Insurance denials and diagnostic rates in a pediatric genomic research cohort.

PURPOSE: This study aimed to assess the amount and types of clinical genetic testing denied by insurance and the rate of diagnostic and candidate genetic findings identified through research in patients who faced insurance denials. METHODS: Analysis consisted of review of insurance denials in 801 patients enrolled in a pediatric genomic research repository with either no previous genetic testing or previous negative genetic testing result identified through cross-referencing with insurance prior-authorizations in patient medical records. Patients and denials were also categorized by type of insurance coverage. Diagnostic findings and candidate genetic findings in these groups were determined through review of our internal variant database and patient charts. RESULTS: Of the 801 patients analyzed, 147 had insurance prior-authorization denials on record (18.3%). Exome sequencing and microarray were the most frequently denied genetic tests. Private insurance was significantly more likely to deny testing than public insurance (odds ratio = 2.03 [95% CI = 1.38-2.99] P = .0003). Of the 147 patients with insurance denials, 53.7% had at least 1 diagnostic or candidate finding and 10.9% specifically had a clinically diagnostic finding. Fifty percent of patients with clinically diagnostic results had immediate medical management changes (5.4% of all patients experiencing denials). CONCLUSION: Many patients face a major barrier to genetic testing in the form of lack of insurance coverage. A number of these patients have clinically diagnostic findings with medical management implications that would not have been identified without access to research testing. These findings support re-evaluation of insurance carriers' coverage policies.

Survey assessing policies regarding patient age and provision of fertility treatment in the United States.

PURPOSE: To determine what policies exist regarding age and provision of fertility treatment in United States fertility clinics. METHODS: Medical directors of the Society for Assisted Reproductive Technology (SART) member clinics were surveyed regarding clinic demographics and current policies pertaining to age and provision of fertility treatment. Univariate comparisons were performed using Chi-square and Fisher exact tests as appropriate, with significance set at P ≤ 0.05. RESULTS: Of the 366 clinics surveyed, 18.9% (69/366) responded. A majority of clinics who responded 88.4% (61/69) reported having a policy regarding patient age and provision of fertility treatment. Responding clinics with an age policy did not differ from those without a policy on the basis of geographical location, (p = 0.5), insurance mandate status (p = 0.9), practice type (p = 0.4), or annual number of ART cycles (p = 0.7). Of all clinics who responded, 73.9% (51/69) had a maximum maternal age for autologous IVF, with a median of 45 years (range 42-54). Similarly, 79.7% (55/69) of responding clinics had a maximum maternal age for donor oocyte IVF, with a median of 52 years (range 48-56). Slightly under half, 43.4% (30/69) of responding clinics had a maximum maternal age for fertility treatment other than IVF (including ovulation induction or ovarian stimulation with or without IUI) with a median of 46 years (range 42-55). Of note, only 4.3% (3/69) of responding clinics had a policy with respect to maximum paternal age, with a median of 55 years (range 55-70). The most commonly cited reasons for having an age-limit policy were maternal risks of pregnancy, lower ART success rates, fetal/neonatal risks, and concerns about patients' ability to parent at an older age. More than half 56.5% (39/69) of responding clinics reported making exceptions to these policies, most commonly for patients who have pre-existing embryos. The majority of medical directors who responded to the survey believed there should be an ASRM guideline regarding maximum maternal age for autologous IVF 71% (49/69), donor oocyte IVF 78% (54/69) and other fertility treatments 62% (43/69). CONCLUSIONS: Most fertility clinics who responded to this national survey reported having a policy regarding maternal age (but not paternal age) and provision of fertility treatment. Policies were based on risk of maternal/fetal complications, lower success rates at older age, and concerns about patients' ability to parent at an older age. The majority of medical directors of responding clinics believed there should be an ASRM guideline regarding age and provision of fertility treatment.

The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women.

PURPOSE: As obesity becomes increasingly prevalent, its impact on fertility has been a subject of great debate. Nearly all prior research is retrospective and evaluates obesity utilizing body mass index (BMI), which may overestimate adiposity in individuals with a greater amount of lean muscle and underestimate adiposity in those with less muscle mass. METHODS: We prospectively evaluated 2013 couples undergoing infertility treatment with in vitro fertilization (IVF). Percent body fat (%BF) was measured by use of a bioelectric impedance analysis (BIA) scale at baseline. BMI was also determined. Ovarian reserve parameters, ovarian response to controlled ovarian hyperstimulation, and semen analyses were measured in correlation with their %BF and BMI. RESULTS: Females classified as obese based on %BF or BMI had lower serum FSH. However, when the analysis was limited to women without PCOS (n = 1706), obesity based on %BF or BMI was associated with lower serum AMH. Female obesity-regardless of a PCOS diagnosis-did not affect number of mature oocytes retrieved. Males who were in obese %BF category were found to have lower TMSC compared with normal weight counterparts (p < 0.05); however, the observed decrease was not significant enough to limit the success of assisted reproductive technologies. CONCLUSIONS: These findings suggest that while obesity may affect ovarian reserve in women variably depending on presence of PCOS, it does not affect number of mature oocytes available after COH. Similarly, while a high %BF in males is associated with lower TMSC, the observed difference is unlikely to affect IVF outcomes.

Three-dimensional ultrasound diagnosis of T-shaped uterus is associated with adverse pregnancy outcomes after embryo transfer.

RESEARCH QUESTION: Is T-shaped uterine cavity morphology associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst? DESIGN: In this secondary analysis of a prospective cohort study, 648 patients with three-dimensional ultrasound (3D-US) data obtained on the day before embryo transfer were categorized into three groups according to uterine cavity morphology: normal (n = 472), intermediate (n = 166) and T-shaped (n = 10). Quantitative uterine cavity dimensions were used to evaluate uterine cavity morphology. Pregnancy outcomes, including live birth, clinical miscarriage and ectopic pregnancy, were compared among the groups. RESULTS: The prevalence of a T-shaped uterus in this cohort was 1.5%. Uterine cavity morphology was strongly associated with the ratio of interostial distance and isthmic diameter (P < 0.01). Live birth rates were 66.5% for normal, 65.7% for intermediate and 40.0% for T-shaped cavity morphology. Women with a T-shaped uterus had an increased risk of clinical miscarriage (40.0% versus 7.0% for normal and 9.0% for intermediate cavity morphology, P < 0.01) and ectopic pregnancy (10.0% versus 1.1% for normal and 1.9% for intermediate cavity morphology, P = 0.05). When evaluating interostial distance and isthmic diameter ratio to determine pregnancy outcomes, a cut-off value of 2 was noted to have weak predictive value for live birth, but not clinical miscarriage or ectopic pregnancy. CONCLUSIONS: T-shaped uterine cavity morphology is associated with adverse pregnancy outcomes after transfer of a single thawed euploid blastocyst. Given the low prevalence of this condition, quantifying the magnitude of risk will require a larger cohort of patients.

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.

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.

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.

Comparing Attitudes About Genomic Privacy and Data Sharing in Adolescents and Parents of Children Enrolled in a Genomic Research Repository.

BACKGROUND: Sharing of genomic data aims to make efficient use of limited resources, which may be particularly valuable in rare disease research. Adult research participants and parents of pediatric research participants have shown support for data sharing with protections, but little is known about adolescent attitudes on genomic privacy and data sharing. METHODS: In-depth interviews were conducted with 10 adolescents and 18 parents of children enrolled in a pediatric genomic research repository. Interview transcripts were analyzed for themes on attitudes toward genomic privacy, restricted-access data sharing, and open-access data sharing. Findings in adolescent and parent participants were compared and contrasted. RESULTS: No adolescents endorsed privacy concerns for restricted-access data sharing. Both adolescents and parents saw value in data sharing for reaching the goals of research and discussed trust in institutions and researchers to protect their data and use it as intended. Adolescents were more likely than parents to accept open-access data sharing, including after risks were discussed. CONCLUSIONS: In this exploratory study, adolescents and parents enrolled in a genomic research repository shared many attitudes about genomic data sharing, but adolescents were less concerned about privacy and more agreeable toward open-access data sharing. Future research is needed to investigate this hypothesis in expanded populations and settings, and to clarify whether adolescent attitudes change with age and experiences.

A survey study evaluating donor gamete utilization rates, patient satisfaction and fertility treatment outcomes according to desired race and ethnicity.

OBJECTIVE: To evaluate donor gamete utilization, patient satisfaction, and fertility treatment outcomes of patients pursuing treatment with donor gametes stratified by the desired race and ethnicity of the gamete donor. DESIGN: Survey study SUBJECTS: Patients planning to undergo treatment using donor sperm and/or donor oocytes at a single academic fertility clinic in the Southeastern United States between 2015 and 2020. INTERVENTION OR EXPOSURE: None MAIN OUTCOME MEASURES: Utilization rates of donor gametes, satisfaction with donor gamete selection and fertility treatment outcomes stratified by race and ethnicity of patient, as well as that of their gamete donor. RESULTS: Four hundred fifty patients were eligible for inclusion and 170 (38%) responded to the survey. Amongst the respondents, 59% desired a non-Hispanic White gamete donor and 20% desired a non-Hispanic Black gamete donor. Patients seeking a non-Hispanic Black gamete donor had lower odds of utilizing donor gametes (OR = 0.13, 95% CI 0.04 - 0.40) compared to individuals seeking a non-Hispanic White gamete donor. When evaluating satisfaction with donor gamete selection, patients seeking a non-Hispanic Black gamete donor reported lower satisfaction compared to individuals seeking a non-Hispanic White gamete donor (OR 0.19, 95% CI [0.09-0.43]). When evaluating fertility outcomes, Non-Hispanic Black patients and those utilizing non-Hispaninc Black gamete donors were found to have a lower odds of successful conception compared to non-Hispanic White patients (OR=0.18, 95% CI 0.07-0.46) and individuals seeking non-Hispanic White gamete donors (OR=0.26, 95% CI 0.09-0.75), respectively. CONCLUSION: Patients seeking non-Hispanic Black donor gametes have lower utilization rates, less satisfaction with gamete donor selection, and lower odds of conception when compared to those seeking non-Hispanic White gamete donors. These findings highlight the need for more racial diversity within donor gamete banks, as well as within the donor pools available through agencies and fertility clinics.

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.

The Appraisal of Body Content (ABC) trial: Increased male or female adiposity does not significantly impact in vitro fertilization laboratory or clinical outcomes.

OBJECTIVE: To investigate the impact of obesity as determined by bioelectric impedance analysis (BIA) and body mass index (BMI) on in vitro fertilization (IVF) laboratory and clinical outcomes. DESIGN: Prospective cohort study. SETTING: Academic-affiliated private practice. PATIENT(S): A total of 1,889 infertile couples undergoing IVF from June 2016 to January 2019. INTERVENTION(S): Female patients and male partners underwent BIA and BMI measurement at the time of oocyte retrieval. Embryology and clinical outcomes were prospectively tracked with comparison groups determined by percentage of body fat (%BF) and BMI categories. MAIN OUTCOME MEASURE(S): Fertilization rate, blastocyst formation rate, euploidy rate, miscarriage rate, sustained implantation rate, live birth rate, rates of low birth weight/very low birth weight, prematurity rates. RESULT(S): Fertilization rates and euploidy rates were equivalent among all women. Blastocyst formation rates were slightly higher (55%) in women with an obese %BF compared with all other %BF categories (51%); however, this trend was not noted in women defined as obese by BMI. Miscarriage rates, sustained implantation rates, and live birth rates were equivalent among all women. The rate of very low birth weight was low but increased in obese women (3%) versus underweight, normal-weight, and overweight counterparts (0%-1.3%) as determined by %BF and BMI. Obesity in men did not significantly affect any embryologic or clinical outcomes. CONCLUSION(S): Although maternal obesity imposes a small but increased risk of very low birth weight infants, most embryology and pregnancy outcomes are equivalent to normal weight patients. Paternal obesity does not appear to affect IVF, pregnancy, or delivery outcomes.

Interpretation of noninvasive prenatal testing results following in vitro fertilization and preimplantation genetic testing for aneuploidy.

BACKGROUND: The positive predictive value of noninvasive prenatal testing is approximately 69% in the general population. However, positive predictive value is dependent on the prevalence of the disease in the population being tested. Patients who undergo in vitro fertilization with preimplantation genetic testing for aneuploidy and transfer a euploid embryo are presumably a lower risk population than the general population. OBJECTIVE: In this study, we explored the positive predictive value of noninvasive prenatal testing in women undergoing in vitro fertilization with preimplantation genetic testing for aneuploidy and subsequent transfer of a euploid embryo. STUDY DESIGN: This study was a retrospective cohort study. All patients who underwent in vitro fertilization with preimplantation genetic testing for aneuploidy followed by transfer of a single euploid embryo between 2014 and 2019 at a university-affiliated fertility center were contacted. Noninvasive prenatal testing results were reviewed and those with positive noninvasive prenatal testing were identified. Results of any subsequent prenatal or postnatal diagnostic testing were used to classify each positive noninvasive prenatal testing as a true positive or a false positive. The prevalence and positive predictive value of positive noninvasive prenatal testing was calculated. RESULTS: A total of 1139 patients that underwent noninvasive prenatal testing after transfer of a euploid embryo were identified, 8 of which had positive noninvasive prenatal testing screens. Although 6 of these patients had subsequent definitive prenatal diagnostic testing that revealed a euploid karyotype concordant with their preimplantation genetic testing for aneuploidy results, 1 patient opted out of diagnostic testing and later delivered a normal baby. Of note, 1 patient who had noninvasive prenatal testing positive for Turner syndrome underwent amniocentesis, which confirmed Turner mosaicism (45,X karyotype in 80% of cells). Therefore, the positive predictive value of noninvasive prenatal testing in this patient cohort was 12.5%. CONCLUSION: Clinicians and patients should recognize that patients undergoing transfer of a euploid embryo are at a relatively lower risk for fetal aneuploidy than the general population, and the positive predictive value of noninvasive prenatal testing is lower in this setting.

Consistency in rates of diagnosis of embryonic mosaicism, segmental abnormalities, and "no call" results among experienced embryologists performing preimplantation genetic testing for aneuploidy.

OBJECTIVE: To determine whether differences exist in rates of subchromosomal abnormalities, mosaicism, and "no call" results among embryologists performing and loading trophectoderm biopsies for preimplantation genetic testing for aneuploidy (PGT-A). DESIGN: Retrospective cohort. SETTING: Large infertility center. PATIENTS: All patients undergoing in vitro fertilization with PGT-A. INTERVENTIONS: The NexCCS next generation sequencing platform was used for PGT-A. The χ2 testing assessed differences in rates of primary outcomes between embryologists. Intraclass correlation coefficients evaluated inter-embryologist reliability in rates of abnormal and no call results. Median absolute performance difference (MAPD) scores, which quantify the impact of technical variation on analytical performance, were averaged for individual embryologists. Analysis of variance assessed differences in mean MAPD scores. MAIN OUTCOME MEASURES: Interoperator variability in rates of mosaic, segmental, and no call results. RESULTS: Four embryologists performed 30,899 biopsies and 6 embryologists loaded specimens into designated tubes. Among individuals performing trophectoderm sampling, rates of mosaicism were 4.3% to 6.1%, segmental errors were 9.0% to 10.7%, and inconclusive results were 1.1% to 2.9%. For those loading, the incidence of mosaicism was 4.2% to 5.9%, subchromosomal abnormalities was 9.7% to 10.4%, and no call results was 1.2% to 2.2%. The intraclass correlation coefficient was 0.978 for embryologists performing biopsies and 0.981 for those loading. Differences in mean MAPD scores were within 0.6% and 0.2% of each other for doing biopsies and loading embryologists, respectively. CONCLUSIONS: Rates of mosaicism, segmental, and no call PGT-A results are consistent among experienced embryologists. Due to the large sample size included, differences within 1% of the mean were deemed clinically irrelevant despite statistical significance.

A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia.

This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive azoospermia. All cases at a single center between 2012 and 2016 were included. Operative approach was selected at the surgeon's discretion and included microepididymal sperm aspiration or testicular sperm extraction. Blastocyst culture was exclusively utilized prior to transfer. The primary outcome was live birth rate. Secondary outcomes included fertilization rate, blastulation rate, euploidy rate, and implantation rate. A mixed effects model was performed. Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed. The live birth rate was equivalent (48.6% vs 50.5%, P = 0.77). However, on mixed effects model, epididymal sperm resulted in a greater likelihood of fertilization (adjusted OR: 1.37, 95% CI: 1.05-1.81, P = 0.02) and produced a higher blastulation rate (adjusted OR: 1.41, 95% CI: 1.1-1.85, P = 0.01). As a result, the epididymal sperm group had more supernumerary blastocysts available (4.3 vs 3, P < 0.05). The euploidy rate was no different. Pregnancy rates were no different through the first transfer cycle. However, intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient. Thus, the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort.

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.

The impact of contemporary preimplantation genetic screening and diagnosis on the detection of aneuploidy and inherited genetic diseases.

Pre-implantation genetic screening and diagnosis represent important tools for embryo selection in patients undergoing in vitro fertilization. Methods have evolved in recent years and it can be challenging to remain up to date on the current technology. This review article seeks to provide an overview of pre-implantation genetic screening and diagnosis methods, the associated clinical outcomes, and the limitations of this technology.

Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage.

OBJECTIVE: To determine if preimplantation genetic testing for aneuploidy (PGT-A) is cost-effective for patients undergoing in vitro fertilization (IVF). DESIGN: Decision analytic model comparing costs and clinical outcomes of two strategies: IVF with and without PGT-A. SETTING: Genetics laboratory. PATIENTS: Women ≤ 42 years of age undergoing IVF. INTERVENTION(S): Decision analytic model applied to the above patient population utilizing a combination of actual clinical data and assumptions from the literature regarding the outcomes of IVF with and without PGT-A. MAIN OUTCOME MEASURE(S): The primary outcome was cumulative IVF-related costs to achieve a live birth or exhaust the embryo cohort from a single oocyte retrieval. The secondary outcomes were time from retrieval to the embryo transfer resulting in live birth or completion of treatment, cumulative live birth rate, failed embryo transfers, and clinical losses. RESULTS: 8,998 patients from 74 IVF centers were included. For patients with greater than one embryo, the cost differential favored the use of PGT-A, ranging from $931-2411 and depending upon number of embryos screened. As expected, the cumulative live birth rate was equivalent for both groups once all embryos were exhausted. However, PGT-A reduced time in treatment by up to four months. In addition, patients undergoing PGT-A experienced fewer failed embryo transfers and clinical miscarriages. CONCLUSION: For patients with > 1 embryo, IVF with PGT-A reduces healthcare costs, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage when compared to IVF alone.

Celiac disease is not more prevalent in patients undergoing in vitro fertilization and does not affect reproductive outcomes with or without treatment: a large prospective cohort study.

OBJECTIVE: To study the prevalence of celiac disease in the infertile population undergoing in vitro fertilization (IVF) and assess outcomes. DESIGN: Prospective cohort study. SETTING: A single infertility center from January 2016 to March 2017. PATIENT(S): Women 18-45 years of age participating in IVF. INTERVENTION(S): Patients had serum tissue transglutaminase (tTG) and endomysial (EMA) IgA testing to screen for celiac disease and completed a 10-question "yes or no" survey to assess their medical history, previous testing, dietary habits, and pertinent symptoms. MAIN OUTCOME MEASURE(S): IVF cycle outcomes were compared between seronegative and seropositive patients. RESULT(S): Of 1,000 patients enrolled, 995 completed serologic screening and 968 underwent oocyte retrieval. Eighteen patients screened positive for both tTG and EMA (1.8%) and 10 additional patients (1.0%) screened positive for one of the two antibodies. The number of mature oocytes retrieved, fertilization rates, and blastulation rates were equivalent between seronegative and seropositive patients. There were 987 patients who completed the questionnaire (98.7%), and 84 reported being gluten free (8.5%). Those who reported being gluten free were no more likely to be antibody positive than the general population. Furthermore, a low-gluten diet was not associated with markers of ovarian reserve, oocytes retrieved, fertilization, blastulation, sustained implantation and pregnancy loss rates. CONCLUSION(S): The prevalence of seropositive celiac disease was consistent with that of the general population (2.8%). Patients who were seropositive for celiac disease-related antibodies had outcomes equivalent to seronegative patients, and patients with a gluten-free diet did not have improved outcomes.

Characterization of reproductive endocrinology and infertility (REI) fellowship applicants: guiding our mentees toward success.

BACKGROUND: Advanced subspecialty training in reproductive endocrinology and infertility (REI) entails a competitive application process with many data points considered. It is not known what components weigh more heavily for applicants. Thus, we sought to study the REI fellow applicant and compare 1) those who apply but do not receive an interview, 2) those who receive an interview but do not match, and 3) those who successfully match. METHODS: This retrospective cohort study was conducted at a single REI fellowship program from 2013 to 2017. Academic variables assessed included standardized test scores and total number of publications listed on their curriculum vitae. Logistic regression models were constructed to determine variables that were predictive of being offered an interview in our program and of matching in any program. RESULTS: There were 270 applicants, of which 102 were offered interviews. Interviewed applicants had significantly higher mean USMLE 1 and CREOG scores, as well as total publications and total abstracts. There was no difference in Step 2 and Step 3 scores or in number of book chapters. Of those interviewed, USMLE scores remained predictive of matching in any program; however, publications and scientific abstracts were no longer predictive. CONCLUSIONS: The decision to offer applicants interviews appears to be influenced by objective standardized test scores, as well as a threshold of academic productivity. These items are less predictive of matching once the interview process begins, indicating that other factors, such as performance during the interview day, may be more heavily weighted.