Racial-Ethnic Comparison of Treatment for Papillary Thyroid Cancer in the Military Health System.

PURPOSE: We aimed to compare Asian or Pacific Islander, Black, Hispanic, and non-Hispanic White patients in treatment for papillary thyroid cancer (PTC) in the equal access Military Health System to better understand racial-ethnic cancer health disparities observed in the United States. METHODS: We used the MilCanEpi database to identify a cohort of men and women aged 18 or older who were diagnosed with PTC between 1998 and 2014. Low- or high-risk status was assigned using tumor size and lymph node involvement. Treatment with surgery (e.g., thyroidectomy) overall and treatment by risk status [active surveillance (low-risk) or adjuvant radioactive iodine (RAI) (high-risk)] was compared between racial-ethnic groups using multivariable logistic regression and expressed as adjusted odds ratios (AOR) with 95% confidence intervals (CIs). RESULTS: The study included 598 Asian, 553 Black, 340 Hispanic, and 2958 non-Hispanic White patients with PTC. Asian (AOR = 1.21, 95% CI 0.98, 1.49), Black (AOR = 1.07, 95% CI 0.87, 1.32), and Hispanic (AOR = 0.92, 95% CI 0.71, 1.19) patients were as likely as White patients to receive surgery. By risk status, there were no significant racial-ethnic differences in receipt of active surveillance or thyroidectomy for low-risk PTC or in thyroidectomy or total thyroidectomy with adjuvant RAI for high-risk PTC. CONCLUSIONS: In the Military Health System, where patients have equal access to care, there were no overall racial-ethnic differences in surgical treatment for PTC. As American Thyroid Association guidelines evolve to include more conservative treatment, further research is warranted to understand potential disparities in active surveillance and surgical management in U.S. healthcare settings.

Importance of IGF-I levels in IVF: potential relevance for growth hormone (GH) supplementation.

PURPOSE: Growth hormone (GH) supplementation in association with in vitro fertilization (IVF) is worldwide again increasing, even though study outcomes have been discrepant. Since GH acts via insulin-like growth factor-1 (IGF-1), its utilization in IVF would only seem to make sense with low IGF-1. We, therefore, determined whether IGF-I levels affect IVF outcomes. METHODS: Retrospectively, 302 consecutive first fresh, non-donor IVF cycles were studied, excluding patients on GH supplementation. Patients were divided into 3 subgroups: IGF-1 in lower 25th percentile (group A, < 132 ng/mL, n = 64); 25th-75th percentile (B, 133-202 ng/mL, n = 164), and upper 25th percentile (C, > 202 ng/mL, n = 74). IGF-1 was tested immunochemiluminometric with normal range at 78-270 ng/mL. Because of the study patients' adverse selection and low pregnancy chances, the main outcome measure for the study was cycle cancellation. Secondary outcomes were oocyte numbers, embryos transferred, pregnancies, and live births. RESULTS: Group A was significantly older than B and C (P = 0.019). IGF-1 decreased with increasing age per year by 2.2 ± 0.65 ng/mL (P = 0.0007). FSH was best in group B and worst in A (trend, P = 0.085); AMH was best in B and worst in A (N.S.). Cycle cancellations were lowest in C (11.6%) and highest in A (25.0%; P = 0.042). This significance further improved with age adjustment (P = 0.021). Oocytes, embryo numbers, pregnancies, and live birth rates did not differ, though oocyte numbers trended highest in B. CONCLUSIONS: Here presented results support the hypothesis that IGF-1 levels affect IVF outcomes. GH treatments, therefore, may be effective only with low IGF-1.

Euploid miscarriage is associated with elevated serum C-reactive protein levels in infertile women: a pilot study.

PURPOSE: Increased serum C-protein (CRP) levels reduce fecundity in healthy eumenorrheic women with 1-2 pregnancy losses. Subclinical systemic inflammation may impede maternal immune tolerance toward the fetal semi-allograft, compromising implantation and early embryonic development. Some miscarriages with normal karyotypes could, therefore, be caused by inflammation. Whether pre-pregnancy CRP relates to karyotypes of spontaneously aborted products of conception (POCs) was investigated. METHODS: A study cohort of 100 infertile women with missed abortions who underwent vacuum aspirations followed by cytogenetic analysis of their products of conception tissue was evaluated at an academically affiliated fertility center. Since a normal female fetus cannot be differentiated from maternal cell contamination (MCC) in conventional chromosomal analyses, POC testing was performed by chromosomal microarray analysis. MCC cases and incomplete data were excluded. Associations of elevated CRP with first trimester pregnancy loss in the presence of a normal fetal karyotype were investigated. RESULTS: Mean patients' age was 39.9 ± 5.8 years; they demonstrated a BMI of 23.9 ± 4.6 kg/m2 and antiMullerian hormone (AMH) of 1.7 ± 2.4 ng/mL; 21.3% were parous, 19.1% reported no prior pregnancy losses, 36.2% 1-2 and 6.4% ≥ 3 losses. Karyotypes were normal in 34% and abnormal in 66%. Adjusted for BMI, women with elevated CRP were more likely to experience euploid pregnancy loss (p = 0.03). This relationship persisted when controlled for female age and AMH. CONCLUSIONS: Women with elevated CRP levels were more likely to experience first trimester miscarriage with normal fetal karyotype. This relationship suggests an association between subclinical inflammation and miscarriage.

Degree of mosaicism in trophectoderm does not predict pregnancy potential: a corrected analysis of pregnancy outcomes following transfer of mosaic embryos.

BACKGROUND: Preimplantation genetic screening (PGS) is increasingly utilized as an adjunct procedure to IVF. Recently healthy euploid live birth were reported following transfer of mosaic embryos. Several recent publications have surmised that the degree of trophectoderm (TE) mosaicism in transferred embryos is predictive of ongoing pregnancy and miscarriage rates. METHODS: This is a corrected analysis of previously published retrospective data on vitro fertilization (IVF) cycle outcomes involving replacement of 143 mosaic and 1045 euploid embryos tested by PGS, utilizing high-resolution next-generation sequencing (NGS) of TE and determination of percentages of mosaicism. Receiver operating curves (ROCs) and measurement of area under the curve (AUC) were used to evaluated the accuracy of the predictor variable, proportion of aneuploid cells in a TE biopsy specimen, with IVF outcomes, ongoing pregnancy and miscarriage rates. RESULTS: Confirming findings of the previously published report we also found higher ongoing pregnancy rates (63.3% vs. 39.2%) and lower miscarriage rates (10.2% vs. 24.3%) with euploid embryo transfers than with mosaic embryo transfer. There, however, were no significant differences in ongoing pregnancy or miscarriage rates among mosaic embryo transfers at any threshold of aneuploidy. Based on AUC, TE biopsies predicted ongoing pregnancy for euploid, as well as mosaic embryos, in a range of 0.50 to 0.59 and miscarriage in a range from 0.50 to 0.66 CONCLUSIONS: Degree of TE mosaicism was a poor predictor of ongoing pregnancy and miscarriage.

Older women using their own eggs? Issue framed with two oldest reported IVF pregnancies and a live birth.

RESEARCH QUESTION: What level of IVF pregnancy success is currently possible in women of extremely advanced age? DESIGN: This study reports on outcomes in women aged 43-51 years at the Centre for Human Reproduction, an academically affiliated private clinical fertility and research centre in New York City. RESULTS: During the study years of 2014-2016, 16 pregnancies were established, all through day 3 transfers. Based on 'intent to treat' (cycle start), clinical pregnancy rates were 4/190 (2.1%), 5/234 (2.1%) and 7/304 (2.3%) and live birth rates were 2/190 (1.1%), 1/234 (0.43%) and 4/304 (1.3%) in 2014, 2015 and 2016, respectively. With reference to embryo transfer, clinical pregnancy rates were 4/140 (2.9%), 5/159 (3.1%) and 7/167 (4.2%) and live birth rates were 2/140 (1.4%), 1/159 (0.63%) and 4/167 (2.4%) for the same years. The results for 2016 also included what are probably the two oldest autologous IVF pregnancies ever reported in the literature. These results were obtained with patient ages, percentage of cycle cancellations and other adverse outcome parameters steadily increasing year by year. CONCLUSIONS: Female age above 42 is widely viewed as the ultimate barrier to conception with IVF. Data reported here, although small and preliminary, demonstrate that potential outcomes are better than widely perceived, while pregnancy and live birth rates remain significantly inferior to donor egg recipient cycles. However, for selected women at very advanced ages, especially with higher egg/embryo numbers, autologous oocyte IVF offers a better option than widely acknowledged, if they are given individualized age-specific care.

Systematic review of worldwide trends in assisted reproductive technology 2004-2013.

BACKGROUND: Assisted Reproductive Technology (ART) has undergone considerable changes over the last decade, with consequences on ART outcomes in different regions of the world being unknown. METHODS: We conducted a systematic review of published national and regional ART registry data to assess how changes in clinical practice between 2004 and 2013 have impacted outcomes in Australia and New Zealand, Canada, Continental Europe, the United Kingdom (U.K.), Japan, Latin America, and the United States (U.S.). The data reflect 7,079,145 total ART cycles utilizing both fresh and previously cryopreserved embryos from autologous oocytes that resulted in 1,454,724 live births. This review focused on the following measures: ART cycle volume, use of cryopreserved embryos, single embryo transfer (SET), live birth rates in fresh and frozen-thawed cycles, and perinatal outcomes in recent years. RESULTS: SETs and utilization of frozen-thawed embryos increased worldwide over the study period. In 2012 SET utilization in all ART cycles was highest in Japan and Australia/New Zealand (82.6% and 76.3% respectively) and lowest in Latin America (16.0%). While gradual improvements in live birth rates were observed in most regions, some demonstrated declines. By 2012-2013, fresh cycle live birth rates were highest in the U.S. (29%) and lowest in Japan (5%). In Japan, the observed decline in fresh cycle live birth rate coincided with transition to minimal stimulation protocols, transfer of frozen-thawed rather than fresh embryos, and implementation of an SET policy. Similarly, implementation of an SET policy in parts of Canada was followed by a decline in fresh cycle live birth rate. Increasing live birth rates in frozen-thawed embryo cycles, seen all over the world, partially compensated for declines in fresh ART cycles. During 2012-2013 Australia/New Zealand and Japan reported the lowest multiple delivery rates of 5.6 and 4% respectively while the US had the highest of 27%. In recent years, preterm delivery rates in all regions ranged between 9.0 to 16.6% for singletons, 53.9 to 67.3% for twins, and 91.4 to 100% for triplets and higher order multiples. Inconsistencies in the way perinatal outcome data are presented by various registries, made comparison between regions difficult. CONCLUSIONS: ART practices are characterized by outcome differences between regions. International consensus on the definition of ART success, which accounts for perinatal outcomes, may help to standardize worldwide ART practice and improve outcomes. TRIAL REGISTRATION: PROSPERO ( CRD42016033011 ).

Effect of race and ethnicity on utilization and outcomes of assisted reproductive technology in the USA.

BACKGROUND: The purpose of this study was to determine the utilization and live birth rates of assisted reproductive technology (ART) modalities among various racial and ethnic groups in recent years. METHODS: We reviewed ART data reported to the Society for Assisted Reproductive Technologies Clinic Outcome Reporting System (SART CORS) for autologous ART and third-party ART (3ART) cycles which involved donor oocytes, sperm, embryos and gestational carrier, performed in the U.S. between 2004 and 2013. To gauge demand by various racial/ethnic groups for ART services, we examined fertility rates and demographics of the entire U.S. birth cohort over the same time interval. RESULTS: Of 1,132,844 autologous ART cycles 335,462 resulted in a live birth (29.6%). An additional, 217,030 3ART cycles resulted in 86,063 live births (39.7%). Hispanic and Black women demonstrated high fertility and lower utilization rates of autologous ART and 3ART. Caucasian and Asian women exhibited lower fertility rates and higher autologous ART and 3ART utilization. Autologous ART resulted in higher live birth rates among Caucasian and Hispanic women and lower rates among Asian and especially Black women. 3ART improved live birth rates in all races/ethnicities, though Black women experienced lower live birth rates with most modalities. Spontaneous abortion rates were higher among Black women following autologous ART and some 3ART modalities than those among Caucasian women. CONCLUSION: Utilization of ART is inversely related to fertility rates. Autologous ART produces lower live birth rates among Asian and Black women. 3ART results in relatively low live birth rates among Black women. TRIAL REGISTRATION: SART CORS #57 , Registered 5/14/2015.

Association of skewed X-chromosome inactivation with FMR1 CGG repeat length and anti-Mullerian hormone levels: a cohort study.

BACKGROUND: Premutation range CGGn repeats of the FMR1 gene denote risk toward primary ovarian insufficiency (POI), also called premature ovarian failure (POF). This prospective cohort study was undertaken to determine if X-chromosome inactivation skew (sXCI) is associated with variations in FMR1 CGG repeat length and, if so, is also associated with age adjusted antimüllerian hormone (AMH) levels as an indicator of functional ovarian reserve (FOR). METHODS: DNA samples of 58 women were analyzed for methylation status and confirmation of CGGn repeat length. Based on previously described FMR1 genotypes, there were 18 women with norm FMR1 (both alleles in range of CGG n=26-34), and 40 women who had at least one allele at CGGn<26 or CGG>34 ( not-norm FMR1). As part of a routine evaluation of ovarian reserve, patients at our fertility center have their serum AMH assessed at first visit. Regression models were used to test the association of ovarian reserve, as indicated by serum AMH, with sXCI. RESULTS: sXCI was significantly lower among infertility patients with norm FMR1 (6.5 ± 11.1, median and IQR) compared to those with not-norm FMR1 (12.0 ± 14.6, P = 0.005), though among young oocyte donors the opposite effect was observed. Women age >30 to 38 years old demonstrated greater ovarian reserve in the presence of lower sXCI as evidenced by significantly higher AMH levels (GLM sXCI_10%, f = 11.27; P = 0.004). CONCLUSIONS: Together these findings suggest that FMR1 CGG repeat length may have a role in determining X-chromosome inactivation which could represent a possible mechanism for previously observed association of low age adjusted ovarian reserve with FMR1 variations in repeat length. Further, larger, investigations will be required to test this hypothesis.

CDC-reported assisted reproductive technology live-birth rates may mislead the public.

The Centre for Disease Control and Prevention (CDC) publicly reports assisted reproductive technology live-birth rates (LBR) for each US fertility clinic under legal mandate. The 2014 CDC report excluded 35,406 of 184,527 (19.2%) autologous assisted reproductive technology cycles that involved embryo or oocyte banking from LBR calculations. This study calculated 2014 total clinic LBR for all patients utilizing autologous oocytes two ways: including all initiated assisted reproductive technology cycles or excluding banking cycles, as done by the CDC. The main limitation of this analysis is the CDC report did not differentiate between cycles involving long-term banking of embryos or oocytes for fertility preservation from cycles involving short-term embryo banking. Twenty-seven of 458 (6%) clinics reported over 40% of autologous cycles involved banking, collectively performing 12% of all US assisted reproductive technology cycles. LBR in these outlier clinics calculated by the CDC method, was higher than the other 94% of clinics (33.1% versus 31.1%). However, recalculated LBR including banking cycles in the outlier clinics was lower than the other 94% of clinics (15.5% versus 26.6%). LBR calculated by the two methods increasingly diverged based on proportion of banking cycles performed by each clinic reaching 4.5-fold, thereby, potentially misleading the public.

Impact of preimplantation genetic screening on donor oocyte-recipient cycles in the United States.

OBJECTIVE: Our objective was to estimate the contribution of preimplantation genetic screening to in vitro fertilization pregnancy outcomes in donor oocyte-recipient cycles. STUDY DESIGN: This was a retrospective cross-sectional study of US national data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2005 and 2013. Society for Assisted Reproductive Technology Clinic Outcome Reporting relies on voluntarily annual reports by more than 90% of US in vitro fertilization centers. We evaluated pregnancy and live birth rates in donor oocyte-recipient cycles after the first embryo transfer with day 5/6 embryos. Statistical models, adjusted for patient and donor ages, number of embryos transferred, race, infertility diagnosis, and cycle year were created to compare live birth rates in 392 preimplantation genetic screening and 20,616 control cycles. RESULTS: Overall, pregnancy and live birth rates were significantly lower in preimplantation genetic screening cycles than in control cycles. Adjusted odds of live birth for preimplantation genetic screening cycles were reduced by 35% (odds ratio, 0.65, 95% confidence interval, 0.53-0.80; P < .001). CONCLUSION: Preimplantation genetic screening, as practiced in donor oocyte-recipient cycles over the past 9 years, has not been associated with improved odds of live birth or reduction in miscarriage rates.

Utilization of third-party in vitro fertilization in the United States.

BACKGROUND: The use of in vitro fertilization that includes third-party in vitro fertilization is increasing. However, the relative contribution of third-party in vitro fertilization that includes the use of donor oocytes, sperm, or embryo and a gestational carrier to the birth cohort after in vitro fertilization is unknown. OBJECTIVE: The purpose of this study was to examine the contribution of third-party in vitro fertilization to the in vitro fertilization birth cohort over the past decade. STUDY DESIGN: This retrospective analysis investigated 1,349,874 in vitro fertilization cycles that resulted in 421,525 live births and 549,367 liveborn infants in the United States from 2004-2013. Cycles were self-reported by fertility centers to a national registry: Society for Assisted Reproductive Technologies Clinic Outcome Reporting System. RESULTS: Third-party in vitro fertilization accounted for 217,030 (16.1%) of all in vitro fertilization cycles, 86,063 (20.4%) of all live births, and 115,024 (20.9%) of all liveborn infants. Overall, 39.7% of third-party in vitro fertilization cycles resulted in a live birth, compared with 29.6% of autologous in vitro fertilization cycles. Use of third-party in vitro fertilization increased with maternal age and accounted for 42.2% of all in vitro fertilization cycles and 75.3% of all liveborn infants among women >40 years old. Oocyte donation was the most common third-party in vitro fertilization technique, followed by sperm donation. Over the study period, annual cycle volume and live birth rates gradually increased for both autologous in vitro fertilization and third-party in vitro fertilization (P<.0001 for all). Live birth rates were the highest when multiple third-party in vitro fertilization modalities were used, followed by oocyte donation. CONCLUSION: Third-party in vitro fertilization use and efficacy have increased over the past decade, now comprising >20% of the total in vitro fertilization birth cohort. In women who are >40 years old, third-party in vitro fertilization has become the dominant treatment.

Definition by FSH, AMH and embryo numbers of good-, intermediate- and poor-prognosis patients suggests previously unknown IVF outcome-determining factor associated with AMH.

BACKGROUND: Though outcome models have been proposed previously, it is unknown whether cutoffs in clinical pregnancy and live birth rates at all ages are able to classify in vitro fertilization (IVF) patients into good-, intermediate- and poor prognosis. METHODS: We here in 3 infertile patient cohorts, involving 1247, 1514 and 632 women, built logistic regression models based on 3 functional ovarian reserve (FOR) parameters, including (1) number of good quality embryos, (2) follicle stimulating hormone (FSH, mIU/mL) and (3) anti-Müllerian hormone (AMH, ng/mL), determining whether clinical pregnancy and live birth rates can discriminate between good, intermediate and poor prognosis patients. RESULTS: All models, indeed, allowed at all ages for separation by prognosis, though cut offs changed with age. In the embryo model, increasing embryo production resulted in linear improvement of IVF outcomes despite transfer of similar embryo numbers; in the FSH model outcomes and FSH levels related inversely, while the association of AMH followed a bell-shaped polynomial pattern, demonstrating "best" outcomes at mid-ranges. All 3 models demonstrated increasingly poor outcomes with advancing ages, though "best" AMH even above age 43 was still associated with unexpectedly good pregnancy and delivery outcomes. Excessively high AMH, in contrast, was at all ages associated with spiking miscarriage rates. CONCLUSIONS: At varying peripheral serum concentrations, AMH, thus, demonstrates hithero unknown and contradictory effects on IVF outcomes, deserving at different concentrations investigation as a potential therapeutic agent, with pregnancy-supporting and pregnancy-interrupting properties.

What affects functional ovarian reserve, thyroid function or thyroid autoimmunity?

BACKGROUND: Thyroid dysfunction is the most common autoimmune endocrine disorder in women of reproductive age, and is associated with menstrual irregularities, anovulation and infertility. Whether it is thyroid function or thyroid autoimmunity that affects functional ovarian reserve (FOR, i.e., the small growing ovarian follicle pool) reflected in anti-Müllerian hormone (AMH) has, however, remained under dispute. METHODS: We investigated in 225 infertile women whether thyroid function, after adjustment for thyroid autoimmunity, affects FOR within what is considered normal thyroid function (TSH, 0.4-4.5µIU/mL) by assessing AMH levels in reference to TSH levels, stratified for TSH < or ≥3.0µIU/mL. Thyroid autoimmunity was defined by presence of anti-thyroid peroxidase, -thyroglobulin and/or -thyroid receptor antibodies. RESULTS: Mean age of studied women was 38.4 ± 5.0 years; their mean AMH was 1.3 ± 2.0 ng/mL and mean TSH 1.8 ± 0.9 µIU/mL. Thyroid autoimmunity was present in 11.1 % of patients. Women with TSH <3.0µIU/mL presented with significantly higher AMH compared to those with TSH ≥3.0µIU/Ml (P = 0.03). This difference remained significant after adjustment for thyroid autoimmunity as well as age (P = 0.02). CONCLUSIONS: Even after adjustment for thyroid autoimmunity and age, TSH <3.0µIU/mL in euthyroid infertility patients is associated with significantly better FOR (higher AMH) than TSH ≥3.0µIU/mL. This observation suggests a direct beneficial effect of lower TSH levels on follicular recruitment, and warrants investigations of thyroxin supplementation in infertile women with TSH levels ≥3.0µIU/mL in attempts to improve FOR.

Different effectiveness of closed embryo culture system with time-lapse imaging (EmbryoScope(TM)) in comparison to standard manual embryology in good and poor prognosis patients: a prospectively randomized pilot study.

BACKGROUND: Previously manual human embryology in many in vitro fertilization (IVF) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging. Whether such systems perform comparably to manual embryology in different IVF patient populations has, however, never before been investigated. We, therefore, prospectively compared embryo quality following closed system culture with time-lapse photography (EmbryoScope™) and standard embryology. We performed a two-part prospectively randomized study in IVF (clinical trial # NCT92256309). Part A involved 31 infertile poor prognosis patients prospectively randomized to EmbryoScope™ and standard embryology. Part B involved embryos from 17 egg donor-recipient cycles resulting in large egg/embryo numbers, thus permitting prospectively alternative embryo assignments to EmbryoScope™ and standard embryology. We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo. RESULTS: Part A revealed in poor prognosis patients no differences in day-3 embryo scores, implantation and clinical pregnancy rates between EmbryoScope™ and standard embryology. The EmbryoScope™, however, more than doubled embryology staff time (P < 0.0001). In Part B, embryos grown in the EmbyoScope™ demonstrated significantly poorer day-3 quality (depending on embryo parameter between P = 0.005 and P = 0.01). Suspicion that conical culture dishes of the EmbryoScope™ (EmbryoSlide™) may be the cause was disproven when standard culture dishes demonstrated no outcome difference in standard incubation. CONCLUSIONS: Though due to small patient numbers preliminary, this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology. Appropriately designed and powered prospectively randomized studies appear urgently needed in well-defined patient populations before the uncontrolled utilization of these instruments further expands. TRIAL REGISTRATION: NCT02246309 Registered September 18, 2014.

IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred.

Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (≥2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (<1500 g) or severe prematurity (birth at <32 weeks gestation). Each neonate was analysed as a separate outcome. A total of 713 IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor-prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis.

Characteristics Associated With Survival in Surgically Nonresected Pancreatic Adenocarcinoma in the Military Health System.

OBJECTIVES: Pancreatic cancer is often diagnosed at advanced stages with high-case fatality. Many tumors are not surgically resectable. We aimed to identify features associated with survival in patients with surgically nonresected pancreatic cancer in the Military Health System. METHODS: We used the Military Cancer Epidemiology database to identify the Department of Defense beneficiaries aged 18 and older diagnosed with a primary pancreatic adenocarcinoma between January 1998 and December 2014 who did not receive oncologic surgery as treatment. We used Cox Proportional Hazard regression with stepwise procedures to select the sociodemographic and clinical characteristics related to 2-year overall survival, expressed as adjusted hazard ratios (aHR) and 95% CIs. RESULTS: Among 1148 patients with surgically nonresected pancreatic cancer, sex, race-ethnicity, marital status, and socioeconomic indicators were not selected in association with survival. A higher comorbidity count (aHR 1.30, 95% CI: 1.06-1.59 for 5 vs. 0), jaundice at diagnosis (aHR 1.57, 95% CI: 1.33-1.85 vs. no), tumor grade G3 or G4 (aHR 1.32, 95% CI: 1.05-1.67 vs. G1/G2), tumor location in pancreas tail (aHR 1.49, 95% CI: 1.22-1.83 vs. head) or body (aHR 1.30, 95% CI: 1.04-1.62 vs. head), and metastases were associated with survival. Patients receiving chemotherapy (aHR 0.66, 95% CI: 0.57-0.76) had better survival compared with no treatment. CONCLUSIONS: In a comprehensive health system, sociodemographic characteristics were not related to survival in surgically nonresected pancreatic cancer. This implicates access to care in reducing survival disparities in advanced pancreatic cancer and emphasizes the importance of treating patients based on clinical features.

Treatment of pancreatic adenocarcinoma in relation to survival in the U.S. Military Health System.

BACKGROUND: Pancreatic cancer has a high case fatality and relatively short survival after diagnosis. Treatment is paramount to improving survival, but studies on the effects of standard treatment by surgery or chemotherapy on survival in U.S. healthcare settings is limited. Further, variability in access to care may impact treatment and outcomes for patients. We aimed to assess the relationship between standard treatment(s) and survival of pancreatic adenocarcinoma in a population with access to comprehensive healthcare. METHODS: We used the Military Cancer Epidemiology (MilCanEpi) database, which includes data from the Department of Defense cancer registry and medical encounter data from the Military Health System (MHS), to study a cohort of 1408 men and women who were diagnosed with pancreatic adenocarcinoma between 1998 and 2014. Treatment with surgery or chemotherapy in relation to overall survival was examined in multivariable time-dependent Cox regression models. RESULTS: Overall, 75 % of 441 patients with early-stage and 51 % of 967 patients with late-stage pancreatic adenocarcinoma received treatment. In early-stage disease, surgery alone or surgery with chemotherapy were both associated with statistically significant 52 % reduced risks of death, but chemotherapy alone was not. In late-stage disease, surgery alone, chemotherapy alone, or both surgery and chemotherapy significantly reduced the risk of death by 42 %, 25 %, and 52 %, respectively. CONCLUSIONS: Our findings from the MHS demonstrate improved survival after treatment with surgery or surgery with chemotherapy for early- or late-stage pancreatic cancer and after chemotherapy for late-stage pancreatic cancer. In the era of immunotherapy and personalized medicine, further research on treatment and survival of pancreatic cancer in observational settings is needed.

Survival Among Patients With Multiple Myeloma in the United States Military Health System Compared to the Surveillance, Epidemiology, and End Results (SEER) Program.

BACKGROUND: Access to health care is an important factor affecting survival of patients with multiple myeloma (MM) in the U.S. general population. The U.S. Military Health System (MHS) provides universal health care to beneficiaries and has been associated with improved survival across multiple malignancies. In this study, we compared survival of MHS beneficiaries with MM with MM patients from the U.S. general population. MATERIALS AND METHODS: The Department of Defense's Automated Central Tumor Registry (ACTUR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to extract data for MM patients from MHS and the U.S. general population, respectively. Patients had histologically confirmed MM between 1987 and 2013 and were followed through 2015 for overall survival. Two SEER patients were matched to each ACTUR patient by age group, sex, race, and diagnosis year group. Five and 10-year survival was compared between ACTUR and SEER patients to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) with adjustment for potential confounders. RESULTS: Median survival of the ACTUR patients was 47.1 months (95% CI: 43.9-50.4) compared to 33.0 months (95% CI, 32.0-35.0) of the SEER patients. Five and 10-year death rates were significantly lower for ACTUR patients than the SEER patients with an adjusted HR of 0.74 (95% CI, 0.68-0.81) and 0.79 (95% CI, 0.74-0.85), respectively. The survival advantage of ACTUR patients was preserved when stratified by age, sex, race, and diagnosis year. CONCLUSION: MHS beneficiaries with MM had improved overall survival compared to MM patients from the U.S. general population.

The utility of all-freeze IVF cycles depends on the composition of study populations.

BACKGROUND: Because often introduced without proper validation studies, so-called "add-ons" to IVF have adversely affected in vitro fertilization (IVF) outcomes worldwide. All-freeze cycles (embryo banking, EB) with subsequently deferred thaw cycles are such an "add-on" and, because of greatly diverging reported outcomes, have become increasingly controversial. Based on "modeling" with selected patient populations, we in this study investigated whether reported outcome discrepancies may be the consequence of biased patient selection. RESULTS: In four distinct retrospective case control studies, we modeled in four cohort pairings how cryopreservation with subsequent thaw cycles affects outcomes differently in good-, average- and poor-prognosis patients: (i) 127 fresh vs. 193 frozen donor-recipient cycles to model best-prognosis patients; (ii) 741 autologous fresh non-donor IVF cycles vs. 217 autologous frozen non-donor IVF cycles to model average prognosis patients; (iii) 143 favorably selected autologous non-donor IVF cycles vs. the same 217 frozen autologous cycles non-donor to monitor good- vs. average-prognosis patients; and (iv) 598 average and poor-prognosis autologous non-donor cycles vs. the same 217 frozen autologous non-donor cycles to model poor vs. average prognosis patients. In best-prognosis patients, EB marginally improved IVF outcomes. In unselected patients, EB had no effects. In poor-prognosis patients, EB adversely affected IVF outcomes. Unexpectedly, the study also discovered independent-of-age-associated chromosomal abnormalities, a previously unreported effect of recipient age on miscarriage risk in donor-egg recipients. CONCLUSIONS: In poor-prognosis patients, EB cycles should be considered contraindicated. In intermediate-prognosis patients EB does not appear to change outcomes, not warranting additional cost and time delays. Therefore, only good-prognosis patients are candidates for EB, though they will experience only marginal benefits that may not be cost-effective.

Nondisparate Survival of Non-Hispanic Black Women With Breast Cancer Despite Less Favorable Pathology: Effect of Access to and Provision of Care Within a Military Health Care System.

Introduction: Breast cancer mortality rates are 40% higher in non-Hispanic Blacks (NHBs) than in non-Hispanic White (NHWs) in the United States. All women treated within the Murtha Cancer Center at Walter Reed National Military Medical Center (MCC/WRNMMC) have health insurance and are provided multidisciplinary health care. Pathological factors and outcomes of NHBs and NHWs treated within the MCC/WRNMMC were evaluated to determine whether equal-access health care reduces disparate phenotypes and survival between the racial groups. Methods: Between 2001 and 2018, 368 NHB and 819 NHW women were diagnosed with breast cancer at MCC/WRNMMC. Differences between NHBs and NHWs in epidemiological and pathological characteristics were evaluated. Overall and breast cancer-specific 5- and 10-year survival rates were compared between races. Results: Compared with NHWs, NHBs were significantly more likely to have a body mass index ≥30 kg/m2, to be unmarried, to have tumors of higher grade, later stage, with lymph node metastases, and to be hormone receptor negative (HR-)/human epidermal growth factor receptor 2 positive (HER2+) or triple negative. After adjustment for demographic factors, NHBs remained significantly more likely to have tumors diagnosed at a higher grade and later stage, and to be HR-/HER2+ or triple negative. Neither 5- nor 10-year overall or breast cancer-specific survival differed significantly between the racial groups after adjusting for demographic and pathological variables. Discussion: Despite having tumors with less favorable pathological characteristics, overall and disease-free survival disparities were not observed for NHBs treated at MCC/WRNMMC. These data suggest that survival disparities of NHBs with breast cancer can be diminished with provision of quality care.