Does embryo biopsy, independent of vitrification, impact perinatal outcomes? An analysis of perinatal outcomes following preimplantation genetic testing biopsy in fresh and frozen embryo transfer cycles.

Objective: To compare neonatal outcomes in pregnancies resulting from embryos that have undergone preimplantation genetic testing (PGT) biopsy compared with no biopsy in both fresh and frozen embryo transfers (ETs) and determine whether findings are mediated by multiple births. Design: Retrospective cohort study. Setting: Society of Assisted Reproductive Technologies-Clinical Outcomes Reporting System data, 2014-2015. Patients: Autologous in vitro fertilization treatment cycles using fresh or frozen blastocyst ET, with or without PGT biopsy. Interventions: Not applicable. Main Outcome Measures: Large for gestational age (LGA), small for gestational age, and preterm delivery. Secondary outcomes included high birthweight, low birthweight, and clinical pregnancy measures. Outcomes were evaluated using log-binomial regression models with repeated measures. Models were used to estimate the controlled direct effects of biopsy on birth outcomes that were not mediated by multiple gestations. Results: In fresh ET, biopsy was associated with an increase in LGA (relative risk [RR] 1.45, confidence interval [CI] 1.04-2.02) that persisted in the model mediated for multiple gestation (RR 1.36, 95% CI 1.01-1.83) but was not present in an analysis restricted to elective single ET (RR 0.99, 95% CI 0.91-1.09). In frozen ET, there were no differences in any of the primary outcomes after accounting for multiple gestations. Conclusions: In a large multicenter database, there were no differences in neonatal outcomes after PGT biopsy in frozen ET cycles, and an increase in LGA was noted in fresh transfers that persisted even after accounting for multiple gestations but was not present in analysis restricted to elective single ET.

Frozen autologous and donor oocytes are associated with differences in clinical and neonatal outcomes compared with fresh oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System Analysis.

Objective: To study the clinical and neonatal outcomes of embryos derived from frozen oocytes relative to fresh oocytes in both autologous and donor oocyte cycles after fresh embryo transfer (ET). Design: This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015. Setting: The Society for Assisted Reproductive Technology Clinic Outcome Reporting System database was used to identify autologous and donor oocyte cycles that resulted in a fresh ET during 2014 and 2015. Patients: There were 154,706 total cycles identified that used embryos derived from fresh or frozen oocytes and resulted in a fresh ET, including 139,734 autologous oocyte cycles and 14,972 donor oocyte cycles. Interventions: Generalized linear regression models were used to compare the clinical and neonatal outcomes of frozen oocytes relative to fresh oocytes. Models were adjusted for maternal age, body mass index, smoking status, parity, infertility diagnosis, number of embryos transferred, and preimplantation genetic testing. An additional sensitivity analysis was performed to examine singleton pregnancies separately. Main Outcome Measures: The live birth (LB) rate was the primary outcome. Secondary outcomes include pregnancy and birthweight outcomes. Results: Differences in clinical and neonatal outcomes between fresh and frozen-thawed oocytes after fresh ET were observed. Specifically, our study found a higher incidence of high-birthweight infants after the use of frozen oocytes relative to fresh oocytes in both autologous oocytes (12.5% [frozen] vs. 4.5% [fresh], adjusted risk ratio [aRR] 2.67, 95% confidence interval [CI] 1.65-4.3) and donor oocyte cycles (6.2% [frozen] vs. 4.6% [fresh], aRR 1.42, 95% CI 1.1-1.83). This finding remained true when the analysis was restricted to singleton gestations only for both groups: autologous (17.3% [frozen] vs. 7.1% [fresh], aRR 2.77, 95% CI 1.74-4.42) and donor oocytes (9.4% [frozen] vs. 7.8% [fresh], aRR 1.38, 95% CI 1.07-1.77). Additionally, we observed a decrease in LB (aRR 0.81, 95% CI 0.77-0.85); clinical pregnancy (aRR 0.83, 95% CI 0.8-0.87); and an increase in biochemical pregnancy loss (aRR 1.22, 95% CI 1.05-1.43) after the use of frozen oocytes in donors, but not autologous cycles. Conclusions: Our findings of an increased incidence of high-birthweight infants after the transfer of embryos derived from frozen oocytes in both autologous and donor oocyte cycles raise questions about oocyte vitrification and deserve further study. Additionally, the finding of a decreased likelihood of LB with frozen-donor oocytes compared with fresh donor oocytes is an important finding, especially because more patients are seeking to use frozen oocytes in their donor egg cycles. Future research should be directed toward these findings to optimize the use of frozen oocytes in clinical practice.

Similar pregnancy outcomes from fresh and frozen donor oocytes transferred to gestational carriers: a SART database analysis isolating the effects of oocyte vitrification.

PURPOSE: This work aimed to study clinical and neonatal outcomes of embryos derived from frozen compared to fresh donor oocytes in gestational carrier cycles. METHODS: This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015, comprising of 1284 fresh transfer cycles to gestational carrier recipients of embryos resulting from fresh (n = 1119) and vitrified/thawed (n = 165) donor oocytes. Models were adjusted for gestational carrier age, preimplantation genetic testing (PGT-A), number of embryos transferred, multiple gestation, and fetal heart reduction. As our models were part of a larger analysis, intended parent BMI, smoking status, and parity were also adjusted for, but did not influence outcomes in this analysis. RESULTS: There was no significant difference in probability of live birth rates when comparing embryos derived from fresh and frozen donor oocytes in gestational carrier cycles. There were also no significant differences in biochemical pregnancy losses or clinical miscarriage. There were no significant differences noted in low birthweight or high birthweight infants derived from fresh versus frozen donor oocyte after transfer into a gestational carrier. CONCLUSIONS: The analysis of fresh and frozen donor oocytes in gestational carrier cycles provides the opportunity to assess for a possible effect of vitrification on the oocyte by controlling for differences in the uterine environment. We observed no significant differences in live birth, pregnancy loss, low birthweight or high birthweight infants when comparing fresh and frozen donor oocytes in gestational carrier cycles.

Circulating Vascular Endothelial Growth Factor and Soluble fms-Like Tyrosine Kinase-1 as Biomarkers for Endometrial Remodeling Across the Menstrual Cycle.

OBJECTIVE: To characterize variation in circulating vascular endothelial growth factor (VEGF) and its receptor, soluble fms-like tyrosine kinase-1 (sFLT-1), across the menstrual cycle in normal ovulating women in relation to reproductive hormones to identify the utility of VEGF and sFLT-1 as peripheral biomarkers of endometrial remodeling. METHODS: Ninety-six healthy, regularly menstruating ovulatory women, aged 18-44 years, enrolled in the BioCycle Study, a prospective cohort study at a U.S. academic research center. Vascular endothelial growth factor and sFLT-1 were measured in concurrently collected plasma, serum, and urine up to eight times across a single cycle. Reproductive hormones were measured in serum. Mean concentrations of VEGF and sFLT-1 were compared across phases of the cycle, and correlations between specimen types were calculated. Harmonic models estimated associations between VEGF and sFLT-1 and characteristics of hormonal patterns. RESULTS: No variation in VEGF or sFLT-1 levels were detected over the menstrual cycle. Median (25th percentile, 75th percentile) concentrations of VEGF during the menstrual cycle were 31.2 pg/mL (24.1, 56.9) in plasma, 194.1 pg/mL (125.4, 350.2) in serum, and 101.7 pg/mL (64.2, 165.8) in urine. Plasma and serum measures were consistently correlated, whereas urinary measures were not. Vascular endothelial growth factor was not consistently associated with reproductive hormone concentrations, although sFLT-1 was associated with higher mean and amplitude of estradiol. CONCLUSION: Circulating VEGF and sFLT-1 did not vary across the menstrual cycle and therefore are unlikely to be useful peripheral biomarkers of endometrial changes across the menstrual cycle. For studies measuring circulating VEGF for other reasons, plasma may be the preferred medium and timing to menstrual cycle phase need not be considered for reproductive-age women.

Systematic Review and Meta-Analysis of Selected Cancers in Petroleum Refinery Workers.

OBJECTIVE: We studied the risk of 11 cancers of a priori interest in petroleum refinery workers. METHODS: Iterative searches identified 36 studies for the 11 cancer sites. Statistical heterogeneity and publication bias were assessed to enhance interpretation of meta-relative risks. RESULTS: Statistical heterogeneity was marked for mesothelioma, but was largely due to study quality. Higher quality studies showed a meta-relative risk (RR) of 3.22, (95% prediction interval 1.45 to 7.23). Melanoma (meta-RR = 1.23) and acute lymphoid leukemia (meta-RR = 1.51), showed results consistent with higher risk, but both were driven by one or two studies. Eight other cancer outcomes showed summary meta-RR's consistent with unity. CONCLUSIONS: Most cancer outcomes are consistent with background risk in refinery workers. This work has clarified an excess mesothelioma risk, conditional on study quality stratification. Continued surveillance is warranted for melanoma and ALL.