Improved implantation rates of day 3 embryo transfers with the use of an automated time-lapse-enabled test to aid in embryo selection.

OBJECTIVE: To determine if an automated time-lapse test (TL-test) combined with traditional morphology for embryo selection and day 3 transfer results in improved clinical outcomes. DESIGN: Prospective concurrent-controlled pilot study. SETTING: IVF clinic and laboratory. PATIENT(S): A total of 319 female patients <41 years old, with day 3 embryo transfer, fewer than three failed IVF cycles, and at least four zygotes (2-pronuclear) on day 1. INTERVENTION(S): Automated time-lapse embryo assessment combined with morphologic assessment in the study (test) group compared with morphologic assessment only (control group). MAIN OUTCOME MEASURE(S): Embryo implantation, pregnancy, and multiple pregnancy rates. Subanalysis of implantation potential of embryos based on the TL-test (TL-high vs. TL-low) scores. RESULT(S): Implantation and clinical pregnancy rates were significantly higher in the test group compared with the control group (implantation rates 30.2% vs. 19.0%, clinical pregnancy rates 46.0% vs. 32.1%, respectively). Multiple pregnancy rates were not statistically different (26.7% vs. 18.3%). Test group patients receiving at least one TL-high embryo had significantly higher implantation rates than patients receiving only TL-low embryos (36.8% vs. 20.6%). TL-high compared with TL-low embryos had significantly higher implantation rates (44.7% vs. 20.5%). Among morphologically good embryos, TL-high embryos were more likely to implant than TL-low embryos (44.1% vs. 20.6%). CONCLUSION(S): This is the first report demonstrating improved implantation rates in patients receiving day 3 embryo transfers based on the combined use of a TL-test along and traditional morphology. Our findings confirm that the noninvasive TL-test adds valuable information to traditional morphologic grading. CLINICAL TRIAL REGISTRATION NUMBER: NCT01671657.

Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study.

Computer-automated time-lapse analysis has been shown to improve embryo selection by providing quantitative and objective information to supplement traditional morphology. In this multi-centre study, the relationship between such computer-derived outputs (High, Medium, Low scores), embryo implantation and clinical pregnancy were examined. Data were collected from six clinics, including 205 patients whose embryos were imaged by the Eeva(TM) System. The Eeva scores were blinded and not considered during embryo selection. Embryos with High and Medium scores had significantly higher implantation rates than those with Low scores (37% and 35% versus 15%; P < 0.0001; P = 0.0004). Similar trends in implantation rates were observed in different IVF centres each using their own protocols. Further analysis revealed that patients with at least one High embryo transferred had significantly higher clinical pregnancy rates than those with only Low embryos transferred (51% versus 34%; P = 0.02), although patients' clinical characteristics across groups were comparable. These data, together with previous research and clinical studies, confirm that computer-automated Eeva scores provide valuable information, which may improve the clinical outcome of IVF procedures and ultimately facilitate the trend of single embryo selection.

Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development.

OBJECTIVE: To characterize atypical dynamic embryo phenotypes identified by time-lapse microscopy, evaluate their prevalence, and determine their association with embryo development. DESIGN: Retrospective multicenter cohort study. SETTING: Five IVF clinics in the United States. PATIENT(S): Sixty-seven women undergoing IVF treatment with 651 embryos. INTERVENTION(S): Embryo videos were retrospectively analyzed for atypical phenotypes. MAIN OUTCOME MEASURE(S): Identification of four groups of atypical embryo phenotypes: abnormal syngamy (AS), abnormal first cytokinesis (A1(cyt)), abnormal cleavage (AC), and chaotic cleavage (CC). Prevalence and association with embryo morphology and development potential were evaluated. RESULT(S): A high prevalence of atypical phenotypes was observed among embryos: AS 25.1% (163/649), A1(cyt) 31.0% (195/639), AC 18% (115/639) and CC 15% (96/639). A high percentage of embryos with atypical phenotype(s) had good quality on day 3 (overall grade good or fair): AS 78.6% (70/89); A1(cyt) 79.7% (94/119), AC 86.4% (70/81), and CC 35.2% (19/54), but the blastocyst formation rates for these embryos were significantly lower compared with their respective control groups: AS 21.5% vs. 44.9%, A1(cyt) 21.7% vs. 44.6%, AC 11.7% vs. 43.1%, and CC 14.0% vs. 42.3%. CONCLUSION(S): Embryos exhibiting atypical phenotypes are highly prevalent in human embryos and show significantly lower developmental potential than control embryos. CLINICAL TRIAL REGISTRATION NUMBER: NCT01369446.

Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial.

OBJECTIVE: To assess the first computer-automated platform for time-lapse image analysis and blastocyst prediction and to determine how the screening information may assist embryologists in day 3 (D3) embryo selection. DESIGN: Prospective, multicenter, cohort study. SETTING: Five IVF clinics in the United States. PATIENT(S): One hundred sixty women ≥ 18 years of age undergoing fresh IVF treatment with basal antral follicle count ≥ 8, basal FSH <10 IU/mL, and ≥ 8 normally fertilized oocytes. INTERVENTION(S): A noninvasive test combining time-lapse image analysis with the cell-tracking software, Eeva (Early Embryo Viability Assessment), was used to measure early embryo development and generate usable blastocyst predictions by D3. MAIN OUTCOME MEASURE(S): Improvement in the ability of experienced embryologists to select which embryos are likely to develop to usable blastocysts using D3 morphology alone, compared with morphology plus Eeva. RESULT(S): Experienced embryologists using Eeva in combination with D3 morphology significantly improved their ability to identify embryos that would reach the usable blastocyst stage (specificity for each of three embryologists using morphology vs. morphology plus Eeva: 59.7% vs. 86.3%, 41.9% vs. 84.0%, 79.5% vs. 86.6%). Adjunctive use of morphology plus Eeva improved embryo selection by enabling embryologists to better discriminate which embryos would be unlikely to develop to blastocyst and was particularly beneficial for improving selection among good-morphology embryos. Adjunctive use of morphology plus Eeva also reduced interindividual variability in embryo selection. CONCLUSION(S): Previous studies have shown improved implantation rates for blastocyst transfer compared with cleavage-stage transfer. Addition of Eeva to the current embryo grading process may improve the success rates of cleavage-stage ETs.

Implementation of an inexpensive method of vitrification and warming of human cleavage-stage embryos using cut standard straws.

The aim of this report is to describe our experience and results with implementation of a cut standard straw technique for vitrification and warming of day 3 cleavage-stage human embryos. Detailed description of the method and results of 63 frozen embryo transfers performed with this technology are discussed, and it is concluded that this method provides a reliable, inexpensive, and effective option of embryo vitrification at a cleaved stage.

Economic cost for implementation of the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 in an egg donor program.

OBJECTIVE: To assess the economic cost of implementing the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 for infectious screening of egg donors in our practice during the first year. DESIGN: Physicians and employees of our practice were surveyed to ascertain the scope of duties and the number of hours spent to implement the regulations. The economic cost to the practice and the cost of additional laboratories were calculated. SETTING: Private practice. PATIENT(S): Egg donors and recipient couples who underwent treatment in our center from May 25, 2005 (the day regulations became effective) to May 25, 2006; and physicians, administrators, and staff who were employed by the practice during this time frame. INTERVENTION(S): Using a questionnaire, structured interviews were conducted for all physicians and employees of our practice. The information regarding number of hours was provided to our chief financial officer, who calculated the cost to the practice. The cost that recipient couples paid for laboratory tests that would not otherwise be required to meet American Society for Reproductive Medicine guidelines and the cost of an external audit were also added to the overall practice costs to determine a total cost associated with the regulations in the first year. MAIN OUTCOME MEASURE(S): List of activities associated with implementation of the regulations, personnel hours involved to implement the regulations, and economic cost to the practice and to recipient couples. RESULT(S): The total number of personnel hours spent by our practice in preparation for implementation of the regulations was 623.3 hours. In the first year, 675.2 additional hours were required to implement the regulations for 40 donors who cycled during this time. The economic cost to the practice for both preparation and implementation of the regulations was $219, 838, and the cost of additional laboratory work borne by the recipient couples was $15,880. Thus, the total cost was calculated to be $235,718 at 1 year after implementation of the regulations. CONCLUSION(S): Implementation of the FDA 21 CFR, Part 1271 was associated with a very high economic cost, even if the costs incurred by the government to develop and implement the regulation are excluded.

Correlation of thyroid stimulating hormone (TSH) level with pregnancy outcome in women undergoing in vitro fertilization.

OBJECTIVE: The aim of this study was to determine if pregnancy outcome for women undergoing in vitro fertilization is correlated with pre-conception thyroid-stimulating hormone level. STUDY DESIGN: We performed a retrospective cohort study of in vitro fertilization cycles in our private practice with an initial positive serum human chorionic gonadotropin level and thyroid-stimulating hormone level available (n = 364). We examined whether or not birth outcome differed between cycles in which the thyroid-stimulating hormone was > 2.5 mIU/L compared with cycles with a thyroid-stimulating hormone level of < or = 2.5 mIU/L. Logistic regression was used to determine the association between thyroid-stimulating hormone level and spontaneous abortion rate. RESULTS: Delivery outcome was available for 195 cycles, 36% of which had a thyroid-stimulating hormone level > 2.5. The gestational age at delivery was higher in cycles with a thyroid-stimulating hormone < or = 2.5 than for cycles with a thyroid-stimulating hormone > 2.5 (38.5 vs 38.0 weeks for singletons, 36.0 vs 34.6 weeks for twins, overall P = .012 for thyroid-stimulating hormone level). The mean birth weight for cycles with a thyroid-stimulating hormone < or = 2.5 was higher than for cycles with a thyroid-stimulating hormone > 2.5 (7.33 vs 6.78 lbs for singletons, P = .024 and 5.36 vs 4.83 lbs for twins, P = .023). Restricting analysis to cycles where the woman was not taking thyroid replacement did not change the overall conclusions. There was a trend toward increasing risk of miscarriage with increasing thyroid-stimulating hormone level in nondonor cycles, controlling for age and day 3 follicle-stimulating hormone level, but this trend did not reach statistical significance. CONCLUSION: A pre-conception thyroid-stimulating hormone level > 2.5 mIU/L is associated with a lower gestational age at delivery and lower birth weight in women undergoing in vitro fertilization.