The origin and possible mechanism of embryonic cell-free DNA release in spent embryo culture media: a review.

The presence of cell-free DNA in spent embryo culture media (SECM) has unveiled its possible utilization for embryonic ploidy determination, opening new frontiers for the development of a non-invasive pre-implantation genetic screening technique. While a growing number of studies have shown a high concordance between genetic screening using cell-free DNA (cfDNA) and trophectoderm (TE), the mechanism pertaining to the release of cfDNA in SECM is largely unknown. This review aims to evaluate research evidence on the origin and possible mechanisms for the liberations of embryonic DNA in SECM, including findings on the self-correction abilities of embryos which might contribute to the presence of cfDNA. Several databases including EMBASE, PUBMED, and SCOPUS were used to retrieve original articles, reviews, and opinion papers. The keywords used for the search were related to the origins and release mechanism of cfDNA. cfDNA in SECM originates from embryonic cells and, at some levels, non-embryonic cells such as maternal DNA and exogenous foreign DNA. The apoptotic pathway has been demonstrated to eliminate aneuploid cells in developing mosaic embryos which might culminate to the release of cfDNA in SECM. Nonetheless, there is a recognized need for exploring other pathways such as cross-talk molecules called extracellular vesicles (EVs) made of small, round bi-layer membranes. During in vitro development, embryos physiologically and actively expel EVs containing not only protein and microRNA but also embryonic DNA, hence, potentially releasing cfDNA of embryonic origin into SECM through EVs.

Genetic algorithm-assisted machine learning for clinical pregnancy prediction in in vitro fertilization.

BACKGROUND: A clinical pregnancy prediction model was developed by implementing machine learning technology that uses a combination of static images and medical data to calculate the outcome of an in vitro fertilization cycle. OBJECTIVE: To provide a system that can accurately and sufficiently assist with decision making that is critical to in vitro fertilization cycles, primarily embryo selection. STUDY DESIGN: Historical medical data, which consist of clinical information and a complete transferred embryo image dataset, of 697 patients who underwent unique in vitro fertilization were collected. Various techniques of machine learning were used, namely decision tree, random forest, and gradient boosting; each technique used the same data configuration for performance comparison and was subsequently optimized using genetic algorithm. RESULTS: A prediction model with a peak accuracy of approximately 65% was achieved. Significant differences in the performances of the 3 selected algorithms were apparent. Nonetheless, additional metric measurements, such as receiver operating characteristic, area under the receiver operating characteristic curve score, accuracy, and loss, suggested that the gradient boosting model performed the best in predicting clinical pregnancy. CONCLUSION: This study served as a stepping stone toward the application of in vitro fertilization prediction models that use machine learning techniques. However, additional validation steps are required to boost the model's performance for its implementation in the clinical setting.

A Homogeneous Ensemble of Robust Pre-defined Neural Network Enables Automated Annotation of Human Embryo Morphokinetics.

Background: The purpose of the current study was to reduce the risk of human bias in assessing embryos by automatically annotating embryonic development based on their morphological changes at specified time-points with convolutional neural network (CNN) and artificial intelligence (AI). Methods: Time-lapse videos of embryo development were manually annotated by the embryologist and extracted for use as a supervised dataset, where the data were split into 14 unique classifications based on morphological differences. A compilation of homogeneous pre-trained CNN models obtained via TensorFlow Hub was tested with various hyperparameters on a controlled environment using transfer learning to create a new model. Subsequently, the performances of the AI models in correctly annotating embryo morphologies within the 14 designated classifications were compared with a collection of AI models with different built-in configurations so as to derive a model with the highest accuracy. Results: Eventually, an AI model with a specific configuration and an accuracy score of 67.68% was obtained, capable of predicting the embryo developmental stages (t1, t2, t3, t4, t5, t6, t7, t8, t9+, tCompaction, tM, tSB, tB, tEB). Conclusion: Currently, the technology and research of artificial intelligence and machine learning in the medical field have significantly and continuingly progressed in an effort to develop computer-assisted technology which could potentially increase the efficiency and accuracy of medical personnel's performance. Nonetheless, building AI models with larger data is required to properly increase AI model reliability.

Traction Splinting for midshaft femoral fractures in the pre-hospital and Emergency Department environment-A systematic review.

INTRODUCTION: Pain and hemorrhage are common in midshaft femoral fractures. Traction splints (TSs) can reduce pain and control hemorrhage, but evidence of their effectiveness in femoral fractures is still lacking. Through a systematic review, we aimed to analyze and discuss the potential role of TSs in the prehospital and emergency department (ED) setting. METHODS: The Embase, CINAHL, Cochrane, and PubMed databases were searched up to January 2022. All studies on femoral fractures in the prehospital or ED setting that compared TSs with immobilization or no intervention were included. Articles not written in English, German, or Dutch were excluded. Two authors screened all articles, assessed their quality, and included them if both agreed on their inclusion. The risk of bias was assessed using the modified Methodological Index for Non-Randomized Studies (MINORS). The primary outcome measures were pain and hemorrhage control, while the secondary outcome measures were survivability, morbidity, and complications. RESULTS: A total of 1,248 articles matched the search strategy, 24 articles were assessed for eligibility based on their abstracts, resulting in 20 articles being included in the synthesis. Ten articles reviewed the effects of TSs on pain, while five reported that the use of a TS was appropriate. All five articles that reviewed blood loss found benefits from the use of a TS. One study found significantly fewer pulmonary complications in patients who were splinted earlier at the scene of injury (level III). No difference was found in complications or mortality between prehospital patients receiving a TS or no TS (level III). None of the studies noted that TSs were a necessity in the ED setting; however, some argued that a TS is a necessary and useful prehospital tool in rural or military areas. CONCLUSION: TS use is associated with a decreased necessity for blood transfusions and fewer pulmonary complications. No favorable effects were found in terms of pain relief. We recommend the use of TSs in situations where one is likely to encounter a femoral fracture as well as when the time to definitive treatment is long. Further well-designed studies are required to validate these recommendations.

The outcome of Gynecologic Cancer Patients With The Covid-19 Infection: A Systematic Review And Meta-Analysis

ObjectiveCancer is a comorbidity that leads to progressive worsening of Covid-19 with increased mortality. This is a systematic review and meta-analysis to yield evidence of adverse outcomes of Covid-19 in gynecologic cancer. MethodsSearches through PubMed, Google Scholar, ScienceDirect, and medRxiv to find articles on the outcome of gynecologic cancer with Covid-19 (24 July 2021-19 February 2022). Newcastle-Ottawa Scale tool is used to evaluate the quality of included studies. Pooled odds ratio (OR), 95% confidence interval (CI), random-effects model were presented. This study was registered to PROSPERO (CRD42021256557). ResultsWe accepted 51 studies (1991 gynecologic cancer with Covid-19). Covid-19 infection was lower in gynecologic cancer vs hematologic cancer (OR 0.71, CI 0.56-0.90, p 0.005). Severe Covid and death were lower in gynecologic cancer vs lung and hematologic cancer (OR 0.36, CI 0.16-0.80, p 0.01), (OR 0.52, CI 0.44-0.62, p <0.0001), (OR 0.26, CI 0.10-0.67 p 0.005), (OR 0.63, CI 0.47-0.83, p 0.001) respectively. Increased Covid death is seen in gynecologic cancer vs breast, non-covid cancer, and non-cancer covid (OR 1.50, CI 1.20-1.88, p 0.0004), (OR 11.83, CI 8.20-17.07, p <0.0001), (OR 2.98, CI 2.23-3.98, p <0.0001) respectively. ConclusionGynecologic cancer has higher Covid-19 adverse outcomes compared to non-cancer, breast cancer, non-metastatic, and Covid-19 negative population. Gynecologic cancer has fewer Covid-19 adverse outcomes compared to other cancer types, lung cancer, and hematologic cancer. These findings may aid health policies and services during the ongoing global pandemic.

Role of three-dimensional Doppler ultrasonography and leukemia inhibitory factor from endometrial secretion in predicting endometrial receptivity in IVF treatment: a pilot study.

PURPOSE: This pilot study aimed to evaluate the potential synergistic role of three-dimensional power Doppler angiography ultrasound and the expression of Leukemia Inhibitory Factor (LIF) protein in predicting the endometrial receptivity of fresh In-Vitro Fertilization (IVF) cycles. MATERIALS AND METHODS: This prognostic cohort study involved 29 good prognosis women who underwent fresh IVF cycles with fresh blastocysts transfer. Serial measurements of sub-endometrial parameters including vascularity index (VI), flow index (FI), and vascularization flow index (VFI) were conducted consecutively via power Doppler angiography on the day of oocyte maturation trigger, oocyte retrieval, and blastocyst transfer. Aspiration of endometrial secretion was performed on the day of embryo transfer. RESULTS: The mean index of VI and VFI on the trigger and oocyte retrieval day and also LIF protein concentration at the window of implantation were significantly higher in clinically pregnant women than that of the non-pregnant women (p < 0.05). The area under the curve (AUC) of VI and VFI was shown to have a powerful predictive value to forecast receptive endometrium on either trigger day (0.788 and 0.813, respectively) or oocyte retrieval day (0.813 and 0.818). Likewise, LIF concentration on the day of embryo transfer was adequate to become a predictor for endometrial receptivity (AUC 0.874). A combination of the VI and VFI on the trigger day and LIF concentration at specific cut-off values (VI > 5.381, VFI > 1.483, LIF 703.5 pg/mL) produced an algorithm with high AUC (0.881) and high specificity (94.4%) for an adequate prediction of non-receptive endometrium. CONCLUSION: VI and VFI index assessed on maturation trigger day and the expression of LIF protein concentration at the window of implantation provided sufficient information to predict endometrial receptivity. A large randomized control trial is needed to validate these findings.

Review of computer vision application in in vitro fertilization: the application of deep learning-based computer vision technology in the world of IVF.

In vitro fertilization has been regarded as a forefront solution in treating infertility for over four decades, yet its effectiveness has remained relatively low. This could be attributed to the lack of advancements for the method of observing and selecting the most viable embryos for implantation. The conventional morphological assessment of embryos exhibits inevitable drawbacks which include time- and effort-consuming, and imminent risks of bias associated with subjective assessments performed by individual embryologists. A combination of these disadvantages, undeterred by the introduction of the time-lapse incubator technology, has been considered as a prominent contributor to the less preferable success rate of IVF cycles. Nonetheless, a recent surge of AI-based solutions for tasks automation in IVF has been observed. An AI-powered assistant could improve the efficiency of performing certain tasks in addition to offering accurate algorithms that behave as baselines to minimize the subjectivity of the decision-making process. Through a comprehensive review, we have discovered multiple approaches of implementing deep learning technology, each with varying degrees of success, for constructing the automated systems in IVF which could evaluate and even annotate the developmental stages of an embryo.

Morphokinetics of embryos after IMSI versus ICSI in couples with sub-optimal sperm quality: A time-lapse study.

An investigation was conducted to determine the influence of two sperm selection modalities, IMSI and ICSI, on the morphokinetics, dynamic development and ploidy status of embryos derived from males with sub-optimal sperm profiles during IVF program. A total of 209 PGTA-tested top-quality blastocysts (IMSI = 129, ICSI = 80) from 84 couples (IMSI = 51, ICSI = 33) were assessed retrospectively. This study found that both IMSI and ICSI yielded comparable embryo morphokinetics, except for the T7, TEB and CC3 parameters (p < 0.05). A significant lower incidence of multinucleation was observed in the IMSI group when compared to the ICSI group (48.8% vs. 71.3%, p = 0.002), while other parameters of embryo development such as direct cleavage, distorted cytoplasmic movement, reverse cleavage and vacuole(s) appearance did not differ (p > 0.05). No differences were noticed in the proportion of generating chromosomally euploid embryos (44.2% vs. 51.3%, p = 0.394, respectively, for IMSI and ICSI). The implementation of IMSI or ICSI in couples with sub-optimal sperm profiles resulted in embryos with comparatively similar morphokinetics. Furthermore, the incidence of multinucleation at the two- to four-cell stage was lower following the practice of IMSI, although the method did not improve the proportion of gaining euploid embryos.

Embryo Banking with Mild Ovarian Stimulation for IVF: An Alternative Strategy for Poor Prognosis Patients.

BACKGROUND: Management of Poor Ovarian Reserve (POR) in in vitro fertilization remains a difficult challenge. The purpose of this retrospective cohort study was to compare the effectiveness of embryo banking strategy over a cohort of several mild stimulation cycles (Embryo Banking Strategy for Poor Prognosis/Embargo) to conventional full-dose antagonist protocol for IVF. METHODS: Subjects identified as having poor ovarian response (POR) based on the Bologna criteria were recruited. In total, there were 113 subjects included in the analysis. Fifty-three subjects underwent embryo banking procedure (Embargo) protocol, and sixty subjects underwent the conventional full-dose antagonist protocol for IVF. The Chi-square test was used to compare the clinical pregnancy rate, miscarriage rate as well as live birth rate, while the Mann-Whitney U test was utilized to analyze the cost per clinical pregnancy between the two groups. A p<0.05 was considered statistically significant. RESULTS: The two studied groups showed similar outcomes regarding clinical pregnancy rate, miscarriage rate, as well as live birth rate (p=0.966, p=0.310, and p= 0.469, respectively). Cost analysis of subjects who underwent mild ovarian stimulation followed by Embargo revealed the high cost of the protocol compared to conventional full-dose antagonist protocol ($10.507±6.181 vs. $9.533±2.530, p=0.002). CONCLUSION: The clinical outcomes of both protocols were comparable. Embargo procedure was not efficient in improving the overall clinical outcomes in patients who were expected poor ovarian responders as the protocol costed more comparing with conventional full-dose antagonist protocol. A larger prospective randomized control trial is needed to evaluate this finding.

Genetic and antigenic characterization of influenza A/H5N1 viruses isolated from patients in Indonesia, 2008-2015.

Since the initial detection in 2003, Indonesia has reported 200 human cases of highly pathogenic avian influenza H5N1 (HPAI H5N1), associated with an exceptionally high case fatality rate (84%) compared to other geographical regions affected by other genetic clades of the virus. However, there is limited information on the genetic diversity of HPAI H5N1 viruses, especially those isolated from humans in Indonesia. In this study, the genetic and antigenic characteristics of 35 HPAI H5N1 viruses isolated from humans were analyzed. Full genome sequences were analyzed for the presence of substitutions in the receptor binding site, and polymerase complex, as markers for virulence or human adaptation, as well as antiviral drug resistance substitutions. Only a few substitutions associated with human adaptation were observed, a remarkably low prevalence of the human adaptive substitution PB2-E627K, which is common during human infection with other H5N1 clades and a known virulence marker for avian influenza viruses during human infections. In addition, the antigenic profile of these Indonesian HPAI H5N1 viruses was determined using serological analysis and antigenic cartography. Antigenic characterization showed two distinct antigenic clusters, as observed previously for avian isolates. These two antigenic clusters were not clearly associated with time of virus isolation. This study provides better insight in genetic diversity of H5N1 viruses during human infection and the presence of human adaptive markers. These findings highlight the importance of evaluating virus genetics for HPAI H5N1 viruses to estimate the risk to human health and the need for increased efforts to monitor the evolution of H5N1 viruses across Indonesia.

Does the addition of salpingectomy or fimbriectomy to hysterectomy in premenopausal patients compromise ovarian reserve? A prospective study.

OBJECTIVE: To evaluate changes in ovarian reserve in patients following hysterectomy, with or without bilateral salpingectomy or fimbriectomy. STUDY DESIGN: Open-label, prospective cohort trial of patients undergoing hysterectomy for benign uterine indications. Levels of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and ultrasonic measures of peak systolic flow velocity/diastolic velocity (S/D) ratio and resistance index (RI) in the ovarian artery were taken from patients before and 6 weeks after hysterectomy, hysterectomy+salpingectomy or hysterectomy+fimbriectomy. RESULTS: The study period was from November 2011 to May 2014. Sixty patients were included in the final analysis, after two patients were lost to follow-up and one patient underwent bilateral oophorectomy. Of these 60 patients, 16 underwent hysterectomy alone (control group), and 44 were included in the study group (22 patients underwent hysterectomy+fimbriectomy and 22 patients underwent hysterectomy+salpingectomy). The mean age of patients was 46 years (standard deviation 4.07 years). Between-group dfferences in FSH, AMH, ovarian volume, ovarian artery S/D ratio and ovarian artery RI were not significant. CONCLUSION: The addition of salpingectomy or fimbriectomy to routine hysterectomy in premenopausal patients does not diminish ovarian reserve.

The Added Value of SPECT/CT in Sentinel Lymph Nodes Mapping for Endometrial Carcinoma.

OBJECTIVES: This study was designed to evaluate the detection rate (DR) and sensitivity of sentinel lymph node (SLN) mapping in patients with endometrial cancer using TC99m colloid and blue dye and to evaluate the contribution of preoperative planar lymphoscintigraphy (PLSG) and SPECT/CT. METHODS: A retrospective analysis of patients who underwent SLN mapping as part of their primary surgery for endometrial cancer. Patients underwent preoperative PLSG and later with additional SPECT/CT. Intraoperative detection was performed using TC99m colloid and blue dye by cervical injections. SLNs were sent separately for pathologic evaluation with ultrastaging. RESULTS: Fifty-three patients were included in this study. Successful preoperative mapping was achieved in 31 of 37 patients (84 %) who underwent SPECT/CT compared with only 30 of 45 patients (67 %) who underwent PLSG. SPECT/CT localizations of SLNs were anatomically accurate in 91 % of cases. Intraoperative DR of at least one SLN was 77 %, whilst the bilateral DR was 49 %. DR was significantly better using combined blue dye and TC99m colloid injections compared with blue dye alone: 81 versus 57 % for unilateral and 54 versus 28 % for bilateral mapping (P = 0.01, 0.009, respectively). Six cases of nodal metastasis were diagnosed: four by positive SLNs, and two cases were diagnosed using side-specific full dissection according to the SLN algorithm when SLN detection failed. There were no cases of false-negative results. CONCLUSIONS: SLN detection using cervical injections of TC99m colloid and blue dye is feasible and sensitive for patients with endometrial cancer. SPECT/CT aids to accurate locating of the SLN.

Compact 2D nonlinear photonic crystal source of beamlike path entangled photons.

We demonstrate a method to generate entangled photons with controlled spatial shape by parametric down conversion (PDC) in a 2D nonlinear crystal. A compact and novel crystal source was designed and fabricated, generating directly path entangled photons without the use of additional beam-splitters. This crystal supports two PDC processes, emitting biphotons into two beamlike modes simultaneously. Two coherent path entangled amplitudes of biphotons were created and their interference observed. Our method enables the generation of entangled photons with controlled spatial, spectral and polarization properties.

Can parametrectomy be avoided in early cervical cancer? An algorithm for the identification of patients at low risk for parametrial involvement.

AIMS: To assess the rate of parametrial involvement in a large cohort of patients who underwent radical hysterectomy for cervical cancer and to suggest an algorithm for the triage of patients to simple hysterectomy or simple trachelectomy. METHODS: Multicenter retrospective study of patients with cervical cancer stage I through IIA who underwent radical hysterectomy and pelvic lymphadenectomy. The patients were divided into 2 groups according to whether or not the parametrium was involved. The two groups were compared with regard to the clinical and histopathological variables. Logistic regression of the variables potentially assessable prior to definitive hysterectomy such as age, tumor size, lymph-vascular space invasion (LVSI) and nodal involvement was performed. RESULTS: Five hundred and thirty patients had specific histological data on parametrial involvement and in 58 (10.9%) patients, parametria was involved. Parametrial involvement was significantly associated with older age, tumors larger than 2 cm, deeper invasion, LVSI, involved surgical margins, and the presence of nodal metastasis. By triaging patients with a tumor ≤ 2 cm and no LVSI, the parametrial involvement rate was 1.8% (2/112 patients). With further triage of patients with negative nodes, the rate of parametrial involvement was 0% (0/107 patients). CONCLUSION: Using a pre-operative triage algorithm, patients with early small lesions, no LVSI and no nodal involvement may be spared radical surgical procedures and parametrectomy. Further prospective data are urgently needed.

Can angle of progression in pregnant women before onset of labor predict mode of delivery?

OBJECTIVES: The angle of progression (AOP), measured by transperineal ultrasound, has been used to assess fetal head descent during labor. Our aim was to assess whether, before onset of labor, parous women have a narrower AOP than do nulliparous women and if a narrow AOP is associated with a higher rate of Cesarean delivery. METHODS: In this prospective, observational study, we performed transperineal ultrasound in pregnant women not yet in labor at ≥ 39 weeks' gestation who delivered within 1 week of sonography. The AOP was compared as follows: in nulliparous women, between those who had a Cesarean section and those who delivered vaginally; and among women who delivered vaginally, between those who were nulliparous and those who were parous. RESULTS: Included in the study were 100 nulliparous and 71 parous women. Among those who delivered vaginally (n = 161), the median AOP before onset of labor was narrower in parous than in nulliparous women (98° (interquartile range (IQR)), 90-107° vs 104° (IQR, 97-113°), P < 0.001). Among the 100 nulliparous women, (1) the median AOP before onset of labor was narrower in those who went on to deliver by Cesarean section (n = 9) than in those delivered vaginally (n = 91) (90° (IQR, 85.5-93.5°) vs 104° (IQR, 97-113°), P < 0.001); (2) an AOP ≥ 95° (derived from the receiver-operating characteristics curve) was associated with vaginal delivery in 99% of women; and (3) 89% (8/9) of women who delivered by Cesarean section had an AOP < 95°. Among the 71 parous women, only one delivered by Cesarean section and all of those with an AOP < 95° delivered vaginally. CONCLUSION: A narrow AOP (< 95°) in non-laboring nulliparous women at term is associated with a high rate of Cesarean delivery. Parous women have a narrower AOP than do nulliparous women before the onset of labor; however, unlike in nulliparous women, a narrow AOP in parous women does not appear to be associated with Cesarean delivery and most parous women with such an angle go on to deliver vaginally.

Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors.

OBJECTIVE: To study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting. METHODS: 843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan-Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk. RESULTS: Recurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors. CONCLUSIONS: In patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients.

Direct detection of chicken genomic DNA for gender determination by thymine-DNA glycosylase.

1. Birds, especially nestlings, are generally difficult to sex by morphology and early detection of chick gender in ovo in the hatchery would facilitate removal of unwanted chicks and diminish welfare objections regarding culling after hatch. 2. We describe a method to determine chicken gender without the need for PCR via use of Thymine-DNA Glycosylase (TDG). TDG restores thymine (T)/guanine (G) mismatches to cytosine (C)/G. We show here, that like DNA Polymerase, TDG can recognise, bind and function on a primer hybridised to chicken genomic DNA. 3. The primer contained a T to mismatch a G in a chicken genomic template and the T/G was cleaved with high fidelity by TDG. Thus, the chicken genomic DNA can be identified without PCR amplification via direct and linear detection. Sensitivity was increased using gender specific sequences from the chicken genome. 4. Currently, these are laboratory results, but we anticipate that further development will allow this method to be used in non-laboratory settings, where PCR cannot be employed.

Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: results of a multicenter study.

OBJECTIVE: To quantify the relative risk associated with lower uterine segment involvement (LUSI) on outcome measures in patients with apparent stage I endometroid endometrial cancer. METHODS: A cohort of 769 consecutive patients with endometroid endometrial carcinoma apparent stage I, who underwent surgery in five gynecological oncology centers in Israel; 138 patients with and 631 without LUSI were followed for a median time of 51 months. Local recurrence, recurrence-free and overall survival were compared between the two groups. RESULTS: LUSI was associated with grade 3 tumor (p=0.002), deep myometrial invasion (p<0.001), and the presence of lymphvascular space involvement (p=0.01). There were 22 cases of local recurrences, 40 cases of distal recurrences and 80 patients died. Univariate survival analysis showed that patients with LUSI had trend toward lower regional recurrence-free survival (p=0.09), and significant lower distant recurrence-free survival (p=0.04) and lower overall survival (p=0.002). The Cox proportional hazards model demonstrated a significantly decreased overall survival (HR=2.3; 95% CI 1.3, 3.9; p=0.003) in cases with LUSI. CONCLUSIONS: In patients with apparent stage I endometroid endometrial cancer, the presence of LUSI is a poor prognostic factor, associated with a significantly higher risk of distal recurrence and death. The presence of LUSI warrants consideration when deciding upon surgical staging or postoperative management.