Performances of novel custom 3D-printed cutting guide in canine caudal maxillectomy: a cadaveric study.

Introduction: Caudal maxillectomies are challenging procedures for most veterinary surgeons. Custom guides may allow the procedure to become more accessible. Methods: A cadaveric study was performed to evaluate the accuracy and efficiency of stereolithography guided (3D-printed) caudal maxillectomy. Mean absolute linear deviation from planned to performed cuts and mean procedure duration were compared pairwise between three study groups, with 10 canine cadaver head sides per group: 3D-printed guided caudal maxillectomy performed by an experienced surgeon (ESG) and a novice surgery resident (NSG), and freehand procedure performed by an experienced surgeon (ESF). Results: Accuracy was systematically higher for ESG versus ESF, and statistically significant for 4 of 5 osteotomies (p < 0.05). There was no statistical difference in accuracy between ESG and NSG. The highest absolute mean linear deviation for ESG was <2 mm and >5 mm for ESF. Procedure duration was statistically significantly longer for ESG than ESF (p < 0.001), and for NSG than ESG (p < 0.001). Discussion: Surgical accuracy of canine caudal maxillectomy was improved with the use of our novel custom cutting guide, despite a longer duration procedure. Improved accuracy obtained with the use of the custom cutting guide could prove beneficial in achieving complete oncologic margins. The time increase might be acceptable if hemorrhage can be adequately controlled in vivo. Further development in custom guides may improve the overall efficacy of the procedure.

PROGNOSTIC VALUE OF BLASTOCYST GRADE AFTER FROZEN EUPLOID EMBRYO TRANSFER IN PATIENTS WITH RECURRENT PREGNANCY LOSS.

OBJECTIVE: To determine if trophectoderm (TE) grade or inner cell mass (ICM) grade have predictive value after euploid frozen embryo transfer (euFET) among RPL patients. DESIGN: Retrospective cohort study. SETTING: Single fertility center, 2012-2018. PATIENTS: Patients with ≥ 2 prior pregnancy losses performing PGT-A with ≥1 euploid embryo for transfer. INTERVENTIONS: All patients underwent ICSI, trophectoderm biopsy, blastocyst grading and vitrification, and single euFET. Outcome of the first transfer was recorded. MAIN OUTCOME MEASURES: Live birth (LB) and clinical miscarriage (CM) rates. RESULTS: 660 euFET were included. In a binomial logistic regression analysis accounting for age, BMI, AMH and day of blastocyst biopsy, ICM grade C was not significantly associated with odds of live birth (aOR 0.50, 95% CI 0.24-1.02 p=0.057), miscarriage (aOR 1.67, 95% CI 0.56-5.00, p=0.36) or biochemical pregnancy loss (aOR 1.58, 95% CI 0.53-4.75, p=0.42). TE grade C was significantly associated with odds of live birth (aOR 0.49, 95% CI 0.28-0.86, p=0.01) and was not associated with odds of miscarriage (aOR 2.00, 95% CI 0.89-4.47, p=0.09) or biochemical pregnancy loss (aOR 1.85, 95% CI 0.77-4.44, p=0.17). Blastocyst grade CC had significantly lower LB rate compared to all other blastocyst grades (p<0.05, chi-square analysis). CONCLUSION: Embryo grade CC and TE grade C are associated with decrease in odds of LB after euFET in RPL patients. Embryo grade is not associated with odds of CM in this cohort of RPL patients, suggesting that additional embryonic or uterine factors may influence risk of pregnancy loss.

When next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) yields an inconclusive report: diagnostic results and clinical outcomes after re biopsy.

PURPOSE: To describe diagnostic results following re-biopsy of blastocysts with inconclusive results on preimplantation genetic screening for aneuploidy (PGT-A) and to evaluate the reproductive potential of re-biopsied blastocysts. METHODS: This retrospective cohort study included all trophectoderm biopsies submitted for PGT-A by a large in vitro fertilization center to a single genetics laboratory from June 2016 to October 2018. PGT-A was performed using next-generation sequencing (NGS). No-result blastocysts that underwent re-biopsy were subsequently classified as euploid, aneuploid, mosaic/segmental, or no-result. Ongoing pregnancy and clinical loss rates were assessed following transfer of re-biopsied blastocysts. Logistic regressions were conducted to account for age and blastocyst morphology. RESULTS: Of the trophectoderm biopsies submitted for PGT-A, 635/25,199 (2.5%) were categorized as no-result. Those that underwent re-biopsy (n = 250) had a 95.2% diagnostic rate with 140 (56.0%) receiving euploid diagnoses. Thirty-six re-biopsied blastocysts deemed euploid were subsequently transferred, resulting in 18 (50.0%) ongoing pregnancies and 5 (13.9%) clinical losses. After adjusting for age and blastocyst morphology, there remained a lower ongoing pregnancy rate and a trend towards higher clinical loss rate following transfer of a re-biopsied blastocyst. When compared to blastocysts that underwent the same number of vitrification-warming cycles but only one biopsy, there were no differences in outcomes. CONCLUSIONS: Failure to obtain an analytical result does not change the probability that a given blastocyst is euploid. Pregnancy outcomes following transfer of re-biopsied blastocysts are favorable, but further data must be accrued for an adequately powered comparison with outcomes after transfer of blastocysts biopsied once.

CD8, FoxP3, and CD45RO+ Lymphocytic Infiltrates in Type I and Type II Endometrial Cancers in African American and European American Females.

African American (AA) females with endometrial carcinoma have a significantly worse prognosis with regard to disease-free survival and overall survival than their European American (EA) counterparts and this finding is true across all stages and grades. The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated to be of prognostic significance in a variety of malignancies, including endometrial cancers. This study aims to determine whether clinically significant differences in levels of CD8+ cytotoxic T lymphocytes, FoxP3+ regulatory T lymphocytes, and CD45RO+ memory T lymphocytes exist between races and to document the clinical impact of TILs. One hundred ten patients with endometrial adenocarcinoma, treated with hysterectomy from 2003 to 2011 were studied. Patients were selected to provide equal representation across type and grade for both EAs and AAs. Immunohistochemical stains were used to highlight CD8-positive, FoxP3-positive, and CD45RO-positive TILs at the endometrial-myometrial interface on slides from paraffin-embedded tissue. Patients with "high" or "low" levels of TILs were compared with respect to the race, tumor type, and survival. High levels of CD45RO+ TILs were associated with improved overall survival in EA women (hazard ratio, 0.32; 95% confidence interval, 0.11-0.92; P=0.034). Comparatively, AA women with high levels of CD45RO+ TILs received no survival benefit (hazard ratio, 0.96; 95% confidence interval, 0.35-2.64; P=0.94). High levels of CD8-positive or FoxP3-positive TILs, alone, had no impact on survival. EA patients with TILs containing high levels of CD45RO cells but low levels of CD8+ cells lost the survival benefit; however, limited numbers preclude significant conclusions from this observation. Neither tumor type nor race were predictive of the levels of TILs of any type. Further study with a larger sample size is required to determine the impact of TIL subtype combinations on survival.

High relative deoxyribonucleic acid content of trophectoderm biopsy adversely affects pregnancy outcomes.

OBJECTIVE: To evaluate the association between relative DNA content of the trophectoderm biopsy and pregnancy outcomes. DESIGN: Retrospective cohort study. SETTING: Academic-affiliated private practice. PATIENT(S): This study included patients undergoing their first single embryo transfer after trophectoderm biopsy and comprehensive chromosome screening (CCS) at a single center between January 2010 and February 2014. INTERVENTION(S): In phase 1 of the study, a standard curve was developed to estimate the relative DNA content of trophectoderm biopsies. Phase 2 of the study examined reproductive outcomes in patients undergoing single embryo transfer after trophectoderm biopsy and CCS. Samples were divided into quartiles according to their relative DNA content, and clinical outcomes were compared. MAIN OUTCOME MEASURE(S): Chemical pregnancy rate, clinical implantation rate, ongoing pregnancy rate, live birth rate. RESULT(S): The quartile of highest relative DNA content had a significantly lower live birth rate when compared with the other three quartiles (relative risk 0.84, 95% confidence interval 0.75-0.95). There was no difference between the quartiles regarding age, body mass index, ovarian response, or endometrial thickness. Among those patients who had a live birth, there was no difference in hCG levels, gestational age at delivery, or birth weight with respect to biopsy DNA content. CONCLUSION(S): Trophectoderm biopsies with the highest relative DNA content are associated with lower live birth rates after single embryo transfer. Possible explanations for this phenomenon include diminished accuracy of the euploid diagnosis vs. a mechanical impact of the biopsy. Regardless of the cause, the outcomes emphasize the importance of obtaining appropriately sized trophectoderm biopsies for CCS.

SNP array-based analyses of unbalanced embryos as a reference to distinguish between balanced translocation carrier and normal blastocysts.

PURPOSE: The purpose of the study is to validate a method that provides the opportunity to distinguish a balanced translocation carrier embryo from a truly normal embryo in parallel with comprehensive chromosome screening (CCS). METHODS: A series of translocation carrier couples that underwent IVF with single nucleotide polymorphism (SNP) array-based CCS on 148 embryos were included. Predictions of balanced or normal status of each embryo were made based upon embryonic SNP genotypes. In one case, microdeletion status was used to designate whether embryos were balanced or normal. In 10 additional cases, conventional karyotyping was performed on newborns in order to establish the true genetic status (balanced or normal) of the original transferred embryo. Finally, implantation potential of balanced or normal embryos was compared. RESULTS: Phasing SNPs using unbalanced embryos allowed accurate prediction of whether transferred embryos were balanced translocation carriers or truly normal in all cases completed to date (100 % concordance with conventional karyotyping of newborns). No difference in implantation potential of balanced or normal embryos was observed. CONCLUSIONS: This study demonstrates the validity of a CCS method capable of distinguishing normal from balanced translocation carrier embryos. The only prerequisite is the availability of parental DNA and an unbalanced IVF embryo, making the method applicable to the majority of carrier couples. In addition, the SNP array platform allows simultaneous CCS for aneuploidy with the same platform and from the same biopsy. Future work will involve prospective predictions to select normal embryos with subsequent karyotyping of the resulting newborns.

Lymphovascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases?

OBJECTIVE: Lymphovascular space invasion (LVSI) is a poor prognostic indicator in uterine cancer, primarily due to its association with lymph node metastases. We sought to determine if LVSI provides any prognostic information for uterine cancer subjects in the absence of nodal disease. METHODS: A retrospective review was performed using a database of women treated for uterine cancer at MUSC from 2005 to 2012. Subjects with negative nodes after complete staging were identified. Multiple regression modeling was used to adjust for demographic and histopathologic covariates. The C-index was calculated for models of survival that included LVSI and those that did not. Competing risks analysis was conducted to examine factors associated with time to recurrence. RESULTS: Two hundred and five subjects were completely staged and had negative nodes, 24 with LVSI and 181 without. Factors significantly associated with survival included age, race, stage, grade, histology, and LVSI. Regression models for recurrence-free survival (RFS) and overall survival (OS) had similar C-indices regardless of whether LVSI was included. Competing risks analysis confirmed no significant difference in time to recurrence for subjects with LVSI compared to those without, after adjusting for other prognostic factors (P=0.53). CONCLUSIONS: LVSI is associated with shorter recurrence-free and overall survival in uterine cancer subjects with negative lymph nodes. However, after adjusting for other prognostic factors, LVSI status does not provide additional prognostic information. This finding suggests that recurrence-free and overall survival for uterine cancer patients with negative lymph nodes can be estimated without factoring in LVSI.