Effects of Intrauterine Infusion of Autologous Platelet-Rich Plasma in Women Undergoing Treatment with Assisted Reproductive Technology: a Meta-Analysis of Randomized Controlled Trials
Hu S, Jin Z, Tang Q
Geburtshilfe und Frauenheilkunde. 2023;83(4):453-462
Purpose This meta-analysis was conducted to systematically retrieve relevant randomized controlled trials (RCTs) and evaluate the effects of intrauterine infusion of autologous platelet-rich plasma (PRP) in women with thin endometrium, implantation or pregnancy failure undergoing treatment with assisted reproductive technology (ART). Methods We conducted a systematic review and meta-analysis of the retrieved RCTs. Studies on the intrauterine infusion of PRP in women undergoing treatment with ART that were published in PubMed, the Cochrane library, Web of Science, and Embase from inception until June 2022 were included. The data were extracted and analyzed independently using the fixed-effects or random-effects model according to heterogeneity. Results Seven RCTs involving 861 patients (435 in the intervention group and 426 in the control group) were included. The rates of clinical pregnancy (risk ratio [RR]: 2.51; 95% confidence interval [CI]: 2.0-3.13; PÂ <Â 0.00001), chemical pregnancy (RR: 1.96; 95% CI: 1.58-2.45; PÂ <Â 0.00001), live births (RR: 7.03; 95% CI: 3.91-12.6; PÂ <Â 0.00001), and implantation (RR: 3.27; 95% CI: 1.42-7.52; PÂ =Â 0.005) were significantly higher in the women who received PRP infusion than in the control group. No significant differences were noted in the miscarriage rate (RR: 0.98; 95% CI: 0.39-2.42; PÂ =Â 0.96) between the two groups. Conclusion In summary, intrauterine infusion of PRP may be an effective therapy for women with thin endometrium and recurrent implantation failure (RIF) undergoing treatment with ART. More population-based RCTs are warranted to verify the efficacy of our evidence.
Safety and efficacy of intrauterine balloon tamponade vs uterine gauze packing in managing postpartum hemorrhage: A systematic review and meta-analysis
Abul A, Al-Naseem A, Althuwaini A, Al-Muhanna A, Clement NS
AJOG global reports. 2023;3(1):100135
BACKGROUND There is debate on whether uterine gauze packing or intrauterine balloon tamponade is safer and more effective as a surgical management option for treating postpartum hemorrhage. OBJECTIVE This study aimed to compare intra- and postoperative outcomes of intrauterine balloon tamponade and uterine gauze packing in patients with postpartum hemorrhage. STUDY DESIGN A range of databases such as Cochrane and PubMed were searched using terms including "post-partum haemorrhage," "uterine balloon tamponade," and "uterine gauze packing." All observational studies comparing intrauterine balloon tamponade with uterine gauze packing were included. Five studies were identified enrolling 821 adult patients diagnosed with postpartum hemorrhage. Primary outcomes included blood loss volume, success rates, and maternal mortality. Secondary outcomes comprised requiring additional interventions, postoperative hemoglobin levels, and requiring blood transfusions. Fixed and random models were used for analysis. RESULTS Intrauterine balloon tamponade seemed to be a superior option to uterine gauze packing. Intrauterine balloon tamponade was better in reducing intraoperative blood loss, with a statistically significant improvement (P<.0001). Cases managed with intrauterine balloon tamponade seemed to have statistically significant shorter operative time (P=.023) and hospital length of stay (P=.020) in one study. CONCLUSION Intrauterine balloon tamponade remains more effective and safer as a first-line surgical management option for postpartum hemorrhage compared with uterine gauze packing.
Skin-to-Skin Contact in the Third Stage of Labor and Postpartum Hemorrhage Prevention: A Scoping Review
Ruiz MT, Azevedo NF, Raponi MBG, Fonseca LMM, Wernet M, Silva MPC, Contim D
Maternal and child health journal. 2023
INTRODUCTION Literature supports numerous benefits of skin-to-skin contact for neonatal adaptation to extrauterine life and bonding/attachment, but few studies explore the effects of skin-to-skin contact on maternal outcomes. This review aims to map the evidence on skin-to-skin contact in the third stage of labor for postpartum hemorrhage prevention. METHODS Scoping review, which covered stages recommended by the Institute Joanna Briggs, including studies from the PubMed, EMBASE, CINAHL, LILACS, Web of Science, and Scopus databases, using the descriptors "Postpartum hemorrhage", "Labor stages, third", "Prevention" and "Kangaroo care/Skin-to-skin". RESULTS 100 publications on the subject found, 13 articles met the inclusion criteria, with 10,169 dyads were assessed in all studies. Publications from 2008 to 2021 were mostly written in English and designed as a randomized controlled trial. Skin-to-skin contact was effective and significant in: reducing the duration of the third stage of labor; placenta delivery; uterine contractility and physiological involution; absence of atony, decreasing blood loss with lower rates of erythrocyte and hemoglobin drop; reducing the need for synthetic oxytocin and/or ergometrine to control bleeding; and reducing changing pads per period and length of stay. DISCUSSION Skin-to-skin contact was considered an effective, low-cost, and safe strategy, with positive effects already established in the literature for infants and extremely favorable results in postpartum hemorrhage prevention cases, being highly recommended in assistance for the dyad. Open Science Framework Registry ( https://osf.io/n3685 ).
A Comparative Study of Sublingual Misoprostol Versus Intramuscular Oxytocin in the Active Management of Third Stage of Labor
Mishra S, Tirkey S, Prasad A, Trivedi K
Objective Misoprostol has attracted low-income low-resource countries for the active management of the third stage of labor. The objective of this study was to compare the efficacy of sublingual misoprostol and intramuscular oxytocin in the active management of the third stage of labor. Study design This was a prospective randomized controlled trial in which a total of 407 healthy pregnant women having singleton pregnancy, cephalic presentation, and normal vaginal delivery were divided into two groups. In the first group (n=203), women received 600 µg misoprostol tablet sublingually, and in the second group (n=204), women received 10 IU of intramuscular oxytocin, within 1 minute of the delivery of the baby during the third stage of labor. Three patients from the first group and four patients from the second group were excluded from the analysis due to traumatic postpartum hemorrhage (PPH). The primary outcome was an incidence of PPH. Secondary outcomes were the duration of the third stage of labor, amount of blood loss, fall in hemoglobin concentration after 48 hours of delivery, need for additional uterotonics, and side effects of the drugs. Data were compared using the chi-square and independent samples t-test. Results The incidence of PPH was 6.5% in the misoprostol group as compared to 2% in the oxytocin group (p=0.026). The misoprostol group also had significantly higher blood loss (293.75±125.8 mL) and a greater fall in hemoglobin level (0.58±0.25 g/dL) as compared to that in the oxytocin group (226.13±98.44 mL and 0.45±0.20 g/dL) (p<0.001). The mean duration of the third stage of labor was significantly higher in the misoprostol group (5.31±2.1 min) as compared to that in the oxytocin group (3.65±1.75 min) (p<0.001). The additional need for uterotonics was recorded in 15% of the study participants in the misoprostol group as compared to 8% in the oxytocin group (p=0.028). The incidence of side effects such as shivering and fever was significantly higher in the misoprostol group as compared to the oxytocin group. No significant difference between the two groups was observed concerning the incidence of nausea, vomiting, diarrhea, and headache. Conclusion Intramuscular oxytocin is a safe and useful alternative to sublingual misoprostol in facilitating the third stage of labor with minimal blood loss, fewer incidences of hemorrhage, and fewer adverse effects.
Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis
Young MF, Oaks BM, Rogers HP, Tandon S, Martorell R, Dewey KG, Wendt AS
BMC pregnancy and childbirth. 2023;23(1):264
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BACKGROUND Growing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment. METHODS We conducted an updated systematic review (using PubMed and Cochrane Review) on low (< 110 g/L) and high (≥ 130 g/L) maternal Hb concentrations and associations with a range of maternal and infant health outcomes. We examined associations by timing of Hb assessment (preconception; first, second, and third trimesters, as well as at any time point in pregnancy), varying cutoffs used for defining low and high hemoglobin concentrations and performed stratified analyses by iron-deficiency anemia. We conducted meta-analyses to obtain odds ratios (OR) and 95% confidence intervals. RESULTS The updated systematic review included 148 studies. Low maternal Hb at any time point in pregnancy was associated with: low birthweight, LBW (OR (95% CI) 1.28 (1.22-1.35)), very low birthweight, VLBW (2.15 (1.47-3.13)), preterm birth, PTB (1.35 (1.29-1.42)), small-for-gestational age, SGA (1.11 (1.02-1.19)), stillbirth 1.43 (1.24-1.65)), perinatal mortality (1.75 (1.28-2.39)), neonatal mortality (1.25 (1.16-1.34), postpartum hemorrhage (1.69 (1.45-1.97)), transfusion (3.68 (2.58-5.26)), pre-eclampsia (1.57 (1.23-2.01)), and prenatal depression (1.44 (1.24-1.68)). For maternal mortality, the OR was higher for Hb < 90 (4.83 (2.17-10.74)) than for Hb < 100 (2.87 (1.08-7.67)). High maternal Hb was associated with: VLBW (1.35 (1.16-1.57)), PTB (1.12 (1.00-1.25)), SGA (1.17 (1.09-1.25)), stillbirth (1.32 (1.09-1.60)), maternal mortality (2.01 (1.12-3.61)), gestational diabetes (1.71 (1.19-2.46)), and pre-eclampsia (1.34 (1.16-1.56)). Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent. Lower Hb cutoffs were associated with greater odds of poor outcomes; for high Hb, data were too limited to identify patterns. Information on anemia etiology was limited; relationships did not vary by iron-deficiency anemia. CONCLUSION Both low and high maternal Hb concentrations during pregnancy are strong predictors of adverse maternal and infant health outcomes. Additional research is needed to establish healthy reference ranges and design effective interventions to optimize maternal Hb during pregnancy.
Women during pregnancy or preconception (148 studies, n= 13,839,327).
Updated systematic review on low (< 110 g/L) and high (≥ 130 g/L) maternal haemoglobin (Hb) concentrations and associations with adverse maternal and infant health outcomes.
Low maternal Hb at any time point in pregnancy was associated with: Low birthweight, very low birthweight (VLBW), preterm birth (PTB), small-for-gestational age (SGA), stillbirth, perinatal mortality, neonatal mortality, postpartum haemorrhage, transfusion, pre-eclampsia, and prenatal depression. For maternal mortality, the OR was higher for Hb < 90 (OR, 4.83; 95% CI [2.17, 10.74]) than for Hb < 100 (OR, 2.87; 95% CI [1.08, 7.67]). High maternal Hb was associated with: VLBW, PTB, SGA, stillbirth, maternal mortality, gestational diabetes, and pre-eclampsia. Stronger associations were noted earlier in pregnancy for low Hb and adverse birth outcomes while the role of timing of high Hb was inconsistent.
Hysteroscopic injections of autologous endometrial cells and platelet-rich plasma in patients with thin endometrium: a pilot randomized study
Efendieva, Z., Vishnyakova, P., Apolikhina, I., Artemova, D., Butov, K., Kalinina, E., Fedorova, T., Tregubova, A., Asaturova, A., Fatkhudinov, T., et al
Scientific Reports. 2023;13(1):945
The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6-0.7 × 10(11) of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis.
Active management of the third stage of labour in Ethiopia: A systematic review and meta-analysis
Mihretie GN, Ayele AD, Liyeh TM, Beyene FY, Kassa BG, Arega DT, Belay HG, Worke MD
PloS one. 2023;18(4):e0281343
BACKGROUND Post-partum haemorrhage occurs in over 10% of all births and is the leading cause of maternal mortality, accounting for 25% of all maternal deaths worldwide. Active management of the third stage of labor is the most important intervention for reducing maternal morbidity and mortality by preventing postpartum hemorrhage. Previously, documented primary studies had been great discrepancy, inconsistent results, and there is a lack of comprehensive study. Hence, this systematic review and meta-analysis were intended to assess the prevalence and associated factors of the practice of active management of the third stage of labour among obstetric care providers in Ethiopia. METHOD Cross-sectional studies were systematically searched from January 01, 2010, to December 24, 2020, using PubMed, Google Scholar, HINARI, Cochrane Library, and grey literature. The pooled prevalence of active management of the third stage of labour practice and associated factors was estimated using DerSemonial-Laird Random Effect Model. Stata (version 16.0) was used to analyze the data. The I-squared statistic was used to assess the studies' heterogeneity. A funnel plot and Egger's test were used to check for publication bias. A subgroup analysis was performed to minimize the underline heterogeneity depending on the study years and the sample sizes. RESULTS Seven hundred fifty articles were extracted. The final ten studies were included in this systematic review, including 2438 participants. The pooled prevalence of practices of active management of the third stage of labour among obstetric care providers in Ethiopia was 39.65% (30.86, 48.45%). Educational status (OR = 6.11, 95%CI, 1.51-10.72), obstetric care training (OR = 3.56, 95% CI: 2.66, 4.45), work experience (OR = 2.17, 95%CI, 0.47, 3.87) and knowledge of active management of the third stage of labour (OR = 4.5, 95% CI: 2.71, 6.28) were significantly associated with active management of the third stage of labour practices. CONCLUSION The practice of active management of the third stage of labour in Ethiopia was low. This study showed that educational status, taking obstetric care training, knowledge of AMTSL, and work experience of obstetric care providers were associated with of practices of active management of the third stage of labour. Therefore, obstetric care professionals should improve their academic level, knowledge, and skills in order to provide useful service to AMTSL and save mothers' lives. All obstetric care providers should get obstetric care training. Furthermore, the government should increase obstetric care professionals' educational level.
Tranexamic acid for the prevention of postpartum haemorrhage: the TAPPH-1 pilot randomized trial and lessons learned for trials in Canadian obstetrics
Alam, A. Q., Barrett, J., Callum, J., Kaustov, L., Au, S., Fleet, A., Kiss, A., Choi, S.
Scientific Reports. 2023;13(1):4512
Postpartum haemorrhage (PPH) is a leading cause of maternal morbidity and mortality. While tranexamic acid (TXA) reduces bleeding and transfusion requirements in established PPH, we sought to determine the feasibility of conducting a fully powered trial assessing the effect of prophylactic tranexamic acid, prior to PPH onset, in a Canadian Obstetric setting. With institutional and Health Canada approval, consenting, eligible parturients (singleton, > 32 weeks gestation, vaginal or caesarian delivery) were randomly assigned to receive TXA (1 g intravenously) or placebo (0.9% saline) prior to delivery. Participants, investigators, data collectors/adjudicators, and analysis was blinded. The primary outcome was administration of study intervention to > 85% of randomized individuals. Secondary outcomes included recruitment rate (feasibility) and safety outcomes. Over 8 months, 611 were approached, 35 consented, and 27 randomized (14 TXA, 13 placebo). 89% of randomized participants received the assigned intervention. Recruitment fell below feasibility (23% target). No serious adverse outcomes occurred. Our pilot trial in a Canadian Obstetric setting was unable to demonstrate feasibility to conduct a large, multicentre trial to examine prophylactic use of tranexamic for PPH secondary to the complex regulatory requirements associated with a trial for an off-label, but commonly utilized intervention. These challenges should inform stakeholders on the resources and challenges of conducting future trials using off-label interventions.Trial registration: www.clinicaltrials.gov , NCT03069859 (03/03/2017).
The value of platelet-rich plasma in women with previous implantation failure: a systematic review and meta-analysis
Maged, A. M., El-Mazny, A., Kamal, N., Mahmoud, S. I., Fouad, M., El-Nassery, N., Kotb, A., Ragab, W. S., Ogila, A. I., Metwally, A. A., et al
Journal of Assisted Reproduction and Genetics. 2023
OBJECTIVE To assess the value of intrauterine PRP to improve IVF outcome in women with previous implantation failure. METHODS Screening of Pubmed, Web of Science, and other databases from inception to August 2022 using the keywords related to "platelet-rich plasma" OR "PRP" AND "IVF" "implantation failure." Twenty-nine studies (3308 participants) were included in our analysis, 13 were RCTs, 6 were prospective cohorts, 4 were prospective single arm, and 6 were retrospective analyses. Extracted data included settings of the study, study type, sample size, participants' characteristics, route, volume, timing of PRP administration, and outcome parameters. RESULTS Implantation rate was reported in 6 RCTs (886 participants) and 4 non-RCTs (732 participants). The odds ratio (OR) effect estimate was 2.62 and 2.06, with 95% CI of 1.83, 3.76, and 1.03-4.11, respectively. Endometrial thickness was compared in 4 RCTs (307 participants) and 9 non-RCTs (675 participants), which showed a mean difference of 0.93 and 1.16, with 0.59-1.27 and 0.68-1.65 95% CI, respectively. CONCLUSION PRP administration improves implantation, clinical pregnancy, chemical pregnancy, ongoing pregnancy, live birth rates, and endometrial thickness in women with previous implantation failure.
Maximum Dose Rate of Intrapartum Oxytocin Infusion and Associated Obstetric and Perinatal Outcomes
Son M, Roy A, Grobman WA, Miller ES, Dude A, Peaceman AM, Stetson B
Obstetrics and gynecology. 2023;141(2):379-386
OBJECTIVE Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20 milliunits/min of oxytocin was associated with adverse outcomes. METHODS This is a secondary analysis of a double-blind, single-center, randomized controlled trial of nulliparous patients with singleton gestations at 36 weeks of gestation or later who presented in spontaneous labor randomized 1:1 to either a high-dose oxytocin titration regimen (initial-incremental rate of 6 milliunits/min) or standard-dose titration regimen (initial-incremental rate of 2 milliunits/min) for labor augmentation. A maximum oxytocin dose rate limit was not specified in the study protocol. For this secondary analysis, outcomes of participants who received oxytocin and exceeded a dose rate of 20 milliunits/min at any point in labor were compared with those whose rate remained at 20 milliunits/min or less. In addition, the cumulative proportions of labor and birth outcomes were calculated for each maximum dose rate of oxytocin reached among this study cohort. RESULTS Of the 1,003 participants in the parent trial, 955 (95.2%) received oxytocin, as planned, and were included, with 190 (19.9%) exceeding a maximum dose rate of 20 milliunits/min. Those who exceeded 20 milliunits/min were older and were more likely to have rupture of membranes as their trial entry indication, have hypertensive disorders of pregnancy, receive intrapartum magnesium sulfate infusion, and receive oxytocin for longer. Those whose maximum rates exceeded 20 milliunits/min underwent cesarean delivery more frequently, but the majority (74%) still delivered vaginally. In multivariable analyses, there were no significant associations between maximum oxytocin dose rates greater than 20 milliunits/min and cesarean delivery (adjusted odds ratio [aOR] 1.57, 95% CI 1.00-2.46), peripartum infection (aOR 0.69, 95% CI 0.41-1.19), postpartum hemorrhage (aOR 1.37, 95% CI 0.70-2.71), or neonatal intensive care unit (NICU) admission (aOR 1.72, 95% CI 0.89-3.31). Although 85% of spontaneous vaginal deliveries occurred at maximum oxytocin dose rates of 20 milliunits/min or less, vaginal deliveries continued to occur at higher maximum dose rates. The cumulative proportions of NICU admissions and composite severe neonatal morbidity and mortality cases increased with increasing oxytocin dose rates even with maximum oxytocin dose rates at 20 milliunits/min or less. CONCLUSION In multivariable analyses, there are no significant differences in maternal or perinatal adverse outcomes based on exceeding 20 milliunits/min of oxytocin. These data suggest that oxytocin dosing should be individualized to each patient and not be based on arbitrary thresholds. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT02487797.