implantation failure, defined as two or more failed ETs, undergoing one or more IVF cycle(s).

INTERVENTION(S):
The review was registered in PROSPERO (CRD42017062494) before the start of the literature search. Observational studies were identified by searching electronic databases. The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with persistent CE; and women with cured CE vs. women with normal endometrial histology (negative for CE). The summary measures were reported as odds ratio (OR) with 95% confidence interval (CI).

MAIN OUTCOME MEASURE(S):
Clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), implantation rate (IR), miscarriage rate.

RESULT(S):
A total of 796 patients (from five studies) were included. Women receiving antibiotic therapy (without the histologic confirmation of CE cure) did not show any advantage in comparison with untreated controls (OPR/LBR, CPR, and IR). Patients with cured CE showed higher OPR/LBR (OR 6.81), CPR (OR 4.02), and IR (OR 3.24) in comparison with patients with persistent CE. In vitro fertilization outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR, and IR). Miscarriage rate was not significantly different between groups.

CONCLUSION(S):
Chronic endometritis therapy may improve IVF outcome in patients suffering from recurrent implantation failure. A control biopsy should always confirm CE resolution before proceeding with IVF.

BACKGROUND: Vaginal application of lubricant during labor has been studied to shorten the length ... more BACKGROUND:
Vaginal application of lubricant during labor has been studied to shorten the length of the second stage of labor.

OBJECTIVE:
To evaluate whether vaginal application of lubricant shortens the second stage of labor.

DATA SOURCES:
Electronic databases were searched from their inception until February 2018. No restrictions for language or geographic location were applied.

STUDY ELIGIBILITY CRITERIA:
Randomized controlled trials (RCTs) comparing the use of lubricant of the vaginal canal (ie intervention group) with a control group (ie no lubricant) in pregnant women with singleton gestation and cephalic presentation undergoing spontaneous vaginal delivery at term. Trials on other interventions that might impact second stage of labor (pushing methods, perineal massage, Ritgen's maneuver, etc.) were not included.

STUDY APPRAISAL AND SYNTHESIS METHODS:
All analyses were done using an intention-to-treat approach. The primary outcome was the length of the second stage of labor. Pooled analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of mean difference (MD) with 95% confidence interval (CI).

TABULATION, INTEGRATION, AND RESULTS:
Three RCTs including 512 women evaluating the effect of lubricant application during labor were included in the meta-analysis. All trials included pregnant women with singleton gestations in cephalic presentation at term undergoing spontaneous vaginal delivery. One trial included only nulliparous women, while the other two included both nulliparous and multiparous women. Lubricant application started in the first stage before the active phase of labor, and was done intermittently by the midwife or the physician. A sterile gel was applied into the vaginal canal manually or with an applicator. All trials used water-soluble gel. The quantity of gel used was about 2-5 ml for each vaginal examination. There were no statistically significant differences, comparing women who received lubricant gel during labor with those who did not, in the lengths of second stage of labor (MD -7.11 minutes, 95% CI -15.60-1.38), of the first stage of labor, or of the active phase of the first stage of labor. No between-group differences were noticed in the risk of perineal lacerations, mode of delivery, and in the neonatal outcomes.

CONCLUSION:
Vaginal application of lubricant during labor does not reduce the length of the second stage of labor in pregnant women with singleton gestations undergoing an attempt at spontaneous vaginal delivery at term.

INTRODUCTION: There is inconclusive evidence to support any criteria for starting pharmacologic t... more INTRODUCTION:
There is inconclusive evidence to support any criteria for starting pharmacologic therapy after diet in women with gestational diabetes mellitus (GDM). We aimed to analyze the most used criteria for starting pharmacologic treatment for patients with GDM.

MATERIAL AND METHODS:
Electronic databases were searched from their inception to September 2017. We included all randomized controlled trials (RCTs) of GDM managed initially by diet and exercise reporting criteria for starting pharmacologic therapy. RCTs in women with pregestational diabetes were excluded. Data regarding glucose values used for starting pharmacologic therapy were extracted and carefully reviewed.

RESULTS:
We included 15 RCTs (4307 women) in the meta-analysis. For fasting glucose target, 8/14 (57%) used a value lower or equal to 90 mg/dL and the remainder used values < 99 mg/dL. Of the 10 RCTs targeting 2-hour postprandial values, the majority (9/10, 90%) used 120 mg/dL. The majority of RCTs (13/15, 87%) recommended pharmacologic therapy if either 1 or 2 values per 1- or 2-week period were higher than the target values: 7/13 (54%) used 1 value and 6/13 (46%) used 2 values higher than target values. One RCT (7%) used > 50% of the values higher than the target values and another one (7%) used > 30%.

CONCLUSION:
The majority of RCTs (87%) used very tight criteria of either 1 or 2 values over the target values in the 1 or 2-week period for starting pharmacologic treatment for patients with GDM; more than 50% used 2 values.

INTRODUCTION: To explore the effect of maternal fluorinated steroid therapy on fetuses affected b... more INTRODUCTION:
To explore the effect of maternal fluorinated steroid therapy on fetuses affected by second degree immune-mediated atrioventricular block (AVB).

MATERIAL AND METHODS:
Studies reporting the outcome of fetuses with immune-mediated second degree AVB diagnosed on prenatal ultrasound and treated with fluorinated steroids compared to those not treated were included. The primary outcome was the overall progression of AVB to either continuous or intermittent third degree AVB at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used.

RESULTS:
5 studies (71 fetuses) were included. The progression rate to AVB at birth in fetuses treated with steroids was 52% (95% CI 23-79) while in fetuses not receiving steroid therapy was 73% (95% CI 39-94). The overall rate of regression to either first degree, intermittent first/second degree or sinus rhythm in fetuses treated with steroids was 25% (95% CI 12-41) compared to 23% (95% CI 8-44) of those not treated. Stable (constant) second degree AVB at birth was present in 11% (95% CI 2-27) of cases in the treated group and in none of the new-borns in the untreated group, while complete regression to sinus rhythm occurred in 21% (95% CI 6-42) of fetuses receiving steroids versus 9% (95% CI 0-41) of those untreated.

CONCLUSIONS:
There is still limited evidence as to the benefit of administered fluorinated steroids in terms of affecting outcome of fetuses with second degree immune-mediated AVB. This article is protected by copyright. All rights reserved.

IMPORTANCE Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is... more IMPORTANCE Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is unclear if a cervical pessary can reduce the risk of spontaneous preterm delivery. OBJECTIVE To test whether in asymptomatic women with singleton pregnancies and no prior spontaneous preterm birth but with short cervical length on transvaginal ultrasound, use of a cervical pessary would reduce the rate of spontaneous preterm birth at less than 34 weeks of gestation. DESIGN, SETTING, AND PARTICIPANTS Parallel-group, nonblinded, randomized clinical trial conducted from March 1, 2016, to May 25, 2017, at a single center in Italy. Asymptomatic women with singleton gestations, no previous spontaneous preterm births, and cervical lengths of 25 mm or less at 18 weeks 0 days to 23 weeks 6 days of gestation were eligible. INTERVENTIONS Patients were randomized 1:1 to receive either cervical pessary (n = 150) or no pessary (n = 150). The pessary was removed between 37 weeks 0 days and 37 weeks 6 days of gestation or earlier if clinically indicated. The control group received standard care. For cervical length of 20 mm or shorter, women in both groups were prescribed vaginal progesterone, 200 mg/d, until 36 weeks 6 days of gestation. No bed rest or activity restriction was recommended. MAIN OUTCOMES AND MEASURES The primary end point was spontaneous preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse events.

IMPORTANCE: Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It i... more IMPORTANCE:
Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is unclear if a cervical pessary can reduce the risk of spontaneous preterm delivery.

OBJECTIVE:
To test whether in asymptomatic women with singleton pregnancies and no prior spontaneous preterm birth but with short cervical length on transvaginal ultrasound, use of a cervical pessary would reduce the rate of spontaneous preterm birth at less than 34 weeks of gestation.

DESIGN, SETTING, AND PARTICIPANTS:
Parallel-group, nonblinded, randomized clinical trial conducted from March 1, 2016, to May 25, 2017, at a single center in Italy. Asymptomatic women with singleton gestations, no previous spontaneous preterm births, and cervical lengths of 25 mm or less at 18 weeks 0 days to 23 weeks 6 days of gestation were eligible.

INTERVENTIONS:
Patients were randomized 1:1 to receive either cervical pessary (n = 150) or no pessary (n = 150). The pessary was removed between 37 weeks 0 days and 37 weeks 6 days of gestation or earlier if clinically indicated. The control group received standard care. For cervical length of 20 mm or shorter, women in both groups were prescribed vaginal progesterone, 200 mg/d, until 36 weeks 6 days of gestation. No bed rest or activity restriction was recommended.

MAIN OUTCOMES AND MEASURES:
The primary end point was spontaneous preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse events.

RESULTS:
Among 300 women who were randomized (mean age, 29 [SD, 6.3] years; mean gestational age, 22 [SD, 1.3] weeks), 100% completed the trial. The primary end point occurred in 11 women (7.3%) in the pessary group and 23 women (15.3%) in the control group (between-group difference, -8.0% [95% CI, -15.7% to -0.4]; relative risk, 0.48 [95% CI, 0.24-0.95]). During follow-up, the pessary group had a higher rate of increased or new vaginal discharge (86.7% vs 46.0%; between-group difference, +40.7% [95% CI, +30.1%-+50.3%]; relative risk, 1.88 [95% CI, 1.57-2.27]).

CONCLUSIONS AND RELEVANCE:
Among women without prior spontaneous preterm birth who had asymptomatic singleton pregnancies and short transvaginal cervical length, use of a cervical pessary, compared with no pessary use, resulted in a lower rate of spontaneous preterm birth at less than 34 weeks of gestation. The results of this single-center, nonblinded study among selected pregnant women require confirmation in multicenter clinical trials.

INTRODUCTION: To compare both the prevalence of gestational diabetes mellitus (GDM) as well as ma... more INTRODUCTION:
To compare both the prevalence of gestational diabetes mellitus (GDM) as well as maternal and neonatal outcomes by either the one-step or the two-step approaches.
MATERIAL AND METHODS:
Electronic databases were searched from their inception until June 2017. We included all randomized controlled trials (RCTs) comparing the one-step with the two-step approaches for the screening and diagnosis of GDM. The primary outcome was the incidence of GDM.
RESULTS:
Three RCTs (n = 2333 participants) were included in the meta-analysis. 910 were randomized to the one step approach (75 g, 2 hrs), and 1423 to the two step approach. No significant difference in the incidence of GDM was found comparing the one step versus the two step approaches (8.4 versus 4.3%; relative risk (RR) 1.64, 95% CI 0.77-3.48). Women screened with the one step approach had a significantly lower risk of preterm birth (PTB) (3.7 versus 7.6%; RR 0.49, 95% CI 0.27-0.88), cesarean delivery (16.3 versus 22.0%; RR 0.74, 95% CI 0.56-0.99), macrosomia (2.9 versus 6.9%; RR 0.43, 95% CI 0.22-0.82), neonatal hypoglycemia (1.7 versus 4.5%; RR 0.38, 95% CI 0.16-0.90), and admission to neonatal intensive care unit (NICU) (4.4 versus 9.0%; RR 0.49, 95% CI 0.29-0.84), compared to those randomized to screening with the two step approach.
CONCLUSIONS:
The one and the two step approaches were not associated with a significant difference in the incidence of GDM. However, the one step approach was associated with better maternal and perinatal outcomes.

INTRODUCTION: To evaluate if women meeting criteria for gestational diabetes mellitus (GDM) by t... more INTRODUCTION:

To evaluate if women meeting criteria for gestational diabetes mellitus (GDM) by the One Step test as per International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria but not by other less strict criteria have adverse pregnancy outcomes compared to GDM negative controls. The primary outcome was the incidence of macrosomia, defined as birth weight >4,000 grams.
MATERIAL AND METHODS:

Electronic databases were searched from their inception until May 2017. All studies identifying pregnant women negative at the Two Step test, but positive at the One Step test for IADPSG criteria. We excluded studies that randomized women to the One Step versus the Two Step tests; studies that compared different criteria within the same screening method; randomized studies comparing treatments for GDM; and studies comparing incidence of GDM in women doing the One Step test versus the Two Step test.
RESULTS:

Eight retrospective cohort studies, including 29,983 women, were included. 5 study groups and 4 control groups were identified. The heterogeneity between the studies was high. Gestational hypertension, preeclampsia, and large for gestational age, as well as in some analyses cesarean delivery, macrosomia and preterm birth, were significantly more frequent, and small for gestational age in some analyses significantly less frequent, in women GDM positive by the One Step, but not the Two Step.
CONCLUSION:

Women meeting criteria for GDM by IADPSG criteria but not by other less strict criteria have an increased risk of adverse pregnancy outcomes such as gestational hypertension, preeclampsia, and large for gestational age, compared to GDM negative controls. Based on these findings, and evidence from other studies that treatment decrease these adverse outcomes, we suggest screening for GDM using the IADPSG criteria

INTRODUCTION: There is inconclusive evidence from randomized controlled trials (RCTs) to support... more INTRODUCTION:

There is inconclusive evidence from randomized controlled trials (RCTs) to support any specific criteria for pharmacologic therapy dose adjustment in diabetes in pregnancy. Our objective was to analyze the criteria for dose adjustment of pharmacologic treatment for diabetes mellitus (DM) in pregnancy.
MATERIAL AND METHODS:

Data sources: MEDLINE, OVID and Cochrane Library were searched from their inception to September 2017. Selection criteria included all trials of DM in pregnancy managed by oral hypoglycemic agents or insulin reporting criteria for pharmacologic therapy dose adjustment. RCTs in women with pregestational DM and gestational DM (GDM) were included. For each trial, data regarding glucose values used for pharmacologic therapy dose adjustment were extracted and carefully reviewed.
RESULTS:

Of 51 RCTs on therapy for GDM or pregestational DM, 17 (4,230 women) were included as they reported criteria for pharmacologic therapy dose adjustment. Most of them (88%, 15/17) included women with GDM only. For RCTs including women with GDM, 12/16 (75%) used the two step approach; 3 (19%) used the one step approach; 1 (6%) used either the one or two step approach. Regarding the type of initial therapy, 13 (77%) RCTs used different types and doses of insulin; 9 (53%) used metformin; 5 (30%) used glyburide; and 1 (6%) used placebo. In most RCTs glucose monitoring was assessed four times daily, i.e. fasting (all RCTs) and 2 hours (15 RCTs, 88%) after each of the three main meals - breakfast, lunch, and dinner. For fasting glucose target, all used a value <105 mg/dL; 9 (53%) used 95 mg/dL as target. Of the 15 RCTs using 2 hour-postprandial value as target, 11 (73%) had 120 mg/dL as cutoff. Regarding the criteria for pharmacologic therapy dose adjustment, we found six different criteria. The majority of RCTs (9/17, 53%) used either 1 or 2 values per week higher than the target values, of which two thirds used only 1 value (35% of total), and one third (18% of total) 2 values. Five RCTs (29%) used >50%, 1 (6%) used >30%, and 1 (6%) used >20% of the values higher than the target value; while 1 (6%) used appearance of glycosuria.
CONCLUSIONS:

When evaluating RCTs which included criteria for pharmacologic GDM therapy dose adjustment, the most common criteria for diagnosis was the two step test, and the most common used therapies were insulin and metformin. Regarding glucose monitoring, the most common frequency was four times per day, fasting and 2 hours after each main meal, using as target glucose values 95mg/dL and 120mg/dL, respectively. Importantly, we found six different criteria for pharmacologic GDM therapy dose adjustment, with the majority using very tight criteria of either 1 or 2 values per week higher than the target values, of which two thirds used only 1 value, and one third 2 values

OBJECTIVE: To evaluate the benefits and harms of discontinuation of oxytocin after the active ph... more OBJECTIVE:

To evaluate the benefits and harms of discontinuation of oxytocin after the active phase of labor is reached.
DATA SOURCES:

Electronic databases (ie, MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, ScienceDirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from their inception until April 2017.
METHODS OF STUDY SELECTION:

We included all randomized controlled trials comparing discontinuation (ie, intervention group) and continuation (ie, control group) of oxytocin infusion after the active phase of labor is reached, either after induction or augmentation of labor. Discontinuation of oxytocin infusion was defined as discontinuing oxytocin infusion when the active phase of labor was achieved. Continuation of oxytocin infusion was defined as continuing oxytocin infusion until delivery. Only trials in singleton gestations with vertex presentation at term were included. The primary outcome was the incidence of cesarean delivery.
TABULATION, INTEGRATION, AND RESULTS:

Nine randomized controlled trials, including 1,538 singleton gestations, were identified as relevant and included in the meta-analysis. All nine trials included only women undergoing induction of labor. In the discontinuation group, if arrest of labor occurred, usually defined as no cervical dilation in 2 hours or inadequate uterine contractions for 2 hours or more, oxytocin infusion was restarted. Women in the control group had oxytocin continued until delivery usually at the same dose used at the time the active phase was reached. Women who were randomized to have discontinuation of oxytocin infusion after the active phase of labor was reached had a significantly lower risk of cesarean delivery (9.3% compared with 14.7%; relative risk 0.64, 95% CI 0.48-0.87) and of uterine tachysystole (6.2% compared with 13.1%; relative risk 0.53, 95% CI 0.33-0.84) compared with those who were randomized to have continuation of oxytocin infusion until delivery. Discontinuation of oxytocin infusion was associated with an increase in the duration of the active phase of labor (mean difference 27.65 minutes, 95% CI 3.94-51.36).
CONCLUSION:

In singleton gestations with cephalic presentation at term undergoing induction, discontinuation of oxytocin infusion after the active phase of labor at approximately 5 cm is reached reduces the risk of cesarean delivery and of uterine tachysystole compared with continuous oxytocin infusion. Given this evidence, discontinuation of oxytocin infusion once the active stage of labor is established in women being induced should be considered as an alternative management plan.

BACKGROUND: In in vitro fertilization (IVF) techniques only 20 to 25% of the transferred embryos... more BACKGROUND:

In in vitro fertilization (IVF) techniques only 20 to 25% of the transferred embryos lead to a pregnancy OBJECTIVE: To evaluate the beneficial effects of SP or semen applied at the time of oocyte aspiration or embryo transfer SEARCH STRATEGY: Electronic databases were searched from their inception until August 2017.
SELECTION CRITERIA:

We included all randomized controlled trials (RCTs) evaluating the effects of SP or semen in IVF treatment. Trials were considered if women were exposed to any kind of SP or semen (either SP/semen injection or sexual intercourse) around the time of oocyte pickup and embryo transfer.
DATA COLLECTION AND ANALYSIS:

The primary outcome was clinical pregnancy rate (CPR).
MAIN RESULTS:

Eight RCTs, including 2,128 women undergoing to IVF, were included in the meta-analysis. Women randomized in the intervention group had a significantly higher rate of CPR compared to controls (30.0% vs 25.1%; RR 1.20, 95% CI 1.04 to 1.39). No significant differences were found in the secondary outcomes, including livebirth rate, biochemical pregnancy, miscarriage, multiple pregnancies and birth weight. The subgroup analysis (4 RCTs, 780 participants), including only those RCTs in which prepared undiluted SP was injected just after oocyte pick up, concurred with the overall analysis for the primary outcome (46.3% vs 37.2%; RR 1.23, 95% CI 1.05 to 1.45).
CONCLUSIONS:

As intravaginal or intracervical SP application around the time of oocyte pickup was associated with higher CPR. Local application SP may be considered as a potential treatment to improve implantation. This article is protected by copyright. All rights reserved.