No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
Authors: Ahlström A , Lundin K , Cimadomo D , Coticchio G , Selleskog U , Westlander G , Winerdal J , Stenfelt C , Callender S , Nyberg C , Åström M , Löfdahl K , Nolte L , Sundler M , Kitlinski M , Liljeqvist Soltic I , Bohlin T , Baumgart J , Lindgren K E , Gülen Yaldir F , Rienzi L , Lind A K , Bergh C 
Published: October 2023

Abstract

STUDY QUESTION
Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?

SUMMARY ANSWER
There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, &lt;37 weeks), low birth weight (LBW, &gt;2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.

WHAT IS KNOWN ALREADY
Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.

STUDY DESIGN, SIZE, DURATION
This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).

PARTICIPANTS/MATERIALS, SETTING, METHODS
From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.

MAIN RESULTS AND THE ROLE OF CHANCE
In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87–1.41) and LBW (adjusted OR 0.86, 95% CI 0.66–1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67–1.45 and adjusted OR 0.98, 95% CI 0.62–1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08–1.60) and LBW (adjusted OR 1.36, 95% CI 1.08–1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53–0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68–1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.

LIMITATIONS, REASONS FOR CAUTION
This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.

WIDER IMPLICATIONS OF THE FINDINGS
Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.

STUDY FUNDING/COMPETING INTEREST(S)
The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare.

TRIAL REGISTRATION NUMBER
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