Utilidad de las prostaglandinas intravenosas en el espasmo vascular neonatal / Use of intravenous prostaglandins in neonatal vasospasm

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Prostaglandins for Postpartum Hemorrhage: Pharmacology, Application, and Current Opinion.

BACKGROUND: Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide. Medical intervention plays an important role in the prevention and treatment of PPH. Prostaglandins (PGs) are currently recommended as second-line uterotonics, which are applied in cases of persistent bleeding despite oxytocin treatment. SUMMARY: PG agents that are constantly used in clinical practice include carboprost, sulprostone, and misoprostol, representing the analogs of PGF2α, PGE2, and PGE1, respectively. Injectable PGs, when used to treat PPH, are effective in reducing blood loss but probably induce cardiovascular or respiratory side effects. Misoprostol is characterized by oral administration, low cost, stability in storage, broad availability, and minimal side effects. It remains a treatment option for uterine atony in low-resource settings, but its effectiveness as a uterotonic for independent application may be limited. Key Messages: The present review article discusses the physiological roles of various natural PGs, evaluates the existing evidence of PG analogs in the prevention and treatment of PPH, and finally provides a reference to assist obstetricians in selecting appropriate uterotonics.

Umbilical vein injection for management of retained placenta.

BACKGROUND: Retained placenta is a common complication of pregnancy affecting 1% to 6% of all births. If a retained placenta is left untreated, spontaneous delivery of the placenta may occur, but there is a high risk of bleeding and infection. Manual removal of the placenta (MROP) in an operating theatre under anaesthetic is the usual treatment, but is invasive and may have complications. An effective non-surgical alternative for retained placenta would potentially reduce the physical and psychological trauma of the procedure, and costs. It could also be lifesaving by providing a therapy for settings without easy access to modern operating theatres or anaesthetics. Injection of uterotonics into the uterus via the umbilical vein and placenta is an attractive low-cost option for this. This is an update of a review last published in 2011. OBJECTIVES: To assess the use of umbilical vein injection (UVI) of saline solution with or without uterotonics compared to either expectant management or with an alternative solution or other uterotonic agent for retained placenta. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 June 2020), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing UVI of saline or other fluids (with or without uterotonics), either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta. We considered quasi-randomised, cluster-randomised, and trials reported only in abstract form. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach. We calculated pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), and presented results using 'Summary of findings' tables. MAIN RESULTS: We included 24 trials (n = 2348). All included trials were RCTs, one was quasi-randomised, and none were cluster-randomised. Risk of bias was variable across the included studies. We assessed certainty of evidence for four comparisons: saline versus expectant management, oxytocin versus expectant management, oxytocin versus saline, and oxytocin versus plasma expander. Evidence was moderate to very-low certainty and downgraded for risk of bias of included studies, imprecision, and inconsistency of effect estimates. Saline solution versus expectant management There is probably little or no difference in the incidence of MROP between saline and expectant management (RR 0.93, 95% CI 0.80 to 1.10; 5 studies, n = 445; moderate-certainty evidence). Evidence for the following remaining primary outcomes was very-low certainty: severe postpartum haemorrhage 1000 mL or greater, blood transfusion, and infection. There were no events reported for maternal mortality or postpartum anaemia (24 to 48 hours postnatal). No studies reported addition of therapeutic uterotonics. Oxytocin solution versus expectant management UVI of oxytocin solution might slightly reduce in the need for manual removal compared with expectant management (mean RR 0.73, 95% CI 0.56 to 0.95; 7 studies, n = 546; low-certainty evidence). There may be little to no difference between the incidence of blood transfusion between groups (RR 0.81, 95% CI 0.47 to 1.38; 4 studies, n = 339; low-certainty evidence). There were no maternal deaths reported (2 studies, n = 93). Evidence for severe postpartum haemorrhage of 1000 mL or greater, additional uterotonics, and infection was very-low certainty. There were no events for postpartum anaemia (24 to 48 hours postnatal). Oxytocin solution versus saline solution UVI of oxytocin solution may reduce the use of MROP compared with saline solution, but there was high heterogeneity (RR 0.82, 95% CI 0.69 to 0.97; 14 studies, n = 1370; I² = 54%; low-certainty evidence). There were no differences between subgroups according to risk of bias or oxytocin dose for the outcome MROP. There may be little to no difference between groups in severe postpartum haemorrhage of 1000 mL or greater, blood transfusion, use of additional therapeutic uterotonics, and antibiotic use. There were no events for postpartum anaemia (24 to 48 hours postnatal) (very low-certainty evidence) and there was only one event for maternal mortality (low-certainty evidence). Oxytocin solution versus plasma expander One small study reported UVI of oxytocin compared with plasma expander (n = 109). The evidence was very unclear about any effect on MROP or blood transfusion between the two groups (very low-certainty evidence). No other primary outcomes were reported. For other comparisons there were little to no differences for most outcomes examined. However, there was some evidence to suggest that there may be a reduction in MROP with prostaglandins in comparison to oxytocin (4 studies, n = 173) and ergometrine (1 study, n = 52), although further large-scale studies are needed to confirm these findings. AUTHORS' CONCLUSIONS: UVI of oxytocin solution is an inexpensive and simple intervention that can be performed when placental delivery is delayed. This review identified low-certainty evidence that oxytocin solution may slightly reduce the need for manual removal. However, there are little or no differences for other outcomes. Small studies examining injection of prostaglandin (such as dissolved misoprostol) into the umbilical vein show promise and deserve to be studied further.

Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial.

OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomised placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6 ± 2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66-1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. TWEETABLE ABSTRACT: Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.

Prostanoids in scleroderma microangiopathy: clinical and pharmacoeconomic comparison between two intravenous regimens.

Objectives: Intravenous iloprost (ILO) has widely demonstrated its effectiveness and safety in systemic sclerosis (SSc) patients. Unfortunately, there is no clear consent about dosage, duration, frequency, and infusion modality. The aim of this study was to compare two different therapeutic schemes in the same cohort of consecutive SSc subjects, evaluating differences in terms of effectiveness [digital ulcer (DU) outcome], safety, and direct healthcare costs.Method: This was a retrospective observational study of 47 patients classified with SSc treated with intravenous ILO for severe Raynaud's phenomenon and/or DUs. Two regimens were compared: a continuous inpatient scheme and a daily outpatient scheme. Demographics and clinical data, concomitant therapies, adverse events, and data on resource use and costs were collected.Results: The number of DUs rose slightly with the switch from the continuous to the daily scheme (0.61 ± 1.2 vs 1.1 ± 1.7). Moreover, in the daily scheme there was an increase in the number of therapeutic cycles (2.4 ± 0.7 vs 4.71 ± 1.4, p < 0.001) and an increase in patients treated with other vasoactive drugs. There was a reduction in ILO tolerability and more than half of the patients suspended the treatment. Five patients required hospitalization for severe and refractory DUs in the daily scheme. Moreover, the costs of the two treatments were comparable [median 7174 (range 2748-18 524) EUR vs 6284 (3232-22 706) EUR, p = 0.712].Conclusion: Treatment with a daily scheme of ILO is characterized by worse tolerability and a higher dropout rate compared to a low-flow regimen, with similar costs. We suggest that a low-flow continuous therapeutic scheme is preferable in SSc patients.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies.

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENTWhat is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%.What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Women's experiences of outpatient induction of labour with double balloon catheter or prostaglandin pessary: A qualitative study.

BACKGROUND: One quarter to one third of women experience induction of labour. Outpatient induction of labour may be safe and effective but women's views of this setting and of different methods of induction are sparse. AIM: To explore women's experiences of outpatient induction of labour with either prostaglandin pessary or double balloon catheter. METHODS: Qualitative study using semi-structured, audio-recorded interviews with twenty-one women recruited to a feasibility trial of outpatient induction of labour. Transcripts were coded and analysed using a thematic framework approach. FINDINGS: Two key themes were identified. 'Ownership of induction of labour' concerned how women understood and experienced the induction of labour process and tried to maintain control of a procedure managed by medical professionals. Women felt unprepared for the steps in the process and for the time it would take. The balloon method was preferred as it was considered a gentler start to the process, although some women reported it was painful on insertion. 'Importance of place' reflected women's associations of the home with comfort, ease of support and distraction, and the hospital with safety yet also with discomfort and delays. DISCUSSION: This sample of women were keen to start induction without hormones. The randomised controlled trial design may have biased the sample towards women who wanted to experience the balloon method and outpatient setting where these were not usually offered, thus further cohort studies would be beneficial. CONCLUSIONS: Women were positive about experiencing the early stages of induction of labour at home with the balloon catheter.

Non-steroidal anti-inflammatory drugs, prostaglandins, and COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Can we induce labor by mechanical methods following preterm premature rupture of membranes?

OBJECTIVE: To evaluate the use of the intracervical balloon compared with locally applied prostaglandins for cervical ripening for induction in patients with preterm premature rupture of membranes. METHODS: Monocentric, retrospective (from 2002 to 2017) observational cohort study of singleton pregnancies complicated by preterm premature rupture of membranes and induced between 34 and 37 weeks. The primary outcome measure was balloon catheter efficiency evaluated by Cesarean section rate. Secondary outcomes were : interval from induction to delivery, labor duration, oxytocin use, intrauterine infection rate, maternal complications (i.e., postpartum hemorrhage and endometritis), and neonatal complications. RESULTS: 60 patients had cervical ripening with prostaglandins alone and 58 had balloon catheter. Demographic characteristics were similar between the groups, except for induction term and neonatal weight. There was not a significant difference in occurrence of Cesarean section rate (p = 0.14). Nor were there significant differences in time from induction to birth (p = 0.32) or in intrauterine infection rate (p = 0.95). Labor duration was shorter (p = 0.006) and total oxytocin dose lower (p = 0.005) in patients induced by prostaglandins alone. Concerning neonatal outcomes, there were more transfers to intensive care (p = 0.008) and more respiratory distress (p = 0.005) among newborns induced by prostaglandins. CONCLUSION: Compared with locally applied prostaglandins, balloon catheter induction is not associated with an increase of Cesarean section rate in patients with preterm premature rupture of membranes.

Anti-Mullerian hormone and its relationship to ovulation response and fertility in timed AI Bos indicus heifers.

This study evaluated the association between plasma anti-Mullerian hormone (AMH) concentration and fertility in Nelore (Bos indicus) heifers submitted to timed artificial insemination (TAI). At the onset of the synchronization protocol, heifers (n = 289) received a subcutaneous P4 ear implant (3 mg) and 2 mg of oestradiol benzoate. Eight days later, the P4 implant was removed and 0.5 mg of oestradiol cypionate, prostaglandin (0.265 mg, i.m.) and equine chorionic gonadotropin (300 UI, i.m.) was administered, and TAI was performed 48 hr after ear implant removal. Ovarian ultrasound evaluations were performed to measure number of ovarian follicles, dominant follicle size and ovulation response. Pregnancy diagnosis was performed by ultrasound 30 days after AI. Heifers with greater circulating AMH had more antral follicles, a smaller dominant follicle near timed ovulation and lower ovulation response to the timed AI protocol compared to heifers with lower circulating AMH. Although AMH and pregnancy outcome had a quadratic-shaped pattern, AMH was not significantly associated with fertility. In conclusion, heifers with lower AMH had larger follicles towards the end of the synchronization protocol and greater ovulation responses, whereas greater circulating AMH was unrelated to conception success.

A review of the treatment of male pattern hair loss

Introduction: Androgenetic alopecia is a common hair loss disorder affecting up to 80% of males by the age of 80. It is characterized by androgen related progressive thinning of hair in a defined pattern. It results in diminished self-esteem, reduced confidence and distress in affected men, irrespective of age or stage of baldness. An effective treatment for hair baldness is needed.Areas covered: In androgenetic alopecia, hair follicles undergo progressive miniaturization. Genetic factors and androgens are key role-players in disease pathogenesis. Herein the authors review the pharmacologic treatment of androgenetic alopecia, which involves 5 alpha reductase inhibitors, minoxidil and prostaglandins. Non-pharmacologic approaches are also explored.Expert opinion: Androgenetic alopecia progresses over time and although the current available medical treatments like finasteride and minoxidil are effective in arresting the progression of the disease, they allow only partial regrowth of hair at its best. Early treatment achieves a more optimal outcome. Non-pharmacologic treatments like PRP can be considered in patients refractory to medical treatment.Abbreviations: MPHL: male pattern hair loss; AGA: androgenetic alopecia; DHT: dihydrotestosterone; 5AR: 5-alpha-reductase; VEGF: vascular endothelial growth factor; PG's: prostaglandins (PG's); PGD2R: prostaglandin D2 receptor; VPA: valproic aid; SR: Serenoa Repens; PRP: platelet-rich plasma; PDGF: platelet derived growth factor; TGF: transforming growth factor; ERK: extracellular signal-regulated kinase; PKB: protein kinase B; LLLT: low-level laser therapy; ROS: reactive oxygen species; RCT: randomized control trial; SFRP1: secreted frizzled related protein 1; DP: dermal papilla; PDE5: phosphodiesterase 5.

Comparing Foley Catheter to Prostaglandins for Cervical Ripening in Multiparous Women.

OBJECTIVE: This study sought to test the hypothesis that among multiparous women requiring cervical ripening, mechanical ripening with a Foley catheter is more effective than prostaglandin preparations. METHODS: This was a retrospective analysis of multiparous women with a singleton gestation who required cervical ripening in a single tertiary center from 2014 to 2019. Women who underwent cervical ripening with a Foley catheter (Foley group) were compared with women who underwent cervical ripening using a controlled-release dinoprostone vaginal insert (PGE2-CR group) or dinoprostone vaginal gel (PGE2-gel group). The primary outcome was the ripening-to-delivery interval. RESULTS: A total of 229 women met the study criteria (Foley group: 95; PGE2-CR group: 83; PGE2-gel group: 51). Women in the Foley group had a significantly shorter ripening-to-delivery interval compared with women in the PGE2-CR group (16.2 ± 9.2 hours vs. 27.0 ± 14.8 hours; P < 0.001) and were more likely to deliver within 12 hours (47.4% vs. 12.0%; P < 0.001; adjusted relative risk [aRR] 3.87; 95% confidence interval [CI] 2.07-7.26) and within 24 hours (78.9% vs. 49.4%; P < 0.001; aRR 1.61; 95% CI 1.26-2.06). Women in the Foley group were also less likely to require a second ripening method compared with women in the PGE2-CR group (1.1% vs. 8.4%; P = 0.018; aRR 7.26; 95% CI 2.99-17.62). These differences were not observed when comparing the Foley and the PGE2-gel groups. The cesarean section rate was similar among the Foley group (9.5%), PGE2-CR group (9.6%; P = 0.970), and PGE2-gel group (11.8%; P = 0.664). CONCLUSION: In multiparous women requiring cervical ripening, all methods of cervical ripening have a similar success rate. However, the use of a PGE2-CR insert is associated with a considerably longer interval to delivery compared with a Foley catheter or PGE2 gel.

Induction of labor with an unfavorable cervix.

PURPOSE OF REVIEW: Recent evidence supports elective induction of labor after 39 weeks; however, labor induction in patients with an unfavorable cervix, a Bishop score less than 6, may take several days. In this review, we focus on the efficacy and safety of methods of labor induction for the unfavorable cervix. RECENT FINDINGS: Recent evidence on the use of mechanical cervical preparation with transcervical balloons suggests balloons are the most effective option for decreasing time to delivery in the nulliparous patient. Single and double balloons are equally effective, with a volume of more 30 ml being more effective. The addition of misoprostol or oxytocin concurrently with a balloon further expedites time to delivery. SUMMARY: Mechanical dilation should be considered when available and technically possible for labor induction in patients with an unfavorable cervix. Misoprostol is an effective adjunct to trans-cervical balloons, further decreasing time to delivery as compared with balloon alone. When misoprostol is contraindicated, oxytocin is a safe, effective, alternative adjunct to trans-cervical balloons. More research is needed to evaluate safe outpatient options, induction methods in the setting of prior cesarean with an unfavorable cervix, and to directly compare misoprostol with oxytocin as adjuncts to transcervical balloons.

Induction of vitellogenesis, methyl farnesoate synthesis and ecdysteroidogenesis in two edible crabs by arachidonic acid and prostaglandins.

The present study investigated the effect of arachidonic acid (AA) and selected prostaglandins on the regulation of vitellogenesis, ecdysteroidogenesis and methyl farnesoate (MF) synthesis in the freshwater crab Oziotelphusa senex senex and the giant mud crab, Scylla serrata Administration of AA and prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) significantly increased ovarian index, oocyte diameter and ovarian vitellogenin levels and ecdysteroid and MF levels in the hemolymph of crabs. Secretions of MF and ecdysteroids from in vitro cultured mandibular organs (MO) and Y-organs (YO) isolated from intermolt crabs injected with AA, PGF2α and PGE2 were greater when compared with controls. In contrast, injection of prostaglandin D2 (PGD2) had no effect on vitellogenesis, ecdysteroid and MF levels in circulation. In vitro secretion of MF from MO explants isolated from avitellogenic crabs incubated with AA, PGF2α and PGE2 increased in a time-dependent manner. Conversely, incubation of YOs isolated from avitellogenic crabs with AA, PGF2α and PGE2 had no effect on secretion of ecdsyteroids. These results implicate prostaglandins in the regulation of reproduction by inducing the synthesis of MF and consequent ecdysteroid synthesis in brachyuran crabs, and provide an alternative molecular intervention mechanism to the traditional eyestalk ablation methodology to induce vitellogenesis and ovarian maturation in crustaceans.

Presence of a sexually active goat buck enhances ovulation occurrence in seasonally anestrous does after ovulation and luteolysis induction in hormonally-treated goats in seasonal anestrus.

In seasonally anestrous goat does, ovulations can be induced by combining a treatment regimen including progestagen, eCG and prostaglandins. Nonetheless, ovulations occur only once and then does return to a seasonally anestrous state. This study was performed to determine whether the presence of a sexually active buck can stimulate a second ovulation after induced luteolysis using prostaglandins following the first ovulation. Three groups of seasonally anestrous does were treated to induce ovulations using an intra-vaginally inserted sponge containing a progestin combined with eCG and prostaglandin administrations. Goats that had ovulations were treated with a prostaglandin 11 days after progestin sponge removal. After the prostaglandin injection, does continued to be isolated from bucks (n = 8), were penned with a control buck (n = 9), or were penned with a sexually active buck (n = 10). The proportion of goats having ovulations after imposing the ovulation-induction protocol was greater than 80% and did not differ among treatment groups (P >  0.05). The proportion of does having ovulations after injecting prostaglandins was greater when does were penned with a sexually active buck (8/10) than does penned with a control buck (0/9) or that were isolated from bucks (0/8; P < 0.05). It is concluded that in seasonally anestrous goat does induced to have ovulations using a hormonal treatment regimen, the presence of a sexually active buck can induce a second ovulation when there is an induced luteolysis.

Trombosis tumoral en vena pulmonar inferior derecha por metástasis de condrosarcoma y embolia sistémica / Tumor thrombosis in right inferior pulmonary vein due to chondrosarcoma metastasis and systemic embolism

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Effect of topical prostaglandins on the biomechanics and shape of the cornea.

PURPOSE: To investigate the effect of topical prostaglandin (PG) eyedrops on the biomechanics and shape of the cornea. METHODS: Consecutive patients with primary open-angle glaucoma who had been treated with the same anti-glaucoma PG (114 eyes, 57 patients) or ß-blocker (36 eyes, 18 patients) eyedrops in 1 eye alone for more than 3 months at Inouye Eye Hospital or Miyata Eye Hospital. The biomechanical properties of the cornea were measured using a Corvis ST device (Oculus, Wetzlar, Germany). Corneal tomography was measured with a Casia 1 or 2 (Tomey Corp., Nagoya, Japan). The biomechanical parameters and tomographic features of the cornea were compared between PG-treated eyes, ß-blocker-treated eyes, and contralateral eyes using a mixed-effect model adjusted for intraocular pressure and corneal thickness and a linear model adjusted for age, sex, intraocular pressure, and corneal thickness. RESULTS: The PG-treated eyes had a significantly smaller applanation 1 time, the highest concavity radius, and a larger deformation amplitude than the contralateral eyes. Also, the PG-treated eyes had a significantly smaller applanation 1 time and applanation 2 velocity but a larger peak distance than the ß-blocker-treated eyes. There were no significant differences in any of the Casia parameters between the PG-treated eyes and the contralateral eyes. CONCLUSION: The results of this study suggest that topical PG makes biochemical changes to the cornea but does not alter its shape.

Short-term dietary protein supplementation improves reproductive performance of estrous-synchronized ewes when there are long intervals of prostaglandin or progesterone-based treatments for timed AI.

To evaluate the reproductive effects of a short-term dietary protein supplementation (Days -10 to -3) before timed AI (TAI = Day 0), 471 Merino ewes grazing native pastures were estrous-synchronized when there were either long intervals between prostaglandin administrations (two prostaglandin injections 15 or 16 d apart; PG15 and PG16, respectively) or with a progesterone-eCG (P4-eCG) protocol, resulting in a 3 × 2 experimental design. Ovulation rate on Day 8 (OR), non-estrous-return to Day 21 (NRR21), and fertility, prolificacy and fecundity on Day 70 were evaluated. The interaction between estrous synchronization protocol and supplementation was not significant for any of these variables (P > 0.05). Supplementation increased OR, prolificacy and fecundity (+0.14, +0.15 and +0.14, respectively, P < 0.01), but did not affect NRR21 or fertility of ewes (+6.2% and +6.7% respectively, P > 0.05). Ewes treated using the PG15 and PG16 protocols had a lesser OR (-0.27), prolificacy (-0.22) and fecundity (-0.20) than ewes treated using P4-eCG protocol (P < 0.01 for each), and similar NRR21 and fertility (-5.4% and -7.9% respectively, P > 0.05 for both variables), without significant differences between the PG15 and PG16 groups. In conclusion, a short-term dietary protein supplementation before TAI improved OR, prolificacy and fecundity of ewes which were estrous-synchronized by imposing long interval PG (15 or 16 d apart) or P4-eCG-based protocols. There was a greater OR, prolificacy and fecundity when there was use of the P4-eCG compared to long interval PG-based protocols. Estrous-non-return rate after AI and fertility as a result TAI were not affected by either the supplementation or the estrous synchronization protocols used.

Induction of labour in case of premature rupture of membranes at term with an unfavourable cervix: protocol for a randomised controlled trial comparing double balloon catheter (+oxytocin) and vaginal prostaglandin (RUBAPRO) treatments.

INTRODUCTION: Premature rupture of membranes (PROM) occurs at term in 8% of pregnancies. Several studies have demonstrated that the risk of chorioamnionitis and neonatal sepsis increases with duration of PROM. Decreasing the time interval between PROM and delivery is associated with lower rates of maternal infections. In case of an unfavourable cervix, the use of prostaglandin for cervical maturation demonstrates some advantages over oxytocin. The use of double balloon catheter in reduction of PROM duration has not been evaluated in the literature. METHODS AND ANALYSIS: We are conducting a prospective, monocentric, randomised clinical trial on pregnant women with an unfavourable cervix showing PROM at term (RUBAPRO).After 12-24 hours of PROM, women are randomly assigned to one group treated with a double balloon catheter for 12 hours, with oxytocin administered after 6 hours or to the control group treated with 24 hours of vaginal prostaglandin followed by oxytocin infusion alone. Patients (n=80) are randomised at a 1:1 ratio with stratification on parity.The inclusion criteria are a Bishop score of <6, cephalic presentation at term and confirmed PROM. Women with suspected chorioamnionitis; group B streptococcus (GBS) carrier; a history of caesarean delivery or any contraindication for vaginal delivery are excluded.The time from induction to delivery is the primary outcome. Secondary outcomes were mode of delivery, maternofetal morbidity and the effect of parity on strategies for reduction of PROM duration.To sufficiently demonstrate a difference (10 hours) between groups-with a statistical power of 90% and a two-tailed α of 5%-40 patients per group will be required. ETHICS AND DISSEMINATION: Written informed consent is required from participants.National Ethics Committee approval was obtained in August 2017. The results will be published in a peer-reviewed journal and presented at relevant conferences. Access to raw data will be available only to members of the research team. TRIAL REGISTRATION NUMBER: NCT03310333.