Effectiveness and safety of gonadotropins used in female infertility: a population-based study in the Lazio region, Italy.

PURPOSE: Infertility is a topic of growing interest, and female infertility is often treated with gonadotropins. Evidence regarding comparative safety and efficacy of different gonadotropin formulations is available from clinical studies, while real-world data are missing. The present study aims to investigate effectiveness and safety of treatment with different gonadotropin formulations in women undergoing medically assisted procreation treatments in Latium, a region in central Italy, through a real-world data approach. METHODS: A retrospective population-based cohort study in women between the ages of 18 and 45 years who were prescribed with at least one gonadotropin between 2007 and 2019 was conducted. Women were enrolled from the regional drug dispense registry, and data on their clinical history, exposure to therapeutic cycles (based on recombinant "REC" or extractives "EXT" gonadotropin, or combined protocol "CMD" (REC + EXT)), and maternal/infantile outcomes were linked from the regional healthcare administrative databases. Multivariate logistic regression models were applied to estimate the association between exposure and outcomes. RESULTS: Overall, 90,292 therapeutic cycles prescribed to 35,899 women were linked to pregnancies. Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with conception rate (RRREC adj = 1.06, 95% CI: 1.01-1.12; RRCBD adj = 1.17, 95% CI: 1.11-1.24). Maternal outcomes occurred in less than 5% of deliveries, and no significant differences between treatments were observed (REC vs EXT, pre-eclampsia: RR adj = 1.24, 95% CI: 0.86-1.79, ovarian hyperstimulation syndrome: RR adj = 1.25, 95% CI: 0.59-2.65, gestational diabetes: RR adj = 1.06, 95% CI: 0.84-1.35). Regarding infantile outcomes, similar results were obtained for different gonadotropin formulations (REC vs EXT: low birth weight: RR adj = 0.98, 95% CI: 0.83-1.26, multiple births: RR adj = 1.06, 95% CI: 0.92-1.23, preterm birth: RR adj = 1.03, 95% CI: 0.92-1.26). CONCLUSIONS: Efficacy and safety profiles of REC proved to be similar to those of EXT. Regarding the efficacy in terms of conception rate and birth rate, protocols using the combined approach performed slightly better. Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin formulations.

Very tight vs. tight control: what should be the criteria for pharmacologic therapy dose adjustment in diabetes in pregnancy? Evidence from randomized controlled trials.

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 (4230 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, three (19%) the one-step approach and one (6%) either the one- or two-step approach. Regarding the type of initial therapy, 13 (77%) RCTs used different types and doses of insulin; nine (53%) used metformin; five (30%) used glyburide; and one (6%) used placebo. In most RCTs, glucose monitoring was assessed four times daily, i.e. fasting (all RCTs) and two 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; nine (53%) used 95 mg/dL as target. Of the 15 RCTs using a two-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 one or two values per week higher than the target values, of which two-thirds used only one value (35% of total), and one-third (18% of total) two values. Five RCTs (29%) used >50%, one (6%) >30%, and one (6%) >20% of the values higher than the target value; one (6%) used the appearance of glycosuria. CONCLUSIONS: When evaluating RCTs which included criteria for pharmacologic GDM therapy dose adjustment, the most common criterion 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 two hours after each main meal, using as target glucose values 95 and 120 mg/dL, respectively. Importantly, we found six different criteria for pharmacologic GDM therapy dose adjustment, with the majority using very tight criteria of either one or two values per week higher than the target values, of which two-thirds used only one value, and one-third used two values.

Maternal steroid therapy for fetuses with second-degree immune-mediated congenital atrioventricular block: a systematic review and meta-analysis.

INTRODUCTION: The aim of this study was to explore the effect of maternal fluorinated steroid therapy on fetuses affected by second-degree immune-mediated congenital atrioventricular block. MATERIAL AND METHODS: Studies reporting the outcome of fetuses with second-degree immune-mediated congenital atrioventricular block diagnosed on prenatal ultrasound and treated with fluorinated steroids compared with those not treated were included. The primary outcome was the overall progression of congenital atrioventricular block to either continuous or intermittent third-degree congenital atrioventricular block at birth. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used. RESULTS: Five studies (71 fetuses) were included. The progression rate to congenital atrioventricular block at birth in fetuses treated with steroids was 52% (95% confidence interval 23-79) and in fetuses not receiving steroid therapy 73% (95% confidence interval 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% confidence interval 12-41) compared with 23% (95% confidence interval 8-44) in those not treated. Stable (constant) second-degree congenital atrioventricular block at birth was present in 11% (95% confidence interval 2-27) of cases in the treated group and in none of the newborns in the untreated group, whereas complete regression to sinus rhythm occurred in 21% (95% confidence interval 6-42) of fetuses receiving steroids vs. 9% (95% confidence interval 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 congenital atrioventricular block.

Intravenous fluid rate for reduction of cesarean delivery rate in nulliparous women: a systematic review and meta-analysis.

INTRODUCTION: The National Institute of Child Health and Human Development, American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine have emphasized the need to promote vaginal delivery and have offered recommendations to safely prevent primary cesarean delivery. However, there has been limited discussion regarding management of intravenous fluids and other aspects of labor management that may influence mode of delivery. Therefore the aim of our study was to determine whether an intravenous fluid rate of 250 vs. 125 mL/h is associated with a difference in cesarean delivery rate. MATERIAL AND METHODS: Searches were performed in MEDLINE, OVID, Scopus, ClinicalTrials.gov, the PROSPERO International Prospective Register of Systematic Reviews, Embase, Web of Science, and the Cochrane Library for randomized controlled trials. We included all randomized controlled trials comparing intravenous fluid rates of 250 vs. 125 mL/h in nulliparous women in spontaneous labor at term with singleton pregnancies at ≥36 weeks. Studies were included regardless of the type of intravenous fluids used and regardless of whether oral intake was restricted during labor. Studies including multiparous women or women whose labor was induced were excluded. The primary outcome was the incidence of cesarean delivery. We planned to assess a subgroup analysis according to type of fluids used and according to restriction of oral fluid intake. RESULTS: Seven trials including 1215 nulliparous women in spontaneous labor at term were analyzed; 593 (48.8%) in the 250 mL/h group, and 622 (51.2%) in the 125 mL/h group. Five studies used lactated Ringer's solution, one used normal saline in dextrose water, and in one study it was unclear which intravenous fluid was used. Women who received intravenous fluids at 250 mL/h had a significantly lower incidence of cesarean delivery for any indication (12.5 vs. 18.1%; RR 0.70, 95% CI 0.53-0.92; seven studies, 1215 participants; I2 = 0%) and for dystocia (4.9 vs. 7.7%; RR 0.60, 95% CI 0.38-0.97; five studies, 1093 participants; I2 = 18%), a significantly shorter mean duration of labor of about one hour (mean difference -64.38 min, 95% CI -121.88 to -6.88; six studies, 1155 participants; I2 = 83%) and a significantly shorter mean length of second stage of labor (mean difference -2.80 min, 95% CI -4.49 to -1.10; 899 participants; I2 = 22%) compared with those who received intravenous fluid at 125 mL/h. No differences were found in the other secondary outcomes. There were no maternal or perinatal deaths and only one woman, in the 125 mL/h group, developed pulmonary edema. The findings persisted regardless of the type of intravenous fluid used. No significant reduction in the incidence of cesarean delivery was demonstrated in women with unrestricted oral intake; however, this was limited to only two studies evaluating 254 women. CONCLUSIONS: Our findings provide evidence that the duration of labor in low-risk nulliparous women may be shortened by a policy of intravenous fluids at a rate of 250 mL/h rather than 125 mL/h. A rate of 250 mL/h seems to be associated with a reduction in the incidence of cesarean delivery compared to 125 mL/h. The number needed to treat to prevent one cesarean delivery is 18 women. Our data support increased hydration among nulliparous women in labor when oral intake is restricted. Further study is needed regarding risks and benefits of increased hydration among women with unrestricted oral intake, those undergoing induction of labor, and those with medical comorbidities.

Cervical Pessary for Preventing Preterm Birth in Singleton Pregnancies With Short Cervical Length: A Systematic Review and Meta-analysis.

OBJECTIVES: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in singleton gestations with a second trimester short cervix. METHODS: Electronic databases were searched from their inception until February 2016. We included randomized clinical trials (RCTs) comparing the use of the cervical pessary with expectant management in singletons pregnancies with transvaginal ultrasound cervical length (TVU CL) ≤25 mm. The primary outcome was incidence of SPTB <34 weeks. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). RESULTS: Three RCTs (n = 1,420) were included. The mean gestational age (GA) at randomization was approximately 22 weeks. The Arabin pessary was used as intervention in all three trials, and was removed by vaginal examination at approximately 37 weeks. Cervical pessary was not associated with prevention of SPTB <37 (20.2% vs 50.2%; RR 0.50, 95% CI 0.23 to 1.09), <34, <32, and <28 weeks, compared to no pessary. No differences were found in the mean of GA at, interval from randomization to delivery, incidence of preterm premature rupture of membranes and of cesarean delivery, and in neonatal outcomes. The Arabin pessary was associated with a significantly higher risk of vaginal discharge. CONCLUSIONS: In singleton pregnancies with a TVU CL ≤25mm at 200 -246 weeks, the Arabin pessary does not reduce the rate of spontaneous preterm delivery or improve perinatal outcome. Individual patient data meta-analysis may clarify whether cervical pessary may be beneficial in subgroups, such as only singleton gestations without prior SPTB or by different CL cutoffs.

Outcome of Fetuses with Supratentorial Extra-Axial Intracranial Cysts: A Systematic Review.

OBJECTIVE: To investigate the incidence of associated anomalies, aneuploidy, cyst progression, need for surgery and neurodevelopmental outcome in fetuses with extra-axial supratentorial intracranial cysts. DATA SOURCES: Medline, Embase and CINAHL databases were searched and the following outcomes analyzed: associated central nervous system (CNS) and extra-CNS anomalies detected at the scan, chromosomal anomalies, additional CNS anomalies detected only at prenatal MRI, additional CNS anomalies detected only after birth, cyst progression in utero, neurological outcome and need for surgery. Two authors reviewed all abstracts independently. Results were reported as proportions, and between-study heterogeneity was explored using the I² statistic; fixed or random effect models were used accordingly. RESULTS: Ten studies involving 47 fetuses were included in the meta-analysis. Arachnoid cysts (n = 24) had associated CNS anomalies and extra-CNS in 73% (95% CI 56-88) and 14% (95% CI 4-29), respectively. The most common associated anomalies were ventriculomegaly and callosal abnormalities. Chromosomal abnormalities were present in 6% (95% CI 0-30), but fetuses with isolated cysts were always euploid (0/7; 95% CI 0-29). Fetal MRI and postnatal examination identified 5 additional cases (21%, 95% CI 1-57). Cavum veli interpositi (CVI) cysts had associated CNS and extra-CNS anomalies in 31% (95% CI 13-52) and 6% (95% CI 0-29), respectively. No chromosomal or callosal anomalies were found in these cases. In isolated CVI cysts, no cases of associated anomalies were detected postnatally. Intrauterine regression occurred in 23% of CVI cysts and in none of the arachnoid cysts. In children with arachnoid cyst, the occurrence of hydrocephaly and mass effect on the adjacent structures were observed in 23.9% (95% CI 8.3-4.4) and 26.8% (95% CI 4.0-60.1), respectively. None of the cases included had abnormal motor outcome or intelligence. The rate of surgery was 34.7% (95% CI 16.0-56.4). None of the children with a prenatal diagnosis of isolated CVI cyst experienced any of the adverse outcomes explored in this review. CONCLUSIONS: Extra-axial supratentorial cysts diagnosed in utero are frequently associated with other neural and extra-neural anomalies. However, this may represent the consequence of a selection bias. Interhemispheric arachnoid cysts were typically associated with callosal anomalies. Abnormal karyotypes were seen only in fetuses with multiple anomalies. Arachnoid, but not CVI, cysts frequently increased in size throughout gestation.

Long-term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome.

OBJECTIVE: The objective of this study is to determine the ability of metformin treatment in reducing the prevalence of metabolic syndrome (MS) and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome (PCOS). DESIGN: Clinical Trial. PATIENTS: We recruited 140 hyperinsulinaemic overweight women with PCOS in their reproductive age. Metformin treatment (500 mg × 3/die) was prescribed to each patient for twelve months. MEASUREMENTS: The primary outcome was to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) and MS in hyperinsulinaemic overweight patients with PCOS. The secondary outcome was to evaluate, in the same patients, the effects of metformin therapy on endocrine, metabolic and hepatic parameters. RESULTS: At basal evaluation, NAFLD was diagnosed in 81 of 140 patients with PCOS (57·85%); MS was present only in the NAFLD group (32·09%vs 0%; P < 0·001). After twelve months, metformin is able to significantly reduce, in the same group, the prevalence of MS (28·9%vs 13·5%; P < 0·01). An improvement of hepatic parameters and a significant decrease in oligomenorrhea (85·7%vs 19%, P < 0·001) were also observed. CONCLUSIONS: Treatment with metformin is indicated in all hyperinsulinaemic overweight patients with PCOS, especially in those with NAFLD. These data appear even more interesting considering their increased risk to develop metabolic and hepatic complications.

Fetal brain hemodynamics in pregnancies at term: correlation with gestational age, birthweight and clinical outcome.

INTRODUCTION: The primary aim of this study was to ascertain the strength of association between cerebral blood flow assessed in anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries and the following clinical outcomes: small for gestational age (SGA), induction of labor (IOL) for oligohydramnios and caesarean section (CS) for nonreassuring fetal status (NRFS) during labor. MATERIAL AND METHODS: Retrospective analysis of prospectively collected data on consecutive singleton pregnancies from 40 0/7 to 41 6/7 week of gestation. UA, ACA, MCA, PCA pulsatility index (PI) were measured from 40 weeks of gestations. Furthermore, the ratios between cerebral blood flow and UA (CPR, ACA/UA and PCA/UA) were calculated and correlated with the observed outcomes. RESULTS: Two hundred twenty-four singleton pregnancies were included in the study. Mean PI of either ACA (p = .04), MCA (p = .008), and PCA (p = .003) were lower in the SGA compared to non-SGA group; furthermore, mean PCA PI was significantly lower than MCA PI (p = .04). Furthermore, CPR (p = .016), ACA/UA (p = .02), and PCA/UA (p = .003) were significantly lower in the SGA group compared to controls. UA, ACA, MCA, and PCA PI were higher in women undergoing IOL for oligohydramnios compared to controls. Logistic regression analysis showed that CPR and PCA/UA ratio were independently associated with SGA. SGA, ACA PI, and ACA/UA were independently associated with CS for NRFS. Finally, birthweight centile, were independently associated with IOL oligohydramnios. Despite this, the predictive accuracy of Doppler in detecting any of the explored outcome was only poor to moderate. CONCLUSION: Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor. However, the predictive accuracy of Doppler at term is only poor to moderate, thus advising against its use in clinical practice as a standalone screening test for adverse perinatal outcome in pregnancies at term. Key Message Redistribution of cerebral blood flow at term is significantly associated with SGA, IOL for oligohydramnios and CS for NRFS in labor.

Tranexamic acid for treatment of primary postpartum hemorrhage after vaginal delivery: a systematic review and meta-analysis of randomized controlled trials.

Background: Postpartum hemorrhage (PPH) is responsible for about 25% of maternal deaths worldwide. Antifibrinolytic agents, mainly tranexamic acid (TXA), have been demonstrated to reduce blood loss in patients with established PPH.Objective: The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the effectiveness of TXA administration in women with established primary PPH after vaginal delivery.Data sources: The search was conducted using electronic databases from inception of each database through February 2018. Review of articles also included the abstracts of all references retrieved from the search. No restrictions for language or geographic location were applied.Study design: Selection criteria included RCTs comparing the use of TXA in women with established primary PPH after vaginal delivery with control (either placebo or no treatment). Trials in women undergoing cesarean delivery and trials in prevention of PPH were excluded. The primary outcome was the incidence of hysterectomy. The summary measures were reported as summary relative risk (RR) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird.Tabulation, integration, and results: Two trials including 14,363 women with established primary PPH after vaginal delivery were analyzed. Women who received TXA soon after the diagnosis of PPH had a significantly lower incidence of hysterectomy (0.5% vs 0.8%; RR 0.63, 95% CI 0.42-0.94), compared to those who did not. The risk of thrombotic events was not increased in the TXA group.Conclusion: In women with established PPH after vaginal delivery, the use of TXA reduces the risk of hysterectomy and does not increase the risk of thrombotic events. We recommend 1 g plus a second dose of 1 g if bleeding continues after 30 min.

Maternal steroid therapy for fetuses with immune-mediated complete atrioventricular block: a systematic review and meta-analysis.

INTRODUCTION: To explore the effect of maternal fluorinated steroid therapy on fetuses affected by immune-mediated complete atrio-ventricular block (CAVB) in utero. MATERIAL AND METHODS: Pubmed, Embase, Cinahl, and ClinicalTrials.gov databases were searched. Only studies reporting the outcome of fetuses with immune CAVB diagnosed on prenatal ultrasound without any cardiac malformations and treated with fluorinated steroids compared to those not treated were included. The primary outcome observed was the regression of CAVB; secondary outcomes were need for pacemaker insertion, overall mortality, defined as the occurrence of either intrauterine (IUD) or neonatal (NND) death, IUD, NND, termination of pregnancy (TOP). Furthermore, we assessed the occurrence of all these outcomes in hydropic fetuses compared to those without hydrops at diagnosis. Meta-analyses of proportions using random effect model and meta-analyses using individual data random-effect logistic regression were used to combine data. RESULTS: Eight studies (162 fetuses) were included. The rate of regression was 3.0% (95%CI 0.2-9.1) in fetuses treated and 4.3% (95%CI 0.4-11.8) in those not treated, with no difference between the two groups (odds ratio (OR): 0.9, 95%CI 0.1-15.1). Pacemaker at birth was required in 71.5% (95%CI 56.0-84.7) of fetuses-treated and 57.8% (95%CI 40.3-74.3) of those not treated (OR: 9, 95%CI 0.4-3.4). There was no difference in the overall mortality rate (OR: 0.5, 95%CI 0.9-2.7) between the two groups; in hydropic fetuses, mortality occurred in 76.2% (95%CI 48.0-95.5) of the treated and in 23.8% (95%CI 1.2-62.3) of the untreated group, while in those without hydrops the corresponding figures were 8.9% (95%CI 2.0-20.3) and 12% (95%CI 8.7-42.2), respectively. Improvement or resolution of hydrops during pregnancy occurred in 76.2% (95%CI 48.0-95.5) of cases treated and in 23.3% (95%CI 1.2-62.3) of those nontreated with fluorinated steroids. CONCLUSIONS: The findings from this systematic review do not suggest a potential positive contribution of antenatal steroid therapy in improving the outcome of fetuses with immune CAVB.

Uterine massage for preventing postpartum hemorrhage at cesarean delivery: Which evidence?

BACKGROUND: Cesarean delivery could be complicated by postpartum hemorrhage (PPH), the first cause of maternal death. OBJECTIVES: To evaluate the efficacy of uterine massage in preventing postpartum hemorrhage at cesarean delivery. DATA SOURCES: Electronic databases from their inception until October 2017. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included all RCTs comparing uterine massage alone or as part of the active management of labor before or after delivery of the placenta, or both, with non-massage in the setting of cesarean delivery. DATA COLLECTION AND ANALYSIS: The primary outcome was PPH, defined as blood loss >1000 mL. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI). RESULTS: Only 3 RCTs comparing uterine massage vs no uterine massage were found. The quality of these 3 trials in general was very low with high or unclear risk of bias. All of them included only women in the setting of spontaneous vaginal delivery and none of them included cesarean delivery, and therefore the meta-analysis was not feasible. CONCLUSIONS: There is not enough evidence to determine if uterine massage prevents postpartum hemorrhage at cesarean delivery.

Chewing gum improves postoperative recovery of gastrointestinal function after cesarean delivery: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: To examine whether chewing gum hastens the return of gastrointestinal function after a cesarean delivery. METHODS: All randomized controlled trials comparing the use of chewing gum in the immediate postoperative recovery period (i.e. intervention group) with a control group were included in the meta-analysis. The primary outcome was the time to first flatus in hours. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI). RESULTS: Seventeen trials, including 3041 women, were analyzed. Trials were of moderate to low quality with different inclusion criteria. In most of the included trials chewing gum was given right after delivery, three times a day for 30 min each and until the first flatus. Women who were randomized to the chewing gum group had a significantly lower mean time to first flatus (MD - 6.49 h, 95%CI -8.65 to -4.33), to first bowel sounds (MD - 8.48 h, 95%CI -9.04 to -7.92), less duration of stay (MD - 0.39 days, 95%CI -0.78 to -0.18), lower time to first feces (MD - 9.57 h, 95% CI -10.28 to 8.87) and to the first feeling of hunger (MD - 2.89 h, 95%CI -4.93 to -0.85), less number of episodes of nausea or vomiting (RR 0.33, 95%CI 0.12 to 0.87), less incidence of ileus (RR 0.39, 95%CI 0.19 to 0.80) and significantly higher satisfaction. CONCLUSIONS: Gum chewing starting right after cesarean delivery three times a day for about 30 min until the first flatus is associated with early recovery of bowel motility. As this is a simple, generally inexpensive intervention, providers should consider implementing cesarean postoperative care with gum chewing.

Absent ductus venosus: case series from two tertiary centres.

INTRODUCTION: Congenital absence of the ductus venosus (ADV) is a rare vascular anomaly often associated with fetal cardiac and extracardiac anomalies, aneuploidies, and hydrops. The prognosis depends on the patterns of abnormal venous circulation, on the associated malformations and on chromosomal aberrations. METHODS: We performed a retrospective audit of all consecutive cases with ADV referred in our centres and analysed the outcomes. RESULTS: A total of six cases with prenatally diagnosed ADV were identified. The gestational age at diagnosis ranged from 15 to 35 weeks. Karyotyping was performed in all cases. Normal karyotype was found in five out of the six cases. Overall, four neonates survived at 28 days follow-up. The other two died 48 h after delivery: both of them had extrahepatic ADV. DISCUSSION: Absence of the ductus venosus may be compatible with normal fetal development without relevant disturbance of circulation and oxygenation independently from type of abnormal venous circulation.

Less-Restrictive Food Intake During Labor in Low-Risk Singleton Pregnancies: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate benefits and harms of food intake during labor. DATA SOURCES: Electronic databases such as MEDLINE and ClinicalTrials.gov were searched from their inception until October 2016. METHODS OF STUDY SELECTION: We included randomized trials comparing a policy of less-restrictive food intake with a policy of more restrictive food intake during labor. The primary outcome was the mean duration of labor. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of either a relative risk or a mean difference with 95% confidence interval (CI). TABULATION, INTEGRATION, AND RESULTS: Ten trials, including 3,982 laboring women, were included. All the studies involved laboring singletons considered at low risk because they had no obstetric or medical complications that would increase the likelihood of cesarean delivery. In three studies, women were allowed to select from a low-residue diet throughout the course of labor. One study had honey date syrup as the allowed food intake. Five studies had carbohydrate drinks as food intake in labor. The last one was the only trial that allowed unrestrictive food intake. In the included studies, all women in the intervention group were allowed the assigned food intake until delivery, whereas women in a control group were allowed only ice chips, water, or sips of water until delivery. A policy of less-restrictive food intake was associated with a significantly shorter duration of labor (mean difference -16 minutes, 95% CI -25 to -7). No other benefits or harms in obstetric or neonatal outcome were noticed. Regurgitation during general anesthesia and Mendelson syndrome did not occur in either group. CONCLUSION: Women with low-risk singleton pregnancies who were allowed to eat more freely during labor had a shorter duration of labor. A policy of less-restrictive food intake during labor did not influence other obstetric or neonatal outcomes nor did it increase the incidence of vomiting. Operative delivery rates were similar.

Vaginal Cleansing Before Cesarean Delivery: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy of vaginal cleansing before cesarean delivery in reducing postoperative endometritis. DATA SOURCES: MEDLINE, Ovid, EMBASE, Scopus, Clinicaltrials.gov, and Cochrane Library were searched from their inception to January 2017. METHODS OF STUDY SELECTION: Selection criteria included all randomized controlled trials comparing vaginal cleansing (ie, intervention group) with a control group (ie, either placebo or no intervention) in women undergoing cesarean delivery. Any method of vaginal cleansing with any type of antiseptic solution was included. The primary outcome was the incidence of endometritis. Meta-analysis was performed using the random-effects model of DerSimonian and Laird to produce summary treatment effects in terms of relative risk (RR) with 95% CI. TABULATION, INTEGRATION, AND RESULTS: Sixteen trials (4,837 women) on vaginal cleansing immediately before cesarean delivery were identified as relevant and included in the review. In most of the included studies, 10% povidone-iodine was used as an intervention. The most common way to perform the vaginal cleansing was the use of a sponge stick for approximately 30 seconds. Women who received vaginal cleansing before cesarean delivery had a significantly lower incidence of endometritis (4.5% compared with 8.8%; RR 0.52, 95% CI 0.37-0.72; 15 studies, 4,726 participants) and of postoperative fever (9.4% compared with 14.9%; RR 0.65, 95% CI 0.50-0.86; 11 studies, 4,098 participants) compared with the control group. In the planned subgroup analyses, the reduction in the incidence of endometritis with vaginal cleansing was limited to women in labor before cesarean delivery (8.1% compared with 13.8%; RR 0.52, 95% CI 0.28-0.97; four studies, 440 participants) or those with ruptured membranes (4.3% compared with 20.1%; RR 0.23, 95% CI 0.10-0.52; three studies, 272 participants). CONCLUSION: Vaginal cleansing immediately before cesarean delivery in women in labor and in women with ruptured membranes reduces the risk of postoperative endometritis. Because it is generally inexpensive and a simple intervention, we recommend preoperative vaginal preparation before cesarean delivery in these women with sponge stick preparation of povidone-iodine 10% for at least 30 seconds. More data are needed to assess whether this intervention may be also useful for cesarean deliveries performed in women not in labor and for those without ruptured membranes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO International prospective register of systematic reviews, https://www.crd.york.ac.uk/PROSPERO/, CRD42017054843.

Discontinuing Oxytocin Infusion in the Active Phase of Labor: A Systematic Review and Meta-analysis.

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.

Cervical pessary for preventing preterm birth in twin pregnancies with short cervical length: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in twin pregnancies with an asymptomatic transvaginal ultrasound cervical length (TVU CL) in the second trimester. METHODS: We performed a meta-analysis including all randomized clinical trials (RCTs) comparing the use of cervical pessary (i.e. intervention group) with expectant management (i.e. control group). The primary outcome was incidence of SPTB <34 weeks. RESULTS: Three trials, including 481 twin pregnancies with short cervix, were analyzed. Two RCTs defined short cervix as TVU CL ≤25 mm and one as TVU CL ≤38 mm. Pessary was not associated with prevention of SPTB, and the mean gestational age at delivery and the mean latency were similar in the pessary group compared to the control group. Moreover, no benefits were noticed in neonatal outcomes. CONCLUSIONS: Use of the Arabin pessary in twin pregnancies with short TVU CL at 16-24 weeks does not prevent SPTB or improve perinatal outcome.

A comparison between amniotic fluid index and the single deepest vertical pocket technique in predicting adverse outcome in prolonged pregnancy.

OBJECTIVE: to compare perinatal outcome in induced postterm pregnancies with normal amniotic volume and in patients with prolonged pregnancy undergone induction for oligohydramnios, evaluated by two different ultrasonographic methods. METHODS: amniotic fluid volume was measured, using Single Deepest Vertical Pocket (SDVP) and Amniotic Fluid Index (AFI), in 961 singleton uncomplicated prolonged pregnancies. In 109 of these patients, hospitalization was planned for induction of labor, during or after 42 weeks of gestation, for oligohydramnios, postterm pregnancy and other indications in 47, 51 and 11 cases, respectively. Perinatal outcome included: rate of caesarean section, fetal distress, non reassuring fetal heart tracing, presence of meconium, umbilical artery pH < 7.1, Apgar score at 5 minutes < 7, admission to neonatal intensive care unit (NICU). RESULTS: oligohydramnios was diagnosed in 4.89% of cases, when at least one of the two methods was used. A reduced AFI and SDVP value identified 4.47% and 3.75% of cases, respectively, even if without statistical difference. No statistical differences were reported in perinatal outcomes in postterm versus prolonged pregnancies with oligohydramnios, also in relation to the two different ultrasonographic methods. CONCLUSIONS: oligohydramnios is more frequently diagnosed using AFI than SDVP, consequently determining a higher rate of induction of labor. Moreover, perinatal outcome in prolonged induced pregnancies is not affected by oligohydramnios.

Effects of drospirenone-ethinylestradiol and/or metformin on CD4(+)CD28(null) T lymphocytes frequency in women with hyperinsulinemia having polycystic ovary syndrome: a randomized clinical trial.

OBJECTIVE: To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS). DESIGN: Randomized clinical trial. INTERVENTIONS: Ninety three patients with hyperinsulinemic PCOS were age matched and body mass index matched and randomized to receive a 6 months daily treatment with DRSP (3 mg)/EE (0.03 mg), or metformin (1500 mg), or DRSP/EE combined with metformin. MAIN OUTCOME MEASURES: CD4(+)CD28(null) T-cell frequencies. RESULTS: The DRSP/EE and metformin groups did not show any significant change in the CD4(+)CD28(null) frequency compared to the baseline. Interestingly, a statistically significant decrease in CD4(+)CD28(null) frequency occurred after 6 months of DRSP/EE-metformin (median 3-1.5; P < .01). Of note, this statistically significant association was confirmed after adjusting for baseline values in DRSP/EE-metformin group by analysis of covariance (P < .05). CONCLUSIONS: In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.