Is time-lapse monitoring a safe alternative? Obstetric and neonatal outcomes of a multicenter randomized controlled trial

Abstract Study question Are there obstetric or neonatal risks associated with time-lapse monitoring and uninterrupted embryo culture compared to interrupted standard culture and conventional embryo selection? Summary answer The application of time-lapse monitoring using the Geri+ incubator is a safe alternative to standard culture and selection in terms of obstetric and neonatal results. What is known already There is very limited evidence regarding the safety of time-lapse monitoring (TLM) from prospective randomized controlled trials (RCT). Recent RCTs have demonstrated that the application of time-lapse monitoring does not increase (cumulative) live birth rates or the time to pregnancy within one year. However, while most studies only report pregnancy rates, it is essential to also study the safety of this commonly used method. Study design, size, duration The obstetric and neonatal outcomes of patients scheduled for day three single embryo transfer who participated in our multicenter RCT on TLM were studied. Three groups were compared: 1) TLE (Time-Lapse Eeva): embryo selection based on the Eeva® Test (a day three TLM algorithm, used adjunctively with morphology) and uninterrupted culture. 2) TLR (Time-Lapse Routine): routine morphological embryo selection and uninterrupted culture. 3) CON (Control): routine morphological embryo selection and interrupted culture. Participants/materials, setting, methods In total, 1731 IVF/ICSI patients undergoing their first, second or third oocyte pickup were randomized. Obstetric and neonatal data were registered for all pregnancies occurring after fresh and cryo embryo transfers associated with the initial oocyte pickup cycle as well as natural conceptions within one year. Adjusted relative risks with 95% CI were calculated; in view of the three groups and many comparisons only p-values are presented. Main results and the role of chance A total of 838 women had a live birth during the follow-up period (TLE = 281, TLR = 280, CON = 277; p = 0.98). The rate of serious pregnancy complications was not significantly different between the three groups (TLE = 10.7%, TLR = 10.9%, CON = 11.0%; p = 0.99). Mean gestational age at birth was 39.3 (2.0) weeks, 39.4 (1.6) weeks and 39.3 (2.0) weeks, respectively (p = 0.59). The rate of preterm and very preterm birth did not differ significantly between the three groups (<37 weeks: p = 0.50; <32 weeks: p = 0.20). Average weight at birth was 3396 (598) grams, 3394 (565) grams and 3363 (592) grams, respectively (p = 0.76). Low and very low birthweight also did not differ significantly between the three groups (<2500g: p = 0.77; <1500 g: p = 0.88). Health problems immediately after delivery were reported for eight babies in the TLE group, twelve in the TLR group and eleven in the CON group (p = 0.66). Major congenital malformations occurred in four children in the TLE group, four in the TLR group and seven in the CON group (p = 0.54). Minor congenital malformations were found in five children in the TLE group, three in the TLR group and five in the CON group (p = 0.73). No significant differences were observed for the mode of delivery and the APGAR scores. Limitations, reasons for caution This study reports the safety of time-lapse monitoring using the Geri+ time-lapse incubator, while more systems are currently available. Wider implications of the findings Uninterrupted embryo culture with or without the use of the Eeva® Test selection algorithm does not lead to increased obstetric or neonatal risks when compared to conventional interrupted embryo culture. Our results suggest that TLM is a safe and effective alternative to standard culture and selection. Trial registration number NTR5423