assisted-reproduction/add-ons-and-adjuncts/adjunct-evidence-base therapeutics/prescribing-safety/off-label-prescribinginfertility/uterine-factor/endometrial-receptivity
Pan Z et al., 2026 · Frontiers in endocrinology
[OBJECTIVE] The role of intrauterine PRP infusion in managing recurrent implantation failure (RIF) remains controversial despite its emerging clinical use. This systematic review aims to evaluate its therapeutic potential in RIF patients and further to investigate variations in outcomes based on transfer cycle type, embryo developmental stage, RIF diagnostic criteria, and endometrial thickness. [METHODS] We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) investigating PRP treatment for RIF patients from the beginning of the database to May 2025. [RESULTS] This meta-analysis showed that PRP administration significantly improved clinical pregnancy rate (CPR) [OR = 3.18, 95%CI (2.45, 4.14), I2 = 3%], biochemical pregnancy rate (BPR) [OR = 2.84, 95%CI (2.22, 3.63), I2 = 0%], ongoing pregnancy rate (OPR) [OR = 3.41, 95%CI (2.08, 5.60), I2 = 30%] and live birth rate (LBR) [OR=5.10, 95%CI (1.95, 13.37), I2 = 75%] in women with RIF. However, PRP intrauterine infusion did not reduce miscarriage rate (MR). Notably, the preterm birth rate was significantly higher in the PRP group compared to controls [OR = 8.24, 95%CI (2.09, 32.41), I2 = 0%]. Subgroup analysis demonstrated that PRP improved CPR, BPR and LBR in both the fresh and frozen embryo transfer cycles. Additionally, while PRP increased CPR, LBR and reduced MR in blastocyst transfers [CPR OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%; LBR OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%; MR OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%], these effects were not observed in cleavage-stage embryo transfers. Moreover, PRP administration associated with a higher CPR [OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%], OPR[OR = 4.13, 95%CI (1.79, 9.56), I2 = 48%], LBR [OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%] and a lower MR [OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%] in women with ≥3 prior implantation failure, it did not confer the same benefit to those with a history of ≥2 failed cycles. [CONCLUSION] These findings suggest a possible beneficial role for PRP on pregnancy outcomes to some extent in women with RIF, particularly in cases with ≥3 prior failed transfers, and blastocyst transfer may increase LBR and reduce miscarriage risk. However, further investigation is warranted to determine whether this treatment may pose an increased risk of preterm birth. [SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/prospero/, identifier CRD420251061511.
infertility/uterine-factor/endometrial-receptivity restorative-reproductive-medicine/adjunct-and-emerging-therapies/platelet-rich-plasma-and-regenerative-approachesassisted-reproduction/add-ons-and-adjuncts/adjunct-evidence-base
Chen L et al., 2025 · Frontiers in reproductive health
[OBJECTIVE] To analyze the effect of autologous platelet-rich plasma (PRP) intrauterine perfusion on the clinical outcomes of frozen-thawed embryo transfer in patients with chronic endometritis. [METHODS] A retrospective continuous cohort of 219 patients diagnosed with chronic endometritis at the Reproductive Medicine Center of Affiliated Hospital of Putian University between January 2020 and December 2022, undergoing their first frozen-thawed embryo transfer cycle, was included. All patients received standardized oral doxycycline treatment after diagnosis. Based on whether they received PRP intrauterine perfusion prior to embryo transfer, patients were divided into an observation group (PRP group, n=103) and a control group (non-PRP group, n = 116). Outcome measures included live birth rate per transfer cycle, clinical pregnancy rate per transfer cycle, and early miscarriage rate per clinical pregnancy. [RESULTS] All patients underwent endometrial preparation using a hormone replacement therapy (HRT) protocol. Endometrial thickness on the day before transformation was significantly higher in the PRP group compared to the control group (10.58 ± 1.78 mm vs. 9.79 ± 1.58 mm, P = 0.001). The PRP group exhibited significantly higher clinical pregnancy rate per transfer cycle and live birth rate per transfer cycle than the control group (58.25% vs. 40.52%, P = 0.038; 52.43% vs. 34.48%, P = 0.007). The difference in early miscarriage rate per clinical pregnancy between the PRP group and the control group was not statistically significant (8.33% vs. 14.89%, P = 0.86). The live birth rate per transfer cycle in the single-PRP subgroup was significantly lower than in the multiple-PRP subgroup (44.62% vs. 65.79%, P = 0.038). There were no statistically significant differences in clinical pregnancy rate per transfer cycle or early miscarriage rate per clinical pregnancy between the single-PRP and multiple-PRP subgroups (52.31% vs. 68.42%, P = 0.110; 11.76% vs. 3.85%, P = 0.377). [CONCLUSION] For patients diagnosed with chronic endometritis undergoing their first frozen-thawed blastocyst transfer after standardized antibiotic treatment, adjunctive PRP intrauterine perfusion therapy improves pregnancy outcomes.
assisted-reproduction/add-ons-and-adjuncts/adjunct-evidence-base infertility/uterine-factor/endometrial-receptivityresearch-methods/evidence-synthesis/systematic-reviews
Almohammadi A et al., 2025 · International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
[BACKGROUND] Recurrent implantation failure (RIF) has a multifactorial etiology. An umbrella review was undertaken to evaluate the multiple proposed interventions. [OBJECTIVES] To summarize and assess the strength of evidence of interventions for RIF from published systematic reviews (SR) of randomized clinical trials (RCTs). [SEARCH STRATEGY] After prospective registration (PROSPERO CRD42023414255), a systematic search was conducted in the Cochrane Library, Scopus and Medline from inception until March 2024. [SELECTION CRITERIA] SRs of RCTs, with or without meta-analyses (MA), were included if they reported clinical pregnancy rates (CPR) or live birth rates (LBR). [DATA COLLECTION AND ANALYSIS] The methodological quality of the included SRs was appraised independently in duplicate using the AMSTAR 2 tool. For each intervention, the MAs of RCTs with statistically significant improvements were counted as a percentage of the total assessing the strength of evidence using the GRADE system. [MAIN RESULTS] A total of 47 SRs were included: 32 reviews covered immunomodulatory interventions, 10 (68 RCTs) covered uterine and endometrial interventions, one covered antibiotics, and four (69 RCTs) addressed mixed approaches, including laboratory interventions. AMSTAR 2 appraised 41 (88%) SRs as critically low or low, and 6 (12%) as moderate or high in quality. The SRs often had a level of overlap of RCTs (median 33.3%), inconsistent definitions of RIF, and varied comparisons for the interventions. Considering the significant meta-analytic evidence of high-moderate GRADE strength: Granulocyte colony-stimulating factor (G-CSF) showed improvement in CPR in 9/13 (69.2%) MAs and LBR in 1/7 (14%); intralipid infusion showed improvement in CPR in 4/6 (57.14%) MAs and LBR in 3/4 (75%); peripheral blood mononuclear cells (PBMC) showed improvement in CPR in 4/8 (50%) MAs and LBR 3/5 (60%); platelet-rich plasma (PRP) intervention showed improvement in CPR in 6/10 (60%) MAs and LBR in 1/5 (20%); human chorionic gonadotropins showed improvement in CPR in 3/3 (100%) MAs; growth hormone showed improvement in CPR in 1/1 (100%) MA; low molecular weight heparin showed improvement in CPR in 1/1 (100%) MAs and LBR in 1/2 (50%); hysteroscopy showed improvement in CPR in 1/2 (50%) MAs; and, intentional endometrial injury showed improvement in CPR in 3/4 (75%) MAs and LBR in 2/3 (66.66%). [CONCLUSIONS] Evidence syntheses of RCTs evaluating interventions for RIF suggest a consistent direction, with high to moderate strength, indicating that immunomodulatory treatments, including G-CSF, PBMC, PRP, intralipid infusion, and intentional endometrial injury are likely to be effective. However, this conclusion should be interpreted with caution due to the generally low methodological quality of the included studies and the clinical heterogeneity observed in most SRs.
assisted-reproduction/add-ons-and-adjuncts/adjunct-evidence-base infertility/uterine-factor/endometrial-receptivitytherapeutics/hormonal-agents/gonadotropins
Maleki-Hajiagha A et al., 2020 · Journal of reproductive immunology
Prior studies have provided conflicting results regarding the use of platelet-rich plasma (PRP) in women undergoing in-vitro fertilization (IVF) or intracytoplasmic injection (ICSI). The objective of this study was to evaluate the effect of the intrauterine infusion of PRP on the outcome of embryo transfer (ET) in women undergoing IVF/ICSI. We searched databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials (CENTRAL). Meta-analysis using a random-effects model was performed to calculate the pooled estimates. Seven studies involving 625 patients (311 cases and 314 controls) were included. The probability of chemical pregnancy (n = 3, risk ratio (RR): 1.79, 95 % confidence intervals (CI): 1.29, 2.50; P < 0.001, I2 = 0 %), clinical pregnancy (n = 7, RR: 1.79, 95 % CI: 1.37, 2.32; P < 0.001, I2 = 16 %), and implantation rate (n = 3, RR: 1.97, 95 % CI: 1.40, 2.79; P < 0.001, I2 = 0 %) was significantly higher in women who received PRP compared with control. There was no difference between women who received PRP compared with control group regarding miscarriage (RR: 0.72, 95 % CI: 0.27, 1.93; P = 0.51, I2 = 0 %). Following the intervention, endometrial thickness increased in women who received PRP compared to control group (SMD: 1.79, 95 % CI: 1.13, 2.44; P < 0.001, I2 = 64 %). The findings of this systematic review suggest that PRP is an alternative treatment strategy in patients with thin endometrium and recurrent implantation failure (RIF). Further prospective, large, and high quality randomized controlled trials (RCTs) are needed to identify the subpopulation that would most benefit from PRP.