In recent years the increased efforts intended for improving future outcomes in the laboratory have focused mostly on the search of additional markers of embryo quality to add up present embryo selection criteria. Time-lapse system involves an alternative tool in assisted reproduction techniques, being able to improve the embryo selection from a dynamic and interactive approach while standard embryo assessment implies a subjective and static morphology evaluation and consequently reducing the information gained for embryo selection, time-lapse technology adds several morphokinetic parameters, providing additional input for embryo evaluation. This further information represents a challenge for a potential improvement in implantation rates and reproductive outcomes. This article focuses on the different time-lapse systems burgeoning on the market and the use of morphokinetics as a predictor of embryo implantation.
Objective: To evaluate the effect of different ovarian stimulation protocols on oocyte respiration and to investigate the relationship between oocyte oxygen consumption and reproductive outcome.Design: Prospective observational cohort study.Setting: Infertility clinic in a university hospital.Patient(s): A total of 349 oocytes from 56 IVF treatment cycles in our oocyte donation program.Intervention(s): None.Main Outcome Measure(s): Average oocyte oxygen consumption rate in fmol/s. We correlated oxygen consumption values with ovarian stimulation features, fertilization, embryo quality on days 2 and 3, and implantation.Result(s): Differences in the measured oxygen consumption rates were found depending on which type of gonadotropins were used in the stimulation protocol. Higher consumption rates were found for oocytes that underwent normal fertilization compared with rates from nonfertilized or abnormal oocytes (odds ratio = 1.340; 95% confidence intervals = 1.037-1.732). Furthermore, higher oxygen consumption was observed for those oocytes which generated embryos that implanted compared with those that did not implant (6.21 +/- 0.849 fmol/s vs. 5.23 +/- 0.345 fmol/s.Conclusion(s): Measurement of oxygen consumption rates for individual oocytes before fertilization provides a noninvasive marker of oocyte quality and hence a quantitative assessment of the reproductive potential for the oocyte. (Fertil Steril (R) 2011;96:618-23. (C)2011 by American Society for Reproductive Medicine.)
Time-lapse technology offers access to new information on embryo development, with the potential of improving embryo selection. This study aims to evaluate the accuracy of automatically derived divisional parameters (DP), i.e. time of divisions (t2, t3, t4, t5), duration of cell cycles (cc2, cc3) and synchrony (s2), by comparing the automatically derived parameters with manual observations of embryo developmental patterns. Retrospective automated analysis of human embryo time-lapse images. The time-lapse image series of 247 transferred embryos were analyzed using an algorithm developed for automated detection of DP. Blastomere activity (BA) was calculated as the standard deviation of the difference between two consecutive images of the developing embryo. Cell divisions were identified automatically as peaks in the BA. Manual annotations were made by an embryologist. Evaluations of the absolute error between automatically and manually found DP are listed in the table. The major part of DPs (52-71%) was identified with little time error <0.3 h. Moderate errors in time, 0.3-1.2 h were observed for 21-34% of the DPs, whereas 8-19% of the DPs were identified with a time error of ≥1.2 h. This indicates that although the algorithm in most cases finds the DPs within reasonable limits, some embryos as those with lot of fragmentation still need manual correction.Tabled 1Evaluations of absolute error (E)NE < 0.3h0.3h ≤ E < 1.2hE ≥ 1.2hRMS errorMedian error[#][%][%][%][h][h]t224766%22%12%0.78h0.25ht323771%21%8%0.68h0.25ht423559%30%11%1.02h0.25ht521260%25%15%0.78h0.25hcc223752%30%18%0.99h0.26hcc321159%21%19%0.91h0.25hs223552%34%14%0.99h0.25h Open table in a new tab The results show that most DPs can be identified from the BA with an error below 0.3 h, but for some DPs it is necessary to make manual corrections. Automated detection of embryo morphokinetics can still save time for the embryologist and generate consistent evaluations after operator validation.
To define the best time range for each embryo development event by time-lapse technology based on the subsequent implantation. Retrospective cohort study. We have monitored 885 transferred embryos from 487 couples undergoing their first-second ICSI treatment. We selected 467 for detailed analysis based on either: 100% implantation (n = 111) where number of gestational sacs and transferred embryos matches or 0% implantation (n = 356). Images of the embryos were acquired by time-lapse (EmbryoScope). Photographs were taken every 15 min and all timings were taken relative to the time of ICSI and expressed as hours. Timing was classified in quartiles and grouped in two categories; the first one defined by joining the two central quartiles (IN), the second one includes the rest of the data (OUT). Implantation was compared between categories by a Chi-square test. Variables analyzed were: T2, time of 2nd division; T3, 3rd division; T4, 4th division; T5, 5th division; CC2, duration of 2nd cell cycle (t3-t2) and S2, synchrony between 2nd and 3rd divisions (t4-t3). Out of 885 transferred embryos a total of 318 implanted (35.9%). Biochemical pregnancy rate was 54.2% (n = 264) and ongoing pregnancy rate was 46.8% (n = 228). Table 1 shows the limit values of the IN range, the percentage of implanted IN as well as the p value comparing with the implanted OUT (p) and the sample size (N) for each event.Table 1EventT2T3T4T5CC2S2Range (h) IN24,49 - 28,3035,58 - 40,6036,65 - 41,9049,51 - 56,70<11,99<0,67Implanted (%)28,929,628,132,228,228,2p0,0080,0030,036<0,0010,0320,039N111111111106111111 Open table in a new tab Time-lapse technology allows us to analyze the dynamics of embryo development to determine optimal ranges according to successful implantation. This study, with the largest sample size described with this measuring system, makes it possible to state that cell division rate and synchrony at early embryo development determines the implantation with accuracy and objectivity.
OBJECTIVE: The time-lapse system in the EmbryoScope (ES) can be used for image acquisition of embryos and subsequent analysis of the exact timing of cell division events. The purpose of the study is to link successful implantation of embryos to the exact timing of cell division events by use of the ES. DESIGN: Retrospective analysis on embryos from ICSI cycles. MATERIALS AND METHODS: Included in the study were only transferred embryos with 100% implantation (where the number of gestational sacs confirmed by ultrasound match the number of transferred embryos); or embryos with 0% implantation, (where no biochemical pregnancy was achieved). Images of the embryos were acquired every 20 min during 70 hours in the ES. Subsequently the ES Viewer was used to identify the exact timing of PN formation and fading, and 1st, 2nd and 3rd division. The time of each event was recorded in hours after microinjection. Timing was classified in quartiles and grouped in two categories, the first category defined by the time-range of the two central quartiles, the second category “Out of range” includes the rest of the data. Implantation is compared between the categories by a Chi-square test. RESULTS:Table 1Implantation within the time-range for each variableEventPN formationPN fading∗1st division∗2nd division∗3rd division∗Range (h)7.8 - 11.122.3 - 25.824.4 - 28.235.3 - 40.636.0 - 41.6Implanted (%)2029.528.823.229.7N3247463747For the events marked with ∗ (PN fading, 1st, 2nd and 3rd division), there is a significant difference (p<0.05) between the relative abundance of 100% implantation and 0% implantation inside and outside the given time-range for the event. Open table in a new tab For the events marked with ∗ (PN fading, 1st, 2nd and 3rd division), there is a significant difference (p<0.05) between the relative abundance of 100% implantation and 0% implantation inside and outside the given time-range for the event. CONCLUSION: The timing of PN fading, 1st, 2nd and 3rd division can be significantly linked to successful embryo implantation. Although the amount of data is limited, the analysis shows that the ES has the potential of improving embryo selection through the exact determination of timing of embryo development events.
introduction: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic, serious and potentially fatal complication of ovarian stimulation which affects 1-14% of all IVF/ICSI cycles.A potential new strategy to prevent OHSS and reduce the severity is the use of a dopamine agonist.It was observed that the administration of dopamine agonist in immature rats at low doses simultaneously with HCG prevented an increase in vascular permeability and did not affect angiogenesis due to the availability of dopamine type 2 receptors.A number of clinical trials have recently tested the clinical usefulness of dopamine agonist as a possible way to reduce the occurrence and severity of OHSS.The objective of our systematic review and meta-analysis was to determine whether dopamine agonist can indeed reduce the occurrence and severity of OHSS syndrome in high risk patients undergoing ovarian hyperstimulation in IVF/ICSI treatment cycles.material and methods: We conducted a systematic review and meta-analysis of randomized trials comparing the preventive effect of use of the dopamine agonist cabergoline versus no treatment in IVF/ICSI cycles.Primary outcome was OHSS incidence per randomised woman.Secondary outcomes were live birth rate, ongoing pregnancy rate, clinical pregnancy rate, and miscarriage rate.Searches (until Sep 2009) were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library and databases of abstracts.data collection and analysis: Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion and trial quality and extracted relevant data.Validity was assessed in terms of method of randomisation, allocation concealment and outcomes.Primary outcome measure was OHSS incidence per randomised woman.Secondary outcome measures were Live birth rate clinical pregnancy rate, early miscarriage rate.results: Four randomized trials entailing 570 women were included.There was evidence of statistically significant reduction in the incidence of OHSS in the dopamine agonist group (OR 0.41 95% CI 0.25, to 0.66) with an absolute risk reduction of 12 % (95% CI, 6.07% to 18.2 %).There was no evidence of a reduction in severe OHSS (OR: 0.50, 95% CI 0.20 to 1.26).There was no evidence for a difference in clinical pregnancy rate (OR: 1.07, 95% CI (0.70 to 1.62) and miscarriage rate (OR: 0.31, 95% CI (0.03 to 3.07).conclusion: We conclude that dopamine agonist as a preventive treatment leads to a significantly lower OHSS incidence in high risk patients without compromising pregnancy outcomes, Selected oral communication SeSSion
OBJECTIVE: to make respiration rate measurements of single embryos in the embryology laboratory in order to assess embryo quality and potentially improve selection by using an automated instrument the EmbryoScope C (ES-C).
OBJECTIVE: Fully grown ova are capable of maturing at the nuclear level, but their cytoplasmic competence (CC) is usually compromised. To determine the effect of the duration of MII arrest (time elapsed between extrusion of PB1 and oocyte activation) on CC. DESIGN: We designed a study in which in vitro maturation (IVM) of germinal vesicles (GV) and subsequent artificial oocyte activation were screened in real-time. MATERIALS AND METHODS: Ninety-five GV were cultured in 25μl CCM (Vitrolife) on Embryoscope® slides (Fertilitech). Screening revealed the time at which PB1 extrusion occurred in 87 ova (91.6% IVM rate). Two groups were established by considering the median time at which PB1 extrusion occurred, calculated at 23.3hrs, as a cut off point. An early IVM (E-IVM) group was composed of 46 ova that reached MII at <23.3hrs and a late IVM (L-IVM) group was composed of 41 MII in which PB1 was extruded at ≥23.3hrs. For CC assessment, E- and L-IVM MII were artificially activated by exposure to A23187 and puromicin. After overnight culture, eggs were assessed for PB2 and number of pronuclei (activation response). To determine the effect of duration of MII arrest on CC, ova were artificially activated within the first 12hrs of MII arrest (young ova) or after this time point (aged ova). SPSS 17.0 was used for data analysis. RESULTS: The highest activation rate was achieved in young early IVM ova (86.8%). Significantly lower rates of activation were observed in both aged E- IVM ova and young L- IVM ova (63.0%). Intermediate activation rates were observed in aged L- IVM ova (68.2%). CONCLUSION: This study defines thresholds for the duration of MII arrest in early and late IVM. E-IVM MII are competent at the cytoplasmic level when young, but aging impairs this competence. On the other hand, L-IVM ova seem to require more than 12hrs of MII arrest to acquire CC. Future research should determine the right moment of MII arrest in order to activate (or fertilize) ova when their CC is maximal.