Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women With Uterine Fibroids
The Annals of pharmacotherapy. 2021;:10600280211015987
OBJECTIVE To review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids. DATA SOURCES Literature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings. STUDY SELECTION/DATA EXTRACTION Clinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included. DATA SYNTHESIS Phase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE Women with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option. CONCLUSIONS Elagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.
A 20-cm cut umbilical cord milking may not benefit the preterm infants < 30 week's gestation: A randomized clinical trial
Journal of the Formosan Medical Association = Taiwan yi zhi. 2021
BACKGROUND/PURPOSE To evaluate whether a shorter length (20 cm) of C-UCM has potential benefits, compared to immediate cord clamping (ICC), in very preterm babies. METHODS Inborn preterm infants less than 30 weeks of gestational age (GA) were randomly assigned to the 20-cm C-UMC and ICC groups. The primary outcome was the need for packed red blood cell (pRBC) transfusion before the 21st day of life. The secondary outcomes were short- and long-term outcomes related to premature birth. RESULTS Seventy-six neonates were randomized to the two groups. GA were 27.2 ± 1.8 and 27.5 ± 1.7 weeks (p = 0.389) and birth weights were 987 ± 269 and 1023 ± 313 g (p = 0.601) in the 20-cm C-UCM and ICC groups, respectively. There was no significant difference between the groups in terms of the need for pRBC transfusion before the 21st day of life (59.4% versus 71.8%, adjusted odds ratio [aOR] 0.311, 95% confidence interval [CI] 0.090-1.079). An increased prevalence of late-onset sepsis was observed in the 20-cm C-UCM group compared to the ICC group (21.6% versus 5.1%, aOR 5.434, 95% CI 1.033-23.580). The mortality rates were 13.5% and 2.6% in the 20-cm C-UCM and ICC groups, respectively (aOR 5.339, 95% CI 0.563-50.626). The neurodevelopmental outcomes at 2 years of corrected age between the groups were also not statistically significant. CONCLUSION A 20-cm C-UCM showed no effect on reducing the incidence of pRBC transfusion in preterm babies with GA less than 30 weeks compared with ICC in this small-scale randomized controlled trial.
A narrative review of platelet-rich plasma (PRP) in reproductive medicine
Journal of assisted reproduction and genetics. 2021
PURPOSE Platelet-rich plasma (PRP) has become a novel treatment in various aspects of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology, dentistry, and diabetic wound healing. PRP is now starting to become an area of interest in reproductive medicine more specifically focusing on infertility. Poor ovarian reserve, menopause, premature ovarian failure, and thin endometrium have been the main areas of research. The aim of this article is to review the existing literature on the effects of autologous PRP in reproductive medicine providing a summation of the current studies and assessing the need for additional research. METHODS A literature search is performed using PubMed, MEDLINE, and CINAHL Plus to identify studies focusing on the use of PRP therapy in reproductive medicine. Articles were divided into 3 categories: PRP in thin lining, PRP in poor ovarian reserve, and PRP in recurrent implantation failure. RESULTS In women with thin endometrium, the literature shows an increase in endometrial thickness and increase in chemical and clinical pregnancy rates following autologous PRP therapy. In women with poor ovarian reserve, autologous intraovarian PRP therapy increased anti-Mullerian hormone (AMH) levels and decreased follicle-stimulating hormone (FSH), with a trend toward increasing clinical and live birth rates. This trend was also noted in women with recurrent implantation failure. CONCLUSIONS Limited literature shows promise in increasing endometrial thickness, increasing AMH, and decreasing FSH levels, as well as increasing chemical and clinical pregnancy rates. The lack of standardization of PRP preparation along with the lack of large randomized controlled trials needs to be addressed in future studies. Until definitive large RCTs are available, PRP use should be considered experimental.
Interventions to minimize blood loss in very preterm infants-A systematic review and meta-analysis
PloS one. 2021;16(2):e0246353
Blood loss in the first days of life has been associated with increased morbidity and mortality in very preterm infants. In this systematic review we included randomized controlled trials comparing the effects of interventions to preserve blood volume in the infant from birth, reduce the need for sampling, or limit the blood sampled. Mortality and major neurodevelopmental disabilities were the primary outcomes. Included studies underwent risk of bias-assessment and data extraction by two review authors independently. We used risk ratio or mean difference to evaluate the treatment effect and meta-analysis for pooled results. The certainty of evidence was assessed using GRADE. We included 31 trials enrolling 3,759 infants. Twenty-five trials were pooled in the comparison delayed cord clamping or cord milking vs. immediate cord clamping or no milking. Increasing placental transfusion resulted in lower mortality during the neonatal period (RR 0.51, 95% CI 0.26 to 1.00; participants = 595; trials = 5; I2 = 0%, moderate certainty of evidence) and during first hospitalization (RR 0.70, 95% CI 0.51, 0.96; 10 RCTs, participants = 2,476, low certainty of evidence). The certainty of evidence was very low for the other primary outcomes of this review. The six remaining trials compared devices to monitor glucose levels (three trials), blood sampling from the umbilical cord or from the placenta vs. blood sampling from the infant (2 trials), and devices to reintroduce the blood after analysis vs. conventional blood sampling (1 trial); the certainty of evidence was rated as very low for all outcomes in these comparisons. Increasing placental transfusion at birth may reduce mortality in very preterm infants; However, extremely limited evidence is available to assess the effects of other interventions to reduce blood loss after birth. In future trials, infants could be randomized following placental transfusion to different blood saving approaches. Trial registration: PROSPERO CRD42020159882.
Eye tracking metrics and leader's behavioral performance during a post-partum hemorrhage high-fidelity simulated scenario
Advances in simulation (London, England). 2021;6(1):4
BACKGROUND The use of eye tracking in the simulated setting can help improve our understanding of what sources of information clinicians are using as they deliver routine patient care. The aim of this simulation study was to observe the differences, if any, between the eye tracking patterns of leaders who performed best in a simulated postpartum hemorrhage (PPH) high-fidelity scenario, in comparison with those who performed worst. METHODS Forty anesthesia trainees from the University of Catania Medical School were divided into eight teams, to enact four times the same scenario of a patient with postpartum hemorrhage following vaginal delivery. Trainees who were assigned the leader's role wore the eye tracking glasses during the scenario, and their behavioral skills were evaluated by two observers, who reviewed the video recordings of the scenarios using a standardized checklist. The leader's eye tracking metrics, extracted from 27 selected areas of interest (AOI), were recorded by a Tobii Pro Glasses 50 Hz wearable wireless eye tracker. Team performance was evaluated using a PPH checklist. After completion of the study, the leaders were divided into two groups, based on the scores they had received (High-Performance Leader group, HPL, and Low-Performance Leader group, LPL). RESULTS In the HPL group, the duration and number of fixations were greater, and the distribution of gaze was uniformly distributed among the various members of the team as compared with the LPL group (with the exception of the participant who performed the role of the obstetrician). The HPL group also looked both at the patient's face and established eye contact with their team members more often and for longer (P < .05). The team performance (PPH checklist) score was greater in the HPL group (P < .001). The LPL group had more and/or longer fixations of technical areas of interest (P < .05). CONCLUSIONS Our findings suggest that the leaders who perform the best distribute their gaze across all members of their team and establish direct eye contact. They also look longer at the patient's face and dwell less on areas that are more relevant to technical skills. In addition, the teams led by these best performing leaders fulfilled their clinical task better. The information provided by the eye behaviors of "better-performing physicians" may lay the foundation for the future development of both the assessment process and the educational tools used in simulation. TRIAL REGISTRATION Clinical.Trial.Gov ID n. NCT04395963 .
The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial
Reproductive sciences (Thousand Oaks, Calif.). 2021
Repeated implantation failure (RIF) is a disorder in which good-quality embryos fail to implant in the endometrium following several in vitro fertilization (IVF) cycles. This study aimed to evaluate the efficiency and safety of intrauterine infusion of platelet-rich plasma (PRP) in improvement of pregnancy outcomes in RIF patients undergoing frozen embryo transfer (FET). A total of 438 women with a history of RIF undergoing FET were assessed for eligibility to enter the study. Patients were randomly assigned to the intervention (PRP) and control groups. The intervention group received an intrauterine infusion of 0.5 ml PRP 48 h before embryo transfer while the control group received standard treatment. The rates of chemical and clinical pregnancy were defined as the primary outcome values. All women were followed up until the study endpoints that included the number of neonates born and pregnancy-related complications. Three hundred and ninety-three participants accomplished the study and their data were analyzed. The chemical pregnancy, clinical pregnancy, and live birth rates were higher in the PRP group than control group (p value: <0.0001; p value: <0.0001; p value: <0.0001 respectively). However, there were no significant differences between the two groups in terms of multiple pregnancies and pregnancy complications except for spontaneous abortion. The spontaneous abortion rate was significantly higher in the control group compared to the PRP group (p value = 0.0262). These results suggest that intrauterine infusion of PRP is an effective and safe route to improve pregnancy outcomes in RIF patients undergoing FET.
The association of endometriosis with placenta previa and postpartum hemorrhage: A systematic review and meta-analysis
American journal of obstetrics & gynecology MFM. 2021;:100417
OBJECTIVE This study aimed to review the effect of endometriosis on the prevalence of placenta previa, postpartum hemorrhage, and surgical outcomes in placenta previa patients with endometriosis. DATA SOURCES In compliance with the Preferred Reporting Items for Systematic Reviews guidelines, a systematic review of the literature was conducted through December 31, 2020, using PubMed, Scopus, and the Cochrane Library. STUDY ELIGIBILITY CRITERIA Comparative studies between pregnant women with and without endometriosis, as well as studies that investigated the surgical outcomes in placenta previa patients with and without endometriosis, were included. STUDY APPRAISAL AND SYNTHESIS METHODS Two reviewers independently screened the titles and abstracts, completed data extraction, and assessed the reporting quality using the Risk Of Bias In Nonrandomized Studies of Interventions tool. RESULTS Nineteen studies (2010 to 2020) met the inclusion criteria (98,463 pregnancies with endometriosis and 7,184,313 pregnancies without endometriosis). In the adjusted-pooled analysis, endometriosis was associated with a higher rate of placenta previa (adjusted odds ratio [aOR] 3.17, 95% confidence interval [CI] 2.58-3.89), whereas the incidence of postpartum hemorrhage was similar between pregnant women with and without endometriosis (aOR 1.15, 95%CI 0.99-1.34). When the analysis was restricted to histologically confirmed endometriosis cases, the relationship of endometriosis with placenta previa (aOR 4.23, 95%CI 1.74-10.30) and postpartum hemorrhage (aOR 1.29, 95%CI 0.50-3.34) was consistent with results from the nonrestricted analysis. No study examined surgical outcomes in placenta previa patients with endometriosis. Three studies examined the effect of endometriosis on surgical outcomes during cesarean delivery: one study showed that endometriosis was associated with increased intraoperative bleeding during emergent cesarean delivery, the other study showed that endometriosis was associated with an increased incidence of postpartum hemorrhage during cesarean delivery (aOR 1.1, 95%CI 1.0-1.2), especially in primiparous, singleton pregnant women (aOR 1.7, 95%CI 1.5-2.0), and another study suggested a significantly higher rate of hysterectomy (7.1%) and bladder injury (7.1%) in those with endometriosis than in those without. CONCLUSIONS Endometriosis can potentially be associated with adverse surgical outcomes during cesarean delivery. Although there is a correlation between endometriosis and increased rate of placenta previa, surgical outcomes in placenta previa patients with endometriosis remain understudied.
Low dose dexamethasone as treatment for women with heavy menstrual bleeding: A response-adaptive randomised placebo-controlled dose-finding parallel group trial (DexFEM)
BACKGROUND The symptom of heavy menstrual bleeding (HMB) diminishes quality-of-life for many mid-age women and imposes substantial societal burden. We investigated our hypothesis that HMB reflects impaired endometrial vasoconstriction due to endometrial glucocorticoid deficiency. Does reversing this deficiency, by short-term luteal-phase treatment with exogenous glucocorticoid (dexamethasone), ameliorate HMB? METHODS In our Bayesian response-adaptive parallel-group placebo-controlled randomised trial, five pre-planned interim analyses used primary outcome data to adjust randomisation probabilities to favour doses providing most dose-response information. Participants with HMB, recruited from Lothian (Scotland) NHS clinics and via community invitations/advertisements, were aged over 18 years; reported regular 21-42 day menstrual cycles; and had measured menstrual blood loss (MBL) averaging ≥ 50 mL over two screening periods. Identically encapsulated placebo, or one of six Dexamethasone doses (0·2 mg, 0·4 mg, 0·5 mg, 0·6 mg, 0·75 mg, 0·9 mg), were taken orally twice-daily over five days in the mid-luteal phase of three menstrual cycles. Participants, investigators, and those measuring outcomes were masked to group assignment. Primary outcome, change in average MBL from screening to 'treatment', was analysed by allocated treatment, for all with data. TRIAL REGISTRATION ClinicalTrials.gov NCT01769820; EudractCT 2012-003,405-98 FINDINGS Recruitment lasted 29/01/2014 to 25/09/2017; 176 were screened, 107 randomised and 97 provided primary outcome data (n = 24,5,9,21,8,14,16 in the seven arms, placebo to 1·8 mg total daily active dose). In Bayesian normal dynamic linear modelling, 1·8 mg dexamethasone daily showed a 25 mL greater reduction in MBL from screening, than placebo (95% credible interval 1 to 49 mL), and probability 0·98 of benefit over placebo. Adverse events were reported by 75% (58/77) receiving dexamethasone, 58% (15/26) taking placebo. Three serious adverse events occurred, two during screening, one in a placebo participant. No woman withdrew due to adverse effects. INTERPRETATION Our adaptive trial in HMB showed that dexamethasone 1·8 mg daily reduced menstrual blood loss. The role of dexamethasone in HMB management deserves further investigation. FUNDING UK MRC DCS/DPFS grant MR/J003611/1.
Aneurysmal subarachnoid hemorrhage during pregnancy: a comprehensive and systematic review of the literature
Neurosurgical review. 2021
Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the management of aSAH in pregnancy. We identified all available literature and compiled management decisions as well as reported outcomes through a systematic literature review without meta-analysis to provide recommendations for management of aSAH during pregnancy. We included a total of 23 articles containing 54 cases of pregnancy-related aSAH in our review. From these reports and other literature, we evaluated information on aSAH pathophysiology, diagnosis, and management with respect to pregnancy. Early transfer to an appropriate facility with neurocritical care, a high-risk obstetric service, and a neurosurgery team available is crucial for the management of aSAH in pregnancy. Intensive monitoring and a multidisciplinary approach remain fundamental to ensure maternal and fetal health.
Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis
Scientific reports. 2021;11(1):1747
The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58-3.00; p < 0.00001; OR 2.03; 95% CI 1.22-3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40-4.16; p = 0.002; OR 3.73; 95% CI 1.13-12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58-3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55-3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.