Surgical nodal assessment for endometrial hyperplasia - A meta-analysis and systematic review.

OBJECTIVE: Endometrial intraepithelial neoplasia (EIN) and atypical hyperplasia (AH) are recognized precursors for endometrial cancer (EC). Most current guidelines do not recommend the routine surgical evaluation of lymph nodes (LN), although recent studies indicate increased use of sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of EIN/AH. We aimed to evaluate the rates of positive LN and its effect on the incidence of upstaging of EIN/AH patients, complications, and adjuvant treatment administration. METHODS: A systematic review and meta-analysis was conducted in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science, Clinicaltrials.gov and Cochrane Library. Included were studies investigating lymph node evaluation in patients diagnosed with EIN/AH, presenting results of LN assessment and/or comparisons of hysterectomy results with and without lymph node assessment. This analysis was registered at PROSPERO International prospective register of systematic reviews (CRD42023443598). RESULTS: A total of 447 studies were initially identified through database searching. The current analysis includes 7 studies comprising 1791 atypical endometrial hyperplasia patients who underwent hysterectomy with lymph node assessment. The incidence of positive lymph nodes among those who had undergone any LN evaluation was found to be 1.1% (95% CI 0.3%-2%). The rate of positive LNs was 1.4% (95% CI 0.2%-1.9%) among those who had undergone specifically SLN. 319 (44.3%, 95% CI 34%-54.7%) patients of the patients initially diagnosed with EIN/AH (n = 699), were finally upgraded to EC diagnosis. Fifteen percent of the final EC diagnosed patients were treated with adjuvant treatment. No significant difference regarding complication rates was noticed. CONCLUSIONS: Our review indicates that the rate of metastatic LNs is <2% in patients undergoing surgical nodal evaluation for EIN/AH. However, the rate of complication for SLN mapping is low and may have an impact on postoperative therapy decisions in those diagnosed with malignancy.

The effect of subsequent pregnancy and childbirth on stress urinary incontinence recurrence following midurethral sling procedure: a meta-analysis.

OBJECTIVE: This study aimed to assess the risk of stress urinary incontinence recurrence and reoperation after a midurethral sling procedure in women with subsequent childbirth and to assess the effect of delivery mode on this risk. DATA SOURCES: An electronic database search was performed using MEDLINE with the OvidSP interface and PubMed, Embase, Web of Science, and the Cochrane Library up to September 20, 2023. STUDY ELIGIBILITY CRITERIA: This study included experimental and nonexperimental studies, composed of randomized controlled and observational (case-control, cohort, and cross-sectional) studies assessing the risk factors for stress urinary incontinence recurrence and reoperation after childbirth in women who had previously undergone a midurethral sling procedure for stress urinary incontinence. METHODS: Analysis was performed using RevMan (version 5.3; Cochrane Collaboration, Oxford, United Kingdom). Quantitative synthesis was used if the included studies were sufficient in numbers and homogeneity. The overall certainty of the evidence was assessed using criteria recommended by the Grading of Recommendations Assessment, Development, and Evaluation Working Group. RESULTS: A total of 2001 studies were identified, of which 6 were eligible for analysis, composed of 381 patients who had at least 1 childbirth after a midurethral sling procedure (study group) and 860 patients who underwent a midurethral sling without having a subsequent childbirth (control group). All included studies were observational, the patients' mean age at the time of the midurethral sling procedure ranged from 34 to 36 years, and the mean time from midurethral sling procedure to delivery ranged from 21 to 31 months. No difference in stress urinary incontinence recurrence (relative risk, 0.1.02; 95% confidence interval, 0.78-1.33) or reoperation (relative risk, 1.37; 95% confidence interval, 0.87-2.17) was found between the study and control groups. The average follow-up time among the included studies of this comparison was 9.8 years (range, 2-18). Furthermore, the mode of delivery (vaginal vs cesarean) did not seem to affect the risk of stress urinary incontinence recurrence. CONCLUSION: Subsequent pregnancy and childbirth did not increase the risk of stress urinary incontinence recurrence or reoperation after a midurethral sling procedure.

Effect of known pathological risk factors on the incidence of metastatic lymph nodes and survival in early-stage vulvar cancer: SEER analysis.

OBJECTIVE: The current study was performed to evaluate the incidence of positive lymph nodes (LNs) in relation to known pathological risk factors, specifically among patients with apparent low-grade, small tumors. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to retrospectively identify patients with vulvar squamous cell carcinoma (SCC) diagnosed between January 1, 2000, and December 31, 2019, with known tumor size and regional LN examined. A comparison between patients who had positive and negative LNs was conducted to identify risk factors for LN metastases in relation to survival. Subgroup analysis was conducted in patients with diagnosed grade 1 vulvar SCC and tumor size up to 2 cm according to the status of LNs. RESULTS: Multivariate analysis found that both grade of disease and tumor size were significant factors in predicting LN status. Among patients with low-grade small tumors up to 2 cm, the odds ratio for positive LNs was 2.5 for those with tumor size larger than 1 cm. In a multivariate survival analysis, older age, larger tumor size, and positive LNs were independently associated with decreased survival. CONCLUSIONS: The current study confirms that among small tumors, those larger than 1 cm have a significantly increased risk for positive nodes compared with those smaller than 1 cm, and, among this specific group, patients with positive nodes have decreased survival. Future studies are needed to answer the question of whether, in the era of the sentinel node procedure, it is safe to omit LN evaluation altogether.

Risk factors for pelvic organ prolapse recurrence following colpocleisis: A meta-analysis.

BACKGROUND: Studies aimed to assess risk factors for pelvic organ prolapse (POP) recurrence following colpocleisis with nonconclusive results. OBJECTIVE: To investigate risk factors for POP recurrence following colpocleisis. SEARCH STRATEGY: MEDLINE, PUBMED, Embase, Web of Science, and Cochrane databases were systematically searched. SELECTION CRITERIA: Experimental and non-experimental studies investigating POP recurrence following colpocleisis. DATA COLLECTION AND ANALYSIS: We assessed the association between preoperative and postoperative physical examination findings, demographics and medical history, and the risk of recurrence following colpocleisis. MAIN RESULTS: A total of 954 studies were identified, of which five studies comprising 2978 patients were eligible for analysis. Both preoperative and postoperative genital hiatus length were significantly longer in the recurrence group (mean difference [MD] 0.48, 95% confidence interval [CI] 0.01-0.94, P = 0.04, I2 = 0% and MD 1.15, 95% CI 0.50-1.81, P = 0.005, I2 = 0%; respectively). Preoperative total vaginal length (TVL) did not differ between groups (MD 0.05, 95% CI -0.40 to 0.50, P = 0.83, I2 = 6%), postoperative TVL was found significantly longer in the recurrence group (MD 0.07, 95% CI -0.03 to 1.38, P = 0.04, I2 = 68%). Both preoperative and postoperative perineal body did not differ between groups. Women with a previous POP surgery were more likely to experience recurrence following colpocleisis (relative risk 2.09, 95% CI 1.18-3.69, P = 0.01, I2 = 0%). Patient's age and previous hysterectomy did not affect recurrence rates. CONCLUSION: Wider preoperative and postoperative genital hiatus as well as longer post-operative TVL and previous POP surgery were associated with a higher risk for recurrence following colpocleisis, highlighting the importance of appropriate patient selection and surgical technique in minimizing this risk.

Attitude of BRCA1/2 mutation carriers towards surgical risk reduction for breast, ovarian and uterine cancer: still much to be done.

OBJECTIVE: To study and quantify the attitude of BRCA1/2 mutation carriers towards surgical risk reduction procedures. METHODS: This cross-sectional national study was conducted by distribution of an anonymous questionnaire on social media platforms and to BRCA1/2 carriers' medical clinic. RESULTS: 530 BRCA1/2 mutation carriers answered the survey. Risk reduction bilateral salpingo-oophorectomy was discussed with 447/489 (91%) of patients and performed in 260/489 (53%). Hormonal replacement therapy was discussed in 280/474 (59%) of patients. Addition of hysterectomy to risk reduction bilateral salpingo-oophorectomy was discussed in 129/481 (27%) of patients and performed in 44/443(10%). Age over 35 years at time of mutation detection was found to be significant in raising risk reduction bilateral salpingo-oophorectomy and hysterectomy performance rates. Risk reduction mastectomy was discussed in 390/471 (83%) of patients and performed in 156/471 (33%). In a multivariate analysis, BRCA1 mutation carriers (OR=1.66 (95% CI 1.07 to 2.57), p=0.024) and a personal cancer history leading to the mutation detection (OR=4.75 (95% CI 1.82 to 12.4), p=0.001) were found to be significant in increasing the likelihood of opting for risk reduction mastectomy. Additionally, highest risk reduction mastectomy performance rates were observed in the group of patients with a first-degree family history of breast cancer under the age of 50 years (OR=1.58 (95% CI 1.07 to 2.32), p=0.01). CONCLUSIONS: This study highlights the high performance rates of risk reduction bilateral salpingo-oophorectomy, while hysterectomy was added in 10%, and that despite high awareness and acceptance rates for risk reduction mastectomy, only 33% had the procedure. The data presented provides insights for the clinician counseling BRCA1/2 mutation carriers, with regards to adherence to recommendations, understanding their concerns towards treatment and management alternatives; and finally, to construct a personalized management medical plan.

Attitude of BRCA1/2 mutation carriers towards fertility preservation, family planning and preimplantation genetic testing for primary prevention of breast and ovarian cancer in the next generation.

PURPOSE: To study the attitude of BRCA1/2 mutation carriers regarding family planning, fertility preservation, and preimplantation genetic testing (PGT). METHODS: A national cross-sectional study was conducted by the distribution of an anonymous questionnaire, from August 2022 to January 2023. The main outcomes measures were discussion, acceptance, and performance rates of fertility preservation and PGT. RESULTS: The questionnaire was completed by 530 BRCA1/2 mutation carriers. The mean (SD) age at mutation detection was 36.4 (9.6) years. At the time of mutation detection, 40% did not have children. Following mutation detection, 37% of responders changed their family planning, mostly choosing to have children earlier or to have less children than planned. Twenty-eight percent of BRCA carriers discussed the option of fertility preservation with a physician, 72% agreed that fertility preservation is an acceptable option for BRCA1/2 mutation carriers and finally 11% underwent oocyte/embryo vitrification before RRBSO. 44% of BRCA carriers discussed the option of PGT, 58% agreed that PGT is justified in BRCA1/2 mutation carriers and finally 8% underwent PGT to select non-carrier embryos. In a multivariate analysis, age under 35 years and the a priori need for fertility treatments were both found significant factors increasing the likelihood of performing fertility preservation and PGT. CONCLUSION: This study emphasizes that despite a substantial proportion of women admitting that mutation detection affected their family planning and high acceptance rates, performance of fertility preservation and PGT remained exceedingly low. Increasing the knowledge and awareness of these issues is important and should be included in multidisciplinary counselling.

Sentinel lymph node sampling versus full lymphadenectomy in endometrial cancer: a SEER database analysis.

OBJECTIVE: To assess the long term outcomes and prognosis of sentinel lymph node sampling compared with full lymph node dissection in endometrial cancer patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for information on women diagnosed with endometrial cancer from 2010 to 2019. We conducted a comparison including overall survival between patients who had undergone sentinel lymph node sampling only and patients who had undergone formal lymph node dissection. Propensity score matching was performed according to the patient's age, type of endometrial cancer, grade and stage of disease, and adjuvant therapy. Subgroup analyses were performed according to type and grade of endometrial cancer. RESULTS: 41411 endometrial cancer patients were identified through the database. After matching, 6019 patients each were included in the sentinel lymph node and lymph node dissection groups. Median (interquartile range (IQR)) follow-up time was 16 (7-31) months in both groups. One year survival rates were longer in the sentinel lymph node group compared with the lymph node dissection group (hazard ratio (HR) 1.61 (95% confidence interval (CI) 1.17 to 2.21); p=0.004). Subgroups analysis according to grade of disease showed that 1 year survival rates were longer in the sentinel lymph node group in patients with endometrioid-type grade 1-2 endometrial cancer (HR 1.70 (95% CI 1.31 to 2.56); p=0.01), while no difference in survival was found between the sentinel lymph node and lymph node dissection groups in the subgroup of patients with high grade endometrial cancer (HR 1.40 (95%CI 0.94 to 2.24); p=0.17). In patients with low grade endometrial cancer included in the sentinel lymph node group, only 7% had lymph nodes positive for malignancy compared with 17% in the high grade group. CONCLUSION: Survival rates were not compromised in endometrial cancer patients undergoing sentinel lymph node sampling versus full lymph node dissection for all grades of disease.

Incidence and characteristics of ovarian cancer following endometrial cancer in the emerging era of conservative management of endometrial cancer-Implications for counseling-A SEER analysis.

OBJECTIVE: To assess the ovarian cancer (OC) risk following endometrial cancer (EC) in patients who underwent ovarian preservation as part of the EC staging. STUDY DESIGN: With permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with EC and following OC were analyzed. Incidence of OC and survival according to the surgical approach were studied. Primary analysis was conducted in women up to and including the age of 49 years. RESULTS: A total of 116 patients up to the age of 49 years were diagnosed with EC and following OC. In this group of patients, no differences in incidence (IRR 0.9, CI 0.56-1.49, p = 0.66) or survival rates (p = 0.71) were found comparing ovarian preservation and bilateral salpingo-oophorectomy (BSO) performance. In an overall analysis of women diagnosed with EC and following OC at any age, incidence of OC did not differ between groups (IRR 1.07, CI 0.83-1.39, p = 0.59) yet when including patients older than 49 years old survival rates were shorter in ovarian preservation patients compared to patients with BSO performed as part of their EC treatment. CONCLUSION: Ovarian preservation in EC patients under the age of 49 years may be considered safe, with no impact on OC incidence or survival, benefiting longer natural hormonal status.

Breast Cancer Patients Are at Increased Risk of Developing Uterine Serous Cancer: Implications for Counseling - A SEER Analysis.

INTRODUCTION: Several studies have investigated whether patients with prior breast cancer (BC) are at an increased risk for endometrial cancer (EC)/uterine serous cancer (USC). We aimed to study this relationship and analyze the effect of prior BC on the incidence and prognosis of USC patients. METHODS: With permission of the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, clinicopathological information of women diagnosed with BC and following USC were analyzed. The recorded data included age at diagnosis, stage of disease, cause of death, interval time between BC and USC diagnosis, and overall survival. RESULTS: The SEER database included 10,021 patients with USC during the years 1975-2015. 698 (6.96%) of these patients had been previously diagnosed with BC. The incidence of USC in patients with BC history was 57 times higher than in women without BC history (p value <0.001). The incidence of USC did not differ between estrogen receptor (ER)-positive and ER-negative BC patients (p value 0.94). The mean survival of USC patients with previous BC history was 8 years (96 months, 95% CI: 85.7-106.2), shorter than in USC patients with no BC history, presenting a mean survival of 10.6 years (127 months, 95% CI: 124.0-130.8) (p value = 0.002). CONCLUSION: Our results highlight the relationship between BC and USC, suggesting an increased risk for USC among BC patients. This clinical association should be introduced to BC patients, and physicians should be alert to any EC presenting symptom in BC survivors.

Five-year survival decreases over time in patients with BRCA-mutated ovarian cancer: a systemic review and meta-analysis.

INTRODUCTION: Short-term survival rates of patients with BRCA-mutated ovarian cancer have been previously shown to be longer than those of non-carriers. We aimed to study the long-term survival rates of these patients and investigate whether the 5-year advantage decreases over time. METHODS: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes (PRISMA) statement. The study protocol can be assessed at PROSPERO International prospective register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO, registration number CRD42019137455). We considered for inclusion studies providing Kaplan-Meier survival curves up to and including 10 years, comparing patients with ovarian cancer with and without BRCA mutations. Our main outcome was the conditional probability of surviving an additional 5 years. RESULTS: A total of 13 references comprising 4565 patients was analyzed, of which 1131 BRCA1/2-mutated carriers and 3434 non-carriers were included. The expected higher 5-year survival rate in BRCA-mutated patients was observed (risk difference (RD)=14.9%, p=0.0002, risk ratio (RR)=1.36, p=0.001). Ten-year survival rates were comparatively less improved in BRCA-mutated patients (RD=8.6%, p=0.042, RR=1.25, p=0.12). After already surviving 5 years, no advantage in probability of further surviving 5 additional years was observed for the BRCA-mutated group (RD=2.9%, p=0.71, RR=0.97, p=0.78). CONCLUSION: Our results provide insight into long-term survival rates and prognosis in patients with BRCA-mutated ovarian cancer which suggest that, despite the improved 5-year prognosis, the conditional probability of surviving an additional 5 years does not show the same advantage. The relatively low long-term advantage highlights the significance of epithelial ovarian cancer recurrence prevention. In the era of poly adenosine ribose inhibitors, future studies should explore the adequate follow-up and the benefit of a longer maintenance treatment phase, aiming to prolong the long-term survival of BRCA-mutated patients.

Should the risk for uterine cancer influence decision making for prophylactic hysterectomy in BRCA1/2 mutated patients- a systematic review and meta-analysis.

OBJECTIVE: To study the possible association between uterine cancer and the BRCA1/2 associated cancer syndrome and discuss the implications of such an association on the clinical managment of patients with BRCA1/2 mutations. METHODS: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Study protocol was prospectively registered at PROSPERO International prospective register of systematic reviews (registration number CRD42020193496). Considered for inclusion were studies providing the diagnosis rate of uterine cancer in patients with BRCA1/2 mutations by comparing observed and expected rate according to a known disease incidence. The results were measured by standardized incidence ratio (SIR). The primary outcome was defined as any uterine cancer diagnosis and subgroup analyses were conducted for uterine serous papillary cancer (USPC) specifically and for BRCA1 and BRCA2 mutations separately. RESULTS: 4591 records were identified through database search; eight studies were finally included, comprising 13,098 patients with BRCA1/2 mutations. BRCA1/2 mutated patients were found to have a significantly higher risk for uterine cancer compared to the general population (SIR = 2.22, 95% CI 1.76-2.8, p < 0.001). A higher incidence of USPC was also found in patients with BRCA1/2 mutations (SIR = 17.97, 95% CI 9.89-32.66, p < 0.001), as well as in a separate analysis for BRCA1 (SIR = 2.81, 95% CI 2.09-3.79, p < 0.001) and BRCA2 (SIR = 1.75, 95% CI 1.09-2.80, p < 0.001) mutations. CONCLUSION: Patients who carry a BRCA1/2 mutation are at a significantly higher risk of developing uterine cancer, specifically USPC, supporting that USPC may be a component of the BRCA1/2 syndrome. The decision to perform concurrent hysterectomy at the time of the risk reduction bilateral salpingo -oophorectomy surgery should be considered individually.

The impact of endometrial injury on reproductive outcomes: results of an updated meta-analysis.

BACKGROUND: It is still unclear whether endometrial injury (EI) has a beneficial effect on reproductive outcomes, and if so, the optimal procedure characteristics are not clear. All previous papers concluded that more research is needed, and as additional studies were recently published, the insights on EI have changed significantly. METHODS: Searches were conducted in MEDLINE, Embase, Web of Science, and Cochrane Library, to identify randomized controlled trials examining the EI effect on IVF outcomes in women at least one previous failed cycle. RESULTS: 2015 references were identified through database searching. Ultimately, 17 studies were included, involving 3016 patients. Clinical pregnancy rate (CPR) (RR = 1.19, [95% CI 1.06-1.32], P = .003) and live birth rate (LBR) (RR = 1.18, [95%CI 1.04-1.34], P = .009) were significantly improved after EI. Number of previous failed cycles, maternal age, and hysteroscopy were found to be relevant confounders. Higher CPR and LBR were found when EI was performed twice, while performing EI once did not significantly improve reproductive rates. CONCLUSION: According to the present meta-analysis, EI may be offered to younger patients with few previous failed cycles and should be additionally studied in an RCT comparing different timing and more than one EI before treatment.

Evaluation of human papilloma virus in semen as a risk factor for low sperm quality and poor in vitro fertilization outcomes: a systematic review and meta-analysis.

OBJECTIVE: To analyze the effect of human papilloma virus (HPV) sperm infection on sperm parameters and in vitro fertilization (IVF) outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENTS: Men with HPV sperm infection and couples undergoing IVF. INTERVENTIONS: Searches were conducted in the following databases: Medline(R), PubMed, Embase, Web of Science, Scopos, and the Cochrane Library. We included studies examining sperm parameters and IVF results in patients with and without HPV sperm infection. MAIN OUTCOME MEASURES: Sperm analysis (concertation, count, volume, motility, morphology), according to the World Health Organization manual, pregnancy rate (PR), and miscarriage rate (MR). RESULTS: Sixteen studies were included in this meta-analysis. The presence of HPV had a significant association with impaired sperm parameters in terms of concentration (mean difference [MD] -4.48, 95% confidence interval [CI] - 6.12 to -2.83), motility (MD -11.71, 95% CI - 16.15 to -7.26), and morphology (MD -2.44, 95% CI - 4.08 to -0.79. A review of the literature regarding ART outcomes showed an association between HPV infection and decreased PR, and an even stronger association between HPV infection and increased MR. CONCLUSION: Our meta-analysis shows a negative effect of HPV on sperm concentration, motility, and morphology. Further subgroup and categorical analysis confirmed the clinical significance of impaired sperm motility in HPV-infected sperm, although the sperm count and morphology must be carefully analyzed. The studies reviewed reported lower PR and increased MR in couples with HPV-infected sperm. As most studies had a moderate risk of bias, these observations warrant further large, well-designed studies before introducing clinical management recommendations. PROSPERO REGISTRATION NUMBER: CRD42019127419.

Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling all Asymptomatic Patients Before Surgical Treatment.

BACKGROUND: In December 2019, a novel coronavirus was identified as the cause of many pneumonia cases in China and eventually declared as a pandemic as the virus spread globally. Few reports were published on the outcome of surgical procedures in diagnosed COVID-19 patients and even fewer on the surgical outcomes of asymptomatic undiagnosed COVID-19 surgical patients. We aimed to review all published data regarding surgical outcomes of preoperatively asymptomatic untested coronavirus disease 2019 (COVID-19) patients. METHODS: This report is a review on the perioperative period in COVID-19 patients who were preoperatively asymptomatic and not tested for COVID-19. Searches were conducted in PubMed April 4th, 2020. All publications, of any design, were considered for inclusion. RESULTS: Four reports were identified through our literature search, comprising 64 COVID-19 carriers, of them 51 were diagnosed only in the postoperative period. Synthesis of these reports, concerning the postoperative outcomes of patients diagnosed with COVID-19 during the perioperative period, suggested a 14/51 (27.5%) postoperative mortality rate and severe mostly pulmonic complications, as well as medical staff exposure and transmission. CONCLUSIONS: COVID-19 may have potential hazardous implications on the perioperative course. Our review presents results of unacceptable mortality rate and a high rate of severe complications. These observations warrant further well-designed studies, yet we believe it is time for a global consideration of sampling all asymptomatic patients before surgical treatment.

The impact of intentional endometrial injury on reproductive outcomes: a systematic review and meta-analysis.

BACKGROUND: Endometrial injury is an intentional damage made to the endometrium, usually produced by a Pipelle catheter. Over the last two decades, endometrial injury has been studied to improve implantation rates and decrease the incidence of implantation failure in invitro fertilization (IVF) cycles. Recently, additional studies of endometrial injury, performed not only in patients with implantation failure but also in intrauterine insemination cycles, have been conducted, and the endometrial injury made by hysteroscopy has been researched. The evidence describing the impact of endometrial injury is controversial; therefore, we conducted a systematic review and meta-analysis to examine the issue. OBJECTIVE AND RATIONALE: Our objective is to review the research that has been done until now and perform a meta-analysis regarding endometrial injury and its influence on implantation success and pregnancy rates in patients with at least one failed IVF cycle. In particular, we aim to study the efficacy of the procedure and look for confounding factors, such as maternal age, in assessing the efficacy of endometrial injury. SEARCH METHODS: The systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Study protocol can be assessed at PROSPERO International prospective register of systematic reviews (registration number CRD42018092773). Searches were conducted by an experienced research librarian in the following databases: MEDLINE(R) using the OvidSP interface and PUBMED, Embase, Web of Science and Cochrane Library. This review considered for inclusion randomized-controlled trials examining the success of performing local endometrial injury on IVF outcomes in women with previous failed IVF cycles. OUTCOMES: Ten studies, comprising a total of 1260 patients, were selected. Overall, when studying the effect of endometrial injury on clinical pregnancy rates (CPRs) and live birth rates (LBRs), higher rates were shown in the endometrial injury group. However, endometrial injury did not significantly improve CPRs and LBRs, when considering sub-group analyses of studies including patients with two or more failed IVF cycles, studies examining older patients or studies which did not include hysteroscopy. There was no significant difference found regarding multiple pregnancy rates, while a handful of studies showed an improvement in miscarriage rates. WIDER IMPLICATIONS: Endometrial injury should be used restrictively and not routinely in clinics. Maternal age and number of previous failed treatment cycles may be contributing factors which can influence the results when studying the effect of endometrial local injury. It is possible that the relative contribution of endometrial receptivity to the chances of implantation decreases with any additional failed cycle. The optimal study to prove the efficacy of local endometrial injury on implantation and pregnancy rates, should be a random-controlled trial studying the effect of local endometrial injury in oocyte donation cycles, in recipients with repeated implantation failure. This kind of study will conclude whether local endometrial injury is an efficient procedure with minimum confounding factors, and may assist in defining the population, even outside of donation cycles, that will benefit from the procedure.