Clinical evaluation of autologous platelet-rich plasma therapy for intrauterine adhesions: a systematic review and meta-analysis
Frontiers in endocrinology. 2023;14:1183209
OBJECTIVE This meta-analysis aims to evaluate the efficacy and safety of autologous platelet-rich plasma (PRP) administration in reducing adhesion recurrence and improving pregnancy outcomes in patients with intrauterine adhesion (IUA). METHODS We conducted a comprehensive search of Pubmed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) from inception to February 10, 2023, without any language or regional restrictions. We used random-effects models to assess odds ratios (OR) and weight mean differences (WMD) with 95% confidence intervals (CI). RESULTS Our meta-analysis included a total of 730 patients from 10 clinical studies (6 RCTs and 4 non-RCTs). The results showed that PRP administration significantly increased endometrial thickness (WMD = 0.79, 95% CI: 0.40-1.19; P < 0.001; I(2) = 0.0%), menstrual volume (WMD = 2.96, 95% CI = 2.30-3.61; P < 0.001; I(2) = 0.0%), and days of menstruation (WMD = 1.13, 95% CI = 0.86-1.41; P < 0.001; I(2) = 0.0%). Additionally, the clinical pregnancy rate was also improved (OR = 1.82, 95% CI: 1.19-2.78; P = 0.006; I(2) = 0.0%). However, there was insufficient evidence to reach a conclusion regarding the effects of PRP on the recurrence rate of moderate to severe IUA, changes in AFS scores, miscarriage rate, and live birth rate. CONCLUSIONS Our analysis confirms that autologous PRP is an effective treatment for IUA. However, the limited sample size suggests that the results should be interpreted with caution. Therefore, larger and well-designed studies are necessary in the future to confirm these findings and explore the optimal PRP dosing regimens further. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023391115.
Effects of Intrauterine Infusion of Autologous Platelet-Rich Plasma in Women Undergoing Treatment with Assisted Reproductive Technology: a Meta-Analysis of Randomized Controlled Trials
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.
Red Blood Cell Transfusion in Patients With Placenta Accreta Spectrum: A Systematic Review and Meta-analysis
Obstetrics and gynecology. 2023;141(1):49-58
OBJECTIVE To evaluate red blood cell use during delivery in patients with placenta accreta spectrum. DATA SOURCES We searched MEDLINE, EMBASE, CINAHL, Cochrane Central, ClinicalTrials.gov, and Scopus for clinical trials and observational studies published between 2000 and 2021 in countries with developed economies. METHODS OF STUDY SELECTION Abstracts (n=4,275) and full-text studies (n=599) were identified and reviewed by two independent reviewers. Data on transfused red blood cells were included from studies reporting means and SDs, medians with interquartile ranges, or individual patient data. The primary outcome was the weighted mean number of units of red blood cells transfused per patient. Between-study heterogeneity was assessed with an I2 statistic. Secondary analyses included red blood cell usage by placenta accreta subtype. TABULATION, INTEGRATION, AND RESULTS Of the 599 full-text studies identified, 20 met criteria for inclusion in the systematic review, comprising 1,091 cases of placenta accreta spectrum. The number of units of red blood cells transfused was inconsistently described across studies, with five studies (25.0%) reporting means, 11 (55.0%) reporting medians, and four (20.0%) reporting individual patient data. The weighted mean number of units transfused was 5.19 (95% CI 4.12-6.26) per patient. Heterogeneity was high across studies (I2=91%). In a sensitivity analysis of five studies reporting mean data, the mean number of units transfused was 6.61 (95% CI 4.73-8.48; n=220 patients). Further quantification of units transfused by placenta accreta subtype was limited due to methodologic inconsistencies between studies and small cohort sizes. CONCLUSION Based on the upper limit of the CI in our main analysis and the high study heterogeneity, we recommend that a minimum of 6 units of red blood cells be available before delivery for patients with placenta accreta spectrum. These findings may inform future guidelines for predelivery blood ordering and transfusion support. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42021240993.
How autologous platelet-rich plasma affects pregnancy and birth outcomes in women with repeated embryo implantation failure: A prisma-compliant meta-analysis
Turkish journal of obstetrics and gynecology. 2023;20(2):154-163
Repeated implantation failure refer to failure to conceive after three or more embryo transfer attempts. Several interventions were offered to improve maternal and fetal outcomes. Our objective was to investigate the impact of platelet-rich plasma (PRP) as a promising intervention to improve both pregnancy and birth outcomes. We searched PubMed, Scopus, Web of Science, and Cochrane Central, in addition to other relevant resources of grey literature. Only clinical trials were eligible to be included. We performed the meta-analysis using a random effects model. Eight randomized clinical trials, enrolling 1038 women with more than 3 implantation failure attempts, were included. We found a significant increase regarding all our prespecified primary outcomes. Chemical pregnancy rate [relative ratio (RR): 1.96, 95% confidence interval (CI): 1.61, 2.39; p<0.001], clinical pregnancy rate (RR: 4.35, 95% CI: 1.92, 2.88; p<0.001), and live birth rate (RR: 4.03, 95% CI: 1.29, 12.63; p=0.02) were found to be statistically significant and increased in patients who received PRP compared with the control group. Implantation rate (RR: 1.98, 95% CI: 1.34, 2.75; p<0.001), miscarriage rate (RR: 0.44, 95% CI: 0.23, 0.83, p=0.01), and multiple pregnancy rate (RR: 2.56, 95% CI: 1.02, 6.42, p=0.04) were also found to be significantly increased in the PRP group. We provide strong evidence on how intrauterine PRP can improve implantation, pregnancy, and birth outcomes in RIF women, which should direct clinicians to consider this intervention as a very effective tool in assisted reproductive techniques.
The value of platelet-rich plasma in women with previous implantation failure: a systematic review and meta-analysis
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.
Maternal low and high hemoglobin concentrations and associations with adverse maternal and infant health outcomes: an updated global systematic review and meta-analysis
BMC pregnancy and childbirth. 2023;23(1):264
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.
Platelet-Rich Plasma Intrauterine Infusion as Assisted Reproduction Technology (ART) to Combat Repeated Implantation Failure (RIF): A Systematic Review and Meta-Analysis
Iranian journal of public health. 2023;52(8):1542-1554
BACKGROUND Repeated implantation failure (RIF) is considered one of the major challenges facing clinician in assisted reproduction technologies (ART) despite the significant advances that have been made in this field. Platelet rich plasma (PRP), also known as autologous conditioned plasma, is a protein concentrate with anti-inflammatory and pro-regenerative characteristics. The use of PRP in women undergoing ART has been studied in the past, with varying degrees of success. The goal of this trial was to see if injecting PRP into the uterus improves pregnancy outcomes in women receiving ART. METHODS PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials were among the databases searched (CENTRAL), from 2015 to 2021. The pooled estimates were calculated using a meta-analysis with a random-effects model. There were 14 studies with a total of 1081 individuals (549 cases and 532 controls). RESULTS There was no difference in miscarriage rates between women who got PRP and those who received placebo (P≤0.90). Chemical pregnancy (P≤0.00), clinical pregnancy (P ≤0.001), and implantation rate (P≤ 0.001) were all significantly higher in women. Endometrial thickness increased in women who got PRP vs women who received placebo after the intervention (P ≤0.001). CONCLUSION PRP may be an alternate therapeutic approach for individuals with thin endometrium and RIF, according to the findings of this comprehensive study. To determine the subgroup that would benefit the most from PRP, more prospective, big, and high-quality randomized controlled trials (RCTs) are needed.
Efficacy of Platelet-Rich Plasma in Women with a History of Embryo Transfer Failure: A Systematic Review and Meta-Analysis with Trial Sequential Analysis
Bioengineering (Basel, Switzerland). 2023;10(3)
Assisted reproductive technology (ART) is used to enhance pregnancy in infertile women. In this technique, the eggs are removed from the ovary and fertilized and injected with sperm to make embryos. Unfortunately, embryo implantation failures still occur in many of these women. Platelet-rich plasma (PRP) therapies use a patient's own platelets to promote tissue healing and growth, including endometrium. The growth factors provided by the platelets play a criterial role on the regenerative ability of PRP. In the last years, PRP treatments have been gaining a lot of popularity to treat women with repeated ART failures. In this study, we collected and summarized all information published in the scientific literature to assess the evidence of the PRP effect on pregnancy. We only considered randomized controlled trials (RCT), a type of study designed to be unbiased and considered at the highest level of evidence. Our analysis indicates that PRP therapies might be an effective treatment in cases of poor responsiveness to conventional ART. However, additional studies (well-designed) are necessary to confirm this beneficial effect of PRP.
Value of intrauterine platelet-rich concentrates in patients with intrauterine adhesions after hysteroscopy: A systematic review and meta-analysis of randomized controlled trials
European journal of obstetrics, gynecology, and reproductive biology. 2022;271:63-70
OBJECTIVE To evaluate the value of intrauterine platelet-rich concentrates among patients with intrauterine adhesions (IUAs) after hysteroscopic adhesiolysis. METHODS Four different databases (PubMed, Cochrane Library, Scopus, and ISI web of science) were searched for the available studies from inception to November 2021. We selected randomized clinical trials (RCTs) that compared platelet-rich concentrates in the intervention group versus no injection of platelet-rich concentrates in the control group among women with intrauterine adhesions after operative hysteroscopy. Revman software was utilized for performing our meta-analysis. Our primary outcomes were the adhesion score and incidence of recurrence of severe intrauterine adhesions postoperatively. Our secondary outcomes were the clinical pregnancy rate, menstrual flow duration in days, and menstrual flow amount (number of pads). RESULTS Five RCTs met our inclusion criteria with a total number of 329 patients. We found that platelet-rich concentrates were linked to a significant reduction in the postoperative adhesion score (MD = -1.00, 95% CI [-1.68, -0.32], p = 0.004). Moreover, there was a significant reduction in the incidence of severe IUAs recurrence among the platelet-rich concentrates group (7.6%) compared to the control group (23.4%) after hysteroscopy (p = 0.001). The clinical pregnancy rate was significantly increased among the platelet-rich concentrates group (37.1%) in comparison with the control group (20.7%) after hysteroscopic adhesiolysis (p = 0.008). There were significant improvements in the menstrual flow duration and amount among the platelet-rich concentrates group (p < 0.001). CONCLUSIONS Intrauterine placement of platelet-rich concentrates is an effective method for the treatment of intrauterine adhesions after hysteroscopy.
Effect of intrauterine infusion of platelet-rich plasma for women with recurrent implantation failure: a systematic review and meta-analysis
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology. 2022;:1-8
This study evaluated the effect of intrauterine perfusion of autologous platelet-rich plasma (PRP) on pregnancy outcomes in women with recurrent implantation failure (RIF). Key biomedical databases were searched to identify relevant clinical trials and observational studies. Outcomes included clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate, and abortion rate. Data was extracted from ten studies (six randomised controlled trials, four cohort studies) involving 1555 patients. Pregnancy outcomes were improved in women treated with PRP compared to controls: clinical pregnancy rate (RR = 1.96, 95% CI [1.67, 2.31], p < 0.00001, I(2) = 46%), chemical pregnancy rate (RR = 1.79, 95% CI [1.54, 2.08], p < 0.00001, I(2) = 29%), implantation rate (RR = 1.90, CI [1.50, 2.41], p < 0.00001, I(2) = 0%), live birth rate (RR = 2.83, CI [1.45, 5.52], p = 0.0007, I(2) = 83%), abortion rate (RR = 0.40, 95% CI [0.18, 0.90], p = 0.03, I(2) = 59%). These data imply PRP has potential to improve pregnancy outcomes in women with RIF, suggesting a promising role in assisted reproductive technology.IMPACT STATEMENTWhat is already known on this subject? Platelet-rich plasma (PRP) is an autologous blood product that contains platelets, various growth factors, and cytokines at concentrations above the normal baseline level. Recent studies have shown that intrauterine infusion of autologous PRP can improve pregnancy outcomes in infertile women.What do the results of this study add? This systematic review and meta-analysis of data from ten studies (n = 1555; 775 cases and 780 controls) investigated the effect of intrauterine perfusion of autologous PRP on pregnancy outcomes in women with recurrent implantation failure (RIF). Findings suggest that pregnancy outcomes, including clinical pregnancy rate, chemical pregnancy rate, implantation rate, live birth rate and abortion rate were improved in women treated with PRP compared to controls.What are the implications of these findings for clinical practice and/or further research? RIF remains a challenge for researchers, clinicians, and patients. Our study identified PRP as a potential intervention in assisted reproduction. As an autologous blood preparation, PRP eliminates the risk of an immune response and transmission of disease. PRP is low cost and effective and may represent a new approach to the treatment of patients with RIF.