Azacitidine Post-transplant Maintenance Improves Disease Progression in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome.

BACKGROUND: Maintenance after allogeneic hematopoietic cell transplantation (alloHCT) with hypomethylating agents has yielded conflicting results. MATERIALS AND METHODS: We conducted a single center retrospective matched-control analysis with the study group (5-azacitidine [AZA] group) including adults with FLT3-negative acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received post-transplant AZA maintenance off clinical trial (n = 93). A matched control group was comprised of contemporaneous AML/MDS patients who did not receive any maintenance (n = 357). Primary endpoint was disease progression. RESULTS: The AZA and control groups had comparable patient and disease characteristics except for older age (median: 61 vs. 57 years, P = .01) and lower hematopoietic comorbidity index (median: 2 vs. 3, P = .04) in the AZA group. The 3-year cumulative incidence of progression in the AZA and control groups was 29% vs. 33% (P = .09). The protective effect of AZA on progression was limited to patients with high-risk AML/MDS (HR = 0.4, 95% CI = 0.2-0.8, P = .009). This led to improved progression-free survival both in high-risk AML and MDS patients with maintenance (HR = 0.2, 95% CI = 0.1-0.6, P = .004 and HR = 0.4, 95% CI = 0.2-0.9, P = .04). CONCLUSION: AZA maintenance was associated with a lower progression rate in patients with high-risk FLT3-negative AML or MDS, and AZA maintenance should be considered for post-alloHCT maintenance in this subset.

Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy and the role of advanced practice providers and pharmacists.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts. Collaborative practice model for monitoring and care of HSCT-TMA. Advanced practice providers and pharmacists contribute to many aspects of patient care in transplant centers, including medication management for complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives. HSCT-TMA is a severe and potentially life-threatening complication that is often underdiagnosed. The collaboration of a multidisciplinary team of advanced practice providers, pharmacists, and physicians can optimize recognition, diagnosis, management, and monitoring of patients with HSCT-TMA, thereby improving outcomes for these patients.

Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era.

Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy-based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.

Transitioning tacrolimus to sirolimus in allogeneic hematopoietic cell transplantation.

OBJECTIVES: Calcineurin inhibitor (CNI) use for acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT) recipients has been associated with toxicities. Toxicities may be managed by converting CNI to sirolimus as often done in solid organ transplantation. This study aimed to characterize allo-HCT patients who completely transitioned from tacrolimus to sirolimus and evaluate the incidence of aGVHD within 100 days post-transition, overall survival (OS), and incidence of relapse. METHODS: Safety and efficacy data were collected at baseline and at day 30 and 90 post-transition from tacrolimus to sirolimus and at one-year post-HCT. RESULTS: Most patients who transitioned had acute leukemia, received a matched unrelated donor allo-HCT, and transitioned due to nephrotoxicity or neurotoxicity. The resolution rate was 83% and 48% in the nephrotoxicity group, 78% and 61% in the neurotoxicity group, 33% and 33% in the group that developed both nephrotoxicity and transplant-associated thrombotic microangiopathy at 30 and 90 days of assessments, respectively. Patients who transitioned before day 55 post-allo-HCT were more likely to develop new or worsening aGVHD. The one-year OS and relapse rates were 37% and 20%, respectively. CONCLUSIONS: The conversion from tacrolimus to sirolimus demonstrates promising resolution of acute toxicities; however, overall mortality remains high.

Approaching treatment of transplant-associated thrombotic Microangiopathy from two directions with Eculizumab and transitioning from Tacrolimus to Sirolimus.

BACKGROUND: In the past, conventional treatment strategies for transplant-associated thrombotic microangiopathy (TA-TMA) have not proven to be very effective. Recently, eculizumab which is a humanized monoclonal antibody that works as a terminal complement inhibitor has demonstrated promise in the treatment landscape of TA-TMA. METHODS AND MATERIALS: This was a single-center retrospective analysis of 20 consecutive adult patients with TA-TMA: 10 patients who received conventional therapy and 10 patients who received eculizumab-based therapy. These patients had undergone allogeneic HSCT at MD Anderson Cancer Center between August 2011 and September 2016. RESULTS: When comparing the treatment outcomes in the two cohorts, none of the patients in the conventional therapy group obtained a hematologic or complete response according to our response criteria whereas seven patients in the eculizumab group achieved a hematologic response with one patient achieving a complete response with organ recovery. In addition, overall survival at the end of assessment was 60% in the eculizumab cohort and 30% in the conventional cohort. One major difference in practice at our institution versus previously published studies is the management of immunosuppression. In a majority of patients, tacrolimus was continued or transitioned to sirolimus for GVHD prophylaxis. CONCLUSION: Response rates and survival were improved for patients who were transitioned to sirolimus, so a two-pronged approach of inhibiting complement along with providing an alternative effective immunosuppressive agent may be beneficial in the treatment of early onset TA-TMA.

Role of nuclear factor-kappa B in feline injection site sarcoma.

BACKGROUND: Chronic inflammation has been implicated in sarcomagenesis. Among various factors, activation of nuclear factor-kappa B (NF-κB) signaling pathway has been documented being able to target genes associated with tumor progression and up-regulate the expression of tumor-promoting cytokines and survival genes in several human solid tumors. Feline injection sites sarcomas (FISS) are malignant entities derived from the mesenchymal origin. The disease has been considered to be associated with vaccine adjuvant, aluminum, which serves as a stimulus continuously inducing overzealous inflammatory and immunologic reactions. To understand the contribution of NF-κB in FISS, detection of activated NF-κB in paraffin-embedded specimens, in vitro establishment of primary cells derived from FISS, and evaluation of the effects of the NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on primary tumor cells were conducted. RESULTS: In this study, nuclear expression of NF-κB p65 was detected in 83.3% of FISS cases and not correlated with tumor grading, sex, and age. Primary cells derived from FISS in three cats exhibiting same immunohistochemical characteristics as their original tumor were successfully established. The NF-κB inhibitor, DHMEQ, was able to prevent nuclear translocation of NF-κB p65, inhibit cell proliferation, migration, and colonization in dosage-dependent manners, and induce cell apoptosis in these primary FISS cells. CONCLUSIONS: High expression rate of nuclear NF-κB p65 in FISS cases and dose-dependent inhibitory effects on the growth of FISS primary cells treated with NF-κB inhibitor suggested that NF-κB might be a potential molecular therapeutic target for FISS.

Characterization of Viral Infections after Antithymocyte Globulin-Based Conditioning in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Antithymocyte globulin (ATG) has been shown to reduce the incidence of graft-versus-host-disease (GVHD) after matched related donor (MRD) and matched unrelated donor (MUD) hematopoietic stem cell transplantation (HCT); however, because of increased risks of infection and relapse, this use has not translated into a significant improvement in post-transplant survival. The goal of this single-center, retrospective cohort analysis was to quantify the incidence of viral reactivation and viral end-organ disease (EOD) within the first 100 days after MUD HCT with ATG-based conditioning compared with MRD HCT without ATG. Fifty-nine adult patients underwent ATG-based MUD HCT compared with 64 patients receiving MRD HCT without ATG. Cytomegalovirus reactivation was the most frequent event in both groups (65% MUD versus 61% MRD), followed by BK virus reactivation (26% versus 24%) and Epstein-Barr virus reactivation (20% versus 9%). A higher percentage of MUD patients experienced viral EOD by day +100 when compared with MRD patients (34% versus 16%, P = .022). This was most notable for EOD involving BK virus (15% versus 6%, P = .14) and Epstein-Barr virus (7% versus 0%, P = .050). Correspondingly, more patients in the MUD group experienced virus-related complications, including hospitalization (24% versus 3%, P < .001), intensive care unit admission (10% versus 6%, P = .19), and mortality (8% versus 4%, P = .44). There were no significant differences in either relapse-free survival (RFS; 62% versus 78%, P = .07) or overall survival (OS; 72% versus 86%, P = .07) at 6 months post-HCT. However, when using the final time point of 21 months in the MUD/ATG group and 23 months in the MRD/no ATG group, MUD patients who received ATG had inferior survival (OS: 27% versus 77%, P = .009; RFS: 40% versus 59%, P = .042). Our results add to and further quantify the infectious risks associated with the use of ATG in MUD transplants and promote the implementation of more intensive preemptive viral monitoring practices in patients receiving ATG-based MUD transplants.

Levofloxacin versus Cefpodoxime for Antibacterial Prophylaxis in Allogeneic Stem Cell Transplantation.

National guidelines recommend antimicrobial prophylaxis for allogeneic stem cell transplant patients during the pre-engraftment period because of increased infection risk during neutropenia. Fluoroquinolones have demonstrated lower rates of bacteremias and incidence of neutropenic fever, but there is limited evidence in the use of alternative antibacterials such as cefpodoxime. The primary objective of this study is to compare the rates of antibiotic prophylaxis failure between levofloxacin and cefpodoxime in allogeneic stem cell transplant recipients. Secondary objectives include comparing and characterizing number and type of infections, mortality at day 100 post-transplant, and hospitalizations for infectious causes in the first 100 days of transplant. This is a single-center, retrospective chart review of adult patients who received an allogeneic stem cell transplant from matched related and matched unrelated donors and antibacterial prophylaxis with levofloxacin or cefpodoxime from January 1, 2011, to October 1, 2014. A total of 142 patients were evaluated (71 levofloxacin, 71 cefpodoxime). Both levofloxacin and cefpodoxime groups had similar rates of neutropenic fever and antibiotic prophylaxis failure (58% versus 58%, P = NS). There were similar incidences of Clostridioides difficile and Multi-drug resistant (MDR) infections among both levofloxacin and cefpodoxime groups. Rates of infections, hospitalizations, and mortality in the first 100 days were similar among both groups. Cefpodoxime can be used as an alternative to levofloxacin for antibiotic prophylaxis in allogeneic stem cell transplant patients.

A Mitochondrial Progesterone Receptor Increases Cardiac Beta-Oxidation and Remodeling.

Progesterone is primarily a pregnancy-related hormone, produced in substantial quantities after ovulation and during gestation. Traditionally known to function via nuclear receptors for transcriptional regulation, there is also evidence of nonnuclear action. A previously identified mitochondrial progesterone receptor (PR-M) increases cellular respiration in cell models. In these studies, we demonstrated that expression of PR-M in rat H9c2 cardiomyocytes resulted in a ligand-dependent increase in oxidative cellular respiration and beta-oxidation. Cardiac expression in a TET-On transgenic mouse resulted in gene expression of myofibril proteins for remodeling and proteins involved in oxidative phosphorylation and fatty acid metabolism. In a model of increased afterload from constant transverse aortic constriction, mice expressing PR-M showed a ligand-dependent preservation of cardiac function. From these observations, we propose that PR-M is responsible for progesterone-induced increases in cellular energy production and cardiac remodeling to meet the physiological demands of pregnancy.

Leflunomide therapy for refractory cytomegalovirus infections in hematopoietic stem cell transplant recipients.

BACKGROUND: Currently, there are no prospective, randomized trials analyzing leflunomide for the treatment of cytomegalovirus infection or disease in allogeneic stem cell transplant patients. OBJECTIVE: The primary objective of this case series was to determine the clinical and virological responses of utilizing leflunomide as therapy for refractory cytomegalovirus infections, unresponsive to first-line therapy in allogeneic stem cell transplant patients. Additionally, patient and leflunomide specific characteristics were identified and determined in this descriptive case series. METHODS: This is a single-center, case series of adult allogeneic stem cell transplant patients with refractory cytomegalovirus infections receiving leflunomide between 1 January 2005 and 31 March 2015. RESULTS: A total of 14 patients with refractory cytomegalovirus infections received leflunomide. All patients received concurrent anti-cytomegalovirus therapy. Nine of 13 patients tested positive for phosphotransferase UL97 and/or viral DNA polymerase UL54 genotype mutations. Nine patients achieved a virological response with undetectable cytomegalovirus titers. Of the 13 patients with teriflunomide serum levels, eight patients maintained levels >40 micrograms/milliliter (mcg/mL). Common adverse effects were pancytopenia (n = 8) and elevated liver function tests (n = 4). CONCLUSIONS: Despite current strategies, refractory or recurrent cytomegalovirus infection and disease remain a clinical challenge to treat in the stem cell transplant patient population. Leflunomide used in combination with other concomitant therapies use for refractory cytomegalovirus infection in clinical practice may be a safe and effective option in the allogeneic stem cell transplant patient population.

Eculizumab for transplant-associated thrombotic microangiopathy in adult allogeneic stem cell transplant recipients.

OBJECTIVE: To evaluate response rates and survival in adults with transplant-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (HSCT) who were treated with eculizumab (ECU). METHODS: Patients were identified retrospectively and data collected through HSCT and pharmacy databases. RESULTS: Ten patients with TA-TMA after allogeneic HSCT were treated with ECU between 2013 and 2016. TA-TMA was diagnosed at a median of 93 days post-HSCT. Organ-specific injury was documented in all ten patients at time of TA-TMA diagnosis, the most common being renal dysfunction (90%). Acute GVHD (70%) and active infection (80%) were common at time of diagnosis. The median time to ECU initiation from TA-TMA diagnosis was 4 days. Seven patients received ECU as first-line therapy in combination with other treatment modalities, while three patients were treated with ECU as second-line therapy. ECU was well tolerated with the exception of one case of severe skin rash leading to discontinuation. ECU achieved an overall hematologic response rate of 70% and an overall survival rate of 60%. One patient achieved a complete response with corresponding organ recovery. CONCLUSION: Early initiation of ECU may not alter the disease process enough to restore organ function, but it may prolong survival.

Adverse Prognostic Factors for Morbidity and Mortality During Peripheral Blood Stem Cell Mobilization in Patients with Light Chain Amyloidosis.

Patients with immunoglobulin light chain (AL) amyloidosis undergoing peripheral blood hematopoietic stem cell (PBSC) mobilization for autologous hematopoietic stem cell transplantation (auto-HCT) can experience significant morbidity and mortality. The purpose of this study was to characterize the adverse events and identify prognostic factors associated with the development of morbidity and mortality in patients with AL amyloidosis who had begun PBSC mobilization for auto-HCT. A retrospective study was performed in 101 consecutive patients with AL amyloidosis who underwent PBSC mobilization for auto-HCT between January 2006 and December 2013. A composite primary endpoint of morbidity and mortality during PBSC mobilization was used. Forty-one patients (41%) experienced at least 1 adverse event, including 4 deaths during PBSC mobilization. Adverse events included in this composite endpoint were cardiac events, thromboembolic events, bleeding events, unplanned hospitalization, weight gain >2% necessitating diuretic intervention, and death. Low serum albumin levels, elevated N-terminal pro-brain natriuretic peptide, and increased interventricular septal thickness were significantly associated with the composite primary endpoint (P = .024, .001, and .006, respectively). The median progression-free survival from the start of PBSC mobilization was 4.7 years, and the median overall survival was 6.5 years. In general, PBSC mobilization is associated with minimal complications, but patients with AL amyloidosis can experience more frequent and severe complications, such as volume overload and weight gain. Careful patient selection is warranted in patients with AL amyloidosis before proceeding to PBSC mobilization and auto-HCT.

State Insurance Mandates and Multiple Birth Rates After In Vitro Fertilization.

OBJECTIVE: To examine the association between state-mandated insurance coverage for in vitro fertilization (IVF) and the incidence of multiple birth while controlling for differences in baseline patient characteristics. METHODS: We conducted a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System from 2007 to 2011 to examine the association between state-mandated insurance coverage for IVF and the incidence of multiple birth while controlling for differences in baseline patient characteristics. Analyses were stratified according to patient age and day of embryo transfer (3 or 5). RESULTS: Of the 173,968 cycles included in the analysis, 45,011 (25.9%) were performed in mandated states and 128,957 (74.1%) in nonmandated states. The multiple birth rate was significantly lower in mandated states (29.0% compared with 32.8%, adjusted odds ratio [OR] 0.87, 99.95% confidence interval [CI] 0.80-0.94). After stratification, this association remained statistically significant only in women younger than 35 years old who underwent transfer on day 5 (33.1% compared with 38.6%, adjusted OR 0.81, 99.95% CI 0.71-0.92). Among women younger than 35 years with day 5 transfer, the elective single embryo transfer rate was significantly higher in mandated states (21.8% compared with 13.1%, adjusted OR 2.36, 99.95% CI 2.09-2.67). CONCLUSION: State-mandated insurance coverage for IVF is associated with decreased odds of multiple birth. This relationship is driven by increased use of elective single embryo transfer among young women undergoing day 5 transfer.

How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012.

OBJECTIVE: To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate (PR). RESULT(S): Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively). CONCLUSION(S): Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients ≤40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients ≤40 years of age should also be considered.

Donor oocytes are associated with preterm birth when compared to fresh autologous in vitro fertilization cycles in singleton pregnancies.

OBJECTIVE: To use a national registry to examine the role of oocyte donation on pregnancy outcomes in singleton pregnancies. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women undergoing autologous cycles and donor oocyte recipients in the United States from 2008-2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, birth weight <2,500 g, small for gestational age birthweight, perinatal death. RESULT(S): The rates of preterm delivery and low birthweight for all members of this cohort were higher than the US national average. Pregnancies resulting from oocyte donation were significantly more likely to end before 34 weeks' and 37 weeks' gestation (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] = 1.03-1.64 for 34 weeks' gestation, adjusted OR = 1.28, 95% CI = 1.12-1.46 for 37 weeks' gestation), and to result in infants weighing <2,500 g (adjusted OR = 1.21, 95% CI = 1.02-1.44). However, once gestational age at delivery is accounted for, these infants are actually at decreased risk of having a small for gestational age birthweight (adjusted OR = 0.72, 95% CI = 0.58-0.89) and of perinatal death (adjusted OR = 0.29, 95% CI = 0.09-0.94). CONCLUSION(S): Data from a national cohort indicate that donor oocyte recipients are more likely to deliver preterm when compared with autologous patients. The effect of donor oocyte donation on birthweight is likely a function of an increased rate of preterm delivery among this population.

Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.

OBJECTIVE: To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended. DESIGN: Retrospective cohort study of United States national registry information. SETTING: Not applicable. PATIENT(S): A total of 13,393 donor-recipient cycles from 2011 to 2012. INTERVENTION(S): Embryos transferred in donor IVF cycles. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate. RESULT(S): There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). CONCLUSION(S): The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles.

Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry.

OBJECTIVE: To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate. RESULT(S): Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance. CONCLUSION(S): Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations.

Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry.

OBJECTIVE: To examine the effect of recipient body mass index (BMI) on IVF outcomes in fresh donor oocyte cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 22,317 donor oocyte cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal recipient BMI (18.5-24.9) were used as the reference group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate (PR), pregnancy loss rate, live birth rate. RESULT(S): Success rates and adjusted odds ratios with 95% confidence intervals for all pregnancy outcomes were most favorable in cohorts of recipients with low and normal BMI, but progressively worsened as BMI increased. CONCLUSION(S): Success rates in recipient cycles are highest in those with low and normal BMI. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMI with respect to clinical pregnancy and live birth rate.