***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 determine if the addition of continuous morphokinetic data improves reproductive outcomes when all embryos are cultured in a closed system . DESIGN Prospect i ve , r and omized , controlled study . SETTING Single academic center . PATIENT(S ) A total of 235 patients undergoing fresh autologous IVF cycles with at least four embryos , cultured in the Embryoscope : 116 patients r and omized to conventional once-daily morphologic embryo screening ( CS ) and 119 to additional time-lapse kinetic monitoring ( TLM ) for selection . INTERVENTION(S ) TLM versus CS . MAIN OUTCOME MEASURE(S ) Intrauterine clinical pregnancy ( CPR ) and implantation ( IR ) rates . RESULT ( S ) CPR and IR were similar overall ( TLM vs. CS , respectively : CPR 68 % vs. 63 % ; IR 51 % vs. 45 % ) and with blastocyst transfers ( CPR 74 % vs. 67 % ; IR 56 % vs. 51 % ) . CPR with day 5 transfer was threefold higher than day 3 transfer , but group ( TLM vs. CS ) was not a significant predictor of clinical pregnancy or implantation . Significantly more multinucleation was detected when CS embryos were retrospectively review ed with the use of TLM ( 7.0 % vs. 35.3 % ) , and multinucleation was independently associated with decreased rates of implantation . Time to the start of blastulation of < 100 hours after insemination and the morphokinetic scoring system used in the TLM group were independently associated with implantation . CONCLUSION ( S ) The addition of time-lapse morphokinetic data did not significantly improve clinical reproductive outcomes in all patients and in those with blastocyst transfers . Absence of multinucleation , timing of blastulation , and morphokinetic score were found to be associated with blastocyst implantation rates . CLINICAL TRIAL REGISTRATION NUMBER NCT02081859 Background Previously manual human embryology in many in vitro fertilization ( IVF ) centers is rapidly being replaced by closed embryo incubation systems with time-lapse imaging . Whether such systems perform comparably to manual embryology in different IVF patient population s has , however , never before been investigated . We , therefore , prospect ively compared embryo quality following closed system culture with time-lapse photography ( EmbryoScope ™ ) and st and ard embryology . We performed a two-part prospect ively r and omized study in IVF ( clinical trial # NCT92256309 ) . Part A involved 31 infertile poor prognosis patients prospect ively r and omized to EmbryoScope ™ and st and ard embryology .  Part B involved embryos from 17 egg donor-recipient cycles result ing in large egg/embryo numbers , thus permitting prospect ively alternative embryo assignments to EmbryoScope ™ and st and ard embryology . We then compared pregnancy rates and embryo quality on day-3 after fertilization and embryologist time utilized per processed embryo . Results Part A revealed in poor prognosis patients no differences in day-3 embryo scores , implantation and clinical pregnancy rates between EmbryoScope ™ and st and ard embryology . The EmbryoScope ™ , however , more than doubled embryology staff time ( P < 0.0001 ) . In Part B , embryos grown in the EmbyoScope ™ demonstrated significantly poorer day-3 quality ( depending on embryo parameter between P = 0.005 and P = 0.01 ) . Suspicion that conical culture dishes of the EmbryoScope ™ ( EmbryoSlide ™ ) may be the cause was disproven when st and ard culture dishes demonstrated no outcome difference in st and ard incubation . Conclusions Though due to small patient numbers preliminary , this study raises concerns about the mostly uncontrolled introduction of closed incubation systems with time lapse imaging into routine clinical embryology . Appropriately design ed and powered prospect ively r and omized studies appear urgently needed in well-defined patient population s before the uncontrolled utilization of these instruments further exp and s . Trial registration NCT02246309 Registered September 18 , 2014 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 To determine whether incubation in the integrated EmbryoScope time-lapse monitoring system ( TMS ) and selection supported by the use of a multivariable morphokinetic model improve reproductive outcomes in comparison with incubation in a st and ard incubator ( SI ) embryo culture and selection based exclusively on morphology . DESIGN Prospect i ve , r and omized , double-blinded , controlled study . SETTING University-affiliated private in vitro fertilization ( IVF ) clinic . PATIENT(S ) Eight hundred forty-three infertile couples undergoing intracytoplasmic sperm injection ( ICSI ) . INTERVENTION(S ) No patient intervention ; embryos cultured in SI with development evaluated only by morphology ( control group ) and embryos cultured in TMS with embryo selection was based on a multivariable model ( study group ) . MAIN OUTCOME MEASURE(S ) Rates of embryo implantation , pregnancy , ongoing pregnancy ( OPR ) , and early pregnancy loss . RESULT ( S ) Analyzing per treated cycle , the ongoing pregnancy rate was statistically significantly increased 51.4 % ( 95 % CI , 46.7 - 56.0 ) for the TMS group compared with 41.7 % ( 95 % CI , 36.9 - 46.5 ) for the SI group . For pregnancy rate , differences were not statistically significant at 61.6 % ( 95 % CI , 56.9 - 66.0 ) versus 56.3 % ( 95 % CI , 51.4 - 61.0 ) . The results per transfer were similar : statistically significant differences in ongoing pregnancy rate of 54.5 % ( 95 % CI , 49.6 - 59.2 ) versus 45.3 % ( 95 % CI , 40.3 - 50.4 ) and not statistically significant for pregnancy rate at 65.2 % ( 95 % CI , 60.6 - 69.8 ) versus 61.1 % ( 95 % CI , 56.2 - 66.1 ) . Early pregnancy loss was statistically significantly decreased for the TMS group with 16.6 % ( 95 % CI , 12.6 - 21.4 ) versus 25.8 % ( 95 % CI , 20.6 - 31.9 ) . The implantation rate was statistically significantly increased at 44.9 % ( 95 % CI , 41.4 - 48.4 ) versus 37.1 % ( 95 % CI , 33.6 - 40.7 ) . CONCLUSION ( S ) The strategy of culturing and selecting embryos in the integrated EmbryoScope time-lapse monitoring system improves reproductive outcomes . CLINICAL TRIAL REGISTRATION NUMBER NCT01549262 Purpose To assess the effects of light from an integrated optical microscope and evaluate the safety of time-lapse observations using a built-in microscope incubator . Methods We prospect ively compared the fertilization rate and embryonic morphology after intracytoplasmic sperm injection between embryos cultured with time-lapse observations every 15 min in an incubator with an integrated optical microscope and embryos with intermittent observations ( once a day ) in conventional incubators .  Results No significant differences were observed in the fertilization rate ( 57.5 % vs. 57.5 % ) or the rate of excellent-good cleavage embryos ( 36.0 % vs. 36.0 % ) . Conclusions These results suggest that time-lapse observations using an incubator with an integrated optical microscope may therefore be safely utilized in clinical practice STUDY QUESTION Does culture in a closed system result in an increased number of good quality embryos ( GQE ) on Day 2 compared with culture in a conventional system ? SUMMARY ANSWER Culture in a closed system up to 2 days after microinjection results in similar embryo development and morphological quality compared with culture in a conventional incubation system . WHAT IS KNOWN ALREADY Time-lapse imaging ( TLI ) incubators are rapidly being introduced into IVF laboratories worldwide , despite the lack of large prospect i ve r and omized trials demonstrating improvement in embryo development or pregnancy rates . STUDY DESIGN , SIZE , DURATION A r and omized controlled trial including 364 patients ( 365 cycles ) was conducted between May 2010 and February 2014 . After oocyte collection , r and omization was carried out and all of a patients ' oocytes were allocated to culture in either a conventional incubator or a closed incubator system in proportion 1:2 until embryo transfer on Day 2 . A total of 1979 oocytes were injected and cultured in the closed system , and 1000 in the st and ard incubator . The primary end-point was the number of GQE in the two groups . PARTICIPANTS / MATERIAL S , SETTING S , METHODS In total , 364 patients undergoing their first IVF cycle using ICSI , where at least one oocyte was retrieved , were r and omized in a university hospital setting . Two hundred and forty patients were r and omized for culture in a closed system and 124 patients for culture in the conventional incubator system ( control group ) .  Embryo assessment s and final morphological scoring before transfer and cryopreservation were carried out at the same time points for embryos cultured in the conventional incubator and in the closed system . MAIN RESULTS AND THE ROLE OF CHANCE There was no significant difference in the mean ± SD number of GQEs between groups : 2.41 ± 2.27 for the closed system group and 2.19 ± 1.82 for the control group ( P = 0.34 , difference 0.23 , 95 % confidence interval 0.69 ; -0.24 ) . No significant differences were found in the number of 4-cell embryos , implantation- , pregnancy- or ongoing pregnancy rates . A significantly higher miscarriage rate was found in the TLI group compared with the control group ( 33.3 and 10.2 % , P = 0.01 ) . LIMITATIONS , REASONS FOR CAUTION Culture media , temperature and gas levels were similar in the open and closed incubator systems , but different culture dishes were used . Culturing embryos for longer time period ( to the blastocyst stage ) may give different results . Only ICSI patients were included , which may limit the generalizability of the results . Finally , the number of GQEs on Day 2 was used as a surrogate outcome for live birth . WIDER IMPLICATION S OF THE FINDINGS The results are consistent with other , smaller r and omized trials showing no difference in embryo quality when comparing culture in a conventional incubator with that of a closed TLI incubator system 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 
    Output:
    
Conclusions Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection .