Perinatal outcomes among young donor oocyte recipients.

STUDY QUESTION: Is the use of donor oocytes in women <35 years of age associated with an increased risk of adverse perinatal outcomes compared to use of autologous oocytes? SUMMARY ANSWER: Among fresh assisted reproductive technology (ART) cycles performed in women under age 35, donor oocyte use is associated with a higher risk of preterm birth, low birth weight and stillbirth (when zero embryos were cryopreserved) as compared to autologous oocytes. WHAT IS KNOWN ALREADY: Previous studies demonstrated elevated risk of poor perinatal outcomes with donor versus autologous oocytes during ART, primarily among older women. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study using data reported to Centers for Disease Control and Prevention's National ART Surveillance System (NASS) during the period from 2010 to 2015 in order to best reflect advances in clinical practice. Approximately 98% of all US ART cycles are reported to NASS, and discrepancy rates were <6% for all fields evaluated in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all non-banking fresh and frozen ART cycles performed between 2010 and 2015 in women under age 35 using autologous or donor eggs. Cycles using cryopreserved eggs, donated embryos or a gestational carrier were excluded. Among fresh embryo transfer cycles, we calculated predicted marginal proportions to estimate the unadjusted and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for the association between donor versus autologous oocyte use and stillbirth, spontaneous abortion, preterm delivery and low birth weight among singleton pregnancies or births. Stillbirth models were stratified by number of embryos cryopreserved. All models were adjusted for patient and treatment characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 71 720 singleton pregnancies occurring during 2010-2015, singletons resulting from donor oocytes were more likely to be preterm (15.6% versus 11.0%; aRRs 1.39: CI 1.20-1.61) and have low birth weight (11.8% versus 8.8%; aRRs 1.34; CI 1.16-1.55) than those resulting from autologous oocytes. With zero embryos cryopreserved, donor versus autologous oocyte use was associated with increased risk for stillbirth (2.1% versus 0.6%; aRRs 3.73; CI 1.96-7.11); no association with stillbirth was found when ≥1 embryo was cryopreserved (0.54% versus 0.56%; aRR 1.15; CI 0.59-2.25). LIMITATIONS, REASONS FOR CAUTION: The data come from a national surveillance system and is thus limited by the accuracy of the data entered by individual providers and clinics. There may be unmeasured differences between women using donor eggs versus their own eggs that could be contributing to the reported associations. Given the large sample size, statistically significant findings may not reflect clinically important variations. WIDER IMPLICATIONS OF THE FINDINGS: Risks of preterm birth, low birth weight and stillbirth among singleton pregnancies using donor oocytes were increased compared to those using autologous oocytes. Further study regarding the pathophysiology of the potentially increased risks among donor oocyte recipient pregnancy is warranted. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Ambient air pollution and in vitro fertilization treatment outcomes.

STUDY QUESTION: Is air pollution associated with IVF treatment outcomes in the USA? SUMMARY ANSWER: We did not find clear evidence of a meaningful association between reproductive outcomes and average daily concentrations of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3). WHAT IS KNOWN ALREADY: Maternal exposure to air pollution such as PM2.5, nitrogen oxides, carbon monoxide or O3 may increase risks for adverse perinatal outcomes. Findings from the few studies using data from IVF populations to investigate associations between specific pollutants and treatment outcomes are inconclusive. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of 253 528 non-cancelled fresh, autologous IVF cycles including 230 243 fresh, autologous IVF cycles with a transfer of ≥1 embryo was performed between 2010 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We linked 2010-2012 National ART Surveillance System data for fresh, autologous IVF cycles with the ambient air pollution data generated using a Bayesian fusion model available through the Centers for Disease Control and Prevention's Environmental Public Health Tracking Network. We calculated county-level average daily PM2.5 and O3 concentrations for three time periods: cycle start to oocyte retrieval (T1), oocyte retrieval to embryo transfer (T2) and embryo transfer +14 days (T3). Multivariable predicted marginal proportions from logistic and log-linear regression models were used to estimate adjusted risk ratios (aRR) and 95% CI for the association between reproductive outcomes (implantation rate, pregnancy and live birth) and interquartile increases in PM2.5 and O3. The multipollutant models were also adjusted for patients and treatment characteristics and accounted for clustering by clinic and county of residence. MAIN RESULTS AND THE ROLE OF CHANCE: For all exposure periods, O3 was weakly positively associated with implantation (aRR 1.01, 95% CI 1.001-1.02 for T1; aRR 1.01, 95% CI 1.001-1.02 for T2 and aRR 1.01, 95% CI 1.001-1.02 for T3) and live birth (aRR 1.01, 95% CI 1.002-1.02 for T1; aRR 1.01, 95% CI 1.004-1.02 for T2 and aRR 1.02, 95% CI 1.004-1.03 for T3). PM2.5 was not associated with any of the reproductive outcomes assessed. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the use of aggregated air pollution data as proxies for individual exposure. The weak positive associations found in this study might be related to confounding by factors that we were unable to assess and may not reflect clinically meaningful differences. WIDER IMPLICATIONS OF THE FINDINGS: More research is needed to assess the impact of air pollution on reproductive function. STUDY FUNDING/COMPETING INTEREST(S): None.

Live birth and multiple birth rates in US in vitro fertilization treatment using donor oocytes: a comparison of single-embryo transfer and double-embryo transfer.

OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level. RESULTS: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively). CONCLUSIONS: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children.

STUDY QUESTION: Are assisted reproductive technology (ART) treatment factors or infertility diagnoses associated with autism among ART-conceived children? SUMMARY ANSWER: Our study suggests that the incidence of autism diagnosis in ART-conceived children during the first 5 years of life was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF, and lower when parents had unexplained infertility (among singletons) or tubal factor infertility (among multiples) compared with other types of infertility. WHAT IS KNOWN ALREADY: Some studies found an increased risk of autism among ART-conceived infants compared with spontaneously-conceived infants. However, few studies, and none in the USA, have examined the associations between types of ART procedures and parental infertility diagnoses with autism among ART-conceived children. STUDY DESIGN, SIZE, DURATION: Population-based retrospective cohort study using linkages between National ART Surveillance System (NASS) data for 1996-2006, California Birth Certificate data for 1997-2006, and California Department of Developmental Services (DDS) Autism Caseload data for 1997-2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: All live born ART-conceived infants born in California in 1997-2006 (n = 42 383) with 5-year observation period were included in the study. We assessed the annual incidence of autism diagnosis documented in DDS, which includes information on the vast majority of persons with autism in California, and the association of autism diagnosis with ART treatment factors and infertility diagnoses. MAIN RESULTS AND THE ROLE OF CHANCE: Among ART-conceived singletons born in California between 1997 and 2006, the incidence of autism diagnosis remained at ∼0.8% (P for trend 0.19) and was lower with parental diagnosis of unexplained infertility (adjusted hazard risk ratio [aHRR]; 95% confidence interval: 0.38; 0.15-0.94) and higher when ICSI was used (aHRR 1.65; 1.08-2.52), when compared with cases without these patient and treatment characteristics. Among ART-conceived multiples, the incidence of autism diagnosis between 1997 and 2006 remained at ∼1.2% (P for trend 0.93) and was lower with parental diagnosis of tubal factor infertility (aHRR 0.56; 0.35-0.90) and higher when ICSI was used (aHRR 1.71; 1.10-2.66). LIMITATIONS, REASONS FOR CAUTION: Study limitations include imperfect data linkages, lack of data on embryo quality and possible underestimation of autism diagnosis cases. Limitations of the observational study design could affect the analysis by the possibility of residual confounders. Since information about ICSI use was missing for most frozen/thawed embryo transfer cycles, our findings of association of ICSI use and autism diagnosis can only be generalizable to fresh embryo transfer cycles. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides additional evidence of the association between some types of ART procedures with autism diagnosis. Additional research is required to explain the increased risk of autism diagnosis with ICSI use, as well as studies on the effectiveness and safety of ICSI.

N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake.

A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.

Mode of delivery and birth outcomes of macrosomic infants.

This review examines and summarises the literature regarding the mode of delivery of macrosomic infants and subsequent perinatal outcomes. A search of electronic databases was conducted and supplemented with investigation of the references cited in the original articles. Although the rates of obstetric complications differ among high birth weight infants delivered by caesarean section compared to those delivered vaginally, there is currently little evidence that perinatal mortality differs significantly by delivery method. Shoulder dystocia and birth injury occur with greater frequency among macrosomic infants, yet the relative inaccuracy of clinical and ultrasonographic estimates of birth weight among high birth weight infants indicates that a trial of labour may be warranted among non-diabetic mothers with a suspected macrosomic fetus. The majority of studies identified in this review utilised small sample sizes and observational design, thereby hindering valid assessments of the impact of delivery method on the mortality of this population. Consequently, an optimal management strategy has yet to be defined.

Synthesis and biological evaluation of analogs of the marine toxin polycavernoside A.

Second generation analogs of polycavemoside A (2) possessing a side chain at C-15 different from that of the natural toxin have been synthesized. The in vivo toxicities of these new compounds (expressed as the minimal lethal dose) have been evaluated in mice (ip) and compared to 2, its aglycone (8), and polycavemoside B (9). The bioactivity profile of enynene 5 is particularly notable.