Anxiety and depression in recurrent implantation failure after frozen-thawed embryo transfer and efficacy of endometrial receptivity testing

Frozen embryo transfer: evidence-based markers for successful endometrial preparation

ABSTRACTBackground:Recurrent implantation failure is one of the most important problems in the assisted reproduction technologies, such as women who want frozen-thawed embryo transfers. Improvements in embryo culture and transfer techniques notwithstanding, success rates for both implantation and clinical pregnancy remain suboptimal for many patients, especially those with repeated implantation failure. In improving the conditions of embryo transfer, therefore, this has become one of the central focuses of fertility research in trying to enhance the chances of successful implantation.Objectives:The objective of this study is to evaluate whether hyaluronic acid-enhanced transfer medium improves implantation and clinical pregnancy rates (CPR) in frozen-thawed embryo transfer cycles as compared to standard transfer medium, taking into account the effects of patient demographics, exposure duration, and ovarian stimulation protocols on outcomes.Expected Result:Women with repeated implantation failure are anticipated to have greater rates of implantation, clinical pregnancy, and live birth when using HETM as opposed to the control group using standard transfer media. Additionally, optimal exposure durations of HETM (60 and 120 min) are anticipated to further improve outcomes. Secondary outcomes, including early pregnancy loss, multiple birth rates, and adverse pregnancy outcomes, will also be assessed.Conclusion:In conclusion Hyaluronic Acid-Enriched Transfer Medium (HETM) has the potential to enhance implantation rates in assisted reproduction, findings of various studies are inconsistent. Its efficacy can be influenced by patient features and treatment protocols. More studies are required to define the most favorable conditions for the application of HETM, particularly in women with recurrent implantation failure, to optimize its advantage in frozen-thawed embryo transfers.

BackgroundRecurrent implantation failure (RIF) is more common among patients receiving assisted reproductive treatment. Many efforts have been made to increase the incidence of clinical pregnancy among patients with RIF. The effect of the sequential transfer procedure, a two-step interval transfer of a cleavage-stage embryo followed by a blastocyst in one transfer cycle, on the clinical outcomes of RIF patients remains controversial.MethodsIn total, 1774 frozen-thawed embryo transfer (FET) cycles in RIF patients were included. Of these cycles, 302 were sequential embryo transfer (ET) cycles, 979 were double day 3 cleavage-stage ET cycles, and 493 were double blastocyst ET cycles. The primary outcomes were the rates of implantation, clinical pregnancy and multiple pregnancy, and the secondary outcomes were the rates of hCG positive, early miscarriage and ectopic pregnancy.ResultsThe implantation, hCG positive, and clinical pregnancy rates in the sequential ET group (32.1%, 58.9%, 50.7%) were significantly higher than those in the day 3 cleavage-stage ET group (24.9%, 46.5%, 40.4%) and were similar to those in the blastocyst transfer group (30.1%, 56.4%, 47.1%). The early miscarriage rate in the blastocyst transfer group was significantly higher than that in the cleavage-stage ET group (17.2% vs. 8.1%, P <0.05), while the ectopic pregnancy rate in the blastocyst transfer group was significantly lower than that in the cleavage-stage ET group (0.4% vs. 3.0%, P <0.05). The multiple pregnancy rate in the sequential ET group was significantly lower than that in the cleavage-stage ET group (17.0% vs. 25.5%, P <0.05) and the blastocyst transfer group (17.0% vs. 27.6%, P <0.05). When cycles of blastocyst culture failure were excluded, the clinical pregnancy rate was significantly higher (55.7% vs. 47.1%, P <0.05), and the early miscarriage rate and multiple pregnancy rate were significantly lower (8.5% vs. 17.2%, 17.7% vs. 27.6%; P <0.05, respectively) in the sequential ET group than in the double blastocyst ET group.ConclusionsSequential embryo transfer in FET cycles could improve the clinical outcomes of patients with RIF.

Study question Can Hyaluronic acid ( HA) -enriched transfer medium improve the outcome of frozen embryo transfer in women with recurrent implantation failure? Summary answer Hyaluronic acid-based embryo transfer medium significantly improves clinical pregnancy and implantation rates in recurrent implantation failure patients undergoing frozen-thawed embryo transfer. What is known already Recurrent implantation failure (RIF) is a significant challenge in about 10% of patients undergoing assisted reproduction,often influenced by interactions between the embryo and the endometrium,leading to unsuccessful outcomes. Standard embryo transfer media may not adequately support embryo implantation in these patients. Hyaluronic acid (HA) has been proposed as a potential additive to enhance implantation, as it is involved in cellular interactions. Some studies indicate that HA-enriched media may improve embryo attachment and implantation rates, but evidence on its efficacy in RIF patients undergoing frozen-thawed embryo transfer remains limited and inconclusive. Study design, size, duration A prospective randomized controlled trial was conducted at our tertiary IVF Centre from 1st January 2022 to 31st October 2024 to assess the effect of HA-enriched embryo transfer medium on outcomes in recurrent implantation failure (RIF) patients undergoing frozen-thawed embryo transfer (FET). A total of 150 women were randomly assigned to the HA group (n = 75) or the control group (n = 75). Primary outcome was clinical pregnancy while secondary outcome included implantation, miscarriage, and ongoing pregnancy rates. Participants/materials, setting, methods Participants were women under 37 years with normal ovarian reserve and a history of at least three failed fresh or frozen embryo transfers, involving four good-quality embryos across three cycles(RIF). Exclusion criteria included endocrine or uterine disorders, abnormal semen parameters, and use of donor oocytes. A total of 150 women were randomized into either the HA or control group. All underwent hormone replacement therapy (HRT) cycles with transfer of a single grade A thawed blastocyst. Main results and the role of chance Patients in the hyaluronic acid-enriched embryo transfer medium (HA) group showed a statistically significant increase in clinical pregnancy rates (an ultrasonic visualization of at least one gestional sac with or without cardiac activity) compared to the control group (42% vs. 28%, p = 0.035). Furthermore, the implantation rate was higher in the HA group (31% vs. 18%, p = 0.041). However, no significant difference was found in miscarriage rates (12% vs. 15%, p = 0.64) between the two groups. The ongoing pregnancy rate (Pregnancy continuing beyond 12th week ) showed a trend favoring the HA group, though this difference was not statistically significant (38% vs. 32%, p = 0.51). Statistical analysis was performed by the SPSS program for Windows version 25.0. Statistical tests applied according to the distribution of data: for comparing continuous variables-Student t-test and Fisher exact test for categorical variables . The statistical significance was evaluated by calculating the p-value.These findings suggest that HA-based transfer media may offer a potential therapeutic strategy to enhance clinical pregnancy and implantation rates in patients with previous history of RIF. Further research with larger sample sizes and extended follow-up is warranted to confirm these results and evaluate long-term reproductive outcomes. Limitations, reasons for caution This study’s limitations include a relatively small sample size, single-centre design, and limited follow-up period. Additionally, the impact of hyaluronic acid on factors like endometrial receptivity was not explored, which may affect the generalizability of the findings. Wider implications of the findings Hyaluronic acid-enriched embryo transfer medium as an add-on significantly improved clinical pregnancy and implantation rates in recurrent implantation failure patients, suggesting its potential to enhance IVF success in this cohort. Trial registration number Yes

Study question To investigate the influence of paternal age on the live birth rates in oocyte recipient cycles Summary answer Increased paternal age appears to have a negative impact on oocyte recipient cycles when adjusted for sperm quality. What is known already While the effect of maternal age on ART outcomes is well established, the effect of paternal age is unclear. Even systematic reviews assessing the impact of paternal age in oocyte recipient cycles have yielded conflicting results. While Morris et al., 2020 could not demonstrate changes in miscarriage rates or live birth rates with increased paternal age, Murugesu et al., 2022 showed an adverse effect of increased paternal age on miscarriages but did not comment on live birth rates. The challenges of systematic reviews are the heterogeneity of the studies and the possible effect of laboratory and clinical practices. Study design, size, duration This retrospective cohort study was conducted at a single centre. A total of 449 IVF/ICSI oocyte recipient cycles performed between January 2015 and June 2022 were examined. Total of 328 cycles resulting in either fresh or frozen-thawed embryo transfers and meeting the inclusion criteria was analysed. The inclusion criteria were donor age ≤35 years, endometrial thickness ≥ 6 mm and a normal endometrial cavity on aqua scan. We excluded cycles with donor sperm or PGT-A. Participants/materials, setting, methods The couples who used donor oocytes because of diminished ovarian reserve, premature ovarian insufficiency, recurrent implantation failure with autologous oocytes or hereditary disease participated. Paternal and recipient ages were grouped according to previous literature to allow for comparability. The primary outcome was the live birth rate and secondary outcomes were clinical pregnancy and miscarriage rates. Simple and multivariate logistic regression analyses were performed. Main results and the role of chance The median recipient and paternal ages were 42 years (interquartile range [IQR] 19–50) and 42 years (IQR 19–76), respectively. The mean age of the donors was 26 years (IQR 18-35). 55.5% [N = 182] of the cycles corresponded to fresh embryo transfers and 44.5% [N = 146] to frozen embryo transfers. Indications for using donor oocytes were diminished ovarian reserve 54.39%, premature ovarian insufficiency 5.7%, recurrent implantation failure with autologous oocytes 37.05% and hereditary disease 2.85%. The overall live birth rate was 155/328 (45.7%). Live birth outcome appeared to be significantly reduced in paternal age over 46 years after adjusting for semen parameters according to WHO 2010 criteria and for recipient age, with an OR 1.5 (95%,0.85 to 1.98, p &amp;lt; 0.002). Clinical pregnancy outcome was significantly reduced in paternal age over 51 years with OR 0.62 (95%, 0.31 to 1.89, p &amp;lt; 0.0001). The overall miscarriage rate was 15/328 (4.57%) and it was not possible to perform subgroup analysis by paternal age group due to the small numbers. When both maternal and paternal age were retained in the multivariate model, the probability of live birth decreased with paternal age over 51 years and maternal age ≥40 years with OR 0.88 [0.40 to 1.38 [N = 37]). Limitations, reasons for caution This study has some limitations. This is a retrospective study and its relatively small subgroup sizes affected the statistical analysis of miscarriage results. In addition, we did not include any effect of sperm DNA fragmentation in the analysis. Wider implications of the findings The overall live birth outcome was positive. Whilst the study can be used to counsel couples with increased paternal age, it should not be used to preclude patients from treatment. Trial registration number IRB-003C02-09-21

A review of factors influencing the implantation of euploid blastocysts after in vitro fertilization

ObjectiveTo evaluate the effect of intrauterine platelet-rich plasma (PRP) treatment on frozen–thawed embryo transfer (FET) cycles in patients with recurrent implantation failure.Materials and methodsThe study group consisted of 150 patients. The patients were grouped only as those with thin endometria, those with recurrent implantation failure (RIF), and those with both thin endometria and RIF. All participants underwent frozen embryo transfer. The control group consisted of a total of 150 patients who had normal endometrial thickness and did not have a history of RIF and who presented to the clinic due to unexplained infertility. The rates of biochemical pregnancy, clinical pregnancy, miscarriage and live birth were compared among the groups in terms of fertility outcomes.ResultsIn 150 patients with a thin endometrium or a history of RIF who underwent PRP, the endometrial thickness was significantly greater than the pre-PRP endometrial thickness, and this value was found to be statistically significant (7.38 mm vs. 7.96 mm, p < 0.001). In the thin endometrium group, there was also a statistically significant difference between the endometrial thickness measured before and after PRP (5.85 mm vs 6.65 mm, p < 0.001). The rate of not achieving pregnancy in the RIF group without PRP was found to be significantly greater than that in the control group (53.1% vs 28.7%, p < 0.05). There was no significant difference in pregnancy rates between the PRP groups. Morever, no statistically significant relationship was found between pregnancy status and whether or not PRP was performed in RIF patients (p value > 0.05). Overall, although there was an increase in clinical pregnancy and live birth rates in the PRP group compared with the control group, this difference did not reach statistical significance.ConclusionIn patients suffering from a thin endometrium or RIF, although endometrial PRP increases endometrial thickness, it does not significantly improve fertility outcomes.

PurposeTo investigate the impact of antibiotic treatment for chronic endometritis (CE) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycles and the relevant clinical risk factors associated with CE.MethodsA retrospective cohort analysis was conducted on 1352 patients who underwent hysteroscopy and diagnostic curettage at Nanjing Maternal and Child Health Hospital from July 2020 to December 2021. All patients underwent CD138 immunohistochemical (IHC) testing to diagnose CE, and a subset of them underwent FET after hysteroscopy. Patient histories were collected, and reproductive prognosis was followed up.ResultsOut of 1088 patients, 443 (40.7%) were diagnosed with CE. Univariate and multivariate binary logistic regression analyses revealed that parity ≥ 2, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, hydrosalpinx, endometrial polyps, a history of ≥ 2 uterine operations, and RIF were significantly associated with an elevated risk of CE (P < 0.05). Analysis of the effect of CE on pregnancy outcomes in FET cycles after antibiotic treatment indicated that treated CE patients exhibited a significantly lower miscarriage rate (8.7%) and early miscarriage rate (2.9%) than untreated non-CE patients (20.2%, 16.8%). Moreover, the singleton live birth rate (45.5%) was significantly higher in treated CE patients than in untreated non-CE patients (32.7%). Survival analysis revealed a statistically significant difference in the first clinical pregnancy time between treated CE and untreated non-CE patients after hysteroscopy (P = 0.0019). Stratified analysis based on the presence of recurrent implantation failure (RIF) demonstrated that in the RIF group, treated CE patients were more likely to achieve clinical pregnancy than untreated non-CE patients (P = 0.0021). Among hysteroscopy-positive patients, no significant difference was noted in pregnancy outcomes between the treatment and control groups (P > 0.05).ConclusionInfertile patients with a history of parity ≥ 2, hydrosalpinx, a history of ectopic pregnancy, moderate-to-severe dysmenorrhea, endometrial polyps, a history of ≥ 2 uterine operations, and RIF are at an increased risk of CE; these patients should be recommended to undergo hysteroscopy combined with CD138 examination before embryo transfer. Antibiotic treatment can improve the reproductive outcomes of FET in patients with CE, especially those with RIF.

BackgroundSeveral studies have demonstrated that pre-treatment with long-acting Gonadotropin-Releasing Hormone agonists (GnRHa) can significantly enhance the clinical pregnancy rate among recurrent implantation failure (RIF) patients. Investigations have also suggested that GnRHa pre-treatment could ameliorate the clinical pregnancy and live birth rates in polycystic ovary syndrome (PCOS) patients. But there is a dearth of research on whether long-acting GnRHa pre-treatment yields superior clinical outcomes for RIF patients with PCOS.MethodsThe retrospective study enrolled 1602 patients under the age of 40 meeting the criteria for RIF at the Reproductive Medicine Center of Nanjing Drum Tower Hospital, who underwent frozen-thawed embryo transfer (FET) between January 2017 and December 2021. All cycles were categorized into hormone replacement therapy (HRT) Group (n = 1283) and GnRHa-HRT Group (n = 319), contingent on the usage of long-acting GnRHa pretreatment. Primary outcomes investigated in this study was clinical pregnancy rate, while live birth rate and early miscarriage rate were deemed as secondary outcomes. Univariate analysis and a multivariate logistic regression model were employed to assess the impact of GnRHa pretreatment on the clinical pregnancy rate in RIF patients. The influence of long-acting GnRHa pretreatment on clinical pregnancy outcomes was re-examined in PCOS and non-PCOS subgroups. Additionally, an interaction analysis was performed to evaluate the effect of PCOS on the relationship between long-acting GnRHa pretreatment and the clinical pregnancy rate.ResultsMultiple regression analysis showed that long-acting GnRHa pretreatment had a positive impact on the clinical pregnancy rate (aOR = 1.51, 95%CI: 1.15–1.99, P = 0.003). We divided the RIF population into two subgroups, for PCOS patients, although the clinical pregnancy rate was higher in women who received GnRHa pretreatment compared to those who did not, it was not statistically significant (aOR = 1.51, 95%CI: 0.81–2.82, P = 0.195). Interaction analysis suggested that for PCOS patients, there was no significant difference in the clinical pregnancy rate between women who received GnRHa pretreatment and those who did not (P interaction = 0.818), indicating that the effect of GnRHa pretreatment on the clinical pregnancy rate was not influenced by PCOS.ConclusionsOur study demonstrates that long-acting GnRHa pretreatment can enhance clinical pregnancy outcomes in patients with RIF. Among RIF patients without PCOS, the clinical pregnancy rate exhibited a significant increase following GnRHa pretreatment compared to the control group. However, in RIF patients with concurrent PCOS, there was no significant elevation in the clinical pregnancy rate post-GnRHa pretreatment. Therefore, GnRHa pretreatment is effective in improving pregnancy outcomes for RIF patients. However, whether GnRHa pretreatment is suitable for RIF patients with PCOS requires more cautious clinical discussion.

ABSTRACTBackground:This study, conducted in the Wardha district, Recurrent implantation failure (RIF) and thin endometrium are significant challenges in IVF success. Various techniques have been explored to enhance endometrial receptivity. Platelet-rich Plasma (PRP) is an emerging technique that can enhance the endometrium lining and clinical pregnancy rate. This study will demonstrate the effectiveness of the infusion of the Platelet-rich Plasma (PRP) intra utrine for increasing the endometrium lining and compare the success rate in clinical pregnancy outcome in patients after infusing PRP and not infusing PRP undergoing frozen-thawed embryo transfer.Objective:The objective of the study will be to investigate the role of PRP in addressing recurrent implantation failure due to thin endometrium and to assess the success rate of clinical pregnancy outcome in frozen-thawed embryo transfer after inducing PRP in the patient with RIF.Methodology:A total of 190 patients will be selected for the study. The experimental population will be divided into two groups, i.e., 95 patients will be in the Study group, which will be exposed to PRP infusion, and 95 patients will be in the Control group, which will be exposed to the placebo. The study will be conducted on the population with thin endometrium and recurrent implantation failure (RIF) and females below 50 years of age. In this study, the control group and the study group will be compared, and the result of the intervention given to the study group. This study will also demonstrate how PRP is prepared and then injected in the patient.Expected Result:Therefore, the study will demonstrate that PRP improves the endometrium thickness, reduces the recurrent implantation failure, and also increases the clinical pregnancy rate in the patients who are infused with the PRP. It will demonstrate that PRP is very cost-effective as it is an affordable and low-risk adjunct to improve endometrium receptivity.

Study question What is the cumulative ongoing pregnancy rate within one year after visiting the RIF outpatient clinic in patients with RIF after IVF/ICSI treatment? Summary answer The cumulative ongoing pregnancy rate was 42.9% with a mean time to pregnancy of 8.8 months (95% CI 7.5-10.1 months). What is known already An estimated portion of 10-15% of IVF patients experience RIF. Multiple add-on treatments have been proposed, however, evidence for effective clinical therapeutic options still remain scarce. Although it is described that RIF patients might eventually benefit most from a ‘keep calm and carry on’ approach, in practice patients often seek clearer answers on their pregnancy chance and request further investigations/interventions. It would be helpful to give patients insight in their chances of achieving pregnancy after RIF, but at this moment little is known about their prognosis. This is further complicated by the lack of consistency in the definition of RIF. Study design, size, duration A prospective cohort study on 42 RIF patients after one-year follow-up was performed, as part of the MURIM (Multidisciplinary Research on Repeated Implantation Failure and Recurrent Miscarriages) study. Baseline characteristics including an endometrial assessment and ReceptIVFity (vaginal microbiome) test were collected at the RIF outpatient clinic. After a follow-up duration of minimal one year participants were asked to complete a questionnaire regarding fertility treatment and pregnancy outcome. Missing information was received via medical files. Participants/materials, setting, methods RIF patients aged 18 to 38 years old visiting the RIF outpatient clinic at Maastricht University Medical Centre+ between April 2019 until September 2021 were included. RIF was defined as consecutive implantation failure of three high quality embryos or ten embryos without a quality criterion. Clinical characteristics, pregnancy outcome and time to pregnancy was analyzed by survival analysis and cox hazard regression analysis via SPSS version 20.0. A p-value of &amp;lt; 0.05 was considered statistically significant. Main results and the role of chance Forty-two out of 44 contacted patients responded to the questionnaire (response rate = 95.5%). The ongoing pregnancy rate was 42.9% (Standard Deviation (SD): 0.50%) during the first year after visiting the RIF outpatient clinic. Mean time to ongoing pregnancy was 8.8 months (95%-CI: 7.5-10.1 months). The mean amount of embryo transfers (ETs) during this year was 2 (SD: 1.78). The ongoing pregnancy rate per ET (by survival analysis) for the first, third and sixth ET was 33.1%, 49.3% and 63.8%, respectively. To correct for a possible overestimation of the cumulative ongoing pregnancy rate per ET by normal survival analysis, pregnancy rates were calculated again using the number at risk of the total group during the first ET (pessimistic cumulative pregnancy rate). The pessimistic cumulative ongoing pregnancy rates were 33.1%, 42.9% and 48.6%, respectively. When comparing baseline characteristics by univariable cox hazard regression between women with and without ongoing pregnancy, no significant differences were found. Nineteen pregnancies were reported during the one-year follow-up, one conceived spontaneously (5.3%); four via fresh ET (IVF=15.8% and ICSI=5.3%); and 14 by frozen ET (IVF=26.4% and ICSI=47.4%). The pregnancies resulted in 14 livebirths (73.7%); one miscarriage (5.3%); one stillbirth (5.3%); and three ongoing pregnancies (15.8%). Limitations, reasons for caution Although this is the first study that prospectively describes pregnancy prognosis after RIF, it is limited by the short follow-up period and relatively small sample size. The RIF outpatient clinic consultation might have contributed to the obtained pregnancy results but the proportionality is unclear as there is no control group. Wider implications of the findings The obtained ongoing pregnancy prognosis after RIF is encouraging and justifies a conservative approach after three failed ETs. Furthermore, the high pregnancy rate indicates the need of well-defined, individualized diagnostic criteria to define RIF and to be able to deviate between couples with 'bad luck' and an underlying (treatable) cause. Trial registration number NL66835.068.18/METC18-040

Background: Implantation failure, especially recurrent implantation failure (RIF), causes considerable distress in patients who undergo assisted reproductive techniques (ART). Mild pathologies inside the uterine cavity and disturbance of the uterine environment can decrease endometrial receptivity and cause implantation failure. To address this, hysteroscopy combined with endometrial pathological diagnosis has become more widespread. However, the specific time at which to perform the hysteroscopy remains controversial in the clinical practice of ART. Methods: This case-control studies enrolled a total of 1876 in-vitro fertilization embryo transfer (IVF-ET) or intracytoplasmic sperm injection embryo transfer (ICSI-ET) patients with a history of failed implantation were included in this study. From October 2019 to December 2022, these patients underwent office hysteroscopy and subsequent endometrial biopsy for CD138 immunohistochemistry to detect chronic endometritis (CE) in the Department of Reproductive Medicine, West China Second University Hospital, Sichuan University. Endometrial polys (EP) were removed during surgery, and for patients diagnosed with CE, oral doxycycline was taken for two consecutive weeks before the next frozen embryo transfer (FET). Patient demographic characteristics and pregnancy outcomes were reviewed and analyzed by logistic regression to evaluate outcomes. Results: Patients were divided into four groups according to hysteroscopy findings and pathological diagnosis: CE only, CE plus EP, EP only, and neither CE or EP. The biochemical pregnancy (p = 0.009), clinical pregnancy (p = 0.014), and live birth (p = 0.011) rates after the following FET cycle were significantly different between the four groups. Pregnancy outcomes for the CE plus EP group were better than for the other three groups. Multivariate logistic regression analysis revealed that the probability of live birth was significantly related to the mother’s age, the controlled ovarian stimulation (COS) protocol, the number of times with failed embryo transfer (ET) cycle, endometrial histology findings, the interval time between hysteroscopy and FET, the endometrial thickness on the day of embryo transfer, and the number and type of embryos transferred (p &lt; 0.05). Conclusions: Office hysteroscopy combined with diagnosis of endometrial pathology is a valuable approach for women with a history of implantation failure. This approach is not limited to RIF patients, and results in an increased pregnancy rate and shorter time to live birth in ART.

Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis

Should patients be screened for chronic endometritis before assisted reproductive technology?

Study question Does the infusion of autologous platelet rich plasma (PRP) to the uterus improve the outcomes of embryo transfer of thin endometrial or recurrent implantation failure (RIF) patients? Summary answer Autologous PRP uterine infusion may improve the result of embryo transfer (ET) in RIF group and thin/scarred endometrial group. What is known already Autologous PRP has been proposed to improve the outcomes of various treatment procedures. In infertility, several trials have reported an improvement in endometrial thickness in patients having thin endometrium thus previously cancelled ET cycles. Uterine injection of PRP shortly before ET has been proposed to improve the results of ET in patients having RIF. Platelets in PRP would be activated via different pathways to release growth factors and cytokines. In this study, we applied our in-house-developed PRP extraction kits that use a mechanical activation/platelet breaking down method to infuse/inject into the uterine of the poor prognosis transfer patients. Study design, size, duration This study includes two phases: Phase 1 (04/2019–12/2019): we tested the safety and effectiveness of the PRP extraction kits in 30 volunteers regardless of the gender by derma-rolling process using PRP extracted by our kits. Phase 2 (02/2020–12/2020): 111 IVF patients who had thin/scarred endometrium previously having at least one cancelled ET cycle (group 1) or patients who had at least two implantation failure ETs (group 2) were enrolled in the study. Participants/materials, setting, methods 20 mL blood was drawn from the vein. After centrifugation, PRP was filtrated through a filter to break down platelets releasing growth factors/cytokines. Firstly, 30 volunteers (average age of 34.4 ± 5.5) were derma-rolled on the facial skin twice (one week apart). Secondly, IVF group 1 was uterine-infused with 0.5 mL PRP on day 7/8 of the ET cycle, both groups were uterine-infused with 0.5 mL PRP two days (40–48 hours) before ET. Main results and the role of chance 0.5 mL of PRP before filtering was measured and calculated to have 8–12 folds increase of platelet concentration. In phase 1, no side-effects or complications were recorded. The average skin pore size reduced by approximately 0.01 mm2 in all patients two weeks after treatment. In phase 2, the average age was 35.6 ± 6.1. Group 1 had 31 patients and group 2 had 99 ones. In group 1, five patient did not obtained improvement in endometrium then ET cycles were cancelled, one patient did not have blastocyst to transfer and 25 patients had endometrium of at least 7 mm thick before ET and ET (100 frozen ET) were carried on. One couple was not contactable. Out of 24 couples, 13 had biochemical pregnancy (54.2%) and 11 had clinical pregnancy (44.0%). Group 2 had 80 patients. One of them did not have embryo to transfer. 37/79 embryo transfers had biochemical pregnancy (46.8%) and 44.3% clinical pregnancy. No complication was recorded. In our cohort, several successful patients had more than 7 unsuccessful ETs previously. For reference, in 2020, our clinic had 4260 ETs in total, the clinical pregnancy rate was 60.1%, the average age was 31.82 years old. Limitations, reasons for caution Each case in phase 2 of this study had a complicated fertility medical history therefore it was impossible to select the control group. This study is descriptive only. The size of each group was relatively small requiring ongoing data recording. Wider implications of the findings: This study support the idea that cytokines and growth factors in PRP may help to prepare endometrium for ET, safely and effectively. Trial registration number Not applicable