***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To quantify the effect on reproductive outcome of culturing and selecting embryos using a novel time-lapse monitoring system ( TMS ) . DESIGN Retrospective observational cohort study . SETTING University-affiliated private center . PATIENT(S ) Donation and autologous intracytoplasmic sperm injection ( ICSI ) cycles from ten IVF clinics using similar procedures , cultured in TMS ( n = 1,390 ) or in a st and ard incubator ( SI ; n = 5,915 ) . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rate confirmed by ultrasound in week 7 . RESULT ( S ) A logistic regression analysis , which included all significant confounding factors , was used to evaluate the effect of culturing and selecting embryos with the use of TMS . Comparing clinical pregnancy rates per oocyte retrieval with TMS and SI treatments gave a crude effect of odds ratio [ OR ] 1.190 ( 95 % confidence interval [ CI ] 1.058 - 1.337 ) . Oocyte source , maternal age , day of transfer , and number of retrieved oocytes were identified as significant confounding factors . After accounting for confounding factors , the effect of TMS culture was OR 1.201 ( 95 % CI 1.059 - 1.363 ) . Limiting analysis to treatments with embryo transfer and including number of transferred embryos as a confounding factor likewise gave a significant effect of TMS with OR 1.157 ( 95 % CI 1.018 - 1.315 ) . CONCLUSION ( S ) Analysis of retrospective data indicated that culturing and selecting embryos by TMS significantly improved the relative probability of clinical pregnancy ( + 20.1 % per oocyte retrieval , + 15.7 % per embryo transfer ) . The elevated clinical pregnancy rate was attributed to a combination of stable culture conditions and the use of morphokinetic parameters for embryo selection OBJECTIVE Both pronuclear morphology and early zygote cleavage have been used in combination with day 3 criteria to predict implantation and pregnancy . However , in routine practice , it is impractical to use both these criteria to select embryos on day 3 . The objective of the present study was to find which of the two criteria is more predictive in terms of implantation and pregnancy . DESIGN R and omized study . SETTING Hospital-based fertility center . PATIENT(S ) A total of 330 IVF/ICSI patient cycles . INTERVENTION(S ) Patients were r and omized to two groups . The embryos of one group were classified into subgroups A , B , and C based on pronuclear morphology ( group 1 ) and the embryos of the second group were classified into subgroups A , B , and C based on early cleavage status ( group 2 ) . MAIN OUTCOME MEASURE(S ) Comparisons were made of implantation and pregnancy rates between groups 1 and 2 , between subgroups within each group , and between the corresponding subgroups of groups 1 and 2 . Progression of zygotes from day 1 to day 3 in group 1 was recorded , and retrospective analysis of pronuclear morphology of zygotes in group 2 was performed . RESULT ( S ) The overall implantation and pregnancy rates tended to be slightly higher for group 1 compared to group 2 patients , but not statistically significant . Further , there was no significant difference between the corresponding subgroups . Implantation and pregnancy rates of subgroup A zygotes from each group were significantly higher ( P<.01 ) than the rates of subgroup C. CONCLUSION ( S ) There was no significant difference between the two groups in terms of implantation and pregnancy . However , pronuclear morphology is a more satisfactory criterion than early cleavage to assist embryo selection on day 3 . This is because zygotes with early cleavage ability can be identified from their pronuclear morphology . Thus , observation for early cleavage on day 1 and assessment of progression of embryos on day 2 in addition to pronuclear morphology scoring is not necessary in the selection of embryos for transfer on day 3 OBJECTIVE To evaluate embryos with direct cleavage ( ≤5 hours ) from two to three cells ( DC2 - 3 )  and correlate this morphokinetic parameter to  implantation and ongoing pregnancy . DESIGN Clinical multicenter retrospective study . SETTING Private in vitro fertilization ( IVF ) centers . PATIENT(S ) From three clinics , a total of 979 treatments including 5,225 embryos using autologous or donated oocytes , of which 1,659 embryos were transferred . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Clinical pregnancy confirmed by ultrasound in week 7 . RESULT ( S ) Of the total embryo cohort , 715 ( 13.7 % ) underwent direct cleavage from two to three cells , 1,659 embryos were transferred to recipients , and 109 of the transferred embryos cleaved directly from two to three cells ( 6.6 % ) . Only one DC2 - 3 embryo was known to result in a clinical pregnancy ( 1 % ) and 80 ( 73.4 % ) DC2 - 3 embryos did not implant . Of the 1,550 embryos transferred not showing DC2 - 3 , 203 embryos were from treatments with 100 % implantation ( 13.1 % ) , and 804 ( 51.8 % ) embryos did not implant . The known implantation rate of DC2 - 3 embryos was statistically significantly lower than for embryos with a normal cleavage pattern ( 1.2 % vs. 20.2 % , respectively ) . CONCLUSION ( S ) Embryos with DC2 - 3 had a statistically significantly lower implantation rate than embryos with a normal cleavage pattern , suggesting that rejection of these embryos for transfer could improve the implantation rate BACKGROUND Time-lapse observation presents an opportunity for optimizing embryo selection based on morphological grading as well as providing novel kinetic parameters , which may further improve accurate selection of viable embryos . The objective of this retrospective study was to identify the morphokinetic parameters specific to embryos that were capable of implanting . In order to compare a large number of embryos , with minimal variation in culture conditions , we have used an automatic embryo monitoring system . METHODS Using a tri-gas IVF incubator with a built-in camera design ed to automatically acquire images at defined time points , we have simultaneously monitored up to 72 individual embryos without removing the embryos from the controlled environment . Images were acquired every 15 min in five different focal planes for at least 64 h for each embryo . We have monitored the development of transferred embryos from 285 couples undergoing their first ICSI cycle . The total number of transferred embryos was 522 , of which 247 either failed to implant or fully implanted , with full implantation meaning that all transferred embryos in a treatment implanted . RESULTS A detailed retrospective analysis of cleavage times , blastomere size and multinucleation was made for the 247 transferred embryos with either failed or full implantation . We found that several parameters were significantly correlated with subsequent implantation ( e.g. time of first and subsequent cleavages as well as the time between cleavages ) . The most predictive parameters were : ( i ) time of division to 5 cells , t5 ( 48.8 - 56.6 h after ICSI ) ; ( ii ) time between division to 3 cells and subsequent division to 4 cells , s2 ( ≤ 0.76 h ) and ( iii ) duration of cell cycle two , i.e. time between division to 2 cells and division to 3 cells , cc2 ( ≤ 11.9 h ) . We also observed aberrant behavior such as multinucleation at the 4 cell stage , uneven blastomere size at the 2 cell stage and abrupt cell division to three or more cells , which appeared to largely preclude implantation . CONCLUSIONS The image acquisition and time-lapse analysis system makes it possible to determine exact timing of embryo cleavages in a clinical setting . We propose a multivariable model based on our findings to classify embryos according to their probability of implantation . The efficacy of this classification will be evaluated in a prospect i ve r and omized study that ultimately will determine if implantation rates can be improved by time-lapse analysis BACKGROUND This study was undertaken to determine what characteristics should be recorded on which days to build a predictive model for selection of Day 3 embryos . METHODS Embryos failing to form a clinical sac or that formed a viable fetus ( to > or = 12 weeks ) , and transferred singly ( n = 269 ) or in pairs ( n = 1326 ) were scored for early cleavage and pronuclear status on Day 1 , and cell number , fragmentation , and symmetry on Days 2 and 3 , with number of nuclei per blastomere also recorded on Day 2 . Seven c and i date models were identified using a priori clinical knowledge and univariate analyses . Each model was fit on a training-set and evaluated on a test-set with resampling , with discrimination assessed using the area under the ROC curve ( AUC ) and calibration assessed using the Hosmer-Lemeshow statistics . RESULTS Models built using Day 1 , 2 or 3 scores independently on the 30 re sample d data sets showed that Day 1 evaluations provided the poorest predictive value ( median AUC = 0.683 versus 0.729 and 0.725 , for Day 2 and 3 ) . Combining information from Day 1 , 2 and 3 marginally improved discrimination ( median AUC = 0.737 ) . Using the final Day 3 model fitted on the whole data set , the median AUC was 0.732 ( 95 % CI , 0.700 - 0.764 ) , and 68.6 % of embryos would be correctly classified with a cutoff probability equal to 0.3 . CONCLUSIONS Day 2 or Day 3 evaluations alone are sufficient for morphological selection of cleavage stage embryos . The derived regression coefficients can be used prospect ively in an algorithm to rank embryos for selection STUDY QUESTION Can the pronuclei ( PN ) morphology and the time of PN breakdown ( PNB ) predict the potential of embryos to result in live birth ? SUMMARY ANSWER In comparison to embryos result ing in no live birth , PNB occurred significantly later in embryos result ing in live birth and never earlier than 20 h 45 min . None of the tested scoring systems were shown to predict the live birth outcome in a time-lapse set-up . WHAT IS KNOWN ALREADY The PN morphology is supported as a prominent embryo selection parameter in single light microscopy observations , although controversial results have been reported . STUDY DESIGN , SIZE , DURATION This was a prospect i ve study of 159 embryos , all of which were later transferred . The PN morphology of 46 embryos which result ed in live birth was compared with that of 113 embryos which result ed in no live birth . PARTICIPANTS , SETTING From 1 March 2010 to 30 August 2011 , 130 couples underwent fertility treatment by ICSI .  Embryo culture was performed in a time-lapse set-up from fertilization to intrauterine transfer . PN morphological assessment was performed on every embryo replaced , using six different scoring systems at different times . MAIN RESULTS AND THE ROLE OF CHANCE No embryo with PNB earlier than 20 h 45 min result ed in live birth . All six PN assessment models showed no significant distribution of scores ( P = NS ) between the live birth and no live birth groups at 16 h post-fertilization ( PF ) , 18 h PF and 40 min before PNB . The outcomes of assessment s changed significantly ( P < 0.001 ) over time and the time of PNB was found to be the optimal stage to evaluate the PN morphology . LIMITATIONS , REASONS FOR CAUTION The study includes only embryos reaching the 4-cell stage after ICSI , and transferred at 44 h PF . WIDER IMPLICATION S OF THE FINDINGS The PN morphology changes over time , indicating that the single light microscopy observation approach is deficient in comparison to time-lapse . Although the assessment of the PN morphology does not improve embryo selection , the timing of PNB should be included in embryo selection parameters BACKGROUND The objective of this investigation was to determine the inter- and intraobserver agreement when assessing embryo quality  .  METHODS This investigation included 4002 cleaved embryos from 7535 oocytes retrieved in 688 patients undergoing IVF cycles in a multicentre trial .  Embryos were evaluated locally at the inverted microscope at 28 , 44 and 68 h ( + /-1 h ) post-insemination . Digital images of the embryos were assessed central ly by three blinded embryologists . To assess reproducibility , 215 r and omly selected cleaved embryos from 33 patients were re-evaluated by the three central embryologists . RESULTS The interobserver agreement among the central embryologists ( using the same method of evaluation ; 2D images ) was good for classification of top- quality embryos ( kappa 0.71 - 0.73 ) , excellent for classification of normally developed embryos ( kappa 0.83 - 0.86 ) and good-excellent for classification of transferable embryos ( kappa 0.78 - 0.82 ) . The interobserver agreement between local and consoli date d central assessment ( different methods of evaluation , inverted microscopy versus 2D images ) was good for all three embryo classifications ( kappa 0. 
    Output:
    
While several studies suggest higher implantation rates for fast-cleaving embryos and those with a timely duration ( i.e. all time points within the defined ranges ) of the 2-cell and 3-cell stages , no single morphokinetic parameter has been consistently shown to predict implantation potential .
Sparse , often incomplete and largely heterogeneous data suggest that TLM may be able to distinguish between high and low-implantation potential embryos .